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Clin Transl Allergy 2016, 6(Suppl 3):31
DOI 10.1186/s13601-016-0121-z
MEETING ABSTRACTS
7th drug hypersensitivity meeting: part
one
Malaga, Spain. 21–23 April 2016
© 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium,
provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/
publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Oral Abstracts
O1
Functionally distinct HMGB1 isoforms correlate withphysiological
processes indrug‑induced SJS/TEN
Daniel F. Carr1, Wen‑Hung Chung2, Rosalind E. Jenkiins1, Mas Chaponda1,
Gospel Nwikue1, Elena M. Cornejo Castro1, Daniel J. Antoine1, Munir
Pirmohamed1
1University of Liverpool, Liverpool, United Kingdom; 2Chang Gung
Memorial Hospital, Taipei, Taiwan
Correspondence: Daniel F. Carr
Clinical and Translational Allergy 2016, 6(Suppl 3):O1
Background: Stevens Johnson syndrome (SJS) and toxic epidermal
necrolysis (TEN) are serious, life threatening severe immune-mediated
cutaneous reactions with mortality ranging from 10 to 30%. The com-
monest causes are drugs. SJS/TEN is characterised by widespread epider-
mal detachment due to keratinocyte cell death. Increased concentrations
of cytotoxic molecules may act as potential serum biomarkers of SJS/TEN.
However, to date no mechanism based biomarker has been validated for
diagnostic utility in this eld. HMGB1 is a well-validated biomarker of cell
death and inammation. This study investigated whether HMGB1 repre-
sents a valid, utilisable biomarkers for drug-induced SJS/TEN.
Materials and methods: Serum samples from nevirapine-treated
Malawian HIV patients (27 MPE, 12 DRESS, 12 SJS/TEN cases and
matched tolerant controls) were analysed for total HMGB1 by ELISA.
Novel mass-spectrometric protocols were also used to analyse post-
translationally modied forms of HMGB1. In addition serum from 20
Taiwanese SJS patients (ve carbamazepine, eight allopurinol, ve
phenytoin, two sulfamethoxazole) both during and post-reaction were
analysed for HMGB1 isoforms.
Results: There was a signicant elevation of mean total serum HMGB1
at time of reaction in patients with nevirapine-induced MPE (6.0 ng/
ml), HSS (6.3 ng/ml) and SJS/TEN (15.9 ng/ml) compared to tolerant
controls at weeks (1.3ng/ml) (p<0.001). Analysis of post-translationally
modied isoforms of the HMGB1 in the dierent phenotypes (Fig.1)
showed patients with MPE and DRESS had elevation the acetylated
form of HMGB1 which is a marker of innate immunity. By contrast, SJS/
TEN patient sera contained comparable levels of acetylated HMGB1,
but also had very high levels of the non-acetylated form, which is asso-
ciated with cell death/tissue injury. The tolerant control patients had
low levels of the unacetylated form. This pattern of HMGB1 isoform
elevation was replicated in the Taiwanese SJS cohort.As patients recov-
ered, the total HMGB1 concentrations went down, although there was
still signicant elevation of the sulphonyl (partially reduced) HMGB1
isoform which has no known immune function and may represent a
marker of innate immunity returning to “steady state”.
Conclusions: In conclusion, our data suggest that post-translationally
modied HMGB1 may represent mechanism-based diagnostic and
prognostic markers for drug-induced SJS/TEN. This needs to be stud-
ied in more patients.
Keywords: Stevens Johnson syndrome; HMGB1; Biomarker; Hypersensitivity
O2
Hypersensitivity reactions tobeta‑lactams, does the t cell
recognition pattern inuence the clinical picture?
Natascha Wuillemin, Dolores Dina, Klara K. Eriksson, Daniel Yerly
University Hospital Bern, Bern, Switzerland
Correspondence: Dolores Dina
Clinical and Translational Allergy 2016, 6(Suppl 3):O2
Background: Worldwide, beta-lactam antibiotics can commonly cause
hypersensitivity reactions (HR) with various clinical pictures from
minor aections like maculopapular exanthema (MPE) and urticaria to
severe cutaneous adverse reactions (SCAR) and anaphylaxis. Currently,
two dierent concepts provide rational explanations how a drug can
initiate a drug HR by activating human T cells—the hapten concept
and the pharmacological interaction with immune receptor (p–i) con-
cept. In this study, we investigated the relationship between the reac-
tivity pattern of drug-reacting T cells found in the peripheral blood of
allergic patients and their clinical picture.
Open Access
Clinical and
Translational Allergy
Fig. 1 Serum levels of post‑translationally modified isoforms of
HMGB1 in nevirapine treated patients at time of hypersensitivity reac‑
tion (2 weeks post commencement of treatment for tolerant patients)
These abstracts have been published as part of Clinical and Translational Allergy Volume 6 Suppl 2, 2016. The full contents of the
supplement are available online at http://ctajournal.biomedcentral.com/articles/supplements/volume‑6‑supplement‑3. Please
note this article is part one of two
Published: 25 August 2016
Page 2 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
Materials and methods: We expanded beta-lactams reacting T cells
from drug allergic individuals, including patients with typically IgE
mediated hypersensitivity reactions such as urticaria or anaphylaxis as
well as patients with T cell mediated reactions such as MPE and SCAR.
The drug-reacting T cells were analyzed in terms of their phenotype
(CD4+/CD8+) and the recognition pattern of AMX, e.g. hapten or p–i.
Results: From patients with type I HR to amoxicillin, T cell clones (TCC)
could be generated and analysed. They showed amoxicillin reactivity
according to the hapten mechanism: antigenic complexes were stably
presented and antigen presentation machinery was essential for T cell
activation. TCC from patients suering from MPE showed similar fea-
tures. Three patients with DRESS to amoxicillin or ceftriaxone could be
included. Drug reacting T cells from those patients showed exclusively
reactivity according to pi-concept. Stimulatory antigenic complexes
were not stably presented for T cell activation and addition of drug to
TCC in the presence of antigenic presenting cells lead to immediate
activation, measured by calcium intake.
Conclusions: We conclude that T cells from type I HR and MPE patients
recognize beta-lactams according to the hapten mechanism. In con-
trast, in patients with SCAR, the p–i concept might also be relevant for
beta-lactams recognition. Consequently, the current preclinical risk
evaluation of new drugs to cause severe HR, which is solely based on
their ability to form haptens, might be insucient.
Keywords: Hapten; PI; Amoxcillin
O3
Specic binding characteristics ofHLA alleles associated
withnevirapine hypersensitivity
Rebecca Pavlos1, Elizabeth Mckinnin1, David Ostrov2, Bjoern Peters3, Soren
Buus4, David Koelle5, Abha Chopra1, Craig Rive1, Alec Redwood1, Susana
Restrepo6, Austin Bracey6, Jing Yuan7, Silvana Gaudieri8, Mary Carrington9,
David Haas10, Simon Mallal10, Elizabeth Phillips10
1Murdoch University, Perth, Australia; 2University of Florida, Gainesville,
USA; 3La Jolla Institute for Allergy and Immunology, La Jolla, USA; 4Univer‑
sity of Copenhagen, Copenhagen, Denmark; 5University of Washington,
Seattle, USA; 6Univesrity of Florida, Gainesville, USA; 7Boehringer Ingel‑
heim Inc, Ridgefield, USA; 8Univesrity of Western Australia, Perth, Australia;
9Ragon Insitute, Cambridge, USA; 10Vanderbilt University, Nashville, USA
Correspondence: Rebecca Pavlos
Clinical and Translational Allergy 2016, 6(Suppl 3):O3
Background: Nevirapine (NVP) is a non-nucleoside reverse tran-
scriptase inhibitor (NNRTI) associated with a hypersensitivity syn-
drome (HSR) in approximately 5% of patients. Multiple class I/II HLA
associations have been described in association with NVP hypersensi-
tivity reaction (HSR) phenotypes. Based on the established models of
drug HSR which highlight the signicance of the HLA peptide binding
groove for specic drug interactions, we compared NVP HSR-asso-
ciated alleles across ethnic groups for similarities in peptide binding
specicities and HLA binding pocket structure.
Materials and methods: HLA typing was performed on DNA from
ClinicalTrials.gov NCT00310843. Univariate and multivariate analyses
stratied for race were performed according to HLA class I/II alleles,
MHCcluster groups and key HLA peptide binding groove amino acids.
Results: Examination of HLA allele peptide binding characteristics,
together with structure of the B and F pockets in the peptide binding cleft
identied a group of HLA-C alleles with common binding properties, and
the same F pocket structure as HLA-C*04:01 that were predictive of cutane-
ous NVP HSR (HLA-C*04:(03/06/07), -C*05:(01/09), -C*18:01) (OR [95% CI]
2.9 [1.6–5.23], p=0.005). Similarly, a group of protective HLA-B alleles with
a characteristic B pocket was identied (HLA-B*15:(01/12/24/25/27/32/35),
-B*52:01) (OR [95 % CI] = 0.2 [0.07–0.5], p = 0.0003). HLA-DRB1 alleles
DRB1*01:(01/02/03), DRB1*04:(04/05/08/10), -DRB1*14:02) which share
the DRB1-P4 pocket were found to associate with cutaneous NVP HSR (OR
[95% CI] 2.15 [1.23–3.24], p=0.0013). Molecular docking suggests that
NVP is able to bind to the B pocket in both HLA-B and HLA-C as well as the
P4 residues in HLA-DRB1.
Conclusions: The cutaneous phenotypes of NVP HSR associates with
dierent HLA-C, HLA-B and DR-alleles respectively that share peptide
binding characteristics and binding pocket structure. Models suggest
that NVP may bind directly to multiple HLA within the antigen binding
cleft in the site normally occupied by peptide. The identied HLA-NVP
interactions will have consequences for peptide binding and T cell
receptor recognition in NVP HSR.
Keywords: Nevirapine; HLA; Peptide binding groove
O4
Do we need tomeasure total ige forthe interpretation
ofanalytical results ofImmunoCAP dnd 3gAllergy specic IgE?
Douwe De Boer1, Paul Menheere1, Chris Nieuwhof2, Judith Bons1
1Central Diagnostic Laboratory, MUMC+, Maastricht, The Netherlands;
2Internal Medicine, MUMC+, Maastricht, The Netherlands
Correspondence: Douwe De Boer
Clinical and Translational Allergy 2016, 6(Suppl 3):O4
Background: Non-specic binding of IgE in invitro IgE allergy tests
contributes to false-positive results. For ImmunoCAP it is stated that
very low levels of allergen specic IgE (sIgE) should be evaluated with
caution when total IgE (tIgE) >1000kU/l. For β-lactams and chlorhex-
idine sIgE the warning limit is 500kU/l. For 3gAllergy no such alerts are
known. These warnings imply to measure tIgE for an interpretation of
analytical results of at least ImmunoCAP sIgE. Goal of this study is to
verify such warning limits for ImmunoCAP as well as 3gAllergy.
Materials and methods: Relationship between sIgE and tIgE was
investigated for ImmunoCAP (Thermo Fisher) and 3gAllergy (Siemens)
penicillin V sIgE as well as for ImmunoCAP chlorhexidine sIgE. Ves
versus 5 sIgE was taken as the 1000kU/l limit control. All tests were
performed according the manufacturers’ instructions.Because Immu-
noCAP and 3gAllergy tIgE have a very strong correlation (r= 0.995),
sIgE of both tests were graphically plotted against ImmunoCAP tIgE
only. An iterative polynomial regression procedure, which excluded
outliers when those after tting were outside the 95 % condence
interval, was applied to check for the nature of a relationship.
Results: For ImmunoCAP penicillin V (r = 0.900) and chlorhexidine
(r=0.888) strong polynomial relations were observed, while for Immu-
noCAP Ves versus ve only very weak relations (r<0.500) were noticed.
For tIgE> 500kU/l most of the penicillin V and chlorhexidine sIgE val-
ues were >0.10kU/l and with increasing tIgE the number of sIgE values
>0.35kU/l increased. For 3gAllergy some results were >0.35kU/l, but the
majority of results was <0.10 kU/l and consequently insucient data
points were obtained for adequate regression.ImmunoCAP is based on
high-capacity binding cellulose and at relatively high concentrations of
tIgE, the frequency of possible false-positive results increases, especially
for penicillin V and chlorhexidine sIgE. 3gAllergy is based on non-speci-
ed polymers attached to a bead, which is also subjected to false-posi-
tive results for penicillin V sIgE, but only at lower levels and frequency.
Conclusions: The warning limit of 500kU/l of tIgE for ImmunoCAP
penicillin V and chlorhexidine sIgE is valid and above the limit false-
positive results are likely. For 3gAllergy penicillin V sIgE a limit is also
needed but at a higher level. Consequently, for the respective tests we
do need to measure tIgE for any sIgE result >0.10kU/l.
Keywords: Total IgE; Penicillin; Chlorhexidine; ImmunoCAP; 3gAllergy
O5
Neutrophil activation insystemic anaphylaxis: results fromthe
multicentric NASA Study
Friederike Jonsson1, Luc De Chaisemartin2, Vanessa Granger2, Caitlin
Gillis1, Aurelie Gouel1, Catherine Neukirch2, Fadia Dib2, Pascale Roland
Nicaise2, Dan Longrois2, Florence Tubach2, Sylvie Martin2, Pierre Bruhns1,
NASA Study Group3
1Institut Pasteur, France, France; 2Hopital Bichat, France, France; 3Institut
Pasteur & Hopital Bichat, France, France
Correspondence: Pierre Bruhns
Clinical and Translational Allergy 2016, 6(Suppl 3):O5
Background: Anaphylaxis is a severe systemic allergic reaction that
can be life-threatening. In about 85% of cases evidence for the acti-
vation of the classical anaphylaxis pathway involving IgE and IgE
receptors can be detected. Recently, an alternative pathway involv-
ing IgG and IgG receptors (FcγRs) on neutrophils has been suggested
Page 3 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
by animal models. We hypothesized that such a mechanism may also
exist in humans and studied this possibility in a multicentric prospec-
tive cohort of patients suspected of perioperative anaphylaxis to neu-
romuscular blocking agents (NMBA).
Materials and methods: Consecutive patients suspected of periopera-
tive anaphylaxis (n=86 cases) were recruited and paired with 86 control
patients. Blood samples were collected for cases and controls promptly
after anesthesia induction. Extensive allergological testing was per-
formed 6–8weeks after the reaction for cases. Circulating elastase, neu-
trophil extracellular traps (NETs), tryptase, histamine, and IgG and IgE
anti-NMBA were measured by ELISA. FcγR expression on the major cell
populations in the blood was analyzed by ow cytometry.
Results: We found higher circulating NETs and elastase levels during
an anaphylactic reaction compared to controls. IgG anti-NMBA were
found in both cases and controls, however for cases the IgG titer was
associated with anaphylaxis severity. Finally, we show a signicant
decrease of FcγR expression specically on neutrophils, pointing
towards their engagement by immune complexes. This decrease not
only correlated signicantly with NET release but also with the severity
of the anaphylactic reaction. Together, our results strongly suggest an
activation of neutrophils by NBMA-IgG complexes during anaphylaxis.
Conclusions: We reveal for the rst time the existence of an IgG-
dependent neutrophil activation pathway during anaphylaxis in
human. This additional mechanism opens potential applications in
anaphylaxis diagnostics and treatment.
Keywords: Anaphylaxis; Drug; Curare; IgG; Neutrophils
O6
Purpuric drug eruptions due toepidermal growth factor receptor
tyrosine kinase inhibitors (EGFR‑TKIs) fornon‑small‑cell lung
cancer (NSCLC): a clinic‑pathological study of32 cases
Kai‑Lung Chen1, Shu‑Ling Liao1, Yi‑Shuan Sheen1, Yung‑Tsu Cho1,
Che‑Wen Yang1, Jau‑Yu Liau2, Chia‑Yu Chu1
1Department of Dermatology, National Taiwan University Hospital
and National Taiwan University College of Medicine, Taipei, Taiwan, Taipei,
Taiwan; 2Department of Pathology, National Taiwan University Hospital
and National Taiwan University College of Medicine, Taipei, Taiwan, Taipei,
Taiwan
Correspondence: Kai‑Lung Chen
Clinical and Translational Allergy 2016, 6(Suppl 3):O6
Background: Epidermal growth factor receptor tyrosine kinase inhibi-
tors (EGFR-TKIs) have been widely used to treat non-small-cell lung
cancer (NSCLC). Skin toxicities related to EGFR-TKIs are common, such
as acneiform eruptions, pruritus, xerosis, and paronychia. However,
purpuric eruptions are rarely seen and only few cases reported. We
conducted this study to classify the purpuric drug eruptions due to
EGFR-TKIs (getinib, erlotinib, or afatinib) for NSCLC with clinic-path-
ological correlations.
Materials and methods: During January 2012 to August 2015, 32
patients were included in this study. We recorded the characteristic,
lag period, and also the peripheral platelet counts while biopsy. Skin
biopsies with tissue culture were undertaken in every patients. DIF
studies were performed in most of them.
Results: We classied the clinical presentations into four dierent types:
purpura only (n=7, 21.9%), eczema craquelé-like (n=5, 15.6%), pus-
tulosis (n= 16, 50 %), and necrolytic migratory erythema (NME)-like
patches (n=8, 25%). Dierent types could be presented on the same
patient concomitantly. 93% (15/16) of pustulosis type specimens grew
Staphylococcus aureus, whereas only 25% (5/20) among other types.
Most of the histopathology showed parakeratosis, hypogranulosis,
perivascular lymphocytic and neutrophilic inltration, endothelial cell
swelling and RBC extravasation. Typical leukocytoclastic vasculitis (LCV)
was found in 13–29% of patients. Most of the DIF showed negative
nding. Most of the patients were responsive to one-week systemic
cefazolin treatment with or without discontinuing the EGFR-TKI.
Conclusions: There are four types of the purpuric drug eruptions due
to EGFR TKIs: purpura, eczema craquelé-like, pustulosis, and NME-like
patches. No signicant histopathological dierences between each
group, and less than one-third of patients presented typical LCV.
Staphylococcus aureus was the most common pathogen identied.
Most of the patients showed dramatic improvement by the treatment
of systemic antibiotics, especially those with pustulosis type.
Keywords: EGFR-TKIs; Purpura; Vasculitis; Staphylococcus
Poster Presentations: Poster Walk 1—Anaphylaxis (P01–P09)
P1
Anaphylactic reactions duringanaesthesia andthe perioperative
period
Rita Aguiar, Anabela Lopes, Natália Fernandes, Leonor Viegas,
M. A. Pereira‑Barbosa
Immunoallergology Department, Hospital de Santa Maria‑Centro Hospi‑
talar Lisboa Norte, Lisbon, Portugal
Correspondence: Rita Aguiar
Clinical and Translational Allergy 2016, 6(Suppl 3):P1
Background: Anaphylaxis incidence in the perioperative setting varies
between 1:10,000 and 1:20,000. Although this value is yet to be deter-
mined in Portugal, an increase in the number of reactions has been
reported. Clinical evaluation is important in order to identify risk fac-
tors and drugs that cause anaphylaxis, so that alternative options can
be found.
The aim of this study was to characterize the reactions of patients
(pts) with perioperative anaphylaxis and for conducting medical tech-
niques requiring sedation.
Materials and methods: Retrospective analysis of medical records
of 57 pts with perioperative anaphylaxis and anaphylaxis undergo-
ing medical procedures with sedation, observed in the immunoaller-
gologic outpatient clinic (2009–2015).
The diagnostic investigation was carried out 6–8weeks after the reac-
tion, included detailed medical history, specic IgE assay to betalac-
tams and latex, skin tests (ST) with the culprit drug and evidence of
provocation when necessary, according to the recommendations of
the SFAR/ENDA.
Results: We studied 56 pts (41 females) with mean age of 50±18years.
Regarding the severity of anaphylaxis and according to Mertes classi-
cation, 24 cases (42.8%) had stage I reaction and 24 cases (42.8%) had
II reaction, 7 cases (12.5%) grade III and 1 case (1.8%) grade IV.
An IgE-mediated mechanism has been established in 34 pts (60.7%).
The major etiologic agents causing IgE-mediated reactions were mus-
cle relaxants in seven pts (12.5%), antibiotics in six cases (10.7%; four
cefazolin, one aminopenicillin, one ciprooxacin), metamizole in three
pts (5.4%), two pts latex (3.6%), seven pts (12.5%) reacted with less
representative agents.
On 10 pts (17.8%) drugs responsible for the reactions were associated
with non-IgE-mediated mechanisms, anti-inammatory (NSAIDs) are
the most frequent agents (ve pts).
In 14 pts (25%) it was not possible to determine a pharmacological
aetiology of the reaction.
Conclusions: More than half of perioperative events (60.7%) have
an IgE-mediated mechanism. Muscle relaxants, antibiotics and pat-
ent blue dye were the most frequently identied agents. In 17.8% of
the reactions was involved a non-IgE-mediated mechanism, namely
NSAIDs. It is important to determine the aetiology of perioperative
reactions for guidance in future surgery, either because the identied
agents are often used outside the perioperative setting.
Keywords: Anaphylatic reactions; Anaesthesia
P2
Anaphylaxis tochlorhexidine: is there a cross‑reactivity
toalexidine?
Antonia Bünter1, Nisha Gupta2, Tatjana Pecaric Petkovic1, Nicole Wirth1,
Werner J. Pichler1, Oliver Hausmann3
1ADR‑AC GmbH, Bern, Switzerland; 2Teleflex Incorporated, Bern, Switzer‑
land; 3Dep. of Rheumatology, Immunology and Allergology, University
Hospital and University of Bern, Bern, Switzerland
Correspondence: Antonia Bünter
Clinical and Translational Allergy 2016, 6(Suppl 3):P2
Page 4 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
Background: Chlorhexidine (CHX) and its diacetate derivative (CHA)
are two forms of the same disinfectant for skin and mucosal surfaces
as well as medical devices. CHX/CHA are bivalent compounds with
biguanide groups and chlorophenyl endings. CHX/CHA can cause IgE-
mediated anaphylaxis. Alexidine (ALX), a related biguanide without
aromatic end groups, has similar bactericidal properties and repre-
sents a potential substitute for CHX/CHA. The allergic potential of ALX
is unknown.
Materials and methods: We investigated whether patients sensitized
to CHX/CHA also react with ALX. We used blood of CHX/CHA-allergic
donors for basophil activation testing (BAT for CD63 and CD203a as
activation markers) with CHA and ALX. In addition, we performed inhi-
bition assays with CHA, chlorguanide (CG) and ALX using a commercial
IgE assay for CHX (ImmunoCAP, ThermoFisher Scientic, Uppsala).
Results: 13 patients from a single tertiary care center with allergic
reactions to CHX within the last 8years were included. 9/13 patients
had still elevated CHX-specic IgE (>0.35 kU/l), although mostly
substantially lower compared to the time of anaphylaxis. In 6/13
patients with CHX-specic IgE >0.7kU/l CAP inhibition studies were
performed. CG showed a strong inhibitory eect in 6/6 and CHA in
3/6 tested sera. ALX induced partial inhibition of CHX positivity in
2/6 sera but at much higher concentrations compared to CHA. 3/13
patients showed a positive BAT with CHA, one of them with additional
positivity to ALX.
Conclusions: Both, CAP inhibition studies as well as BAT analysis show
that patients with documented CHX/CHA allergy do not or only par-
tially react with ALX in these IgE-based assays. Based on this limited
cross-reactivity of CHX/CHA and ALX, ALX may be potential alternative
for CHX-allergic patients. More patients need to be included to sub-
stantiate this assumption. An ALX-specic IgE assay would help to dif-
ferentiate CHX/CHA- and ALX-specic sensitization.
P3
Cefotaxime‑induced severe anaphylaxis ina neonate
Mehtap Yazicioglu1, Pinar G. Ozdemir1, Gokce Ciplak2, Ozkan Kaya3
1Trakya University Department of Pediatric Allergy, Edirne, Turkey; 2Trakya
University Department of Pediatrics, Edirne, Turkey; 3Trakya Hospital,
Edirne, Turkey
Correspondence: Mehtap Yazicioglu
Clinical and Translational Allergy 2016, 6(Suppl 3):P3
Background: Anaphylaxis is dened as a serious generalized aller-
gic or hypersensitivity reaction that is rapid in onset and might
cause death. It is very rare in infancy. In this case report, we present
a neonate who developed anaphylaxis during infusion of rst dose of
cefotaxime.
Report: A-1 month infant was referred to our Pediatric Emergency
Department because of anaphylactic reaction with rash, cyanosis and
respiratory arrest developed after rst dose of cefotaxime treatment.
She was intubated immediately, then extubated after 10min.Physical
examination on admission showed prolonged expirium bilaterally, and
rales at the right lung base. Other ndings were unremarkable. She
was hospitalized and treatment with salbutamol nebules (0.15 mg/
kg/dose, q 6h) was started. Vital ndings were observed closely. On
the 4th day of admission, before discharge, she was consulted with
our pediatric allergy department. She was born full term by Cesarean
delivery, weighing3180g. Her personal and family history was unre-
markable, except her mother described rash and swelling of the lips
and face after spraying cologne. Laboratory investigations on admis-
sion: CBC with white blood cell dierential was within normal range;
C-reactive protein (CRP): 1.35mg/dl (0–0.34); serum total IgE: 2.4U/
ml (0–170). Serum tryptase: 17.7ng/ml (on the 4th day of admission);
serum tryptase 12.3ng/ml (after 2months). Skin prick tests with cefo-
taxime (2mg/ml), and cefotaxime (10mg/ml) were both negative. We
did not perform intradermal tests and drug provocation test with cefo-
taxime. The patient was discharged to be followed with prescription
of epinephrine autoinjector to use in case of anaphylactic emergency,
and the family was educated about about signs and symptoms of ana-
phylaxis and about when and how to use the EpiPen.
How this report contributes to current knowledge: Anaphylaxis
in newborn period is very rare. Our case was interesting that to our
knowledge this is the rst case of anaphylaxis in a newborn induced
by rst dose of an antibiotic. We wished to attract attention that severe
drug reactions can also be seen in early life.
P4
Clinical features anddiagnosis ofanaphylaxis resulting
fromexposure tochlorhexidine
Peter John Cooke
Auckland City Hospital, Auckland, New Zealand
Correspondence: Peter John Cooke
Clinical and Translational Allergy 2016, 6(Suppl 3):P4
Background: The Auckland Anaesthetic Allergy Clinic is jointly pro-
vided by the Departments of Anaesthesia and Immunology. All
patients referred following perioperative anaphylaxis are skin prick
tested with chlorhexidine 2%. This review describes the clinical fea-
tures of the cases in which a diagnosis of allergic anaphylaxis to chlo-
rhexidine was made during the period January 2012 to December
2015.
Materials and methods: Patient data and clinic test results were
archived on a simple Excel spreadsheet. These were reviewed by the
author and a chart review of the chlorhexidine anaphylaxis cases was
undertaken.
Results: A total of 14 patients were diagnosed with chlorhexidine
allergy during the period (11 male and 3 female).
The following manifestations of anaphylaxis were documented: hypo-
tension (12 patients), tachycardia (9), ushing (7), facial swelling (4),
urticaria (3), bronchospasm (2), piloerection (2), agitation (1), gen-
eralized swelling (1). Four patients had CPR during their anaphylaxis,
nine patients had a grade 3 reaction and one patient had a grade 1
reaction. Twelve of the 14 patients received adrenaline. Anaphylaxis
followed the insertion of a chlorhexidine impregnated central venous
line in seven cases, urethral catheterization with chlorhexidine con-
taining gel in three and following topical exposure only in four cases.
Skin testing was performed 30–130days after the anaphylaxis event.
All of the patients diagnosed with chlorhexidine allergy developed
a wheal >3 mm after a s prick test with 2 % chlorhexidine (range
3–20mm). The specic IgE for Chlorhexidine was obtained in 11 of the
14 cases and in 10 of the 11 it was elevated.
During the same period 219 other patients were seen at our clinic and
all received skin prick tests for chlorhexidine 2%. All of these patients
had completely negative tests with a no wheal and no are.
Conclusions: This data shows that patients with chlorhexidine ana-
phylaxis demonstrate typical signs but that hypotension is the most
common manifestation. Convincing skin testing results along with
specic IgE testing and the clinical history provided the basis of the
diagnosis. Chlorhexidine is used in our region for skin preparation
prior to anaesthetic and surgical procedures and four anaphylaxis
cases resulted from topical exposure to chlorhexidine.
Our data also suggests that a skin prick test with 2% chlorhexidine in
alcohol is a satisfactory method of skin testing.
Keywords: Chlorhexidine; Skin prick testing; Specic IgE; Anaphylaxis
P5
Drug‑induced anaphylaxis: ve‑year single‑center survey
Inês Mota, Ângela Gaspar, Filipe Benito‑Garcia, Marta Chambel, Mário
Morais‑Almeida
Immunoallergy Department, CUF Descobertas Hospital, Lisbon, Portugal
Correspondence: Inês Mota
Clinical and Translational Allergy 2016, 6(Suppl 3):P5
Background: Drug-induced anaphylaxis (DIA) is the most common
cause of fatal anaphylaxis. Anaphylaxis related to nonsteroidal anti-
inammatory drugs (NSAID) is typically drug-specic or class-specic,
as well as with beta-lactams (BL) antibiotics (AB). Although skin testing
and drug provocation tests (DPT) can conrm the diagnosis, in severe
cases the diagnosis is mostly based on clinical history. The aim of this
Page 5 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
study was to characterize patients (pts) with DIA and their drug allergy
work-up.
Materials and methods: Systematic review of all pts with clinical his-
tory compatible with DIA reported to our drug allergy center in the
last 5years. All pts were investigated according to ENDA/EAACI recom-
mendations, through skin testing and invitro tests (whether standard-
ized tests available) and DPT (when indicated).
Results: A total of 114 pts were included: mean age 41.5 (SD±16.8)
years, 10% <18 years, 68% female, 72% atopic and 23% had asthma.
Median age of rst anaphylactic episode was 36.5years [1;74], and
19 pts had recurrent DIA. The main causes were NSAID (50 pts) [ace-
tylsalicylic acid (15), ibuprofen (13), metamizol (13), diclofenac (9),
paracetamol (3), etodolac, ketorolac and clonixin (one each)] and AB
(46 pts) [BL (37), quinolones (4), macrolides (3), fosfomycin (1) and
minocycline (1)]. Other drug agents found: neuromuscular blocking
drugs (ve pts), proton pump inhibitors (ve pts), carboplatin (three
pts), corticosteroids (two pts), localanesthetics (two pts), ranitidine,
midazolam and patent blue (1pt each). There was a predominance
of mucocutaneous manifestations (96 %), followed by respiratory
(80%) and cardiovascular (45%) symptoms. In 25% of pts the reac-
tion occurred in hospital setting and 12% had intraoperative ana-
phylaxis. DIA was supported in 72 pts (63%), through skin tests in 62
and the remaining by invitro tests or DPT. Considering the severity of
reactions and the lack of standardized tests for some drugs, patients
whose DIA was based on clinical history were successfully challenged
with alternative drugs.
Conclusions: NSAID and AB were responsible for the majority of DIA.
Anaphylactic reactions were reported at any age. The heterogeneity of
mechanisms involved, the severity of clinical reactions and the lack of
standardized invivo and/or invitro tests do not allow to conrm the
diagnosis in all cases. Patients with DIA should be evaluated in special-
ized centers in order to perform accurate diagnosis, to prevent recur-
rence and to nd safe alternatives.
Keywords: Anaphylaxis; Drug allergy; NSAID; Antibiotics
P6
Intraoperative severe anaphylactic reaction due topatent blue v
dye
Luis Marques, Eva Alcoceba, Silvia Lara
Hospitals Universitaris Santa Maria ‑ Arnau de Vilanova, Lleida, Spain
Correspondence: Luis Marques
Clinical and Translational Allergy 2016, 6(Suppl 3):P6
Background: Intraoperative anaphylactic reactions are a diagnostic
challenge. The chronology of the administration of the multiple drugs
and the beginning of the reaction are important in identifying the cul-
prit drug.
Patent blue V is a well known cause of perioperative anaphylaxis
This dye is a member of the triarylmethane family, which also includes
isosulfan blueand methylene blue. Is used for staging breast cancer,
identifying sentinel lymph nodes. The frequency of reactions is around
0.24–1.1 %. It can be also found in food (food additive E-131) and
cosmetics.
Report: We describe the case of a woman 65years-old with a ductal
carcinoma of the left breast, who suered hypotension (85/60),
bronchospasm with hypoxemia, urticaria, angioedema of the face,
tongue and epiglottis after the administration through the nip-
ple of colorant patent blue V. Anaesthetic induction was done with
fentanyl, propofol and rocuronium. Adrenaline, bronchodilators,
antihistamines, corticosteroids and vasopressive drugs were admin-
istered, being admitted in the ICU. The levels of tryptase were 8.5µg/
ml 20min after the beginning of the reaction, 16.6µg/ml at 2h and
3.23µg/ml at 48h.
One month after the reaction cutaneous tests were done, being posi-
tive for patent blue V (intradermal reaction at 1/10) and negative for
suxamethonium, cis-atracurium, rocuronium, fentanyl, propofol, mida-
zolam, povidone-iodine and latex.
It was the rst time the patient received this dye or any similar dye as
a drug.
Intraoperative anaphylactic shock due to allergy to patent blue V was
diagnosed.
The future use of this dye was prohibited and an advise to avoid stu
which contains this product was given to the patient.
A suspicion of sensitization through foods or cosmetics is possible as
the patient reacted the rst time she received this drug.
How this report contributes to current knowledge: This case con-
rms previous descriptions of reactions with patent blue V: reaction
with the rst exposition and severe allergic reactions, with hypoten-
sion and raise in tryptase levels. Cutaneous test are useful in the diag-
nostic and standardized concentrations have been described by ENDA.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P7
Kounis syndrome inthe setting ofanaphylaxis todiclofenac
Leonor Carneiro‑Leão, Carmen Botelho, Eunice Dias‑Castro, Josefina
Cernadas
Serviço de Imunoalergologia, Centro Hospitalar de São João, Porto,
Portugal
Correspondence: Leonor Carneiro‑Leão
Clinical and Translational Allergy 2016, 6(Suppl 3):P7
Background: Kounis Syndrome (KS), the occurrence of acute coro-
nary events as consequence of allergic or hypersensitivity reactions
has been described for years. It is still relatively unknown and conse-
quently underdiagnosed, leading to inadequate treatment and subse-
quent morbidity. There are three subtypes of KS: type I which occurs
in patients without predisposing cardiovascular factors; type II which
occurs in patients with cardiovascular risk factors; and type III by stent
thrombosis.
Report: A 55year old man, a smoker with type II Diabetes, was admit-
ted to our hospital for myocardial infarction (MI) after taking two pills
of diclofenac 75mg for left leg pain. He complained of immediate gen-
eralized pruritus, malaise, constrictive radiating chest pain, dyspnea,
dizziness and sweating. He was assessed by the mobile medical team
on site as being agitated, hypotensive (BP: 96/74 mmHg) and with
generalized wheezing on chest auscultation. Aggressive uid resuscita-
tion, nebulized salbutamol and IV corticosteroids improved his status
on route to the ER; he was also treated with acetylsalicylic acid 250mg
and sublingual isosorbide dinitrate 5mg. Epinephrine was not given.
ECG conrmed NSTEMI with an elevated troponin I (0.59ng/ml). Serum
tryptase was not measured. He was admitted to the Coronary ICU
and cardiac catheterization showed mild coronary artery disease. He
recalled a previous reaction to diclofenac, with immediate generalized
pruritus. The patient recovery was uneventful. He was then referred to
our Drug Allergy Unit. Oral challenge with meloxicam 15mg was nega-
tive and he was instructed to avoid NSAID’s other than meloxicam.
How this report contributes to current knowledge: MI in the set-
ting of anaphylaxis is underreported. Clinicians should be aware of this
possible complication even in patients without cardiovascular risk fac-
tors in order to diagnose and treat it early. Also, the WAO Anaphylaxis
guidelines recommend a minimum 4h observation period after ana-
phylaxis, 8–10h if there is respiratory or cardiovascular compromise
during the reaction. This allows not only for detection and treatment
of biphasic reactions, but also of secondary cardiovascular events.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P8
Perioperative anaphylaxis audit: Royal Melbourne Hospital
Katherine Nicholls1, William Lay2, Olivia Smith2, Christine Collins1, Gary
Unglik1, Kymble Spriggs1, Priscilla Auyeung1, Jeremy McComish1, Jo A.
Douglass1
1Department of Immunology and Allergy, The Royal Melbourne Hospital,
Parkville, Australia; 2Department of Medicine, University of Melbourne,
Parkville, Australia
Correspondence: Katherine Nicholls
Clinical and Translational Allergy 2016, 6(Suppl 3):P8
Page 6 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
Background: Perioperative anaphylaxis (PA) is a medical emergency,
with potential for mortality. Skin testing (ST) of agents used in the
perioperative period is considered the gold standard for the identi-
cation of likely causative agents [1]. Neuromuscular blocking agents
(NMBA) (58%), antibiotics (12–15%) and latex (16–19%) are the most
commonly implicated causative agents [1, 2]. Chlorhexidine allergy
is also described although its prevalence is not well established and
likely underreported [3, 4].
We conducted a retrospective audit of all patients who underwent
ST and specic IgE testing (SpIgE) for investigation of a perioperative
allergic event. We sought the proportion of patients who had a likely
agent detected and the prevalence of likely causative agents in our
cohort.
Materials and methods: Medical histories were reviewed for all
patients referred for PA who underwent testing in our centre over a
2-year period from September 2013 to August 2015. Data collected
included severity grading [5], acute elevation in Mast cell tryptase
(MCT) (>12 ng/ml or >135 % basal level), and causative agent indi-
cated by the presence of a positive ST or SpIgE to NMBA, latex, antibi-
otics or chlorhexidine. Results are expressed as n (%) and comparisons
performed by Fisher’s exact test.
Results: Of 47 patients identied during this period, ST was posi-
tive in 22 (47%), with NMBA and beta-lactam antibiotics accounting
for 10 (42%) and 7 (29%) of positive results respectively. Of the 27
patients with MCT results, 14/19 (73%) patients with an acute MCT
rise had positive skin or SpIgE tests, compared with only 1 (13%) of
8 patients with no reported MCT rise (P<0.01). Over the same period,
four patients (18%) had positive SpIgE to chlorhexidine (range 0.43–
55.8kUa/l). Reactions graded as severe (Grade 3) were associated with
an increased proportion of positive ST (16/31, 52%) compared with
Grades 1 and 2 (6/16, 38%), however this result did not reach statisti-
cal signicance.
Conclusions: The prevalence of causative agents reects current lit-
erature, with an increased proportion of reactions to antibiotics, and
decreased proportion to latex. Our audit indicated a signicantly
higher proportion of positive ST in those with acutely elevated MCT. In
our cohort, chlorhexidine appeared to be a common allergen.
References
1. Mertes, et al. JACI 2011;128:366–73.
2. Ebo, et al. Allergy 2007;62:471–87.
3. Garvey, et al. JACI 2007;120:409–15.
4. Calogiuri, et al. J Allergy Ther. 2013;4.
5. Brown, et al. JACI 2004;114:371–6.
P9
Recurrent peri‑operative anaphylaxis: a perfect storm
Jonny G. Peter, Paul Potter
University of Cape Town, Cape Town, South Africa
Correspondence: Jonny G. Peter
Clinical and Translational Allergy 2016, 6(Suppl 3):P9
Background: Allergy work-up to identify the causative agent in
patients experiencing peri-operative anaphylaxis is challenging.
Patients have multiple exposures over a short time period; Paper-
based records from remote hospitals are often unavailable to the aller-
gist; and diagnostic testing for many drugs is either unavailable or
sub-optimal.
Report: A 56-year-old man with debilitating osteoarthritis required
hip replacements in order to work. He had no chronic medical
co-morbidities, but labeled penicillin allergy following a child-
hood reaction during prolonged antibiotics for osteomyelitis. He
was referred for testing after three operations in a remote private
South African hospital. Peri-operative anaphylaxis, conrmed with
serial tryptase measurement, occurred in the 1st and 3rd surgeries.
Possible oending agents included: propofol, midazolam, bupiv-
acaine, fentanyl, clindamycin and cyclokapron. Apparently, in the
uneventful 2nd surgery, the drugs were the same except cycloka-
pron was omitted. Cleaning agents used were unknown. In vitro
specic IgE testing was negative to latex but elevated (5.49kUA/l)
for chlorhexidine; Skin testing was positive with chlorhexidine and
intradermal testing generated systemic symptoms and required
treatment. CAST ELISA testing was negative to propofol and bupi-
vacaine. Clindamycin invitro testing was unavailable and in vivo
testing is not recommended. The likely oending agent was chlo-
rhexidine, and the patient was anxious to return to work, thus,
although each anesthetic chart was not available for detailed
review, repeat surgery proceeded. Unfortunately, he experienced
recurrent anaphylaxis despite a chlorhexidine free theatre. Several
months later the anesthetic charts from all four operations were
acquired, and it was clear that an additional oending agent was
likely clindamycin. Avoidance of both clindamycin and chlorhex-
idine resulted in a safe surgery. Subsequent testing allowed the
patient to be ‘de-labeled’ as penicillin allergic.
How this report contributes to current knowledge: Dual sensitiv-
ity is described in about 2% of peri-operative anaphylaxis cases. Thus,
even if a possible causative agent is identied, it remains mandatory
a conduct a detailed review of all anesthetic charts; however, this can
pose a major challenge in countries were records remain paper-based.
The use of alternative drugs in patients carrying a penicillin allergy
label can carry signicant morbidity.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
Poster Walk 2: DH regions andpatient groups (P10–P19)
P10
A rare presentation ofamoxicillin allergy ina young child
Fabrícia Carolino, Eunice Dias De Castro, Josefina R. Cernadas
Serviço de Imunoalergologia, Centro Hospitalar São João E.P.E., Porto,
Portugal
Correspondence: Fabrícia Carolino
Clinical and Translational Allergy 2016, 6(Suppl 3):P10
Background: Fixed drug eruptions (FDE) are characterized by well-
demarcated skin and/or mucosal lesions beginning a few min-
utes to several hours after drug exposure and that reappear at the
exact location on re-exposure to the oending drug. Aminopenicil-
lins are among those drugs most commonly associated with FDE.
Non-pigmenting FDE (NPFDE) is an FDE type that leaves no residual
pigmentation.
Report: The authors report the case of a non-atopic 5years-old boy,
presenting two reproducible episodes of cutaneous lesions (erythe-
matous pruritic plaques) located to the genital area, occurring a few
hours after medication with amoxicillin for upper airways infection.
The antibiotic was changed to a non-beta-lactam drug with progres-
sive symptoms resolution, leaving no residual skin pigmentation. There
was a previous exposure to amoxicillin with tolerance. After the second
episode, the child has already been medicated with a second genera-
tion cephalosporin (cefaclor) and tolerated this drug. Following the rst
evaluation in our Allergy Department, the child was assessed in the
Drug Allergy Unit. No skin tests (intradermal with late reading) were
performed due to age-related constraints. A controlled re-challenge
with oral amoxicillin in the age-recommended intake-dose was per-
formed. Five hours after the end of oral challenge, the child began to
develop a cutaneous exanthema and returned to the hospital for medi-
cal assessment as it was recommended. On physical examination, we
observed swelling and erythematous plaques aecting the inferior part
of penis, the scrotum and the perianal region; the child’s mother con-
rmed that the lesions presented the same location as that of the two
previous episodes. Taking these ndings into account, the nal diag-
nosis was multiple xed drug eruption. The child was treated with oral
antihistamine and corticosteroid, with complete resolution in 3days.
How this report contributes to current knowledge: To the authors’
knowledge, this is the third case reported of this type of drug eruption
in the paediatric age.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
Page 7 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
P11
Adverse drug reactions inchildren: antibiotics or virus?
Ana Sofia Moreira1, Carmo Abreu2, Eva Gomes2
1Centro Hospitalar Vila Nova Gaia e Espinho, Vila Nova Gaia, Portugal;
2Centro Hospitalar do Porto, Porto, Portugal
Correspondence: Ana Sofia Moreira
Clinical and Translational Allergy 2016, 6(Suppl 3):P11
Background: About 10% of Portuguese children report to have had
at least one adverse reaction to drugs and 6% to be allergic to at least
one drug, being the antibiotics the most frequent medication impli-
cated. The diagnostic investigation reveals that in 90% of cases drug
hypersensitivity is not conrmed, what is thought to be related to the
high prevalence of infectious/viral rashes in childhood. Our aim was
to evaluate the main reasons for referral to our pediatric drug allergy
clinic, characterize the reactions mentioned by patients, particularly
with regard to their sazonality and to analyse the results of the diag-
nostic investigation performed.
Materials and methods: Retrospective analysis of medical records
from the pediatric patients followed in our department, in the last
6years, due to suspected drug hypersensitivity.
Results: We studied 364 children of whom 200 (55%) were male.
The median age at the time of the suspected reaction was 3.5years
(6months–17years). Antibiotics were the suspected drug in 84% of
cases (n=305). In 75% (n=274) of patients the symptoms reported
were only cutaneous (maculopapular eruptions or urticaria) and in
72% (n=262) of cases the reaction was nonimmediate. Drug hyper-
sensivity was conrmed in 10 patients (3%). The month in which the
drug reaction occurred was identied by 51% (n=184) of patients.
Sixty percent of the reactions occurred during winter–spring months.
Viral serologies were performed on 74 patients who reported a
recent reaction and positive results for at least one of the viruses
studied were obtained in 14 patients (19%—IgM) and 48 patients
(65%—IgG).
Conclusions: The majority of children studied due to suspected drug
hypersensitivity reported cutaneous symptoms and nonimmedi-
ate reactions. Most reactions occurred before 3years of age, which
according to the literature, concerns the age when infectious rashes
are more frequent. We veried a seasonal pattern in the occurrence
of the suspected drug reactions that is similar to that described for
the most common viral infections in childhood, while the peak for
antibiotic consumption has been reported in autumn. Conrmation
of hypersentisitivity to the suspected drug was possible in 10 of 364
patients, while a possible viral etiology was documented in 14 of 74
patients. Our ndings reinforce the idea that many of the cutaneous
reactions which motivate the study in our department are probably
caused by infections and not by drug hypersensitivity.
Keywords: Children; Drug reactions
P12
Allergic reactions ininvasive medical procedures
Bárbara Kong Cardoso, Elza Tomaz, Sara Correia, Filipe Inácio
Hospital de S.Bernardo ‑ Centro Hospitalar de Setúbal, Setúbal, Portugal
Correspondence: Bárbara Kong Cardoso
Clinical and Translational Allergy 2016, 6(Suppl 3):P12
Background: Surgery associated allergic reactions have been exten-
sively studied and culprit agents have been pointed on several
reports. Nevertheless last decade changes in pharmacological proto-
cols resulted in the increase of possible implicated drugs. In the other
hand, other invasive procedures (diagnostic/therapeutic) have been
increasing in frequency and are also related to allergic events. Our aim
was to seek for new agents involved in perioperative allergy as well as
characterize reactions occurring due to other invasive procedures
Materials and methods: We reviewed the medical records of 28
patients referred to our clinic for allergic reaction associated to an
invasive procedure in the last 2years regarding administered drugs,
type of reaction and results of the allergological workup.
Results: In our study group, 21 were female and 7 male, mean age was
54.7years (2–84).
Fourteen were studied for procedures with general anesthesia related
adverse events: six anaphylatic reactions, six urticaria/angioedema,
one bronchospasm and one hypotension. Positive relevant results
were obtained in 13 patients: one skin prick test (SPT) to metamizol,
two intradermal skin tests (IDT) to midazolam, one to tramadol, three
to ondansetron, one to rocuronium, one to atracurium, two to vecu-
ronium, two to metamizol, one basophil activation test (BAT) to meta-
mizol. One patient was positive to both to atracurium and vecuronium
and one patient had no positive tests.
In nine patients reactions were associated to invasive procedures with
local anesthesia. Positive results were one IDT and BAT to verapamil
(anaphylaxis) and one patch test to iodixanol (maculopapular rash)
in two patients submitted to coronary angiography. Six patients with
adverse reactions during dental treatment and one during a carpal
tunnel surgery had no positive tests.
Five patients had been submitted to procedures without use of any
anesthetic: one with local erythema after an esteroid intra-articular
inltration had a positive patch test to betamethasone dipropionate;
one with an anaphylactic reaction during a colonoscopy had a posi-
tive BAT to metamizol used as analgesic; one with acute urticaria after
contrast injection for a thyroid TC had IDT positive to iomeprol. Two
patients had a negative workup.
Conclusions: Comparing to previous published series ondansetron
seems to be emerging as an important agent in perioperative allergy.
Invasive procedures other than major surgeries are associated to
allergic reactions both immediate and non-immediate, some of them
being severe.
Keywords: Perioperative allergy; Invasive medical procedures; Drug
hypersensitivity
P13
Antibiotic allergy inchildren: room forimprovement
Annabelle Arnold1, Natasha Bear2, Kristina Rueter3, Grace Gong4, Michael
O’Sullivan5, Saravanan Muthusamy1, Valerie Noble1, Michaela Lucas6
1Department of Immunology, Princess Margaret Hospital, Perth, Australia;
2Telethon Kids Institute, Department of Clinical Research and Education,
Princess Margaret Hospital, Perth, Australia; 3Department of Immunol‑
ogy, Department of Clinical Research and Education, Princess Margaret
Hospital, Telethon Kids Institute, Perth, Australia; 4Department of Immu‑
nology, PathWest Laboratory Medicine WA, Princess Margaret Hospital,
Perth, Australia; 5Department of Immunology, Princess Margaret Hospital,
PathWest Laboratory Medicine WA, Fiona Stanley Hospital, School
of Pathology and Laboratory Medicine, University of Western Australia,
Perth, Australia; 6Department of Immunology, Princess Margaret Hospital,
Sir Charles Gairdner Hospital, PathWest Laboratory Medicine WA, School
of Medicine and Pharmacology, School of Pathology and Laboratory
Medicine, University of Western Australia, Institute of Immunology
and Infectious Diseases, Murdoch University, Perth, Australia
Correspondence: Annabelle Arnold
Clinical and Translational Allergy 2016, 6(Suppl 3):P13
Background: Beta-lactam antibiotics remain one of the most eective
treatments of bacterial infections and are the most frequently pre-
scribed antibiotic in children. Allergic reactions to these antibiotics are
common. Nevertheless, strategies for peadiatric antibiotic allergy test-
ing and management remain poorly dened, including issues around
the need for skin testing prior to oral provocation challenges (OPC;
2-dose) and the value of prolonged courses with the culprit antibiotic
after the successful administration of an initial supervised dose.
Materials and methods: To address these issues, we performed a
retrospective cross-sectional analysis of children (6months–16years)
with an antibiotic allergy label who presented to a tertiary pediat-
ric hospital in Western Australia from 2006 to 2015. Data collection
included results of skin prick (SPT), intradermal testing (IDT) and OPCs,
outcome of 5-day antibiotic courses, type of initial reaction, confound-
ing illnesses and co-existing allergies. The data was analysed using
Mann–Whitney U for continuous data and Fishers exact test for cat-
egorical data.
Results: We performed 207 beta lactam antibiotic tests in 172 chil-
dren. In 82 (39.6 %) cases OPCs were performed without preceding
Page 8 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
skin testing (Group 1); three OPCs (3.7%) were unsuccessful with one
child with anaphylaxis. In 125 (60.4 %) cases skin testing was per-
formed (Group 2). Of these, 22 cases (17.6%) were positive by SPT or
IDT; these children were deemed to have conrmed antibiotic allergy.
The remaining 103 cases proceeded to OPC; 4 (3.8%) reacted to OPC,
including two children with anaphylaxis. Finally, 152 cases (from Group
1 or 2) received a 5day course with the culprit antibiotic. This resulted
in a rash in nine children (5.9%) during the course. In both groups con-
founding illnesses, initial reaction, gender and co-existing allergies did
not predict testing outcome.
Conclusions: In our cohort, the rate of allergy conrmed by skin test-
ing was signicantly higher than for those who underwent a direct
challenge (17.6 vs. 3.7%). The rate of reactivity to OPC was compara-
ble for Group 1 and 2. These data further supports that performing
direct supervised OPC with the culprit drug in children may be safe
and potentially may avoid the need for resource intensive skin testing.
Extended courses with the culprit drug should be considered, allowing
conrmation of non-immediate reactions such as cutaneous reactions.
Keywords: Allergy; Antibiotic; Anaphylaxis
P14
Drug hypersensitivity reactions inchildren andresults
ofdiagnostic evaluation
Neringa Buterleviciute, Odilija Rudzeviciene
Vilnius University Faculty of Medicine Centre of Children Pulmonology
and Allergology, Vilnius, Lithuania
Correspondence: Neringa Buterleviciute
Clinical and Translational Allergy 2016, 6(Suppl 3):P14
Background: Patients or parents reported drug allergy in children is
more common than the true drug allergy incidence. The aim of our
study was to evaluate the clinical pattern of patient/parent reported
drug hypersensitivity reactions and results of diagnostic evaluation.
Materials and methods: 15 children who were tested for drug allergy
in 2015 were included in the study: eight boys (53.3%) and seven girls
(46.7 %), age range 1–15 years. We analysed causes, clinical pattern
of reported drug hypersensitivity reactions and results of diagnostic
evaluation.
Results: 26 drug hypersensitivity reactions were reported. Three drug
hypersensitivity reactions were reported in four children, two reac-
tions—in three children. The main suspected drugs were antibiotics
17 (65.4%), NSAIDs—5 (19.2 %) cases, local anaesthetics—4 (15.4%)
cases. Amoxicillin was the most frequently suspected drug (six (23.1%)
cases). 8 (30.8%) reactions appeared during 1h. Skin symptoms were
reported in 24 (92.3%) cases: maculopapular rash—20 (76.9%), angi-
oedema—5 (19.2%) cases. Respiratory and cardiovascular symptoms
were reported in two cases (7.7%). Drug provocation test was positive
only for one child, who experienced angioedema after nimesulide and
ibuprofen intake, and drug provocation test was positive to ibuprofen.
Conclusions: The most common suspected drugs were antibiotics,
especially amoxicillin. Skin was the most frequently aected and mac-
ulopapular rash was the most common symptom. Drug provocation
test was positive only for one patient.
Keywords: Drug hypersensitivity; Chidren; Clinical pattern;
Diagnostics
P15
Nonimmediate cutaneous drug reactions inchildren: are skin
tests required?
Ana Sofia Moreira1, Carmo Abreu2, Eva Gomes2
1Centro Hospitalar Vila Nova Gaia e Espinho, Vila Nova Gaia, Portugal;
2Centro Hospitalar do Porto, Porto, Portugal
Correspondence: Ana Sofia Moreira
Clinical and Translational Allergy 2016, 6(Suppl 3):P15
Background: Delayed urticaria and maculopapular eruptions associ-
ated with antibiotics are the most common reasons for referral to our
pediatric drug allergy clinic. In this context, several studies point to
the limited usefulness of skin tests, even to b-lactam antibiotics, with
some authors advocating the use of drug provocation test without
the need for other previous diagnostic procedures. Our aim was to
describe the cases followed in our department in which this diagnostic
approach was used (exclusive drug provocation test).
Materials and methods: Retrospective analysis of medical records
from children referred to our drug allergy clinic due to suspected
hypersensitivity to antibiotics, who reported nonimmediate cutane-
ous reactions (urticaria or maculopapular eruption) without signs of
severity or systemic involvement. All children underwent provoca-
tion test with the suspected drug without conducting previous skin
tests. The drug provocation test was extended to include the number
of days of treatment reported at index reaction. Data was collected
regarding gender of patients, age at the drug reaction, drug involved,
symptoms reported on the reaction and results of the drug provoca-
tion test.
Results: We evaluated 213 children of which 50% (n = 107) were
male, with a median age of 3years (6 months–17years) at the time
of reaction. In 97 % (n = 206) of the cases the involved antibiotics
were b-lactam (amoxicillin-clavulanic acid in 92 patients, amoxicil-
lin in 89 and cephalosporins in ve cases). Only three children had
positive drug provocations tests. In all cases the symptoms were
similar to those previously reported and easily controlled with oral
antihistamine.
Conclusions: Performing an exclusive drug provocation test in chil-
dren with suspected hypersensitivity to antibiotics, who present with
nonimmediate cutaneous reactions without signs of severity, proved
to be a safe and eective approach.
Keywords: Skin tests; B-Lactams; Diagnosis
P16
Pediatric patients witha history ofpenicillin allergy anda positive
penicillin skin test may not be atan increased risk formultiple
drug allergies
Sara May1, Thanai Pongdee2, Miguel Park3
1University of Nebraska Medical Center, Omaha, USA; 2Mayo Clinic, Jack‑
sonville, USA; 3Mayo Clinic, Rochester, USA
Correspondence: Miguel Park
Clinical and Translational Allergy 2016, 6(Suppl 3):P16
Background: Patients with a sulfonamide allergy or penicillins (PCN)
may be at increased risk for reactions to other drugs. However, the
studies were conducted in adults without PCN skin testing (PST) to
conrm a PCN allergy. We conducted a study to determine if pediat-
ric patients with a history of PCN allergy and a positive PST were at an
increased risk for multiple drug allergies.
Materials and methods: Children (<18years) with a history of PCN
allergy were evaluated with PST and reviewed for basic demographic,
PST results, and other medication allergies listed in the allergy module
in the electronic medical record. A univariate logistic regression analy-
sis was employed to calculate the odds ratio (OR) and the 95% con-
dence interval (CI). P value of 0.05 or less was considered statistically
signicant. The Institutional Review Board (IRB) approved the study.
Results: 778 children underwent penicillin skin test. 703 (90.4%) of
778 patients had a negative PST, 66 (8.5%) were positive, and 9 (1.1%)
were equivocal. The overall mean ± standard deviation (SD) age of
the study group was 5 ± 3.5 years. Three hundred and sixty-seven
(47.1%) were females. 703 children (90.4%) had a negative PST, 66
patients (8.5%) positive PST, and 9 (1.1%) equivocal PST. 181 (23%) of
778 patients reported a history of multiple drug allergies. Among the
181 patients reporting a history of multiple drug allergies, 81 (45%)
were female and 100 (55%) were male. Males were 1.6 times (95%
CI 0.8–1.6, p=0.5) more likely than females to report multiple drug
allergies, although not statistically signicant. 14 (21%) of 66 patients
with a positive PST reported multiple drug allergies compared to 167
(23%) of 712 (p = 0.76) patients with a negative PST. Those patients
with multiple drug allergies and a history of PCN allergy, cephalo-
sporin [15% (114 of 778)] was the most common medication listed in
the allergy module. Other medication listed in the medication allergy
modules were 10% (79) macrolide antibiotics, 9% (71) sulfonamides,
0.4% (3) quinolones, and 1% (9) nonsteroidal anti-inammatory drugs
(NSAIDS).
Page 9 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
Conclusions: PCN allergic pediatric patients may not be at an
increased risk for multiple drug allergies. Among patients with a his-
tory of PCN allergy, cephalosporin, macrolide antibiotics and sulfona-
mide antibiotics were the most common drug allergies listed in the
medication allergy module.
Keywords: Penicillin allergy; Multiple drug allergies; Risk
P17
Proved hypersensitivity todrugs according data ofVilnius
University Hospital Santariskiu Klinikos
Linas Griguola1, Arturas Vinikovas1, Simona Kašinskaite2, Violeta
Kvedariene2
1Vilnius University, Faculty of Medicine, Vilnius, Lithuania; 2Center
of Pulmonology and Allergology, Clinic of Infectious, Chest Diseases, Der‑
matology and Allergology, Vilnius University Hospital Santariskiu Klinikos,
Vilnius, Lithuania
Correspondence: Linas Griguola
Clinical and Translational Allergy 2016, 6(Suppl 3):P17
Background: Adverse reactions to drugs are common problem, but
true hypersensitivity to drug is rare.
Aim of the study: to investigate true hypersensitivity reactions
among female and male with suspicion of drug allergy.
Materials and methods: 755 patients with suspicion of allergic reac-
tions to drugs were addressed to consultations in Pulmonology and
Allergology center by general practitioners. Patients were divided
into groups by sex and suspected drugs: I—Antibiotics (AB), II—
NSAID, III—Other. Each category was divided into subcategories: IA
beta-lactam AB, IB Other AB; IIA ASA, IIB acetaminophen, IIC other
NSAID; IIIA local anesthetics (LA), IIIB iodine containing contrasts
(ICC), IIIC Other.
Results: 755 patients with 980 cases of suspected drug allergy were
investigated: 618(81.85%) females with average age 48.4(SD±15.2)
and 137(18.15%) males with average age 47.6(SD±18).
Female group had 821(83.8%) adverse reactions to drugs. 199(24.2%)
reactions to I (AB): 151(75.9%) were to beta-lactams, from all tested
36(16.9 %) were true hypersensitivity; 46(23.1 %) reactions were
to other-AB, from all tested reactions4(9.1 %) were proved. 2(1 %)
cases were not tested. Accordingly: II (NSAID) had 306(37.3%) reac-
tions: to aspirin—56(18.3 %), 4(9.6 %) were proved; to acetami-
nophen—47(15.3%), 12(40 %) were proved; IIC (Other-NSAID)—203
(66.3 %), 29(19.2 %) were proved. III (Other) had 316(38.5 %) reac-
tions: IIIA (LA)—99(31.3%), 1(1.5%) was proved; IIIB (ICC)—20(6.3%),
2(15.5%) were proved; IIIC (Other)—197(24%), proved—19(15.4%).
Male group had 159(16.2 %) adverse reactions to drugs. I (AB) had
30(18.8%) reactions: IA (beta-lactam)—25(83.3%), from all tested reac-
tions7(21.2%) were proved. Accordingly: IB (other-AB)—5(16.6%), all
negatives. II category had 77(48.4%) reactions: to aspirin—17(22 %),
2(16.6 %) were proved; IIB (acetaminophen)—18(23.4 %), 2(11.8 %)
were proved; IIC (other-NSAID)—42(54.5%), DPTs proved 2(6.9%). III
category had 48(30.2%) reactions: IIIA (LA)—16(33.3%), 1(7.7%) was
proved; IIIB (ICC)—6(12.5, all negatives; IIIC (Other)—26(54.2%), DPTs
proved 4(22.2%). NA—4(2.5%).
Conclusions: Of all reactions true hypersensitivity were proved for:
antibiotics—15.6%, NSAIDs—20.2%, other drugs—11.1 % in female
group and 20% for AB, 10.3 % for NSAIDs, 13.8% for other drugs in
male group.
Keywords: Drug; Hypersensitivity
P18
Self‑reported prevalence ofdrug hypersensitivity reactions
amongstudents inCelal Bayar University, Turkey
Ayse Aktas, Suheyla Rahman, Huseyin Elbi, Beyhan Cengiz Ozyurt
Celal Bayar University, Manisa, Turkey
Correspondence: Ayse Aktas
Clinical and Translational Allergy 2016, 6(Suppl 3):P18
Background: Drug hypersensitivity reactions (DHR) is dened
“unwanted and harmful reactions occurring to drugs prescribed dose”
by World Health Organization (WHO). DHR is an important health
problem because of causing life-threatening condition, extending the
length of stay in hospital and increasing the cost of treatment.
The aim of this study was to determine the prevalence of self-reported
DHR among students at the university.
Materials and methods: A structured questionnaire was carried out
to students of Celal Bayar University in Manisa, Turkey.
Results: 2086 students have participated in our study. 1217 (58.3%)
of them were women, 869 (41.7%) were male. The mean prevalance
of self-reported DHR was 5.3% (111/2086). Drug allergy incidence of
students (male/female) was 3.5 and 6.7%, respectively (p< 0.001).
The most common allergic reactions were rash 52.2%, cardiovas-
cular reactions12.6% and respiratory reactions 11.7 %. Aforemen-
tioned two systems involvement were 23.4%. The most frequently
involved drugs were antibiotics 52.2% (n: 58) and analgesics 24.3%
(n: 27).
Conclusions: The diagnosis of drug allergy is based on a detailed his-
tory of the onset of symptoms/signs’ relationship between the appear-
ance of symptoms and drug use. Misinterpretations just based on the
DHR story can eect the individual treatment options. A denitive
diagnosis can be easily reachable with a complete clinical history,
standardized skin tests and drug provocation tests. Therefore we can
recommend that doctors should be more informed about the man-
agements of DHR due to self-reported DHR is highly prevalant just like
shown in this study.
Keywords: Drug hypersensitivity; Prevalence
P19
Severe drug hypersensitivity reactions inpediatric age
Ozlem Cavkaytar, Betul Karaatmaca, Pinar Gur Cetinkaya, Saliha Esenboga,
Umit M. Sahiner, Bulent E. Sekerel, Ozge Soyer
Hacettepe University School of Medicine Department of Pediatric Allergy,
Ankara, Turkey
Correspondence: Ozge Soyer
Clinical and Translational Allergy 2016, 6(Suppl 3):P19
Background: Epidemiologic data on drug induced anaphylaxis (DIA)
in pediatric age is lacking. The aim of this study is to dene the actual
rate of drug induced anaphylactic reactions in childhood together
with the severity and culprit drug patterns.
Materials and methods: Patients with a history of drug hypersensi-
tivity reaction (DHR) referred between January 2012-December 2015
were included. After lling out an European Network for Drug Allergy
(ENDA) questionnaire, initial skin tests and/or provocation tests were
performed for the oending drug. The severity of anaphylactic reac-
tions was determined as mild, moderate and severe according to
EAACI guidelines on anaphylaxis in childhood.
Results: Among 627 children and adolescents referred due to a DHR,
diagnostic work-up was completed in 532 patients. 103 (19.3%) of
them [54.4 % male, median age (interquartile range; 9.6 years (5.3–
13.3)] had anaphylaxis in the history and diagnostic tests revealed
that 75 (14.1% of all evaluated patients, 72.8% of all patients with a
DIA) of them were actually hypersensitive to the oending drug. The
culprit drugs responsible from actual DIA were antibiotics (36 %),
NSAIDs (22.7 %), chemotherapeutics (20 %), biologicals (6.7), anes-
thetic agents (5.3 %), enzyme therapy (4 %) and others. Majority of
the patients with actual DIA reported moderate (38.7%) and severe
(37.3%) drug induced anaphylactic reactions. History of chronic dis-
ease (44 vs. 17.9 %, p = 0.014), concomitant intake of other drugs
regularly (40 vs. 7.1%, p = 0.001), cyanosis (23 vs. 3.6 %, p = 0.022)
and hospitalization (56.2 vs. 17.9, p=0.001) due to the suspected DIA
and use of chemotherapeutics as the culprit drug (20 vs. 0%, p=0.01)
were more frequent, whereas use of antibiotics was less frequent (71.4
vs. 36%, p=0.001) in patients with actual DIA compared to nonhyper-
sensitive patients. Atopic disease, atopy or family history of atopy or
drug hypersensitivity did not have an impact on actual DIA. It is impor-
tant to note that actual DIA was more frequent in children younger
than 10years of age compared to older adolescents (81.5 vs. 63.3%,
p=0.038).
Conclusions: During childhood, any history of DIA reaction may
not be an actual DHR, however young age, existence of chronic
Page 10 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
disease and use of chemotherapeutics might point out the actual drug
induced anaphylaxis in children and adolescents.
Keywords: Drug hypersensitivity; Anaphylaxis; Child; Pediatric
Poster Walk 3: Desensitisation (P20–P28)
P20
A protocol fordesensitisation tovalaciclovir
Celia Zubrinich, Bianca Tong, Mittal Patel, Michelle Giles, Robyn O’Hehir,
Robert Puy
Alfred Health, Melbourne, Australia
Correspondence: Celia Zubrinich
Clinical and Translational Allergy 2016, 6(Suppl 3):P20
Background: We report a protocol for desensitisation to valaciclovir.
Report: A woman in her 40s developed generalised urticaria on the
second or third day of her initial course of acyclovir (administered ve
times daily) for newly diagnosed genital herpes. The urticaria contin-
ued to cause distress despite substitution to valaciclovir for a further
few days. Antiviral medication was ceased. The rash resolved over
2weeks with the use of anti-histamines.For more than a decade since
then,she has experienced frequent and prolonged conrmed herpetic
recurrences, more often present than not. The attacks had a marked
viral prodrome and signicantly aected her lifestyle.
Recurrent genital herpes may be treated with suppressive antiviral ther-
apy if frequent. Supervised direct challenge to valaciclovir was an option
but desensitisation was favoured because it required a single clinic visit
and, of relevance to the patient, likely entailed less risk. We identied
reports of desensitisation to acyclovir but not valaciclovir. The nal treat-
ment dose of acyclovir (usually 400mg) diers from that of valaciclovir
(500 mg). Acyclovir therapy requires multiple doses per day, whereas
valaciclovir requires only a single daily dose. We developed and present
a 14-dose oral desensitisation protocol that was administered over 3.5h
(Fig.1). The rst 10 doses were valaciclovir in suspension and the nal
four doses were prepared from a 500mg tablet. The patient tolerated
the procedure with no ill eect. There has not been a single herpetic
recurrence in the 12months since the treatment commenced.
How this report contributes to current knowledge: Desensitisation
to valaciclovir may be performed where suppressive therapy for her-
pes is indicated.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P21
A rare case ofdesensitization tomodanil
Josefina Cernadas, Luís Amaral, Fabrícia Carolino
Serviço de Imunoalergologia, Centro Hospitalar de São João E.P.E., Porto,
Portugal
Correspondence: Luís Amaral
Clinical and Translational Allergy 2016, 6(Suppl 3):P21
Background: Modanil is a 2-benzhydrylsulnylethanamide mol-
ecule, belonging to a class of medications called wakefulness promot-
ing agents used to treat excessive sleepiness caused by narcolepsy
(a condition that causes excessive daytime sleepiness) or shift work
sleep disorder. Another use is to prevent excessive sleepiness caused
by obstructive sleep apnea/hypopnea syndrome. It acts as a blocker of
a type of molecule called the dopamine transporter. Rare occurrences
including severe cutaneous adverse reactions, as erythema multi-
forme, SJS, TEN and DRESS, aecting adults and children and probably
allergic, have been reported. Rare cases of angioedema and multi-
organ hypersensitivity reactions have also been described.
Report: The authors describe a case of a 27 year-old male with the
diagnosis of narcolepsy medicated with modanil 100 mg in an
increasing dosage. Four days after beginning the medication, he com-
plained of generalized pruritus, maculopapular exanthema and angi-
oedema of upper and lower limbs. No analytical changes were found
in the acute phase. He was treated with intravenous corticosteroid
and antihistamines and, 4days after complete recovery, the drug was
re-introduced with reproducible signs and symptoms arising 12h after
the intake of 100mg of modanil. Because this was the only therapeu-
tic option for the patient he was referred to our Allergy Department
for desensitization. A suspension of 1mg/ml (100mg/100ml) was pre-
pared and a “tailor made” desensitization protocol was started with an
initial dose of 1mg, followed by doubling doses, taken with 1h inter-
vals. The cumulative dose reached on the rst day was 15mg, 85mg
on the second and 100mg on the third and fourth days. For safety rea-
sons, 100mg/day were taken in the rst week followed by an increase,
to the intended doses (Neurology prescription) in the following weeks:
100+ 100mg on the second week, 100+ 200mg on the third week
and 200+200mg on the fourth and on, as chronic treatment. After we
have achieved tolerance to a dose of 100mg, the slowly increase to the
targeted dose of 200mg twice a day was well tolerated. The patient is
still on the same therapeutic scheme with no further reactions.
How this report contributes to current knowledge: As far as we
know this is the rst case describing a desensitization protocol to
modanil.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P22
A sixteen‑day desensitization protocol indelayed type
hypersensitivity reactions tooral drugs
Semra Demir, Asli Gelincik, Muge Olgac, Raif Caskun, Derya Unal,
Bahauddin Colakoglu, Suna Buyukozturk
Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
Correspondence: Semra Demir
Clinical and Translational Allergy 2016, 6(Suppl 3):P22
Background: Although desensitization in immediate type hyper-
sensitivity reactions due to chemotherapeutics is well described and
standardized for many drugs, common protocols in delayed type
hypersensitivity reactions (DHR) are not standardized. Our aim is to
evaluate the usefulness of the 16-day desensitization protocol which
we had recently described for capasitabine in DHRs caused by various
oral chemotherapeutic drugs.
Materials and methods: We applied our slow desensitization proto-
col which started with 1/100 of the target dose and was completed in
16days with slow incremental doses in patients who had experienced
DHR due to various oral chemotherapeutic drugs.
Results: Four patients (two female, two male) who were referred
to our clinic for desensitization were included. The mean age was
55 ± 22.25 years. The culprit drugs were pazopanib, nilotinib and
lenalidomide. The mean reaction time after the initiation of the drug
was 7.5±2.08days and the reaction types were maculopapular rush
(MPR) in two patients and generalized morbiliform rushes (GMR) in
two patients. Two patients who had experienced MPR caused by lena-
lidomide completed the protocols without any reactions. However, the
other two patients developed pruritus and rush on the 9th and the
15th days of the desensitization protocols. After the reactions were
treated with methylprednisolone, the doses were decreased to the
last tolerated doses and gradually increased afterwards. One of them
completed the desensitization in 28days. However, the second patient
could tolerate almost the ¾ of the targeted dose.
Conclusions: This sixteen-day protocol seems to be a useful guide for
the desensitization in delayed type hypersensitivity reactions espe-
cially in MPR in oral chemotherapeutics. However, the protocol can be
modied in some patients.
Keywords: Delayed type hypersensitivity reactions; Desensitization
P23
Desensitization tointravenous etoposide using a 12 anda 13‑step
protocol. Two cases report
Olga Vega Matute1, Amalia Bernad1, Gabriel Gastaminza1, Roselle
Madamba1, Carlos Lacasa2, M. J. Goikoetxea1, Carmen D’Amelio1, Jose
Rifón3, Nicolas Martínez3, Marta Ferrer1
1Departament of Allergy and Immunology Clínica Universidad de Nav‑
arra, Pamplona, Spain; 2Department of Pharmacy Clínica Universidad de
Page 11 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
Navarra, Pamplona, Spain; 3Departament of Hematology Clínica Universi‑
dad de Navarra, Pamplona, Spain
Correspondence: Amalia Bernad
Clinical and Translational Allergy 2016, 6(Suppl 3):P23
Background: Etoposide is a chemotherapy agent used to treat malig-
nant conditions. Because of the repeated use of this drug in within
time intervals for cancer treatment, there is a high chance as with any
chemotherapeutic agent to induce hypersensitivity reactions (HSR). It
is reported to induce HSR in 6% of the patients.
Report: We present two cases. First is a 7 year old female patient
with acute myeloid leukemia (AML). She had previously received two
courses of treatment with etoposide. In the second course, with the rst
administration she had a reaction consisted with facial erythema and
severe dyspnea. When evaluated in our hospital, she needed treatment
with etoposide for autologous stem-cell transplantation.The second
patient was an 8year old male with refractory acute lymphoid leuke-
mia(ALL-B) that had received six doses of treatment with etoposide. In
the last dose, he reported pharyngeal obstruction and chest erythema.
When evaluated in our hospital, he needed salvage chemotherapy con-
taining etoposide followed by allogenic stem-cell transplantation.
We performed skin prick test with Etoposide, using commercially avail-
able drug solution for intravenous use. In both patients the test was
negative.
Because Etoposide was the most suitable chemotherapeutic option
for both patients, we decided to administer the drug using a desensi-
tization protocol.Castells (2) developed a protocol for desensitization
to drugs with a 12 steps infusion of the target dose. In the rst case
we had to add one step to this protocol because of the dose needed.
She received premedication treatment and 400mg of Etoposide in
a 13 steps protocol, twice in consecutive days. She had no HSR, the
transplantation went well and she is now in complete remission.In
the second patient we followed the 12 step protocol with premedi-
cation treatment and the patient was able to receive the target dose
(150mg). We did three desensitization protocols with the total dose, in
three consecutive days. He had no HSR and he continues in follow up
in our hospital.
How this report contributes to current knowledge: Patients with
HSR to etoposide, in which this drug is the most adequate chemother-
apeutic option for such a severe disease, the desensitization protocol
is a treatment that proved to be eective in order to administer the
treatment.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P24
Drug desensitisation inoncology: the experience ofan
immunoallergology department for5years
Carmelita Ribeiro1, Emília Faria1, Cristina Frutuoso2, Anabela Barros2,
Rosário Lebre2, Alice Pego2, Ana Todo Bom1
1Allergy and Clinical Immunology Department, Coimbra University
Hospital Center, Coimbra, Portugal; 2Oncology Department, Coimbra
University Hospital Center, Coimbra, Portugal
Correspondence: Carmelita Ribeiro
Clinical and Translational Allergy 2016, 6(Suppl 3):P24
Background: Any cancer drug can potentially trigger a hypersensitiv-
ity reaction (HSR), particularly chemotherapy agents and monoclonal
antibodies. The more frequent drugs inducing HSR are the platins
(IgE-mediated reactions) and taxanes (non-immunological reactions).
Desensitisation protocols must be considered when there is no valid
and eective alternative treatment. This is especially relevant for can-
cer patients who are thus able to continue their rst line treatment.
The aim was to describe the experience of an Immunoallergology
Department with desensitization to chemotherapy agents.
Materials and methods: Retrospective review of charts of oncology
patients desensitized in the Immunoallergology Department of CHUC
in the last 5years.
Results: There were a total of 72 desensitisation procedures cor-
responding to 15 patients treated (11 female) during the period in
question, with a mean age of 56years (range 28–73years). The patients
had ovarian cancer (eight patients), lung cancer (three patients), colon
cancer (2), rectal cancer (1) and breast cancer (1). The HSR were all with
moderate to severe immediate reactions: rash, urticaria, laryngeal stri-
dor, bronchospasm, syncope and anaphylaxis (six patients). Eleven
patients were desensitized to platins (carboplatin n=6, cisplatin= 3,
oxaliplatin n = 2), three to taxanes (docetaxel n= 2, nabpaclitaxel
n=1) and one to monoclonal antibodies (panitumumab). In the total
of 72 desensitisation procedures, the range of desensitisation proce-
dures for patient was 17 (maximum) to 2 (minimum) treatmens with
carboplatin. There were ve desensitisation procedures in 2011, 12 in
2012, 19 in 2013, 18 in 2014 and also in 2015. In the 72 desensitisation
did not have any reaction in 59 procedures (82%) and in the others,
the reactions were milder than the initial HSR (only one patient had
anaphylaxis in the third desensitization with cisplatin). All patients
received their daily programmed dose. Five patients discontinued
the desensitization programme (three patients due to progression of
the oncological disease, one patient due to neurological toxicity and
another for anaphylaxis during de desensitization).
Conclusions: In the majority of patients, desensitization procedures
allowed safe reBackground of chemotherapy agents in Immunoaller-
gology centers with experience. This approach must be considered by
Oncologic doctors in the treatment of specic oncologic patients with
previous history of HSR to these drugs.
Keywords: Drug desensitisation; Oncology; Chemotherapy agents;
Platins; Taxanes
P25
Filgrastim anaphylaxis: a successful desensitization protocol
Luis Amaral, Josefina Cernadas
Serviço de Imunoalergologia, Centro Hospitalar de São João E.P.E., Porto,
Portugal
Correspondence: Luis Amaral
Clinical and Translational Allergy 2016, 6(Suppl 3):P25
Background: Filgrastim is a recombinant human granulocyte colony-
stimulating factor (G-CSF) and is used to prevent or treat neutropenia
that is generally associated with chemotherapy. Anaphylatic reactions
to lgrastim are rarely reported and there is only one published suc-
cessful desensitization protocol in a patient with immediate hypersen-
sitivity to lgrastim.
Report: We describe a case of a 47-year-old woman with ductal breast
carcinoma receiving chemotherapy with doxorubicin, cyclophospha-
mide and docetaxel. She developed chemotherapy induced neutro-
penia for which she was started on SC lgrastim [300mcg] days after
the chemotherapy cycle, given once a day, for four consecutive days.
Ten minutes after the 4th dose of lgrastim, she developed facial ery-
thema, labial angioedema, dyspnea and colicky abdominal pain. These
symptoms quickly reversed spontaneously in 48h. Subsequently, l-
grastim was withdrawn and anaphylaxis work-up was done.
A 5-step desensitization protocol was performed using sequential
doses intravenously: 15, 30, 60, 80, 115 to a cumulative dose of 300
mcg diluted in 20ml of saline over approximately 3h. In the following
day she received 300mcg in two steps with success and in 3rd day in
one without any reaction.
How this report contributes to current knowledge: In summary, we
present a successful desensitization protocol for lgrastim in a patient
with a previous life-threatening immediate hypersensitivity reaction.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P26
Galsulfase hypersensitivity anddesensitization ofa
mucopolysaccharidosis VI patient
Luis Felipe Ensina, Carolina Aranda, Ines Camelo Nunes, Ana Maria
Martins, Dirceu Solé
Federal University of São Paulo, São Paulo, Brazil
Correspondence: Luis Felipe Ensina
Clinical and Translational Allergy 2016, 6(Suppl 3):P26
Page 12 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
Background: Mucopolysaccharidosis VI or Maroteaux-Lamy Syn-
drome (MPS VI) is a lysosomal storage disorder caused by deciency of
arylsulfatase B. The enzyme replacement therapy (ERT) with galsulfase
is so far the only specic treatment for MPS VI. Infusion-related reac-
tions (IRR) to ERT can occur and can be severe, precluding further ERT.
However, the interruption of ERT can accelerate the disease progres-
sion and precipitate earlier death. The aim of this study is to report IRR
to galsulfase in a MPS VI Brazilian patient, and his treatment reestab-
lishiment after desensitization.
Materials and methods: a 7 year-old male started presenting
symptoms such as dyspnea and itch during his 44th infusion. No
improvement was observed with premedication (corticosteroids and
antihistamines) in the folowing infusion. ERT were stopped for 4weeks
and the patient underwent skin tests (prick and intradermal). Skin
prick test was performed using the straight concentration of galsulfase
and Intradermal tests with progressive dilutions. Skin tests were also
performed in 10 healthy subjects and in a MPS VI patient without IRR,
to rule out a skin irritant eect, since skin tests with galsulfase have
not been standardized.
Results: Patient presented a positive skin prick test, suggesting an
IgE-mediated reaction. Therefore, a rapid desensitization protocol
was generated. Three solutions (each 250 ml 0.9 % sodium chlo-
ride—1:100, 1:10 and 1:1 respectively) were delivered in 12 consecu-
tive steps at an increasing infusion rate. Pre-medications were used
to block dierent allergy pathways. This protocol has succeeded for
6months, when during the 22th infusion he started to present wheals
in the beginning of the third bag. A new protocol was developed (four
bags—16 steps), but the patient still had symptoms. A 75mg omali-
zumab (Omab) monthly was introduced. Ten days after the Omab, a
new infusion using the same desensitization protocol was performed
with no reaction.
Conclusions: To our knowledge, we are the rst group to use an
adapted 12-step desensitization protocol to galsufase with omali-
zumab. The protocol has shown to be safe and eective for the patient
receiving the enzyme in the recommended dose. Management of
these reactions with desensitization can provide rst line therapy and
permit continued ERT.
Keywords: Omalizumab; Desensitization
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P27
Rapid drug desensitization withbiologicals: one‑center
experience withfour biologicals
Sevim Bavbek, Resat Kendirlinan, Pamir Çerçi, Seda Tutluer, Sadan
Soyyigit, Zeynep Çelebi Sözener, Ömür Aydin, Reyhan Gümüsburun
Ankara University, Ankara, Turkey
Correspondence: Sevim Bavbek
Clinical and Translational Allergy 2016, 6(Suppl 3):P27
Background: Rapid drug desensitization (RDD) induces a tempo-
rary tolerance to biological drugs inducing hypersensitivity reactions
(HSRs) but data are limited regarding use of this outside of the USA.
Therefore in this study we aimed to report our data with RDD to rituxi-
mab, iniximab, cetuximab and trastuzumab.
Materials and methods: The study was conducted as a retrospective
chart review of patients with symptoms of HSRs to biological agents to
which RDD have been performed between January 2012 and January
2016. HSRs were classied as Grade I, II and III based on their sever-
ity. Skin prick/intradermal tests were performed with implicated bio-
logicals. The 12-step RDD protocol developed at Brigham and Women
Hospital was used
Results: Study group consisted of 11 female and four men (mean
age: 54, 21±11years). Majority of the study subjects (66.6%) were
using the biological agents for the treatment of malign diseases.
Twelve subjects had experienced HSR to rituximab, three had HSR to
cetuximab, iniximab and trastuzumab respectively. HSR to cetuxi-
mab, iniximab and trastuzumab occurred during rst infusion and
all were Grade III, 11 of 12 subjects with rituximab hypersensitivity
had reaction during rst infusion, nine had Grade II and three had
Grade III. Of the 15 patients, 86.6 % had respiratory symptoms,
66.6% had cardiovascular, 60% had cutaneous symptoms, and 40%
had gastrointestinal symptoms. Skin tests with rituximab were done
on eight patients, only three resulted in positive in 1/100 dilutions
of intradermal tests, and skin tests were negative on either prick or
intradermal tests with other biologicals. Of 88 RDD, 81 desensitiza-
tions with rituximab, ve desensitizations with cetuximab, and one
desensitization with iniximab and one desensitization with trastu-
zumab were done. There were nine breakthrough reactions (10.1%)
in seven subjects, which were all associated with rituximab and less
severe than initial reactions. Of breakthrough reactions, 55.5% were
cutaneous, followed by cardiovascular (33%), respiratory (22.2 %),
and gastrointestinal (11.1%) symptoms. Reactions mainly occurred
at step 12, and all were successfully under-controlled and except sin-
gle desensitization, all desensitization procedures were completed
with full target dose.
Conclusions: We found RDD is safe and eective, to our knowledge,
in the largest series of biological including Rituximab in our country.
Keywords: Biologicals; Rituximab; Iniximab; Rapid drug
desensitization
P28
Successful desensitization toa high dose ofmethotrexate ina
delayed type hypersensitivity reaction
Josefina Cernadas1, Leonor Carneiro‑Leão1, Fabrícia Carolino1, Marta
Almeida2
1Serviço de Imunoalergologia, Centro Hospitalar de São João, Porto, Por‑
tugal; 2Serviço de Pediatria, Instituto Português de Oncologia do Porto
Francisco Gentil, Porto, Portugal
Correspondence: Leonor Carneiro‑Leão
Clinical and Translational Allergy 2016, 6(Suppl 3):P28
Background: Delayed type hypersensitivity reactions are mediated by
cells rather than by antibodies. They can be life-threatening and classi-
cally constitute a contraindication to desensitization (DZT). However,
in selected cases of uncomplicated exanthemas, when the culprit drug
is irreplaceable or more eective, this option might be considered.
Methotrexate (MTX) is a folic acid antagonist with a major role in the
treatment of B cell acute lymphoblastic leukemia (ALL). The authors
describe a successful DZT to a high dose of IV MTX associated to inth-
rathecal administration, following a delayed-type hypersensitivity
reaction.
Report: We report a case of a 12year old boy under B cell ALL treat-
ment. He was scheduled to receive four cycles of MTX 8000mg IV
perfusion over 24h (10% on the 1st hour, 90% over the remaining
23h, with a constant concentration), followed by inthrathecal admin-
istration of MTX 12mg, cytarabine 30 mg and prednisolone 10mg.
He complained of an intensely pruritic morbilliform exanthema in
his abdomen arising 72h after completion of the rst treatment. The
rash resolved with anti histamines and oral and topic corticosteroids,
over a period of 10days with severe residual hyperpigmentation. No
renal or liver function analytical changes were found during this epi-
sode. Because no alternative treatment was available for his specic
type of leukemia, a decision to perform DZT was made.
The patient (60kg) was pretreated with montelukaste 10mg, starting
2 days before chemotherapy (QT); prednisolone 60 mg was started
the day before QT and maintained over 4days in decreasing doses.
He was admitted and a 14 step DZT protocol to MTX was performed.
The doses administered were doubled in each step until the 14th
step, with a cumulative dose of 1671mg of MTX infused over a period
of 4.5h. The remaining dose, until the target dose of 8000mg was
infused at a small rate during 24.5h. This procedure was followed by
triple inthrathecal treatment, including MTX. The patient was able to
reach the target dose without any reaction. He has now completed 3
of the 4 scheduled cycles.
How this report contributes to current knowledge: To our knowl-
edge this is the rst description of a successful DZT to such a high
dose of MTX in a delayed type reaction. The IV DZT protocol also made
Page 13 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
possible the administration of inthrathecal MTX. Our ndings support
that DZT protocols might be suitable in selected cases, allowing these
patients to safely continue with rst line therapy.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
Poster Walk 4: SJS (P29–P38)
P29
Assessment ofimpact ofinfection ondrug‑induced severe
cutaneous adverse reactions andrhabdomyolysis using the
Japanese adverse drug event report database
Kimie Sai1, Takuya Imatoh1, Ryosuke Nakamura1, Chisato Fukazawa2,
Yasushi Hinomura2, Yoshiro Saito1
1National Institute of Health Sciences, Tokyo, Japan; 2Japan Pharmaceuti‑
cal Information Center, Tokyo, Japan
Correspondence: Kimie Sai
Clinical and Translational Allergy 2016, 6(Suppl 3):P29
Background: Involvement of immune-mediated mechanism has
been demonstrated in a certain type of serious adverse drug reactions
(ADRs), such as severe cutaneous adverse reactions (SCAR) or rhab-
domyolysis (RM), and thus, a possible potentiation of these ADRs by
infection via activating immune reactions is postulated. In this study,
to assess a role of infection in occurrence and severity of SCAR and
RM in Japanese cases, we analyzed a relation of infection to reporting
rates of these ADRs and severe outcomes or periods to onsets using
the Japanese Adverse Drug Event Report database (JADER).
Materials and methods: A total of 302,641 reports regarding primary
suspected drugs from 2009 to 2013 in JADER were used in our analy-
sis. Of these, a total of 3167 SCAR reports (Stevens–Johnson syndrome,
toxic epidermal necrolysis (TEN), or mucocutaneous ocular syndrome)
and 1847 RM reports were included. Infection-Positive (Infect-P) was
dened if the individual case report included data on anti-infectious
drugs or infection-related diseases, either as a primary suspected drug
(PS) or concomitant drugs/diseases (CO). Rates of infections for SCAR
or RM among total reports, and ratios of severe phenotype (TEN for
SCAR) and severe outcomes (no recovery, permanent damage and
death) and period to onset of SCAR or RM were compared between
Infect-P and Infection-Negative (Infect-N).
Results: The reporting ratios for Infect–P (vs. Infect-N) were signi-
cantly higher in SCAR (adjusted odds ratio [95% CI]: 1.8 [1.7–2.0] for PS
and 2.0 [1.8–2.2] for CO, respectively) and lower in RM (0.6 [0.5–0.7] for
PS and 0.8 [0.7–0.9] for CO). The rate of TEN in SCAR was signicantly
higher in Infect-P (vs. Infect-N) (1.3[1.1–1.6] for PS and 2.2 [1.8–2.7] for
CO). Higher rates of severe outcomes by Infect-P (vs. Infect-N) were
observed for SCAR (1.6 [1.2–2.1] for PS and 1.9[1.4–2.5] for CO) and RM
(1.3 [0.8–2.2] for PS and 1.7 [1.0–2.3] for CO). The mean period to onset
of SCAR was shorter for PS (25days) but marginal for CO (40days) in
Infect-P comparing with Infect-N (36 days), and earlier onset of RM
was evident in Infect-P (47days for PS and 191days for CO) comparing
with Infect-N (250days).
Conclusions: This study indicated a substantial association between
infection and occurrence/severity in SCAR as well as RM, showing
much larger impacts on SCAR.
Keywords: Severe cutaneous adverse reactions; Rhabdomyolysis;
Infection; Database
P30
Characterization oferythema multiforme andsevere cutaneous
adverse reactions hospitalizations
Bernardo Sousa‑Pinto, Cláudia Correia, Lídia Gomes, Sara Gil‑Mata, Luís
Araújo, Luís Delgado
Immunology Laboratory ‑ Basic and Clinical Immunology, Faculty
of Medicine, Porto, Portugal
Correspondence: Bernardo Sousa‑Pinto
Clinical and Translational Allergy 2016, 6(Suppl 3):P30
Background: Erythema multiforme (EM) and severe cutaneous
adverse reactions (SCARs) are immunologically-mediated delayed
hypersensitivity reactions triggered after exposition to external agents
such as drugs. We aim to characterize hospitalizations occurring in
Portuguese public hospitals with associated diagnosis of drug-related
EM and SCARs concerning patients’ demographic and clinical charac-
teristics, in-hospital mortality and most frequently associated drug
classes.
Materials and methods: We used a database containing all hospitali-
zations occurred in mainland Portugal public hospitals and analyzed
all episodes with associated diagnosis of drug-related EM or SCARs—
Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and
SJS/TEN overlap syndrome. These hospitalizations were compared
concerning patients’ demographic and clinical characteristics (gender,
age and comorbidities), length of stay, and in-hospital mortality. We
also evaluated the drug classes most frequently associated with these
diagnoses, estimating the number of episodes per million drug pack-
ages sold. A logistic regression was performed to evaluate for factors
signicantly associated with in-hospital mortality among SCARs.
Results: Between 2009 and 2014, there were 122 hospitalizations
with associated diagnosis of EM and 132 with associated diagno-
sis of SCARs. Most EM (65%) and SCARs (55%) episodes occurred in
women. The median age was 63years old for both EM and SCARs.
The frequency of HIV co-infection was higher among SCARs episodes
(9 vs. 2%; p= 0.009). In-hospital mortality varied between 7% (EM)
and 44 % (TEN). Advanced age (OR 1.06; 95 % CI 1.02–1.45), heart
failure (OR 4.93; 95% CI 1.01–23.99), liver disease (OR 7.39; 95% CI
1.07–51.02) and TEN diagnosis (OR 14.66; 95% CI 1.73–124.31) were all
signicantly associated with higher risk of in-hospital mortality among
SCARs episodes. The highest numbers of EM and SCARs episodes per
million drug packages sold concerned antiviral (1.5 and 8.7, respec-
tively) and uric acid metabolism drugs (2.4 and 5.0, respectively).
Conclusions: SCARs are associated with higher mortality than EM.
Advanced age, heart failure, liver disease and TEN diagnoses are
associated with higher in-hospital mortality among SCARs episodes.
Antiviral and uric acid metabolism drugs are the drug classes most fre-
quently associated with SCARs hospitalizations.
Keywords: Erythema multiforme; Severe cutaneous adverse reactions;
Epidemiology; Stevens–Johnson Syndrome; Toxic epidermal necrolysis
P31
Eects ofinfection onincidence/severity ofSJS/TEN
andmyopathy inJapanese cases analyzed byvoluntary case
reports
Ryosuke Nakamura1, Kimie Sai1, Takuya Imatoh1, Yoshimi
Okamoto‑Uchida1, Koji Kajinami2, Kayoko Matsunaga3, Michiko Aihara4,
Yoshiro Saito1
1National Institute of Health Sciences, Tokyo, Japan; 2Kanazawa Medical
University, Ishikawa, Japan; 3Fujita Health University, Aichi, Japan; 4Yoko‑
hama City University, Kanagawa, Japan
Correspondence: Ryosuke Nakamura
Clinical and Translational Allergy 2016, 6(Suppl 3):P31
Background: Immunological mechanisms are supposed to be
involved in the pathogenesis of certain types of serious adverse reac-
tions (ADRs), such as severe cutaneous adverse reactions or rhabdo-
myolysis. Therefore, infection which activates immune system may
aect incidence and severity of ADRs. In this study, we analyzed an
association of concomitant infectious diseases with incidence/severity
of Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)
and myopathy, based on Japanese voluntary case reports.
Materials and methods: Patients who experienced SJS/TEN (259
cases) or myopathy (a total of 129 cases) were recruited through
a nationwide blood sampling network in Japan operated by the
National Institute of Health Sciences under a cooperation of the Min-
istry of Health, Labour and Welfare, Pharmaceuticals and Medical
Devices Agency, and Federation of Pharmaceutical Manufacturers’
Association of Japan. Written informed consent was obtained from all
Page 14 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
recruited patients. Using the case report data, we analyzed rates for
concomitant infectious disease (tuberculosis, hepatitis, AIDS, inuenza
infection, and herpes simplex infection, etc.), and compared the sever-
ity (severe phenotypes or outcomes) and the mean period to onset of
the ADRs between patients with and without infectios diseases.
Results: For SJS/TEN cases, the rate of infectious diseases was 51%, of
which 31% was the cases caused by a primary suspected drug. The
rates of severe phenotype TEN, ocular involvement and permanent
damage were signicantly higher (p< 0.05) and the mean period of
onset of SJS/TEN was signicantly shorter in the infectious patients’
group compared with non-infectious group. The rate of infectious dis-
eases in myopathy was 23%, of which 12% was the cases caused by
a primary suspected drug. The rates of severe phenotype and perma-
nent damage were higher and the mean period of onset of myopathy
was shorter in the myopathy patients with infectious disease than
those without infection, although these dierences were not statisti-
cally signicant.
Conclusions: This study indicated that the incidence and the severity
of SJS/TEN and myopathy are associated with the concomitant infec-
tious disease, especially in the cases of SJS/TEN, which might reect a
greater contribution of immune system as a mechanism of occurrence.
Keywords: SJS; TEN; Myopathy; Infection; Adverse reaction
P32
Ecacy oftumor necrosis factor—a antagonists inStevens–
Johnson syndrome andtoxic epidermal necrolysis: a randomized
controlled trial andimmunosuppressive eects evaluation
Chuang‑Wei Wang1, Shih‑Chi Su1, Shuen‑Iu Hung2, Hsin‑Chun Ho1,
Chih‑Hsun Yang1, Wen‑Hung Chung1
1Department of Dermatology, Drug Hypersensitivity Clinical
and Research Center, Chang Gung Memorial Hospital, Linkou And Kee‑
lung, Taiwan; 2Department and Institute of Pharmacology, School
of Medicine, Infection and Immunity Research Center, National
Yang‑Ming University, Linkou, Taiwan
Correspondence: Chuang‑Wei Wang
Clinical and Translational Allergy 2016, 6(Suppl 3):P32
Background: Stevens–Johnson syndrome (SJS) and toxic epidermal
necrolysis (TEN) are rare, but life-threatening adverse drug reactions.
While the clinical manifestations of SJS/TEN are well-dened, the opti-
mal treatment for these diseases remains unavailable. We aim to evalu-
ate the ecacy and safety of etanercept (anti-TNF-α agent) in patients
with SJS/TEN.
Materials and methods: We enrolled 98 patients with SJS/TEN to per-
form an open, prospective, double-blind and randomized comparison
trial of etanercept versus corticosteroid. We further investigated the
immunologic eects of etanercept in SJS/TEN patients.
Results: This study demonstrated that etanercept had clinical
improvements in patients with SJS/TEN. Etanercept revealed to
be more decreased the SCORTEN-based predicted mortality rate
(predicted rate=17.47 %; observed rate = 8.33%) than in corti-
costeroid use (predicted rate=20.13%; observed rate=15.91 %).
Compared with corticosteroid, etanercept also showed a shorter
skin healing time (The median times are 14days for etanercept and
17days for corticosteroid; P<0.05*) and less side eect for gastroin-
testinal hemorrhage (0% after etanercept use and 11.8% after cor-
ticosteroid use; P<0.05*) in total SJS/TEN patients. For mechanism
study, etanercept signicantly decreased the granulysin and TNF-α
expression in blister uids and plasma (In blister uids: granuly-
sin= 62.5% and TNF-α=50.0% decrease after 2 days treatment;
in plasma: granulysin= 54.7% and TNF-α=69.2% decrease after
15days treatment, all P<0.05*) and increased Treg cells population
(twofold percentage increase after 15days treatment, P <0.01**)
(Fig.2).
Conclusions: This study indicates that etanercept (anti-TNF-α agent)
not only has immunosuppressive eects but also serves as an alterna-
tive medicine for SJS/TEN treatment.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P33
Evolution ofdrug causality inStevens–Johnson syndrome
andtoxic epidermal necrolysis inEurope: analysis of10years
RegiSCAR‑Study
Maren Paulmann1, Ariane Dunant2, Maja Mockenhaupt1, Peggy Sekula3,
Martin Schumacher3, Sylvia Kardaun4, Luigi Naldi5, Teresa Bellón6, Daniel
Creamer7, Cynthia Haddad8, Bruno Sassolas9, Bénédicte Lebrun‑Vignes10,
Laurence Valeyrie‑Allanore8, Jean‑Claude Roujeau8
1Dokumentationszentrum schwerer Hautreaktionen, University Medical
Center, Freiburg, Germany; 2Department of Biostatistics and Epidemiol‑
ogy Unit, Institut Gustave‑Roussy, Villejuif, France; 3Institute of Medical
Biometry and Medical Informatics, University Medical Center, Freiburg,
Germany; 4Reference Center for Cutaneous Adverse Reactions, University
Medical Center, Groningen, The Netherlands; 5Department of Dermatol‑
ogy, Papa Giovanni XXIII Hospital, Bergamo, Italy; 6Institute for Health
Research, University Hospital La Paz–IdiPAZ, Madrid, Spain; 7Department
of Dermatology, King’s College Hospital, London, United Kingdom;
8Reference Center for Toxic and Autoimmune Blistering Diseases, Hopital
Henri Modor, University Paris‑Est, Créteil, France; 9Department of Internal
Medicine and Respiratory Diseases, Hôpital Cavale Blanche, Brest, France;
10Department of pharmacology, Hôpital Pitié‑salpétrière, Paris, France
Correspondence: Maren Paulmann
Clinical and Translational Allergy 2016, 6(Suppl 3):P33
Background: Stevens–Johnson syndrome (SJS)/toxic epidermal
necrolysis (TEN) is rare, but the most severe of all adverse drug reac-
tions due to a high mortality, which is almost 50% in TEN. Good evalu-
ation of risk factors is essential for ecient pharmacovigilance.
Materials and methods: From January 2003 to December 2012 the
international Registry of Severe Cutaneous Adverse Reactions(RegiS-
CAR) included 1096 cases of SJS/TEN collected in seven countries
(France, Germany, Israel, Italy, Netherlands, Spain, United Kingdom).
The diagnoses and dates of onset were validated by an expert group,
blinded for any information on exposures. Causality was established
by using the specic algorithm ALDEN that had previously shown a
good correlation with the results of a case–control analysis in an ear-
lier systematic collection of several hundred cases.
Fig. 2 The clinical improvement in SJS/TEN patients after etanercept
treatment
Page 15 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
Results: In terms of overall causality assessment, at least one medi-
cation was evaluated as the «probable» or «very probable» cause in
744/1096 cases (68%). A medication cause was determined as «pos-
sible» in 209 cases (19%), as «unlikely» in 68 cases (6.2%) and “very
unlikely” in 57 cases (5.2%). 18 patients (1.6%) denied any exposure
to medications. The ve medications most often incriminated («proba-
ble» or «very probable» causality) were allopurinol (n=187; 17%), sul-
famethoxazole (n=80), lamotrigine (n=76), carbamazepine (n=51),
phenytoin (n=42). There were substantial dierences between reac-
tions developing among hospitalized and community patients, e.g.
older age, exposure to a substantially higher number of drugs and a
noticeable role for metamizole among inhospital cases in Germany. In
both groups (inhospital and community cases) we identied a signal
for proton pump inhibitors.
Conclusions: In spite of prior warnings in medical journals and
towards regulatory agencies, allopurinol is still the principal cause
of SJS/TEN in Europe, as it was 10years ago. O-label prescription of
allopurinol for asymptomatic hyperuricemia has not decreased. Sul-
famethoxazole and other anti-infective sulfonamides are still frequent
inducers of SJS/TEN. Lamotrigine is now the third cause and the rst
one among antiepileptic drugs, independent of new indications such
as bipolar disorder. Finally, it is important to note that at least 13% of
SJS/TEN-cases have no drug cause.
Investigation of other possible causes of such «idiopathic cases», e.g.
infections, should be a priority.
P34
Long‑term sequelae inpatients withStevens–Johnson syndrome
andtoxic epidermal necrolysis: a 5‑year analysis
Maren Paulmann1, Carmen Kremmler1, Peggy Sekula2, Laurence
Valeyrie‑Allanore3, Luigi Naldi4, Sylvia Kardaun5, Maja Mockenhaupt1
1Dokumentationszentrum schwerer Hautreaktionen, University Medical
Center, Freiburg, Germany; 2Institute of Medical Biometry and Medical
Informatics, University Medical Center, Freiburg, Germany; 3Reference
Center for Toxic and Autoimmune Blistering Diseases, Hopital Henri
Modor, University Paris‑Est, Créteil, France; 4Department of Dermatol‑
ogy, Papa Giovanni XXIII Hospital, Bergamo, Italy; 5Reference Center
for Cutaneous Adverse Reactions, University Medical Center, Groningen,
The Netherlands
Correspondence: Maren Paulmann
Clinical and Translational Allergy 2016, 6(Suppl 3):P34
Background: Stevens–Johnson syndrome (SJS) and toxic epidermal
necrolysis (TEN) are rare, but severe reactions with blisters and ero-
sions of skin and mucosae. Most often SJS/TEN is induced by drugs,
less frequently by infections, whereas some cases are “idiopathic”.
Severity is determined by skin detachment related to the body sur-
face area (BSA): SJS<10%, TEN >30%, and SJS/TEN-overlap 10–30%
of BSA. The high mortality rate is due to severity as well as age of the
patient. Survivors frequently suer from long-term sequelae, particu-
larly of the mucosae.
Materials and methods: In order to evaluate frequency and extent of
late sequelae in patients with SJS/TEN, a cohort study was performed.
Patients with a validated diagnosis of SJS/TEN, who were included in
the international Registry of Severe Cutaneous Adverse Reactions
(RegiSCAR) between 2003 and 2007, were asked to answer a follow-up
questionnaire.
Results: 112/233 completed follow-up questionnaires could be ana-
lyzed. 62 patients were diagnosed with SJS, 35 with SJS/TEN-overlap,
and 15 with TEN. The mean age is 44years, and approx. 60% are
women. More than 90 % of the patients suer from sequelae after
5years, while the percentage increases with severity of the reaction.
Less than 50% were able to completely return to their normal daily
activities. Sequelae mainly aect skin (73%), mucosa (57%) and nails
(52%). Chronic sequelae of the eyes (67%) are the main issue for the
patients. They include increased photosensitivity, dry eyes, ingrowing
eyelashes (trichiasis), excessive watery eyes (epiphora), inammatory
cicatrization up to blindness. Furthermore, patients describe sleep dis-
turbances and nightmares (29%). In addition, they are afraid of drug
use (65%), and 56% of the patients avoid taking drugs, which may
have a negative impact on their health. Although many patients con-
sider professional psychological support helpful (54%), only 9% had
received it.
Conclusions: This evaluation shows that the majority of patients who
survived SJS/TEN suer from long-term sequelae. An interdisciplinary
approach is not only important in the acute stage of the disease, but
also after discharge from the hospital, including regular check-ups by
specialists for these rare severe reactions.
P35
Major emotional complications anddecreased health related
quality oflife amongsurvivors ofStevens–Johnson syndrome
andtoxic epidermal necrolysis
Roni P. Dodiuk‑Gad1, Cristina Olteanu2, Anthony Feinstein3, Rena
Hashimoto4, Raed Alhusayen4, Sonia Whyte‑Croasdaile5, Yaron
Finkelstein6, Marjorie Burnett7, Shachar Sade8, Robert Cartotto7, Marc
Jeschke7, Neil H. Shear4
1Department of Dermatology, Ha’emek Medical Center, Afula, Israel;
2Faculty of Medicine, University of Toronto, Toronto, Canada; 3Depart‑
ment of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Canada;
4Division of Dermatology, Department of Medicine, Sunnybrook Health
Sciences Centre, Toronto, Canada; 5SJS and TENS Group Canada‑CAST
International, Toronto, Canada; 6Paediatric Emergency Medicine, Clinical
Pharmacology and Toxicology, The Hospital for Sick Children, Toronto,
Canada; 7Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre,
Toronto, Canada; 8Department of Pathology, Sunnybrook Health Sciences
Centre, Toronto, Canada
Correspondence: Roni P. Dodiuk‑Gad
Clinical and Translational Allergy 2016, 6(Suppl 3):P35
Background: Stevens–Johnson Syndrome (SJS) and Toxic Epidermal
Necrolysis (TEN) are life-threatening mucocutaneous reactions, pre-
dominantly drug-induced. In addition to these high mortality rates,
early and late physical complications are common. No studies were
conducted on the emotional status or the general Health-Related
Quality of Life among survivors of SJS/TEN. We aimed to characterize
the long-term emotional complications and health-related quality of
life among SJS/TEN survivors.
Materials and methods: Patients older than 18years who survived
SJS/TEN were assessed using various parameters. Emotional assess-
ment was conducted by three validated questionnaires: Impact of
Events Scale-Revised, General Health Questionnaire, and Hospital
Anxiety and Depression Scale. Health-Related Quality of Life was
assessed by three validated questionnaires: Dermatology Life Quality
Index, EQ-5D, Skindex-29 and one specially designed for the study.
Results: Our cohort consists of 17 patients with mean
51.6 ± 74.7 months (median = 9, range 1–228) following SJS/TEN.
Eleven out of 17 (65%) were found to have symptoms of post-trau-
matic stress (Impact of Events Scale-Revised, mean=22.4±19.9) and
5 (29%) met the criteria for post-traumatic stress disorder, 12 (71%)
had psychological distress (General Health Questionnaire, mean
total score=4.6± 4.2) and 11 (65%) had symptoms of a psychiatric
clinical disorder (Hospital Anxiety and Depression Scale, mean total
score = 14.5 ± 8.4). The Dermatology Life Quality Index indicated
a moderate to extremely large eect on the lives of 9 (53%) partici-
pants (mean total score = 6.9 ± 7.6). Skindex-29 indicated a mild-
severe eect on Health-Related Quality of Life in 10 (59%) participants
(mean=24.6±21.5). Participants rated their general health at a mean
of 66.2/100±18.1 (EQ-5D VAS). Fourteen (82%) participants reported
that SJS/TEN decreased their current quality of life. Twelve (71 %)
reported that SJS/TEN inuenced their current emotional status.
Eleven (65%) reported that SJS/TEN inuenced their current everyday
activities.
Page 16 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
Conclusions: Survivors of SJS/TEN suer from severe long-term emo-
tional complications and decreased health-related quality of life.
Keywords: Stevens–Johnson Syndrome; Toxic epidermal necrolysis;
Emotional complications; SJS/TEN
P36
Retrospective analysis ofStevens–Johnson syndrome
andtoxic epidermal necrolysis inJapanese patients: treatment
andoutcome
Naoko Takamura1, Yumiko Yamane1, Setsuko Matsukura2, Kazuko
Nakamura2, Yuko Watanabe1, Yukie Yamaguchi1, Takeshi Kambara2, Zenro
Ikezawa1, Michiko Aihara1
1Department of Environmental Immuno‑Dermatology## Yokohama City
University, Yokohama, Japan; 2Department of Dermatology## Yokohama
City University Medical Center, Yokohama, Japan
Correspondence: Naoko Takamura
Clinical and Translational Allergy 2016, 6(Suppl 3):P36
Background: Stevens–Johnson syndrome (SJS) and toxic epidermal
necrolysis (TEN) are rare but severe adverse drug reactions with high
mortality.
Materials and methods: To present the clinical characteristics of SJS
and TEN in Japan and evaluate the ecacy of treatments, we retro-
spectively analyzed cases of SJS and TEN treated in Yokohama City
University Hospital and Yokohama City University Medical Center
between January 2000and December 2015.
Results: 60 cases of SJS (24 males and 36 females; average age,
54.2years) and 40 cases of TEN (19 males and 21 females; average age,
56.2years) were included in this study.
31 cases of SJS (51.6%) and all cases of TEN were caused by drugs.
Hepatitis was the most common organ involvement in both SJS and
TEN. Renal dysfunction, intestinal disorder, and respiratory disorder
were also involved in some cases. The major complication was pneu-
monia and sepsis. All cases except for four cases were treated systemi-
cally with corticosteroids. In SJS 40 cases (66.6%) were treated with
corticosteroid alone, Steroid pulse therapy was performed in 40% of
SJS and 90% of TEN. Plasmapheresis and/or immunoglobulin therapy
was combined with steroid therapy performed 17 cases in SJS (42%)
and 26 cases in TEN (65%). Average SCORTEN score was 1.13 in SJS
and 2.32 in TEN. The mortality rate was 6% and the rates for SJS and
TEN were 1.7 and 12.5 %, respectively. The mortality rate was 0 %
treated with combination of corticosteroid, plasmapheresis and
immunoglobulin therapy in SJS and TEN. These were much lower than
predicted mortality according to a severity-of-illness scoring system
for TEN prognosis (SCORTEN) socre.
Conclusions: Treatment with steroid pulse therapy in combination
with plasmapheresis and/or immunoglobulin therapy seems to have
contributed to prognostic improvement in SJS/TEN.
Keywords: SJS; TEN
P37
Severe physical complications amongsurvivors ofStevens–
Johnson syndrome andtoxic epidermal necrolysis
Roni P. Dodiuk‑Gad1, Cristina Olteanu2, Rena Hashimoto3, Hall Chew4,
Raed Alhusayen3, Sonia Whyte‑Croasdaile5, Yaron Finkelstein6, Marjorie
Burnett7, Shachar Sade8, Robert Cartotto7, Marc Jeschke7, Neil H. Shear3
1Department of Dermatology, Ha’emek Medical Center, Afula, Israel;
2Faculty of Medicine, University of Toronto, Toronto, Canada; 3Division
of Dermatology, Department of Medicine, Sunnybrook Health Sciences
Centre, Toronto, Canada; 4Department of Ophthalmology and Vision
Sciences, Sunnybrook Health Sciences Centre, Toronto, Canada; 5SJS
and TENS Group Canada‑CAST International, Toronto, Canada; 6Paediatric
Emergency Medicine, Clinical Pharmacology and Toxicology, The Hospital
for Sick Children, Toronto, Canada; 7Ross Tilley Burn Centre, Sunnybrook
Health Sciences Centre, Toronto, Canada; 8Department of Pathology, Sun‑
nybrook Health Sciences Centre, Toronto, Canada
Correspondence: Roni P. Dodiuk‑Gad
Clinical and Translational Allergy 2016, 6(Suppl 3):P37
Background: Stevens–Johnson Syndrome (SJS) and Toxic Epidermal
Necrolysis (TEN) are considered the most severe types of cutane-
ous adverse reactions to drugs, with high morbidity and mortality
rates. We aimed tocharacterize the long-term physical complications
among SJS/TEN survivors.
Materials and methods: Patients older than 18years who survived
SJS/TEN were assessed by an interview and by skin, oral mucous mem-
brane and detailed ophthalmic exam.
Results: Our cohort consists of 17 patients with mean
51.6 ± 74.7 months (median = 9, range 1–228) following SJS/TEN.
The most commonly reported symptom among survivors was chronic
fatigue/weakness (76 %). The most common cutaneous signs were
post-inammatory dyspigmentation in 77 % of participants, scars
(46 %), and milia (15 %). The most common cutaneous symptoms
were pruritus (53%), photosensitivity (35%), and dry skin (24%). In
the ophthalmic exam, dry eyes were the most common nding in
44%. Other identied signs were: lid adhesions/symblepharon (33%),
chronic ocular surface inammation (33%), loss of visual acuity (22%),
chronic conjunctivitis (22%), keratinization of the tarsal conjunctiva
(22%), lachrymal duct scarring (22 %), blindness (11%), photopho-
bia (11 %), ectropian and trichiasis (11 %), corneal abrasions/ulcers
(11%), conjunctival synechiae (11%), and corneal neovascularization
(11%). The most commonly reported ocular symptoms were dry eyes
in 47% of participants; other symptoms included photophobia (35%),
loss of visual acuity (35%), and ocular pain (24%). Hair loss and nail
loss were reported in 53 and 35% of participants a few months after
TEN, respectively. Other less common complications included genital
synechiae in 18% of female survivors, lupus (12%), renal dysfunction
(12%), and bromyalgia (6%). Tinnitus, tenderness on soles of feet,
abnormal ECG, and vocal cord dysfunction were each reported in 6%
of participants.
Conclusions: Survivors of SJS/TEN suer from severe, long-term physi-
cal complications and require ongoing longitudinal medical follow-up.
Keywords: Physical complications; Stevens–Johnson Syndrome; Toxic
epidermal necrolysis; Long-term complications
P38
Stevens–Johnson syndrome/toxic epidermal necrolysis combined
withhaemophagocytic lymphohistiocytosis: a case report
Brittany Knezevic1, Una Nic Ionmhain1, Allison Barraclough1, Michaela
Lucas2, Matthew Anstey1
1Sir Charles Gairdner Hospital, Perth, Australia; 2Pathwest Laboratory
Medicine, Queen Elizabeth II Medical Centre, Perth, Australia
Correspondence: Michaela Lucas
Clinical and Translational Allergy 2016, 6(Suppl 3):P38
Background: The combination of Stevens–Johnson syndrome/toxic
epidermal necrolysis (SJS/TEN) with haemophagocytic lymphohistio-
cytosis (HLH) is life-threatening and usually fatal in adults. We report
a rare case of a 36 year old male who survived these concomitant
illnesses.
Report: The patient presented with a 1week history of fevers and
u-like symptoms, with onset of a mucocutaneous rash on day ve.
He was admitted to a tertiary intensive care unit (ICU) with a diagno-
sis of SJS/TEN (20–25 % of total body surface area). The potentially
implicated drugs (ibuprofen, codeine and amoxicillin) were promptly
withdrawn, and he received immunosuppressive therapy with
methylprednisolone, intravenous immunoglobulin and cyclosporin
combined with supportive ICU care. He continued to systemically
deteriorate at a time when his skin lesions stabilised. Recognition of
hyperferritinemia (40,900µg/l), unremitting fevers and pancytopenia
in a critically ill patient, clinched the diagnosis of HLH which was con-
rmed on bone marrow biopsy. He received treatment with the HLH-
94 chemotherapy protocol (including etoposide and dexamethasone).
Sequential skin patch tests to ibuprofen and amoxicillin, performed
6 months post-discharge, were negative (codeine patches were not
available). The patient’s negative patch tests were interpreted with
caution, due to previous chemotherapy and the unavoidable delays
to testing, both of which may have led to T lymphocyte depletion and
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Clin Transl Allergy 2016, 6(Suppl 3):31
false negative patch test results. The patient was advised to strictly
avoid all non-steroidal anti-inammatories, aspirin, codeine and amox-
icillin (he had tolerated other opiates and beta-lactams in hospital).
How this report contributes to current knowledge: To our knowl-
edge, this is the rst report of an adult surviving a severe episode of
HLH and SJS/TEN overlap (rather than SJS alone). This case highlights
(1) the potential for HLH to coexist with SJS/TEN and the importance
of early recognition and treatment, (2) the diculties in interpreting
patch tests in patients who have received marrow ablative therapies,
and (3) the complexities of providing recommendations on drug
avoidance to patients with severe cutaneous adverse drug reac-
tions and negative patch test results. Invitro lymphocyte prolifera-
tion assays may be a useful alternative diagnostic tool in this clinical
setting.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
Poster Walk 5: Other organs/unexpected immune reactions (P39–
P47)
P39
A case report ofpatient withanti‑tuberculosis drug‑related
severe liver failure
Toru Usui1, Xiaoli Meng1, John Farrell1, Paul Whitaker2, John Watson2, Neil
French1, Kevin Park1, Dean Naisbitt1
1MRC Centre for Drug Safety Science, Dept Molecular & Clinical Pharma‑
cology, University of Liverpool, Liverpool, United Kingdom; 2Regional
Adult Cystic Fibrosis Unit, St James’s Hospital, Leeds, United Kingdom
Correspondence: Toru Usui
Clinical and Translational Allergy 2016, 6(Suppl 3):P39
Background: Exposure to anti-tuberculosis drugs (ATDs) isoniazid
(INH), ethambutol (ETB), pyrazinamide (PZA) and/or rifampicin (RIF)
is associated with a mild elevation of liver enzymes that occasionally
develops into severe liver injury. We have reported that INH-specic
CD4+ T-cell clones circulate in patients with ATD-related liver injury,
which suggests that the adaptive immune system is involved in the
disease pathogenesis. This study details the nature of the drug anti-
gen-specic T-cell response that develops in a fatal case of ATD-related
liver failure.
Materials and methods: Peripheral blood mononuclear cells were
isolated from a patient who had a severe liver reaction to ATD medica-
tions, ALT 514IU/l and Bilirubin 30mg/dl. A lymphocyte transforma-
tion test (LTT) and IFNγ-ELISPOT assay using ATDs were performed
and clones were generated from ATDs by serial dilution. Drug-specic
clones were identied in terms of cross-reactivity and dose-respon-
siveness and then characterized in terms of CD phenotype and
cytokine secretion.
Results: Positive LTT against multiple drugs (INH, ETB, PZA, RIF, and
activated ester of isonicotinic acid which forms isonicotinic amide
adducts in the cell culture system) was observed. Over 700 T-cell
clones were generated from INH, ETB, PZA, RIF or activated ester of
isonicotinic acid treated peripheral blood mononuclear cells. Antigen-
specic proliferative responses of CD4+/CD8+ clones were identied
with only ETB and RIF. Clones were highly specic and did not cross-
react with other ATDs. Clones are activated to proliferate and secrete
cytotoxic mediators (granzyme B, perforin) and eector cytokines
(IFN-γ, Il-13).
Conclusions: In conclusion, cytotoxic ETB and RIF-specic T-cell clones
have been identied in patient with ATD-related severe liver failure.
Keywords: Isoniazid; Drug-induced liver injury
P40
Acute interstitial nephritis induced byibuprofen
Ana Castro Neves, Susana Cadinha, Ana Moreira, J. P. Moreira Da Silva
Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova De Gaia,
Portugal
Correspondence: Ana Castro Neves
Clinical and Translational Allergy 2016, 6(Suppl 3):P40
Background: Acute Interstitial Nephritis (AIN) is often drug induced
and the most frequently implicated drugs are Non-steroidal anti-
inamatory drugs (NSAIDs) and antibiotics. We report the case of a
patient with AIN induced by Ibuprofen.
Report: A 74year-old-female was admitted at emergency department
with a 10-day history of malaise, anorexia, nausea, diuse myalgias,
fever (38°C) and ank pain, treated with Paracetamol, Ibuprofen and
Ciprooxacin for suspected Pyelonephritis, by her attending physician.
At admission she was febrile (38°C) and prostrated. Laboratory studies
revealed: leukocytosis, acute kidney injury (serum creatinine 5.8mg/
dl, blood urea nitrogen 178mg/dl) and positive C-reactive Protein; uri-
nalysis with leucocituria, proteinuria and hematuria; negative blood
culture. Chest X-ray and ultra sound of kidneys were normal. Treat-
ment with Paracetamol, Ibuprofen and Ciprooxacin was discontinued
and she started Meropenem and intravenous uids. Renal function
improved and she was discharged after 3days. One year later she was
admitted to hospital with similar clinical presentation and diagnosed
with AIN. Ten days prior to this admission she was treated with Cipro-
oxacin and Ibuprofen for Phlebitis. After these two episodes she was
again treated with Ciprooxacin with good tolerance. She was then
referred to our Drug Allergy Clinic for suspected hypersensitivity to
Ibuprofen. Lymphocyte transformation test (LTT) with Ibuprofen was
positive (stimulation index of 13.4 at 10µg/ml). Drug provocation test
(DPT) with the suspected drug was not performed. DPT and long-term
challenge with alternative drugs (Paracetamol and Etoricoxib) were
both negative.
How this report contributes to current knowledge: Renal biopsy is
the only denitive method to establish the diagnosis of AIN. However,
when diagnosis seems likely, a probable precipitating drug can be eas-
ily withdrawn or patient improves readily after withdrawal of the sus-
pected drug, biopsy can be avoidable. Challenge with the suspected
drug remains the gold standard for diagnosis of drug hypersensitivity.
Since AIN is a severe hypersensitivity reaction, DPT with the suspected
drug is contra-indicated. The obvious time relationship between Ibu-
profen treatment and reaction development in both episodes, the
reproducible clinical presentation and positive LT T, suggests Ibuprofen
has been the culprit drug. In cases of severe reactions LTT seems to be
a valuable diagnostic tool.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P41
Cetuximab induced acneiform rash—two case reports
Daniela Ledic Drvar1, Sandra Jerkovic Gulin2, Suzana Ljubojevic
Hadzavdic1, Romana Ceovic1
1Department of Dermatology and Venereology, University Hospital
Center Zagreb and School of Medicine, Zagreb, Croatia; 2Department
of Dermatology and Venereology, General Hospital Sibenik, Sibenik,
Croatia
Correspondence: Sandra Jerkovic Gulin
Clinical and Translational Allergy 2016, 6(Suppl 3):P41
Background: Epidermal growth factor receptor inhibitors (EGFRIs) are
used for treatment of advanced lung, pancreatic, colorectal, and head
and neck cancers. Cetuximab is a monoclonal antibodythat competi-
tively binds to the extracellular domain of EGFR and blocks cytoplas-
mic-domain phosphorilation. It is characterized by frequent cutaneous
adverse reactions (CARs) including acneiform rash (AR), desquama-
tion, xerosis, pruritus, hair abnormalities, paronychia, changes in nails,
mucositis, increased growth of facial hair and eyelashes, and teleangi-
ectasias. AR usually appears between day 2 and week 6 after cetuxi-
mab Background. According to the National Cancer Institute Common
Toxicity Criteria, severity of toxicity of AR is graded into ve grades, and
according to EGFRI-induced AR severity score into mild, moderate and
severe toxicity.
Prophylactic antibiotic treatment with doxycycline 100mg bid for the
rst 6weeks is recommended. Therapeutic plan includes use of grade-
based skin treatment algorithm: (a) mild toxicity—local therapy with
corticosteroids or antibiotics, (b) moderate toxicity—local therapy
with addition of oral antibiotic, and (c) severe toxicity—cetuximab
Page 18 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
dose lowering and therapy for moderate toxicity with an addition
of a methyprednisolone dose pack. If therapy is ineective within
2–4weeks, it is necessary to discontinue cetuximab treatment.
Report: We present two male patients with metastatic colorectal can-
cer who developed papulopustular lesions on the sebum-rich areas of
the face, scalp and trunk accompanied by pruritus and burning sensa-
tions (grade 2/3 or moderate toxicity), 1–3weeks after Background of
cetuximab. One patient developed desquamation of the palms. Come-
dones, primary acne lesions, were lacking. There was no sign of super-
infection. Patients were treated with doxycycline 2×100mg bid for
2weeks, followed by 1×100mg, until the end of cetuximab therapy.
Local therapy included clindamycin lotion, hydrocortisone/oxytetra-
cycline ointment, benzoyl peroxide suspension and emollients. After
3 weeks of treatment, signicant improvement of AR severity was
achieved and there was no need for cetuximab dose reduction.
How this report contributes to current knowledge: Studies have
demonstrated positive correlation between treatment ecacy and
CARs for EGFRI. Since frequency and severity of skin lesions are dose-
dependent, a gradual increase in dose until CARs develop might be a
good strategy to maximize the ecacy of EGFRI.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P42
Enteropathy associated withlosartan
Ana Montoro De Francisco, Talía De Vicente Jiménez, Amelia García
Luque, Natalia Rosado David, José Mª Mateos Galván
Hospital Central de la Defesa, IMIDEF, Madrid, Spain
Correspondence: Ana Montoro De Francisco
Clinical and Translational Allergy 2016, 6(Suppl 3):P42
Background: On August 2012 Rubio-Tapia et al. reported an associa-
tion of olmesartan therapy with an unexplained enteropathy symp-
tomatically resembling celiac disease or sprue. Olmesartan is an
Angiotensin II Receptor Antagonist (ARA II) widely used in high blood
pressure, heart disease and diabetics. On July 2013 the Food Drug
Administration (FDA) approves label changes to include intestinal
problems, Severe Spruelike Enteropathy (SSE) linked to blood pressure
medicine olmesartan.
Losartan was the rst ARA II commercialized in 1995 and it seems to
produce similar Adverse Drug Reactions (ADR) that olmesartan.
Report: Method
Desing: Case report of enteropathy associated with losartan
Scope: Allergy Service, Hospital Central de la Defensa, Madrid.
Period: May 2015
Main variables assessed: demographic and clinical variables, diagnos-
tic criteria, treatment, evolution, causal relationship between drug and
enteropathy according to the modied Karch Lasagna algorithm.
The patient has given written informed consent for the publication
research.
Results: A 81years old woman, diagnosed of hypertension, treated
for 3years with losartan 100mg/d. After starting treatment she refers
chronic diarrhea and since 2years ago worsening diarrhea, abdomi-
nal pain and weight loss. The patient was treated at the emergency
service twice for 3–4 daily episodes of watery, nonbloody diarrhea
associated with abdominal bloating. The patient failed conservative
management including gluten-free diet, oral antibiotic and corti-
costeroid. Additionally to diarrheal syndrome, the patient showed
hoarseness and cough.
Allergologic study: immediate and delayed prick test and specic IgE
were negative for food.
A colonoscopy with colonic biopsies revealed evidence of microscopic
colitis.
Treatment: Losartan withdrawal, achieving complete remission in
4weeks.
The case has been reported to Spanish Postmarketing Surveillance
System.
How this report contributes to current knowledge: The allergist
should keep in mind this possible and rare ADR in patients treated
with losartan (ARA II) showing enteropathy, as discontinuing losartan
leads to clinical improvement.
This enteropathy case is very similar to SSE described in 2012 related
to olmesartan.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P43
Granuloma annulare aftertherapy withcanakinumab
Razvigor Darlenski
Tokuda Hospital Sofia, Sofia, Bulgaria
Correspondence: Razvigor Darlenski
Clinical and Translational Allergy 2016, 6(Suppl 3):P43
Background: Granuloma annulare (GA) is a benign inammatory der-
matosis aecting predominantly females. The disease etiology and
pathophysiology remain unclear. Trauma, association with diabetes
mellitus and medicamentous genesis have been suspected. Patho-
genic mechanisms include cell-mediated immunity (type IV), mac-
rophage activation, and cytokine-mediated degradation of connective
tissue.
Report: Herein we present a 56-years-old male Caucasian patient who
developed skin lesions on the back of the hand 3months after initia-
tion of therapy with canakinumab as a part of a clinical trail for treat-
ment of coronary artery disease. Upon admission the skin changes
involved the dorsum of the hand and were presented by annular pap-
ules and plaques, the largest 3cm in diameter with depressed center
and elevated and inltrated borders. The patient had no other relevant
history of present or past disease beyond the coronary artery diseases
and elevated serum cholesterol levels. He took no other medication
prior or during the disease onset.
Based on the clinical ndings the diagnosis of GA was coined. Cryo-
therapy with liquid nitrogen was performed. Canakinumab was with-
drawn. Skin lesions resolved within the 2weeks later. No new lesions
appeared during the 6months follow up.
How this report contributes to current knowledge: Canakinumab is
a IL-1 beta monoclonal antibody used in rheumatology and in the treat-
ment of autoinammatory syndrome. Recently it was tested in coronary
artery disease, gout and COPD. As a new drug, its safety prole and
unwanted adverse events are still to be challenged. In the described
case we present the development of cutaneous reaction coinciding with
the drug Background. Drug-induced GA has been described in the liter-
ature, e.g. after allopurinol, amlodipine, TNF-alpha inhibitors, gold, and
interferon therapy. As far as we are aware no previous reports exist on
the association between canakinumab therapy and GA.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P44
Hypersensitivity eosinophilic myocarditis or acute coronary
syndrome? Case report
Dario Gulin1, Jozica Sikic1, Jasna Cerkez Habek1, Sandra Jerkovic Gulin2,
Edvard Galic1
1University Hospital Sveti Duh, Zagreb, Croatia; 2General Hospital Sibenik,
Sibenik, Croatia
Correspondence: Sandra Jerkovic Gulin
Clinical and Translational Allergy 2016, 6(Suppl 3):P44
Background: Eosinophilic myocarditis (EM) is a potentially fatal dis-
ease if left untreated. There are numerous drugs that have been impli-
cated in causing the hypersensitivity (HS) form of EM but frequently
the cause of the disease remains unknown as it could have a delayed
presentation for up to 2years. In this case report we present an atypi-
cal clinical presentation of HS EM, possibly caused by hydrochlorothi-
azide (HCT), and signicant coronary artery disease (CAD).
Report: A 63-year-old man presented to the emergency department
with u-like symptoms. He had a history of chronic bronchitis and
arterial hypertension treated with budesonide/formoterol and HCT.
Page 19 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
His general physical examination was unremarkable, without any signs
of heart failure. Complete blood count (CBC) revealed leucocytosis
with slightly eosinophilia and elevated troponin and CRP. ECG showed
no changes in ST/T segment. Echocardiography revealed minimal peri-
cardial eusion for up to 4mm. Initial right pneumonia was observed
on X-ray. He was treated with amoxicillin/clavulanic acid, azithromy-
cin and ibuprofen. Fifth day of hospitalization the signs of disease
became more prominent: CBC revealed 19.2× 109/l leucocytes with
11.2×109/l eosinophils and troponin level was doubled. Pulse doses
of corticosteroids (CS) (methylprednisolone 500mg i.v.) were started
and other therapy was discontinued. Seven hours later patient was
asymptomatic, leucocytes were normal with slightly eosinophilia.
Pulse doses of CS were continued up to 3days when converted to
oral CS. Endomyocardial biopsy showed no inammation. Coronarog-
raphy revealed two-vessel CAD, treated with percutaneous coronary
intervention.
How this report contributes to current knowledge: One of the most
common cause of EM reported in literature is drug HS. In our patient
HCT is a potential cause. Symptoms, levels of troponin, ECG and echo-
cardiographic changes were more suggestive for EM than CAD. Endo-
myocardial biopsy revealed no EM but it was performed third day
after pulse dosage of intra-venous CS, when symptoms completely
vanished. It should be also noted that EM is a focal disease and biopsy
doesn’t have to prove the diagnosis. It is more obvious that CAD was
co-nding, as symptoms of CAD could not be resolved using CS, and
troponin levels would not fall second day after initiating therapy. CBC
with eosinophilic drop powers that hypothesis. Early administration of
systemic CS is necessary regardless of underlying causes, as delayed
treatment may result in fatal outcomes.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P45
Piperacillin‑induced immune haemolytic anaemia: a severe
andfrequent complication ofantibiotic treatment inpatients
withcystic brosis
Philip Specht1, Doris Staab1, Beate Mayer2, Jobst Roehmel1
1Division of Cystic Fibrosis, Pediatric Pneumology and Immunology,
Charité‑Universitätsmedizin Berlin, Berlin, Germany; 2Institute for Transfu‑
sion Medicine, Charité ‑ Universitätsmedizin Berlin, Berlin, Germany
Correspondence: Philip Specht
Clinical and Translational Allergy 2016, 6(Suppl 3):P45
Background: Two mechanisms of drug-induced haemolysis have
been described. Usually both, extravascular and intravascular hae-
molysis, are caused by drug dependent antibodies (ddAb). Extravas-
cular haemolysis presents with mild and less severe clinical symptoms
of anaemia, whereas intravascular haemolysis usually manifests with
a rapid destruction of red blood cells caused by antibody-mediated
complement activation leading to acute clinical symptoms. Interest-
ingly more than 50% of all piperacillin-induced immune haemolytic
anaemia (PIHA) cases investigated at a reference laboratory in Ger-
many were patients with cystic brosis (CF). Therefore the investigated
hypothesis of this study is a higher prevalence for PIHA in patients
with CF as for the general population. Additionally risk factors for PIHA
are systematically assessed.
Materials and methods: Included were all patients with CF older
than 12years who were admitted to the hospital for antibiotic treat-
ment. Past transplantation was an exclusion criterion. Blood samples
were obtained in the beginning and at the end of a given intravenous
treatment. Direct antiglobulin test (DAT) and indirect antiglobulin test
(IAT) were performed using standard techniques. For positive samples
an antibody dierentiation was done. DdAb were investigated using
gel technique. Thus we prepared a 1 mg/ml drug solution or used
exvivo antigens, respectively and incubated it for 30min in presence
of patients’ plasma and group O RBCs. The individual prior exposure
to piperacillin and information concerning atopy and microbiology are
documented.
Results: In the ongoing trial 2 out of 20 patients developed a PIHA.
This is a high prevalence compared to the general expectation of
approximately 1:1,000,000. Both had ddAb but no complement activa-
tion. This is typical for extravascular haemolysis. Clinical symptoms of
haemolysis were mild but there was a drop of haemoglobin by 4mg/
dl. The study will be nished by April 2016.
Conclusions: These results suggest a higher prevalence of PIHA in
patients with CF than expected in the general population. This is
backed by several case reports. Possibly this is due to the exposure
to piperacillin. Therefore PIHA should be considered when treating
patients with CF.
Keywords: Piperacillin; Autoimmune; Haemolysis; Cystic brosis
P46
Progesterone triggered pemphigus foliaceus: case report
Sandra Jerkovic Gulin1, Caius Solovan2, Anca Chiriac3
1Department of Dermatology and Venereology, General Hospital Sibenik,
Sibenik, Croatia; 2Department of Dermatology, University of Medicine
and Pharmacy, Tamisoara, Romania; 3Dermatology Department, Nicolina
Medical Centre, Apollonia University, “P.Poni” Research Institute of Macro‑
molecular Chemistry, Iasi, Romania
Correspondence: Sandra Jerkovic Gulin
Clinical and Translational Allergy 2016, 6(Suppl 3):P46
Background: Pemphigus foliaceus (PF) is a benign variety of pemphi-
gus (P) characterized by acantholysis in the upper part of epidermis,
induced by immunoglobulin G (IgG) autoantibodies (mainly IgG4
subclass) targeting desmoglein -1 (dsg-1). Clinical expression of PF is
based on the presence of scaly and crusted erosions on an erythema-
tous base, accid blisters, minor or no involvement of mucous mem-
branes and with seborrheic distribution and aspect of the lesions in
early stages of the disease. PF is classied into four types: endemic
(fogo selvagem), idiopathic, erythematosus (Senear-Usher syndrome)
and drug-induced. Drugs triggering or inducing PF reported in litera-
ture are penicillamine, bucilamine, captopril, lisinopril, enalapril, fos-
inopril, candesartan, tipronin and rifampicin.
Report: A 45-year-old woman presented with facial erythema, mul-
tiple erythematous papules and plaques, few scaly plaques, shallow
erosions and supercial blisters on an erythematous base localized
on the upper chest and upper back in “V” distribution, acompanied by
pain and burning sensation. Mucous membranes were spared. Lesions
appeared 2months after initiating systemic therapy with medroxypro-
gesterone acetate 10mg daily for 14 days per month for metrorrha-
gia. Biopsy revealed subcorneal cleft within the upper epidermis with
acantholytic keratynocytes. Direct immunouorescence (DIF) of perile-
sional skin showed intercellular, intraepithelial IgG. Indirect immuno-
uorescence (IIF) showed intercellular, intraepithelial IgG, with higher
uorescent intensity in the upper dermis. The diagnosis of possible
drug induced PF was presumed based on clinical, histological and
immunological grounds. The suspected culprit drug—progesterone
was discontinued. Treatment with high-potency topical corticoster-
oid (betamethasone) in combination with gentamicin ointment twice
daily was started. After 4weeks of treatment, lesions resolved almost
completely. Close follow-up was recommended.
How this report contributes to current knowledge: Although PF
often occurs spontaneously, it may be triggered by certain medica-
tions. A case of localized PF induced by topical imiquimod treatment
has been recently reported, based on an unknown mechanism of
acantholysis, probably due to antibodies to dsg-1. Drug as a trigger
must be suspected in every newly diagnosed P. Indentication and
elimination of triggering drug may soothe the clinical symptoms and
shorten the treatment.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P47
Ramipril: triggered generalized pustular psoriasis
Paola Djurinec1, Kresimir Kostovic1, Mirna Bradamante1, Sandra Jerkovic
Gulin2, Romana Ceovic1
1Department of Dermatology and Venereology, University Hospital
Center Zagreb and School of Medicine Zagreb, Zagreb, Croatia; 2Depart‑
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Clin Transl Allergy 2016, 6(Suppl 3):31
ment of Dermatology and Venereology, General Hospital Sibenik, Sibenik,
Croatia
Correspondence: Sandra Jerkovic Gulin
Clinical and Translational Allergy 2016, 6(Suppl 3):P47
Background: Generalized pustular psoriasis (GPP) is an extreme and
serious form of psoriasis (P) with tiny, sterile, yellow pustules on an ery-
thematous base. The clinical presentation of drug-provoked P include
more often generalized plaque P and erythroderma, and rarely pal-
moplantar pustulosis or GGP. Drugs can cause (a) precipitation of P de
novo in predisposed or nonpredisposed individuals; (b) exacerbation
of pre-existing psoriatic lesions; (c) induction of lesions in clinically
normal skin in patients with P; and (d) development of treatment-
resistant P. Angiotensin-converting enzyme inhibitors (ACEIs) are
widely used to control hypertension and are considered to be possi-
ble triggering, exacerbating or inducing agents of P. Rarely, ACEIs have
been reported in the literature as inductors of GPP. We present our rst
case of ramipril-triggered GPP.
Report: 46-year-old women presented with low-grade fever, ery-
thema, small pustules 1–2mm in size and exfoliation involving skin
on trunk, extremities, palms and soles. She had no previous history of
P or family history of P. She began taking the new antihypertensive—
ramipril 2 months before the onset of symptoms. Laboratory nd-
ings showed elevated erythrocyte sedimentation rate and C-reactive
peptide with other biochemical ndings within normal limits. Gram
stained smear examination of pustules were negative and the pus cul-
ture was sterile. We set up a working diagnosis of GPP based on his-
tory, laboratory ndings and clinical picture and the main dierential
diagnosis was acute generalized exanthematous pustulosis. Biopsy
was performed. Ramipril as suspected culprit drug was discontinued
and replaced with valsartan. We started the treatment with acitretin
50mg/day which resulted in good initial therapeutic response. On the
basis of clinical picture, biopsy and satisfactory therapeutic outcome,
the diagnosis of GPP was conrmed.
How this report contributes to current knowledge: Only one case
of ramipril-induced GPP in patient with psoriatic arthritis has been
published in the literature. According to our knowledge, we present a
rst case of ramipril-triggered GPP in an individual without personal
and family history of P. AsP is a common skin disorder, knowledge of
the factors that are inducers, triggers, or aggravators of the disease is
of utmost importance for clinicians. Drug cessation or replacement
may play a crucial role in the treatment outcome so taking a detailed
history is decisive.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
Poster Walk 6: NSAIDs (P48–P56)
P48
Aspirin desensitization incardiovascular disease—Portuguese
experience
Jose Pedro Almeida1, Joana Caiado1, Elisa Pedro1, Pedro Canas Da Silva2,
Manuel Pereira Barbosa1
1Immunoallergology Department, Centro Hospitalar Lisboa Norte/
Hospital Santa Maria, Lisbon, Portugal; 2Cardiology Department, Centro
Hospitalar Lisboa Norte/Hospital Santa Maria, Lisbon, Portugal
Correspondence: Joana Caiado
Clinical and Translational Allergy 2016, 6(Suppl 3):P48
Background: Several studies have demonstrated a reduction in
adverse cardiovascular events with the administration of dual anti-
platelet therapy (aspirin and clopidogrel) to patients (pts) with coro-
nary artery disease, especially in the prevention of thrombosis after
implantation of bare-metal and drug-eluting stents. However, when
pts have aspirin hypersensitivity (AH) this treatment is limited, and
they are maintained on monotherapy with clopidogrel. Aspirin desen-
sitization (AD) is the alternative for these individuals. The aim is to
describe the experience of a Portuguese Allergy Department in AD on
cardiovascular pts, between April 2006 and January 2016.
Materials and methods: Thirty pts with previous history of AH who
needed dual antiplatelet therapy due to cardiovascular disease
(female-14, male-16), mean age 64 years-old, were desensitized to
aspirin. The clinical presentation of AH was asthma (six pts), anaphy-
laxis (four pts), cutaneous rash (seven pts), angioedema (13 pts), in
some cases with very remote reactions (>20years ago). In most pts
(22 out of 30), AD was performed immediately after percutaneous
coronary intervention (PCI). Most AD were performed in Cardiology
Department (27); three pts with planned AD were desensitized at the
Allergy Day-Care Unit; oral doses were increased every 30–60min (tar-
get dose 152.5 mg) under a 4.5-h protocol. Pre-medication was not
administered.
Results: All pts successfully completed AD, although there were two
reactions30min after the procedure: a 63year-old man who devel-
oped acute rhinitis and conjuntivitis, eyelid angioedema and dry
cough; and a 75year-old man who developed acute generalized urti-
caria. All pts were monitored after AD, and are still on daily aspirin
100mg (there were neither hypersensitivity reactions nor drop-outs).
Conclusions: Despite positive clinical history of AH, some pts had a
remote reaction, and due to the emergency of the procedure we were
not able to conrm their AH. This fact could in part explain the low
incidence of reactions during AD; another reason could be the smaller
dose of aspirin used as antiplatelet (100–150mg) compared with the
dose to which they previously reacted (>500mg). Some authors advo-
cate that AD should be performed before PCI, but PCI could provide
greater hemodynamic stability and therefore allow a safer AD. Based
on our experience, AD is safe and ecacious, even when performed
after PCI, with all pts responding to the desensitization procedure.
Keywords: Aspirin hypersensitivity; Drug desensitization; Anaphylaxis
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P49
Asthma and/or rhinitis toNSAIDs withgood tolerance toASA
Gador Bogas1, Natalia Blanca‑López2, Diana Pérez‑Alzate2, Inmaculada
Doña1, José Augusto Agúndez3, Elena García‑Martín3, José Antonio
Cornejo‑García4, Cristobalina Mayorga4, María José Torres1, Gabriela
Canto2, Miguel Blanca5
1Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga,
Spain; 2Allergy Service, Infanta Leonor University Hospital, Madrid, Spain;
3Department of Pharmacology, University of Extremadura, Caceres,
Spain; 4Research Laboratory and Allergy Unit, IBIMA, Regional University
Hospital of Malaga, UMA, Malaga, Spain; 5Allergy Unit, IBIMA, Regional
University Hospital of Malaga, UMA, Malaga, Spain
Correspondence: Gador Bogas
Clinical and Translational Allergy 2016, 6(Suppl 3):P49
Background: Subjects with hypersensitivity reactions to NSAIDs with
airways involvement can develop rhinitis and or asthma after the
intake of ASA and other NSAIDs that are strong COX-1 inhibitors. Some
cases may also respond to weak COX-1 and selective COX-2 inhibitors.
The hallmark characteristic is that symptoms are triggered by asthma
and that in most instances subjects have a pre-existing respiratory
disease. We studied if subjects can be selective responders to some
NSAIDs including weak COX-1 or selective COX-2 inhibitors having
good tolerance to ASA.
Materials and methods: Subjects reporting rhinitis and/or asthma to
a single NSAID with good tolerance to ASA were evaluated. An aller-
gological evaluation was carried out plus a controlled challenge with
ASA for verifying tolerance. In a second step we proceed to a con-
trolled challenge with the culprit drug involved. FEV1 and acoustic
nasal rhynomanometry were measured with values lower that 12 and
30 % respectively considered as a positive response. Also nasal and
bronchial symptoms were recorded.
Results: We conrmed in 21 cases the appearance of nasal and/or
bronchial symptoms by objective parameters (decrease in FEV1 and/or
decrease in nasal volume cavity) after the administration of the drug.
The drugs involved were ibuprofen in four cases, paracetamol in four
cases, desketoprofen in one and etoricoxib in another.
Page 21 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
Conclusions: Selective respiratory responses to a single NSAID with
good tolerance to ASA occur. Although the underlying mechanism
is not known, the classical involvement of the leukotriene’s pathway
occurring is aspirin exacerbated respiratory disease seems to be dis-
carded. This constitutes a new phenotype within the category of
hypersensitivity reactions to NSAIDs.
P50
Clinical characteristics of196 patients withnon‑steroidal
anti‑inammatory drug (NSAIDs) hypersensitivity
Sengül Aksakal1, Aytül Zerrin Sin2, Zeynep Peker Koç2, Fatma Düsünür
Günsen2, Ömür Ardeniz2, Emine Nihal Mete Gökmen2, Okan Gülbahar2,
Ali Kokuludag2
1Karadeniz Technical University Medical Faculty Department of Clinical
Immunology, Trabzon, Turkey; 2Ege University Medical Faculty Depart‑
ment of Allergy and Clinical Immunology, Izmir, Turkey
Correspondence: Aytül Zerrin Sin
Clinical and Translational Allergy 2016, 6(Suppl 3):P50
Background: Nonsteroidal antiinammatory drugs (NSAIDs) as the
most frequently prescribed classes of drugs have been reported to
be the second most common cause of drug hypersensitivity reactions
after beta-lactam antibiotics. In this study we aimed to evaluate the
clinical characteristics of NSAID hypersensitivity based on European
Network for Drug Allergy (ENDA)’s classication.
Materials and methods: 196 patients diagnosed as NSAIDs hyper-
sensitivity between the years of 2013–2014 were enrolled to the
study. The patients were questioned about the other allergic diseases
(rhinitis, asthma, urticarial, personal and familial drug allergy) besides
the demographic features. NSAID reactions were classied as follow:
NSAID induced urticaria/angioedema (NIUA), single NSAID induced
urticaria/angioedema, anaphylaxis or both (SNIUAA), NSAID exacer-
bated cutaneous disease (NECD), NSAIDs exacerbated respiratory dis-
ease (NERD), single NSAID induced delayed hypersensitivity reactions
(SNIDR). Acetylsalicylic acid, diclofenac, paracetamol and meloxicam
were the most frequently preferred drugs for oral provocation test to
distinguish of cross-reactive and IgE-mediated reactions.
Results: Hypersensitivity to NSAIDs was three times common in
female (77%) than male (23%). The patients with NERD had atopic his-
tory the most frequently (50%). 6.6% of patients have drug allergy
in their family. The frequency of hypersensitivities was found respec-
tively as follows: NIUA (46%), SNIUAA (24%), NECD (15%), NERD (8%),
SNIRD (7 %). The patients who had cross-reactive hypersensitivity
to many of NSAIDs could be tolerated paracetamol, meloxicam and
nimesulid. Diclofenac (11 cases 23%), Flurbiprofen (seven cases 15%),
Metamizol (seven cases 15%) were induced SNIUAA respectively, But
according to their chemical structure propionic acid derivatives had
been caused severe anaphylaxis mostly. Commonly seen delayed
reactions due to NSAIDs are maculopapular eruptions and xed drug
eruption.
Conclusions: NSAIDs were caused NIUA, SNIUAA and NECD most fre-
quently (85%) although NERD and delayed reactions were quite rare.
There are still unexplained points in these cases. Therefore there are
needed more clinical studies.
Keywords: Non-steroidal anti-inammatory drug hypersensitivity
P51
Development ofimmediate hypersensitivity toseveral NSAIDs
maintaining good tolerance toASA
Natalia Pérez‑Sánchez1, Natalia Blanca‑López2, Diana Pérez‑Alzate2,
Gador Bogas1, Inmaculada Doña1, María Salas1, María José Torres1, Miguel
Blanca1, Gabriela Canto2
1Allergy Unit, Malaga Regional University Hospital‑IBIMA, Malaga, Spain;
2Allergy Service, Infanta Leonor Hospital, Madrid, Spain
Correspondence: Natalia Pérez‑Sánchez
Clinical and Translational Allergy 2016, 6(Suppl 3):P51
Background: Subjects responding to several NSAIDs including
ASA are considered cross-hypersensitive, whereas those respond-
ing to only one NSAID with tolerance to other chemically unrelated
NSAIDs are considered selective responders. However, in some
cases, patients that develop immediate reactions to several NSAIDs
are classied as cross-hypersensitive without assessing ASA
tolerance.
Report: A 70year-old woman, without allergic history, referred that in
1996 she developed two episodes of urticaria less than an hour after
paracetamol intake. Three years after, she had developed three epi-
sodes of urticaria 90min after dipyrone intake. At that time she was
allergologically evaluated: intradermal test (ID) with dipyrone (2mg/
ml) and paracetamol (0.1mg/ml) were positive. She was challenged
with ASA showing tolerance at full therapeutic doses (500 mg). In
2012, she suered from an episode of facial angioedema and pruritus
in the tongue after celecoxib intake. She reported previous tolerance
to this drug on many occasions.In September 2014, she was re-eval-
uated: ID to paracetamol was negative (0.1mg/ml), and ID and baso-
phil activation test (BAT) to dipyrone were positive. Drug challenges:
60min after achieving a cumulative dose of paracetamol 300mg, she
developed generalized pruritus and urticaria. Two weeks later, she
presented pruritus in the tongue and ears, nasal itching and obstruc-
tion, and wheals in the neck after provocation with a cumulative dose
of 100mg of celecoxib, with no changes in FEV1 values. After another
interval of 2weeks tolerance to etoricoxib was observed at full thera-
peutic doses. Two weeks later the patient tolerated ASA and ibupro-
fen during controlled challenge until therapeutic doses. In addition,
around 2months later the patient received two independent 2days
treatment courses with these drugs, separated by a 2 weeks time
interval.
How this report contributes to current knowledge: Subjects may
develop an immediate response to a number of dierent NSAIDs,
including some COX-1 and/or selective COX-2 inhibitors but tolerate
strong COX-1 inhibitors. This case shows the importance of testing for
ASA tolerance when confronted by a patient who responds to several
chemically unrelated NSAIDs.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P52
Diagnosis ofhypersensitivity reactions toparacetamol ina large
serie ofcases
Inmaculada Doña1, Maria Salas1, Francisca Gomez1, Natalia Blanca‑Lopez2,
Diana Perez‑Alzate2, Gador Bogas3, Esther Barrionuevo1, Maria Jose
Torres1, Inmaculada Andreu4, Miguel Ángel Miranda4, Gabriela Canto2,
Miguel Blanca1
1Regional Hospital of Málaga‑IBIMA, Málaga, Spain; 2Infanta Leonor Hos‑
pital, Madrid, Spain; 3Regional Hospital of Málaga, Málaga, Spain; 4Dpto.
Química/Instituto de Tecnología Química –UPV‑CSIC, Valencia, Spain
Correspondence: Inmaculada Doña
Clinical and Translational Allergy 2016, 6(Suppl 3):P52
Background: The most important drug involved in hypersensitiv-
ity drug reactions (HDR) are NSAIDs. Two mechanisms are involved:
immunological sensitization (specic IgE or T-cell) and pharmaco-
logical (COX-1 inhibition). Paracetamol, one of the drug most highly
consumed all over the world, has been implicated in HDR. The contri-
bution these mechanisms in HDR to paracetamol is not well known.
We studied a large group of patients who developed one/several epi-
sodes indicative HDR to paracetamol.
Materials and methods: Patients with reactions to paracetamol were
classied as cross-hypersensitivity (CH) if they responded to two oth-
ers NSAIDS not chemically related including ASA. If only paracetamol
was implicated, drug provocation test (DPT) with ASA was required:
if positive, they were included as CH and if negative, as selective
responders (SR). In cases who reported respiratory symptoms, nasal
provocation test with L-ASA were performed. Atopy status was also
assessed with prick test to inhalant allergens.
Results: A total of 350 patients with conrmed diagnosis of HDR to
paracetamol were included: 288 (82.28%) resulted to be CH and 62
SR (17.71%). Within the CH group, following the ENDA classication,
181 (62.84%) were NIUA, 25 (8.68%) NERD, 16 (5.55%) NECD, and
in 60 (20.83%) blended reactions. A total of 46 (25.41%) patients
Page 22 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
required a positive DPT for diagnosis. Nasal challenge with L-ASA
was positive in 19 (82.6%) patients with clinical history suggestive
of NERD. Within SR group, 56 cases (90.32%) were SNIUAA (reaction
less than 24), being anaphylaxis the most frequent clinical entity
(29 (51.78%), followed by urticaria/angioedema (16; 28.57%), angi-
oedema (6; 10.71%), urticaria (4; 7.14 %) and xed drug eruption
(1; 1.78%). A total of 18 (32.14%) patients required a positive DPT
to paracetamol for diagnosis. The remaining six (9.67%) cases were
SNIDHR as they had the reaction more than 24h after paracetamol
administration: four (66.66%) maculopapular exanthema and two
(33.33%) exanthema with desquamation. One patient had respira-
tory symptoms and was conrmed as SR.
Conclusions: These data indicate that when patients develop a HDR
to paracetamol after carried out the allergological work-up, the 80%
of patients who developed a positive response were CH with a lower
proportion being SR. DPT was needed in more than 20% of cases to
achieve the diagnosis.
P53
Hypersensitivity toparacetamol according tothe new
classication ofhypersensitivity toNSAIDs
Gabija Didžiokaite1, Olesia Gaidej2, Simona Kašinskaite3, Violeta
Kvedariene3
1Vilnius University, Faculty of Medicine, Vilnius, Lithuania; 2Vilnius Uni‑
versity Hospital Santariskiu Klinikos, Centre of Internal Medicine, Vilnius,
Lithuania; 3Center of Pulmonology and Allergology, Clinic of Infectious,
Chest diseases, Dermatology and Allergology, Vilnius University Hospital
Santariskiu Klinikos, Vilnius, Lithuania
Correspondence: Gabija Didžiokaite
Clinical and Translational Allergy 2016, 6(Suppl 3):P53
Background: Paracetamol is often proposed as a safe alternative
to the patients with hypersensitivity to NSAIDs. However, reactions
induced by this drug can manifest in a wide variety of symptoms.
Aim: To evaluate hypersensitivity to paracetamol in Lithuanian adult
population according to the new classication of hypersensitivity to
NSAIDS.
Materials and methods: We followed 183 adult patients (211 clini-
cal histories) of suspected hypersensitivity to paracetamol in the
Pulmonology and Allergology Centre of Vilnius University Hospital
Santariskiu Klinikos. The median age of patients was 42.5 [32.75–53.25]
years. Most of the patients were females 144 (78.7%). 14 medications
containing paracetamol were reported. ENDA questionnaires were
completed, patch and drug provocation tests (DPTs) were performed
to conrm the diagnosis.
Results: We adapted our clinical cases to the new classication of hyper-
sensitivity to NSAIDs and divided our patients into ve categories. 53
cases (47 patients) were nonimmunologically mediated (cross-reactive)
hypersensitivity reactions to NSAIDs: four cases of “NSAIDs-exacerbated
respiratory disease”, four cases of “NSAIDs-exacerbated cutaneous dis-
ease” and other 45 cases (39 patients) of “NSAIDs-induced urticaria/
angioedema (NIUA)”. 86 cases (75 patients) were immunologically medi-
ated (non-cross-reactive) hypersensitivity reactions to NSAIDs: 63 cases
(55 patients) of “Single-NSAID-induced urticaria/angioedema or ana-
phylaxis (SNIUAA)” and 23 cases (20 patients) of “Single-NSAID-induced
delayed hypersensitivity reactions (SNIRD)”. 10 cases of bronchospasm
without underlying chronic airway respiratory diseases and 62 cases of
anaphylaxis, maculopapular rash and other hypersensitivity reactions
induced not only by paracetamol but also by other NSAIDs could not be
classied according to the criteria of this classication.
Only 25 (13.7 %) patients (mostly SNIUAA (ten patients) and SNIRD
(seven patients)) underwent further allergological work-up with sus-
pected causative drug. Only seven (28%) of them (three SNIUAA, two
NIUA and two SNIRD), had true paracetamol hypersensitivity. For one
patient hypersensitivity was demonstrated by patch test,andfor six by
DPTs. 6 out of 7 positive test results occurred as skin reactions.
Conclusions: True hypersensitivity to paracetamol is rare. In our
research, only patients with skin reactions in their clinical history,
mostly SNIUAA, were conrmed to be hypersensitive to this drug.
Keywords: Paracetamol; Diagnostics; Provocation tests; Drug
hypersensitivity
P54
Ibuprofen andother aryl propionic derivates can induce
immediate selective hypersensitivity responses
Diana Perez‑Alzate1, Natalia Blanca‑López1, Maria Isabel Garcimartin1,
Inmaculada Doña2, Maria Luisa Somoza1, Cristobalina Mayorga3, Maria
Jose Torres4, Gador Bojas2, Jose Antonio Cornejo‑Garcia3, Maria Gabriela
Canto1, Miguel Blanca5
1Allergy Unit, Infanta Leonor University Hospital, Madrid, Spain; 2Allergy
Unit, Regional University Hospital of Malaga, Malaga, Spain; 3Research
Laboratory and Allergy Unit, IBIMA, Regional University Hospital of Mal‑
aga, Malaga, Spain; 4Allergy Unit, Regional University Hospital of Malaga,
Madrid, Spain; 5Allergy Unit, Regional University Hospital of Malaga,
Malaga, Spain, Malaga, Spain
Correspondence: Diana Perez‑Alzate
Clinical and Translational Allergy 2016, 6(Suppl 3):P54
Background: Arylpropionic acid derivatives are the most commonly
prescribed and consumed NSAIDs and very often obtained without
medical prescription. From these the most common is ibuprofen.
Within the group of hypersensitivity reactions to NSAIDs, these drugs
are progressively involved and include those mediated by specic
immunological mechanisms and those classically classied as cross-
intolerance reactions. Within the rst category, IgE mediates or T cell
specic responses may occur. We present a series of cases with an
immediate selective response to ibuprofen and other arylpropionic
derivatives conrmed by drug provocation tests (DPT). In addition to
demonstrate selectivity of the response to these drugs we assessed
cross-reactivity between them.
Materials and methods: Subjects who reported symptoms indicative
of an hypersensitivity reaction to an NSAIDs were evaluated. A DPT
with ASA was carried out to rule out cross-intolerance (non allergic
hypersensitivity). Imputability of the dierent aryl propionic deriva-
tives and assessment of cross-reactivity was carried out by drug prov-
ocation tests. Serum tryptase was quantized in peripheral blood at 2
and 24h post episode and in the aected skin by immunohistochem-
istry at the moment of the appearance of the reaction.
Results: All subjects included had good tolerance to ASA. After proceed-
ing with the aryl propionic acid derivative challenge, 42 cases were clas-
sied as selective immediate responders. Ibuprofen was the drug most
frequently involved, followed by naproxen and desketoprofen. We found
cases than only responded to one single drug and others who responded
to several, conrming cross-reactivity. Quantitation of tryptase levels
in peripheral blood and skin biopsies were indicative of an immediate
selective response with the involvement of mast cell activation.
Conclusions: Ibuprofen and other aryl propionic acid derivatives
can induce selective responses in subjects with NSAIDs hypersen-
sitivity. Further studies are in progress for identifying the possible
adducts (hapten-carrier complexes) implicated and the existence of
cross-reactivity.
Keywords: Aryl-propionic derivates; Ibuprofen; Immediate selective
responses
P55
Subjects developing immediate responses toseveral NSAIDs can
be selective withgood tolerance toASA
Natalia Blanca‑Lopez1, Diana Pérez‑Alzate1, Francisco Javier Ruano Perez1,
Inmaculada Doña2, Maria Luisa Somoza1, Inmaculada Andreu3, Miguel
Angel Miranda3, Cristobalina Mayorga4, Maria Jose Torres2, Jose Antonio
Cornejo‑Garcia4, Miguel Blanca2, Maria Gabriela Canto1
1Allergy Unit, Infanta Leonor University Hospital, Madrid, Spain; 2Allergy
Unit, Regional University Hospital of Malaga, Malaga, Spain; 3Universidad
Politécnica de Valencia, Valencia, Spain; 4Research Laboratory and Allergy
Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain
Correspondence: Natalia Blanca‑Lopez
Clinical and Translational Allergy 2016, 6(Suppl 3):P55
Page 23 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
The published version of this abstract can be found at [1].
Reference
1. Blanca‑Lopez NB, Perez‑Alzate D, Dona I, Somoza ML, Mayorga C, Jose
Torres M, Carnejo‑Garcia JA, Blanca M, Canto G. Multuple selective
responders should not be confouned with cross‑intolerance to Nsaids. J
Allergy Clin Immunol. 2016;137(2, Supplement):AB82.
P56
Utility oflow‑dose oral aspirin challenges fordiagnosis ofaspirin
exacerbated respiratory disease
Elina Jerschow1, Teresa Pelletier2, Zhen Ren3, Golda Hudes4, Marek
Sanak5, Esperanza Morales6, Victor Schuster1, Simon D. Spivack4, David
Rosenstreich7
1Albert Einstein College of Medicine/Montefiore Medical Center, Bronx,
USA; 2Albert Einstein College of Medicine, Bronx, USA; 3Jacobi Medical
Center, NY, USA; 4Albert Einstein College of Medicine/Montefiore Medical
Center, NY, USA; 5Jagiellonian University Medical College, Bronx, Poland;
6Ferkauf Graduate School of Psychology at Yeshiva University, NY, USA;
7Albert Einstein College of Medicine/Montefiore Medical Center, Krakow,
USA
Correspondence: Elina Jerschow
Clinical and Translational Allergy 2016, 6(Suppl 3):P56
The published version of this abstract can be found at [1].
Reference
1. Jerschow E, Ren Z, Hudes G, Sanak M, Morales E, Schuster V, Spivack SD,
Rosenstriech D. Ann Allergy Asthma Immunol 2016. 116(4): 321–8.
Poster Walk 7: NSAID 2 (P57–P65)
P57
Alternate regulation ofcyclooxygenase‑2 (COX‑2) MRNA
expression may predispose patients toaspirin‑induced
exacerbations
Renato Erzen, Mira Silar, Nissera Bajrovic, Matija Rijavec, Mihaela Zidarn,
Peter Korosec
University Hospital for Respiratory Diseases and Allergy Golnik, Golnik,
Slovenia
Correspondence: Renato Erzen
Clinical and Translational Allergy 2016, 6(Suppl 3):P57
Background: Exposure to acetylsalicylic acid (ASA) and other non-
steroidal anti-inammatory drugs (NSAID) may exacerbate respira-
tory disease (asthma, rhinitis), cutaneous diseases (urticaria and
angioedema in patients with chronic urticaria, trigger urticaria, angi-
oedema and anaphylaxis in patients without underlying diseases.
We made a hypothesis that alternate regulation of cyclooxigenase-2
(COX-2) mRNA expression may predispose patients to ASA-induced
exacerbations.
Materials and cons: We performed a prospective study of 40 subjects
(mean age 49years, 27 women) who had suspected hypersensitivity
to ASA or other NSAID. 20 subjects had asthma (10 of them also nasal
polyposis). We performed provocation tests (nasal and/or oral) with
ASA in all of them. In 14 subjects tests were positive (eight nasal). Gene
expression was analyzed in whole blood sample using real-time RT
PCR just before ASA provocation and 4h after provocation. We also
included six Hymenoptera venom allergic patients which were fol-
lowed after systemic reaction (SR) during VIT failure and four healthy
control subjects.
Results: We found signicantly important increase of COX-2 mRNA
expression in patients with ASA provocation test (p=0.004). There
was no dierence in ASA tolerant patients. COX-1 expression was
comparable between ASA tolerant and hypersensitive patients and
showed no dynamic during provocation. There were no changes in
COX-2 expression in subjects with SR during VIT or in healthy control
subjects.
Conclusions: Main ndings in our study are: (1) after provocation with
ASA COX-2 expression is increased in subjects with Aspirin intolerance
in comparison with subjects who tolerate Aspirin; (2) during allergic
reaction like SR in VIT failure we found no dierence in COX-2 expres-
sion; (3) all subjects that were positive on ASA provocation test had
asthma and/or nasal polyposis.
Keywords: Asthma/rhinitis; Hypersensitivity to acetylsalicylic acid;
COX-2 MRNA expression
P58
Anaphylaxis todiclofenac: what aboutthe underlying
mechanism?
Leonor Carneiro‑Leão, Fabrícia Carolino, Luís Amaral, Carmen Botelho,
Eunice Dias‑Castro, Josefina Cernadas
Serviço de Imunoalergologia, Centro Hospitalar de São João, Porto,
Portugal
Correspondence: Leonor Carneiro‑Leão
Clinical and Translational Allergy 2016, 6(Suppl 3):P58
Background: Diclofenac is a phenylacetic acid derivative belonging to
the group of arylcarboxylic acids. NSAIDs have been reported as the
2nd most frequent cause of drug-induced anaphylaxis and diclofenac
was the only NSAID signicantly associated with anaphylaxis. How-
ever, some doubts remain about the pathophysiology of these reac-
tions. Here we describe a case series of anaphylaxis probably induced
by diclofenac.
Materials and methods: Retrospective analysis of patients with sus-
pected anaphylaxis to diclofenac studied in our DAU, who underwent
skin tests (ST). Records were analyzed for clinical signs and symptoms,
severity of reactions, ST and oral challenges (OC). ST were performed
with commercially available IV formulation of diclofenac, in a concentra-
tion of 25mg/ml, diluted from 1×10−4 to 1/1 for IDT and 1/1 for SPT.
Results: A total of 33 patients were enrolled in the nal analysis.
Mean age was 50(±12.75) years, 22(68.8%) were women, 6(18.2 %)
were atopic. The time elapsed until the reaction was less than 1h in
26(83.2%) cases. Seventeen patients had grade 4 anaphylaxis and ten
had history of re-exposure with reproducible symptoms.
Nineteen patients (62.7%) reported reactions only to diclofenac (sin-
gle-reactors) and 12 to other NSAIDs (multiple reactors) (eight to ace-
tylsalicylic acid, two to aceclofenac). Twelve single-reactors (63.2 %)
had positive ST (two with systemic symptoms during the procedure).
Only four multiple reactors (33.3%) had positive tests.
Only one diagnostic OC was performed in order to clarify a doubtful
history and it was positive. OC with alternative drugs were performed
in 29 patients, with meloxicam in 17 and etoricoxib in 9. Two patients
had skin symptoms during the alternative OC and both were from the
multiple reactors group.
Conclusions: We report a large series of anaphylaxis to diclofenac
assessed by skin tests. As the majority of NSAIDs hypersensitivity reac-
tions are considered to be due to a non-immunologic mechanism,
non-irritative concentrations to IDT and specic IgE’s are not available.
Characteristics such as the severity and time of reaction, single-reactor
status and systemic symptoms during skin tests suggest IgE-depend-
ent hypersensitivity in this study. The value of intradermal tests and
their non-irritative concentrations remain to be determined doubtful
history and it was positive.
Keywords: Diclofenac anaphylaxis mechanism
P59
COX‑2 inhibitors: are they always a safe alternative
inhypersensitivity tononsteroidal anti‑inammatory drugs?
Luis Amaral, Fabricia Carolino, Eunice Castro, Josefina Cernadas
Serviço de Imunoalergologia, Centro Hospitalar de São João E.P.E., Porto,
Portugal
Correspondence: Luis Amaral
Clinical and Translational Allergy 2016, 6(Suppl 3):P59
Background: Nonsteroidal anti-inammatory drugs (NSAID) are
one of the most frequent causes of drug-induced hypersensitivity
Page 24 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
reactions worldwide. It is generally assumed that inhibition of cycloox-
ygenase 1 (COX-1) enzyme by the oending drugs plays a relevant
pathogenic role in multiple NSAID reactors. It is generally expected
tolerability to preferential/selective COX-2 inhibitors among patients
with NSAIDs hypersensitivity.
Materials and methods: We reviewed the medical records and
selected patients referred to our drug allergy unit in the past 5years,
with history of reproducible hypersensitivity reactions to NSAIDs COX-1
inhibitors and positive oral challenge (OC) with etoricoxib, a selective
COX-2 inhibitor, and/or to meloxicam, a preferential COX-2 inhibitor.
Results: Inclusion criteria were met in 15 patients, aged 28–68
(47±13 years-old), 12 females. Seven patients were atopic. Eight
patients had asthma, ve chronic rhinosinusitis and nasal polyposis
and three patients had chronic urticaria. The primary NSAIDs hyper-
sensitivity reactions were: eight urticaria and angioedema; four ana-
phylaxis and three asthma exacerbation. Eight patients presented
a positive OC with meloxicam: four with immediate urticaria and
angioedema; three with late-onset of angioedema and one with
asthma exacerbation. One patient with late-onset angioedema to
meloxicam also had a late-onset of angioedema with etoricoxib.
Eight subjects had positive OC with etoricoxib: ve with immediate
urticarial, two with late-onset angioedema and one with anaphylac-
tic reaction.
Conclusions: Based on the results of previous studies, it could be
tempting to prescribe COX-2 inhibitors in cases of multiple reactors to
NSAIDs COX-1 inhibitors, without establishing its tolerance in a proper
setting. However, these data strongly suggest that, before prescribing
an alternative NSAIDs, a provocation test should always be performed.
P60
Management ofpatients withhistory ofNSAIDs reactions prior
tocoronary angioplasty
Mona Al‑Ahmad1, Tito Rodriguez2
1Microbiology Department, Faculty of Medicine, Kuwait University,
Kuwait, Kuwait; 2Al Rashed Allergy Center, Kuwait, Kuwait
Correspondence: Tito Rodriguez
Clinical and Translational Allergy 2016, 6(Suppl 3):P60
Background: History of NSAIDs hypersensitivity is common in some
patients with coronary artery disease who are in need for coronary
angioplasty. These patients require dual antiplatelet therapy to avoid
in-stent thrombosis, and full evaluation of NSAIDs allergy. We present
a cohort of patients with acute coronary syndrome undergoing aspi-
rin desensitization to evaluate the short- and long-term ecacy and
safety
Materials and methods: We developed a dynamic protocol that is
basedon both the patient characteristics and onset of reaction after
NSAIDs. This challenge/desensitization protocol is shorter than previ-
ously published ones. The objective is to asses short and long-term
ecacy and safety prior to stent placement
Results: A total of 19 patients with history of NSAIDs allergy were chal-
lenged with dierent doses of Aspirin. All patients tolerated the oral pro-
tocol at dierent timings of 30–45–90–120min. The dosage given ranges
between (21, 41, 81 and 162mg) of aspirin given by mouth after premedi-
cation with montelukast. We had two patients reacting during the pro-
cedure and one during a 6h-follow-up. All reactions were limited to the
skin. All patients tolerated the required dose of aspirin within 60–150min.
Those requiring urgent catheterization were desensitized within 90min.
Conclusions: Our protocol provide an eective and safe short and
long-time administration of Aspirin 81mg dose in patients with his-
tory of NSAIDs allergy
Keywords: Aspirin; Desensitization; Coronary
P61
Oral drug challenge withnon‑steroidal anti‑inammatory drug
underspirometric control: clinical series of110 patients
João Pedro Azevedo, Emília Faria, Beatriz Tavares, Frederico Regateiro, Ana
Todo‑Bom
Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
Correspondence: João Pedro Azevedo
Clinical and Translational Allergy 2016, 6(Suppl 3):P61
Background: Oral drug challenge (ODC) is the gold standard for the
diagnosis of hypersensitivity reactions to non-steroidal anti-inam-
matory (NSAIDs). If suspicion of respiratory symptoms, the ODC might
include a lung function evaluation (LFE). Aim: To evaluate the lung
function volumes during ODC to NSAIDs performed in our depart-
ment between 2010 and 2015.
Materials and methods: One-hundred and ten ODCs with NSAIDs
under LFE were performed. An alternative drug was tested in 77 of
the patients (70 %) whereas 33 were diagnostic tests (30 %). The
drugs tested were meloxicam (n=46, 41.8%); acetylsalicylic acid (19,
17.4%); etoricoxib (16, 14.6%); nimesulide (15, 13.6%); ibuprofen (4,
3.6%); celecoxib (3, 2.7%); metamizol (3, 2.7%); acetaminophen (3,
2.7%) and diclofenac (1, 0.9%). The criteria for a positive ODC were: a
decrease in FEV1≥20% of baseline, a decrease of MMEF75/25≥25%
of baseline or when major symptoms occurred. Statistical analysis
based on independent sample t test and paired t test.
Results: Seventy-nine patients were female (71.8%) (44.8±15.6years)
and 31 were male (28.2%) (40.5±16.4years). Sixty-two patients had
a previous diagnosis of asthma (56.4%), 18 of which with diagnosis of
NSAID-exacerbated respiratory disease (NERD) (16.4%).
ODC was positive in seven cases (four by decrease of volumes and
three by reported symptoms): ve alternatives and two diagnostic
(four with meloxicam; one ibuprofen, one metamizol; one etoricoxib),
two patients with no previous asthma diagnosis.
Taking into consideration the whole population tested, we observed sta-
tistically signicant decreases in FEV1 and FVC values at 30 and 120min
after medication versus baseline; and alsoa decrease in volumesat 30,
60, 120, 180 and 240min after the second dose vs baseline (p<0.05).
When comparing alternative versus diagnostic ODCs, we found statis-
tically signicant dierences in the measurement of FEV1 at 1h after
the second dose (p<0.05).
Conclusions: The number of positive ODCs was low (6.36%). Patients
with asthma have an increased risk of reaction even with alternative
NSAIDs. There was astatistically signicantdecrease in FEV1 at almost
all timepoints after NSAIDs compared to baseline, evenincluding neg-
ative challenges in the analysis. This suggests that NSAIDs might have
a general eect to reduce FEV1.
Keywords: NSAID; NSAID-exacerbated respiratory disease; Asthma
P62
Prevalence andincidence ofanalgesic hypersensitivity reactions
inColombia
Pablo Andrés Miranda1, Bautista De La Cruz Hoyos2
1Universidad Nacional de Colombia, Cartagena, Colombia; 2Centro de
Especialistas Santo Domingo ‑ Alergologia, Cartagena, Colombia
Correspondence: Pablo Andrés Miranda
Clinical and Translational Allergy 2016, 6(Suppl 3):P62
Background: The most common drug hypersensitivity reactions
(DHR) involve analgesic such as aspirin and other non steroidal anti-
inammatory drugs.
Materials and methods: Records with personal history of allergy anal-
gesics diagnosis (ICD-10 code Z886) of Information System of Social
Protection (SISPRO) between 2010 and 2014 were included. To deter-
mine the prevalence and incidence of AHR, population estimates from
the National Statistics Department of Colombia (DANE) were used.
Results: 1657 cases with personal history of AHR between 2010 and
2015 were identied. 223 cases were conrmed news diagnoses in the
same period. On average 331 cases of AHR per year were estimated.
The estimated annual prevalence AHR were seven cases per million
(2010=6; 2011=7.1; 2012=8.1; 2013=6.8 and 2014=7.2). The esti-
mated annual incidence AHR were 0.9 cases per million (2010= 0.8;
2011= 1.1; 2012=0.9; 2013= 0.8 and 2014=1). Most cases range
between 19 and 59years age (Table1).
Conclusions: Both under-diagnosis and over-diagnosis AHR are com-
mon in the world. Population studies with conrmatory tests AHR in
Colombia are required.
Keywords: Analgesic; Allergy; Hipersensitivity
Page 25 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
P63
Recent endoscopic sinus surgery lessens reactions duringaspirin
challenge inpatients withaspirin exacerbated respiratory disease
Teresa Pelletier1, Waleed Abuzeid2, Nadeem Akbar2, Marc Gibber2, Marvin
Fried2, Weiguo Han1, Taha Keskin2, Robert Tamayev2, Golda Hudes2, Simon
D. Spivack2, David Rosenstreich2, Elina Jerschow2
1Albert Einstein College of Medicine, Bronx, USA; 2Albert Einstein College
of Medicine/Montefiore Medical Center, Bronx, USA
Correspondence: Elina Jerschow
Clinical and Translational Allergy 2016, 6(Suppl 3):P63
Background: Aspirin-exacerbated respiratory disease (AERD) is diag-
nosed clinically through a positive oral graded aspirin challenge.
Upon conrming aspirin hypersensitivity, aspirin desensitization and
treatment has been proven to reduce recurrence of nasal polyposis
and asthma symptoms. However, negative aspirin challenges have
been reported to occur in otherwise aspirin allergic individuals (“silent
challenges”) after intake of antihistamines, leukotriene blockers, or
oral corticosteroids. We sought to determine whether recent endo-
scopic sinus surgery (ESS) also aects reactions to aspirin challenge in
patients with AERD.
Materials and methods: 19 AERD patients underwent two aspirin
challenges: one before and the other after (within 8weeks) their most
recent ESS. Reactions to aspirin were evaluated by changes in forced
expiratory volume in 1 s (FEVl, percent predicted), nasal peak ow
(NPF), and fraction of exhaled nitric oxide (FeNO).
Results: Decreased time between ESS and challenge was associ-
ated with decreased frequency of positive reactions: all 19 patients
with a history averaging 32months (IQR 9–72) since last ESS, reacted
to aspirin. In contrast, only 10 (52.6%) of these patients, challenged
on average of 1.1months (IQR 0.8–1.4) after ESS, reacted to aspirin.
Nine patients (47.4 %) had no clinically apparent reaction to aspi-
rin challenge after recent ESS. In the 10 patients who had a positive
challenge after recent ESS, the decrease in FEV1 during this challenge
was less than during the baseline challenge before ESS: −8.9 ± 1.2
vs. −19.7 ± 3.7 % (p < 0.01), respectively. NPF decrease was also
smaller during the challenge after recent ESS than before recent ESS,
−11.1±5.1 vs. −25.5±6.2% (p<0.01), respectively. FeNO signi-
cantly decreased in all patients during the rst challenge (−22.2 %
(IQR −50.6 to −20.9)) and decreased only in those who had positive
challenges after recent ESS (−32.5% (IQR −35.1 to −22.6; p=0.3).
Conclusions: Recent ESS could contribute to a false-negative aspirin
challenge. Patients who reacted to aspirin during the challenge after
recent ESS had milder reactions comparing to the challenge before
ESS. This presents a clinical dilemma: while appearing safer, aspirin
challenges after a recent ESS may have a decreased diagnostic sen-
sitivity so that some AERD patients could be misclassied as aspirin-
tolerant. Clinicians should consider the possibility of false-negative
challenges after recent ESS.
Keywords: Aspirin exacerbated respiratory disease; Oral graded aspi-
rin challenge; Endoscopic sinus surgery; Silent challenge
P64
Safe use ofimidazole salycilate ina case ofmultiple NSAIDs
induced urticaria‑angioedema
Elisa Boni, Marina Russello, Marina Mauro
Hospital Sant’Anna, Como, Italy
Correspondence: Elisa Boni
Clinical and Translational Allergy 2016, 6(Suppl 3):P64
Background: Hypersensitivity to non-steroidal anti-inammatory
drugs (NSAIDs) has been classied by Ayuso etal. into dierent pheno-
types. Multiple NSAID-induced urticaria-angioedema (MNSAID-UA) is
presumably related to cyclo-oxygenase 1 (COX -1) inhibition. Patients
with MNSAID-UA have reactions to multiple chemically unrelated mol-
ecules while usually they tolerate low COX-1 inhibitors.
Report: We report the case of a 32 years old man who expe-
rienced several episodes of angioedema of lips and face after
intake of acetylsalicylic acid (ASA), in one occasion associated
to the intake of paracetamol. Diagnosis of MNSAID-UA was con-
firmed by oral drug provocation test (DPT) to ibuprofen, a strong
COX-1 inhibitor chemically unrelated to ASA, that induced labial
angioedema. DPT with alternative drugs, defined as low COX-1
inhibitors, was then performed. Angioedema also appeared with
nimesulide and paracetamol. Instead, the patient tolerated imida-
zole salicylate.
How this report contributes to current knowledge: Low COX-1
inhibitors as paracetamol and nimesulide not always are tolerated by
patients with MNSAID-UA. This report conrms the safe use of imida-
zol salicylate in patients with hypersensitivity to ASA presumably due
to non-interference with the cyclo-oxygenase pathway.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P65
Selective hypersensitivity reactions toibuprofen—seven years
experience
Marta Ferreira Neto
CHLN‑HSM, Lisbon, Portugal
Correspondence: Marta Ferreira Neto
Clinical and Translational Allergy 2016, 6(Suppl 3):P65
Background: Immunologically mediated (non cross-reactive)
hypersensitivity reactions to nonsteroidal anti-inammatory drugs
(NSAIDs) are classied in two groups: Single NSAID-induced urti-
caria/angioedema or anaphylaxis and Single NSAID-induced delayed
Table 1 Prevalence and incidence AHR Colombia 2010–2014
2010%
(n) 2011%
(n) 2012%
(n) 2013%
(n) 2014% (n)
Prevalence AHR Colombia
Cases per million
1–5 años 0.4 (1) 5.1 (17) 2.4 (9) 5.2 (17) 3.8 (13)
6–9 años 5.4 (15) 6.9 (23) 4 (15) 5.2 (17) 3.2 (11)
10–14
años 8 (22) 6.3 (21) 9.2 (35) 10.8 (35) 12.1 (42)
15–18
años 8.3 (23) 6.9 (23) 7.4 (28) 7.7 (25) 10.8 (37)
19–26
años 14.9 (41) 13.9 (46) 19.8 (75) 18.8 (61) 16.8 (58)
27–44
años 34.8 (96) 32 (106) 29.8 (113) 26.2 (85) 27.7 (96)
45–59
años 19.2 (53) 19 (63) 16.4 (62) 16.6 (54) 14.5 (50)
>60 años 9.1 (25) 9.7 (32) 11.1 (42) 9.5 (31) 11.3 (39)
Total 100 (276) 100 (331) 100 (379) 100 (325) 100 (346)
Incidence AHR Colombia
Cases per million
1–5 años 0 (0) 0 (0) 0 (0) 2.5 (1) 8.2 (4)
6–9 años 5.4 (3) 0 (0) 2.4 (1) 5 (2) 10.2 (5)
10–14
años 8 (4) 9.3 (5) 9.5 (4) 2.5 (1) 10.2 (5)
15–18
años 8.3 (2) 7.4 (4) 7.1 (3) 10 (4) 18.4 (9)
19–26
años 14.9 (4) 20.4 (11) 21.4 (9) 22.5 (9) 20.4 (10)
27–44
años 34.8 (10) 35.2 (19) 26.2 (11) 25 (10) 16.3 (8)
45–59
años 19.2 (8) 18.5 (10) 23.8 (10) 22.5 (9) 8.2 (4)
>60 años 9.1 (7) 9.3 (5) 9.5 (4) 10 (4) 8.2 (4)
Total 100 (38) 100 (54) 100 (42) 100 (40) 100 (49)
Page 26 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
hypersensitivity reactions. In these entities patients have hypersensi-
tivity to NSAIDS belonging to the same chemical group and tolerate
chemically nonrelated ones. Usually there isn’t an underlying chronic
disease like asthma or urticaria. Ibuprofen (Ib), belonging to Propi-
onic acid derivatives (Pad) group, is one of the most frequently used
NSAIDs, with frequent hypersensitivity drug reactions reports.
Materials and methods: We retrospectively analysed all patients (Pt)
referred to our drug outpatient visit, from January 2008 to Decem-
ber 2015, with a selective history of hypersensitivity reaction to Ib.
Oral drug challenges (ODC) were performed, in order to establish the
diagnosis.
Results: A total of 10 Pt, aged between 18 and 79, 90% female were
included. After intake of Ib, 10(100%) Pt reported cutaneous symp-
toms: 2(20 %) Urticaria (U) and 8(80 %) U/Angioedema. Besides Ib,
Flurbiprofen, Dexcetoprofen and Naproxen were also the culprit drugs
in three dierent Pt.All 10 Pt tolerated Acetaminophen after the reac-
tion. Hypersensitivity reactions were immediate in 3(30%) Pt (<1h),
late (1–6h) in 1(10%) and accelerated (8–24h) in 6(60%). ODC were
performed with Ibuprofen, Acetylsalicylic acid (ASA) and Nimesulide
(N)in 6(60%) patients, and in the remaining4(40%) only withASA
and N. All ODC (100%)with Ib were positive, with reproductible symp-
toms, even in the non immediate reactions. AllPt (100%) had nega-
tiveODC with ASA and N.
Conclusions: Single NSAID-induced urticaria/angioedema to Ib was
established in 10 (100%) Pt and to chemically related compounds of
Pad groupin three (30%) Pt.Women represent the majority, cutane-
ous symptoms are the only clinical presentation and 70% are non-
immediate reactions. Other strong Cox1 inhibitors (except Pad group),
Nimesulida and Acetaminophen are the alternatives in the 10 patients.
Keywords: Selective; Ibuprofen; Oral challenges
Poster Walk 8: Epidemiological methods (P66–P72)
P66
Allopurinol hypersensitivity: a 7‑year review
Lise Brosseron, Daniela Malheiro, Susana Cadinha, Patrícia Barreira,
J. P. Moreira Da Silva
Centro Hospitalar Vila Nova de Gaia/Espinho, EPE, Vila Nova De Gaia,
Portugal
Correspondence: Lise Brosseron
Clinical and Translational Allergy 2016, 6(Suppl 3):P66
Background: Allopurinol, an antihyperuricaemic agent, is used as rst-
line treatment of chronic gout. Allopurinol hypersensitivity (AH) is a
rare but important cause of hypersensitivity reactions, ranging from
mild cutaneous manifestations to life-threatening severe cutaneous
adverse reactions (SCAR). Despite several risk factors have been pro-
posed, the underlying mechanisms remain unknown. Our aim was
to characterize a series of patients with suspected AH referred to our
drug allergy department during a 7-year period (2009–2015).
Materials and methods: A retrospective analysis was performed,
assessing demographic and clinical data. AH was conrmed by a posi-
tive drug provocation test (DPT), positive lymphocyte transformation
test (LTT) or reaction upon desensitization, and considered probable
based only on a suggestive clinical history.
Results: Among a total of 954 patients, 29 (3%) had suspected AH.
The mean age was 69± 10years and 16 (55%) were male. Allopuri-
nol was prescribed for gout in 14 (48%), asymptomatic hyperurice-
mia in 12 (41%) and malignancies in 3 (10%) patients; 20 (69%) were
polymedicated (≥4 drugs). Cutaneous reactions were reported by 27
(93%) subjects (14 exanthema, 5 urticaria/angioedema, 2 xed drug
eruption, 3 vasculitis and 3 DRESS). Twenty-six (90%) reported delayed
reactions (DR), 1 reported immediate reaction and 2 were unable to
recall onset. SPT (3) and patch tests (25) were negative in all patients
tested. LTT performed in 12 patients (ve exanthema, one urticaria/
angioedema, three vasculitis and three DRESS) was positive in four,
negative in ve, doubtful in two and undetermined in one. DPT was
positive in 2 out of 11 and long term challenge in 2 out of 8. Four
patients were submitted to desensitization: three developed reaction
during the procedure, conrming diagnosis; two were able to toler-
ate treatment. AH was conrmed in 10 (35%), considered probable in
six (21%), excluded in seven (24%) and inconclusive in six patients.
Among conrmed AH patients, all were DR and 80 % had started
Allopurinol recently (≤10days).
Conclusions: As previously described in the literature, our study sug-
gests that AH is rare, usually presents with delayed cutaneous symp-
toms and can be related to recent Background of Allopurinol. In the
diagnostic workup of suspected AH, DPT remains the gold-standard
while patch tests appear to be unhelpful. We discuss the useful-
ness of TTL, which seems promising, especially in SCAR where DPT is
contraindicated.
P67
Antibiotic allergy labelling is associated withincreased hospital
readmission rates inAustralia
Brittany Knezevic1, Dustin Sprigg1, Michelle Trevenen2, Jason Seet1, Jason
Trubiano3, William Smith4, Yogesh Jeelall2, Sandra Vale5, Richard Loh6,
Andrew Mclean‑Tooke7, Michaela Lucas7
1Sir Charles Gairdner Hospital, Perth, Australia; 2The University of Western
Australia, Perth, Australia; 3Austin Health, Melbourne, Australia; 4Royal
Adelaide Hospital, Adelaide, Australia; 5Australian Society of Clinical
Immunology and Allergy, Balgowlah, Australia; 6Princess Margaret Hos‑
pital, Perth, Australia; 7Pathwest Laboratory Medicine, Queen Elizabeth II
Medical Centre, Perth, Australia
Correspondence: Michaela Lucas
Clinical and Translational Allergy 2016, 6(Suppl 3):P67
Background: Patients frequently report antibiotic allergies, however
only about 10 % of labelled patients have a true allergy. This study
investigates the documentation of antibiotic “allergy” labels (AALs)
and the eect of labelling on clinical outcomes in an adult tertiary hos-
pital in Australia.
Materials and methods: We performed a retrospective single-centre
cross-sectional analysis of 737 inpatients in a major teaching hospital
in Western Australia. All patients were captured in the 2013 and 2014
National Antimicrobial Prescribing Surveys (NAPS). NAPS is an annual
audit of Australian health services, led by The Australian Commission
on Safety and Quality in Health Care, to assess volume and appropri-
ateness of antimicrobial prescribing. Data collected by detailed chart
review, included antibiotic adverse drug reactions (ADRs), antibiotic
cost, prescribing appropriateness, prevalence of multi-drug resistant
organisms, length of stay, intensive care admission and readmissions.
Results: Complete data were captured for 687 patients. 278 (40%)
were aged 70 or above, 322 (47%) were female and 279 (41%) were
prescribed antibiotics at the time of audit. AALs were recorded in
122 (18%) of all patients. The majority of AALs were penicillin labels
(n= 87; 71 %). Details of the clinical reactions to the culprit antibi-
otic were documented for 80 of 141 (57%) individual allergy labels:
61 described symptoms consistent with drug allergies and 19 were
non-specic symptoms. Five patients were receiving an antibiotic
that would be considered contraindicated according to their docu-
mented allergy status. Females and older patients were signicantly
more likely to have an AAL (gender: OR 2.54, 95% CI=1.69–3.82,
p< 0.001; for a one standard deviation (19.6years) increase in age:
OR 1.31, 95 % CI = 1.06–1.60, p = 0.007). Patients with AALs had
signicantly more hospital readmissions within 4weeks (p=0.001)
and 6months (p= 0.025) of discharge, compared with unlabelled
patients independent of age and gender. The majority of patients
with AALs (84 %) who were readmitted had a diagnosis of an
infection.
Conclusions: This rst Australian study shows that purported AALs
are common but poorly documented in hospital records. Patients with
AALs are signicantly more likely to require readmissions. There may
be a role for antibiotic allergy delabelling to mitigate the clinical and
associated economic burdens for patients with invalid allergy labels.
Keywords: Antibiotic; Allergy; Adverse drug reactions; Delabelling
Page 27 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
P68
Experts’ opinions onsevere cutaneous adverse drug
reactions‑report ofa survey fromthe 9th international congress
oncutaneous adverse drug reactions2015
Roni P. Dodiuk‑Gad1, Cristina Olteanu2, Wen‑Hung Chung3, Neil H. Shear4
1Department of Dermatology, Ha’emek Medical Center, Afula, Israel;
2Faculty of Medicine, University of Toronto, Toronto, Canada; 3Depart‑
ment of Dermatology, Drug Hypersensitivity Clinical and Research Center,
Chang Gung Memorial Hospitals, Taipei, Taiwan; 4Division of Dermatol‑
ogy, Department of Medicine, Sunnybrook Health Sciences Centre,
Linkou, Canada
Correspondence: Cristina Olteanu
Clinical and Translational Allergy 2016, 6(Suppl 3):P68
Background: On June 8th, 2015, the 9th International Congress on
Cutaneous Adverse Drug Reactions (cADR) was held at the 23rd World
Congress of Dermatology. Eighty participants attended the congress
from 23 countries; a variety of specialists with dierent areas of exper-
tise included dermatology, regulatory agencies and public health,
clinical pharmacology, immunology, infectious disease, oncology,
pediatrics, etc. During the Congress, surveys were conducted to learn
about the participants’ experiences and perspectives regarding four
major topics: pharmacogenomics and severe cutaneous adverse drug
reactions (SCAR), drug reaction with eosinophilia and systemic symp-
toms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), Ste-
vens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), and
acute generalized exanthematous pustulosis (AGEP).
Materials and methods: Participants answered survey questions
anonymously through an electronic voting system.
Results: In a survey of the pharmacogenomics of SCAR, 21% of partic-
ipants regularly conducted genetic screening prior to treatment with
carbamazepine (N=53) and 15% of participants regularly conducted
genetic screening prior to administration with allopurinol (N = 52).
Seventy-eight percent reported that there is a lack of knowledge
among physicians regarding genetic screening for Human Leukocyte
Antigens (HLAs) for preventing SCAR in their country (N=51). In a sur-
vey of SJS/TEN, systemic corticosteroids was the preferred treatment
in 45% followed by only supportive treatment in 18%, intravenous
immunoglobulin in 16%, and cyclosporine in 14% (N=51). In a sur-
vey of DRESS/DIHS, 36% regularly assess reactivation of human her-
pesvirus-6 (HHV-6) in their management of patients with DRESS/DIHS
(N= 53), and 33 % monitor late autoimmune complications in these
patients (N=54). In a survey of AGEP, 67% of participants always con-
duct assessment for systemic involvement (N=47).
Conclusions: There is a lack of implementation of regulatory agen-
cies recommendations’ regarding genetic screening prior to treat-
ment with carbamazepine or allopurinol. There is still no international
consensus for the management of patients with SJS/TEN. Assessing
reactivation of HHV-6 and monitoring late autoimmune complications
in patients with DRESS/DIHS is not commonly done. Assessing sys-
temic involvement in patients with AGEP was found to be commonly
conducted.
Keywords: SJS/TEN; DRESS; AGEP
P69
HLA‑A*31‑positive AGEP withcarbamazepine use andother
severe cutaneous adverse drug reactions (SCARs) detected
byelectronic medical records screening
Sabine Müller1, Ursula Amstutz2, Lukas Jörg3, Nikhil Yawalkar4, Stephan
Krähenbühl1
1Department of Clinical Pharmacology and Regional Pharmacovigilance
Center, Inselspital, University Hospital Bern, Bern, Switzerland; 2Univer‑
sity Institute of Clinical Chemistry, Inselspital, University Hospital Bern
and University of Bern, Bern, Switzerland; 3Department of Rheumatology,
Clinical Immunology and Allergology, Inselspital, University Hospital Bern,
Bern, Switzerland; 4Department of Dermatology, Inselspital, University
Hospital Bern, Bern, Switzerland
Correspondence: Sabine Müller
Clinical and Translational Allergy 2016, 6(Suppl 3):P69
Background: Pharmacovigilance (PV) programs based on spontane-
ous reporting of adverse drug reactions (ADRs) are compromised by
underreporting and inconstant data quality. Underreporting of severe
adverse drug reactions by hospitals is in the range of 95% (Drug Saf
2006;29:385–96). This study aims to assess underreporting and to
evaluate the potential of electronic chart screening for SCARs in two
departments (dermatology and allergology) as a proactive case detec-
tion method regarding detection rate and data quality.
Materials and methods: Electronic reports from January 2014 to
December 2015 of the allergology and dermatology units at the
Inselspital Bern (Switzerland) were reviewed monthly for diagnosis of
SCARs (AGEP, SJS/TEN, DRESS) and compared to SCARs reported to the
PV service of the clinical pharmacology unit. Cases were evaluated for
standard PV parameters and results of allergologic and HLA testing if
available.
Results: During this 2-year period, 27 SCARs were registered at our
PV unit. 2 SCAR cases were reported spontaneously (one DRESS, one
SJS), while 25 SCARs were detected proactively (13 AGEP, 9 DRESS, 3
SJS). Interestingly, among the screened charts, a patient with carba-
mazepine-induced AGEP was a carrier for HLA-A*31 (HLA-A*3101 to
be conrmed), possibly associated with carbamazepine-induced AGEP
(Epilepsia 2014;55:496–506).
Conclusions: Spontaneous reporting is insucient, even for severe
ADRs with well-established causality. Combination of chart screening
with standard PV programs is a promising method to enhance detec-
tion rate and signal quality for rare idiosyncratic ADRs.
P70
Patients withsuspected drug allergy: a specic psychological
prole?
Eunice Dias‑Castro1, Ana Leblanc1, Laura Ribeiro2, Josefina R. Cernadas1
1Allergy and Clinical Immunology Department, Centro Hospitalar S.
João EPE, Porto, Portugal; 2Biochemistry Department, Medical Education
and Simulation Department, Faculty of Medicine, University of Porto,
Porto, Portugal
Correspondence: Eunice Dias‑Castro
Clinical and Translational Allergy 2016, 6(Suppl 3):P70
Background: There are several studies demonstrating an important
association between allergic diseases and the psychological charac-
teristics of the patients. The majority involves skin or respiratory dis-
eases and only a few drug allergy (DA). Patients with adverse reactions
to drugs appear to have more psychological disturbances than those
with asthma/rhinitis.
Materials and methods: We evaluated psychological characteristics
of 115 consecutively patients >16 years-old, studied in our Depart-
ment for suspected DA. Four self-completed validated questionnaires
(anxiety, depression, alexithymia, personality type) were used. Evalu-
ation of patient emotions at the time of the reaction was also per-
formed based on a numerical scale to quantify fear/panic and an open
question. The control group included 55 patients from the outpatient
clinic without any history of DA. Description of variables was done
through absolute and relative frequencies. Chi square and Fisher test
were used to evaluate the association between variables and groups.
The magnitude of the associations was measured by the Odds Ratios.
The signicance of the dierence between the medium intensity of
fear/panic at the time of the reaction by gender was evaluated by a
student t-test for independent samples. All the variables with a proof
value<=0.20 in the univariate analysis were considered for the multi-
variate analysis. The level of signicance was considered 5%. Statisti-
cal analysis used the SPSS, version 20.0.
Results: There were no signicant dierences between the two
groups concerning demographic or social characteristics, except
for age (p=0.025). Allergic diseases were signicantly more preva-
lent in the control group (51.1 vs. 87.3%; p < 0.001) but other dis-
eases were signicantly higher in the patient group (67.5 vs. 27.8%;
p<0.001). The majority of the controls were on regular medication
(68.4 vs. 94.2%; p<0.001), although psychiatric medication was more
frequently used in the case group (32.0 vs. 5.8%; p< 0.001). After
Page 28 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
adjustment for age, allergic disease, other diseases and daily medica-
tion, the suspicion of DA did not show any association with psycho-
logical characteristics. The dierences between the medium intensity
of fear/panic at the time of the reaction by gender were statistically
signicant (p=0.022), with males having a lower result (2.7 points
vs. 3.6).
Conclusions: The suspicion of DA did not show any association with
psychological characteristics of the patients. The analysis of those with
conrmed DA is still ongoing.
P71
Use ofan electronic device anda computerized mathematic
algorithm todetect the allergic drug reactions throughthe
analysis ofheart rate variability
Arantza Vega1, Raquel Gutierrez Rivas2, Ana Alonso1, Juan Maria Beitia1,
Belén Mateo1, Remedios Cárdenas1, Juan Jesus Garcia‑Dominguez2
1Hospital Universitario de Guadalajara, Guadalajara, Spain; 2Universidad
de Alcalá, Alcalá De Henares, Spain
Correspondence: Arantza Vega
Clinical and Translational Allergy 2016, 6(Suppl 3):P71
Background: Challenge test (CT) is the gold-standard for the diagno-
sis of drug allergy. Its implementation involves a high consumption
of time and resources and implies the risk of severe adverse reactions
apparence.
Currently there is not a diagnostic tool able to perform an early detec-
tion of the allergic reactions, thus reducing the length of the challenge
test and decreasing the onset of severe allergic reactions.
Heart rate variability has been used for help to the diagnosis of several
illnesses. It has been recently used for the detection of allergic reac-
tions. We explore the use of a heart rate variability monitoring device
to detect in real time the allergic reactions in patients undergoing a
CT.
Materials and methods: Patients, older than 12years, with suspected
drug allergy that, following the normal diagnostic protocol, were
undergoing a CT and agreed to participate. A remote monitoring
device called Shimmer was placed from 10min before the star of the
test until Its completion. Increasing doses of the drug were adminis-
tered at 30 or 60min interval until the end of the test or until the onset
of allergic symptoms. Heart rate variability was analysed by the pro-
posed mathematic algorithm, and Its results were compared to the CT
results.
Results: One hundred and twenty thee patients were studied: 81
women, 42 men, mean age 41.8years (14–92). Drugs tested included
NSAID (50), Betalactamics (40), other antibiotics (8) and others (25).
The drug CT was positive in seven of them (5.6%).
The algorithm detection showed a positive result in nineteen patients
and a negative one in 104. Its sensitivity and specicity were 57
and 87 % respectively. When NSAIDs CT were ruled out the results
improved reaching 100% sensitivity and 96 % specicity. The global
negative predictive value was 97%.
The detection took place at least 90min before the onset of symptoms.
Conclusions: The use of a heart rate variability device with a mathe-
matic algorithm can be a useful tool in drug allergy diagnosis. Further
studies are needed.
Keywords: Challenge test; Heart rate variability; Electronic device
P72
Variation inERAP inuences risk forHLA‑B*57:01 positive
abacavir hypersensitivity
Rebecca Pavlos1, Kaija Strautins1, Ian James1, Simon Mallal2, Alec
Redwood1, Elizabeth Phillips2
1Murdoch University, Perth, Australia; 2Vanderbilt University, Nashville,
USA
Correspondence: Rebecca Pavlos
Clinical and Translational Allergy 2016, 6(Suppl 3):P72
Background: Abacavir (ABC) binds non-covalently to the oor of the
peptide-binding groove of HLA-B*57:01, altering the chemistry and
shape of the antigen binding cleft. This allows previously untolerized
self-peptides to be presented by HLA-B*57:01 to T cells. Endoplasmic
reticulum aminopeptidases (ERAPs) trim peptides for MHC Class I pres-
entation, inuencing the degree and specicity of the CD8+ T-cell
response. Genetic variation within ERAP adds to the positive predic-
tive value (PPV) of the HLA class I risk allele in autoimmune diseases
such as HLA-B27 positive ankylosing spondylitis. Considering the
altered peptide repertoire mechanism of ABC HSR we hypothesize
that variation in ERAP may help explain why 45% of patients carrying
HLA-B*57:01 can tolerate ABC.
Materials and methods: 3′UTR, intron and exon encoded SNPs which
characterise gene haplotypes were examined for ERAP1 in HLA-
B*57:01+ ABC patch test positive (PT+) patients [n=53] and HLA-
B*57:01+ABC tolerant controls [n=22] with sequence-based typing.
Rs2248374, a tag SNP for functional ERAP2 haplotypes was also exam-
ined. Haplotype A is tagged by the (A) allele, while haplotype B is
tagged by rs2248374(G). Fisher exact tests and multiple logistic regres-
sions were used to compare genotypes between ABC HSR PT+ and
tolerant groups.
Results: HLA-B*57:01 + ABC tolerance was associated with
rs27434(GG) (18/22(82%) vs 24/53(45%) in ABC HSR PT+, p=0.005).
This SNP maps to the active site within ERAP1 (AA356). For an HLA-
B*57:01 positive population, with 45% of cases tolerant to abacavir,
the estimated chances of tolerance given rs27434 genotype are
AA (0%), AG (13%) and GG (43 %). A missense mutation within the
domain junction (rs30187(C)) important in conformational change of
ERAP1 (AA528), was overrepresented in HLA-B*57:01+ ABC tolerant
individuals (p = 0.04). Analysis indicated linkage between rs27044
and rs30187, rs17482078 and rs2287987, and between rs30187 and
rs27434 (all p< 0.0001). In a multivariable model with rs27434(GG),
the ERAP2 SNP (rs2248374(G)) that tags haplotype B, characterized by
a truncated protein, was decreased in tolerant individuals (p=0.005).
Conclusions: ERAP variants are important in the development of ABC
HSR. ERAP activity may inuence the repertoire of peptides presented
by HLA-B*57:01 or inuence early changes in immunodominant
epitope selection. This provides a potential pathogenic mechanism for
the development of ABC HSR or ABC tolerance in HLA-B*57:01 carriers.
Keywords: ERAP; Abacavir; HLA-B*57:01
Poster Walk 9: DRESS/AGEP (P73–P81)
P73
A clinical case ofDRESS syndrome ina child afteradministration
ofamoxicillin‑clavulanic acid
Rita Aguiar1, Anabela Lopes1, Ana Neves2, Maria Do Céu Machado2, M. A.
Pereira‑Barbosa1
1Immunoallergology Department, Hospital de Santa Maria‑Centro Hospi‑
talar Lisboa Norte, Lisbon, Portugal; 2Pediatrics Department, Hospital de
Santa Maria‑Centro Hospitalar Lisboa Norte, Lisbon, Portugal
Correspondence: Rita Aguiar
Clinical and Translational Allergy 2016, 6(Suppl 3):P73
Background: Drug rash with eosinophilia and systemic symptoms
(DRESS) syndrome is an uncommon but serious hypersensitivity drug
reaction. It is characterized by a polymorphic disseminated eruption
with fever and multiple organ dysfunction. DRESS syndrome is a rare
entity in children.
The authors describe a case of a children admitted to our hospital for
amoxicillin-clavulanate induced DRESS syndrome.
Materials and methods: case report: Male, 31months-old, presented
to the emergency department with diuse erythema involving trunk
and extremities, sparing palms of hands and feet, angioedema of the
tongue and fever after treatment with amoxicillin/clavulanate for cuta-
neous infection.
Laboratory ndings revealed lymphocytosis, eosinophilia (600/µl), and
elevated serum transaminases AST 139 U/l, ALT 440 U/l, LDH 976U/l.
No previous drug allergies were reported at the time of presentation.
On the second day of hospitalization, the patient’s rash was still persis-
tent ant it appeared petechiae and hemorrhagic suusion suggestive
of vasculitis on the face, forehead and periorbital without worsening
throughout the hospitalization.
Page 29 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
Infectious markers and serological tests were negative. Corticosteroid
treatment was started after exclusion of other potentially serious condi-
tions including infections and hematologic malignancies. The results of
the skin biopsy taken from the lesions revealed supercial perivascular
dermatitis involving spongiotic eosinophils compatible with spongiotic
drug eruption. A dramatic improvement was observed and his clinical and
laboratory ndings were recovered on the 5thday of the treatment.
The high fever, lymphocytosis and eosinophilia were resolved (eosino-
philia rate was 1.8%). ALT 114, AST 57, without changes of cholesta-
sis (GGT 28, LDH 567, total bilirubin 0.2mg/dl). Abdominal ultrasound
unchanged.
Specic IgE β-lactams were negative.
Patch tests with β-lactams revealed positive reaction to amoxicillin.
Conclusions: Given the signicant morbidity early recognition of drug
reaction with eosinophilia and systemic symptoms syndrome and ini-
tiation of appropriate therapy are imperative in limiting morbidity.
In this study, patch testing was a safe and useful method in conrm-
ing the culprit drug in DRESS induced β-lactam. The pathogenesis of
DRESS is not yet entirely claried, but positive patch tests suggest a
drug-dependent delayed hypersensitivity mechanism.
Keywords: DRESS Syndrome; Amoxicillin-clavulanate; Patch testing
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P74
Acute generalized exanthematous pustulosis (AGEP) induced
bymesalazine, reliable andoftenly used drug totreat
inammatory bowel disease
Ceyda Tunakan Dalgiç, Emine Nihal Mete Gökmen, Fatma Düsünür
Günsen, Gökten Bulut, Fatma Ömür Ardeniz, Okan Gülbahar, Ali
Kokuludag, Aytül Zerrin Sin
Ege University Medical Faculty, Department of Allergy and Clinical Immu‑
nology, Izmir, Turkey
Correspondence: Emine Nihal Mete Gökmen
Clinical and Translational Allergy 2016, 6(Suppl 3):P74
Background: Acute generalized exanthematous pustulosis (AGEP) is
a rare eruption characterized by acute, extensive formation of sterile
nonfollicular pustules on edematous- erythematous skin. It is accom-
panied by fever, peripheral blood leucocytosis neutrophilia, and some-
times by facial edema, hepatitis and eosinophilia. Most cases of AGEP
(90%) is caused by drugs and acute infections.
Report: 34year- old female patient with ulserative colitis had been taken
mesalazine tablets 2400mg per day for 1month. After 1month therapy,
a cutaneous reaction characterized by disseminated pustules on an ery-
thematous base happened and mesalazine was stopped. During the
period, lesions was localised to extremities, so topical therapy used. After
the reaction was recovered, because of severe ulserative colitis, 15days
later mesalazine was restarted. Due to the second therapy, after the rst
dosage, she developed multiple disseminated sterile pustules on an
erythematous background, associated with fever and neutrophilia. Lab-
oratory examinations showed the elevation of white blood cells, neutro-
phils, erythrocyte sedimentation rate and C-reactive protein (white blood
cells, 9110/mm3; (64.2% neutrophils, 21.4 % lymphocytes, 2.7% eosin-
ophils, 11.4 % monocytes), erythrocyte sedimentation rate 13 mm/h,
C-reactive protein level 3.27mg/dl). Punch biopsy from pustules revealed
subcorneal pustular formation, perivascular inltration rich in leukocyte
in dermis and acanthosis in epidermis. No accumulation was detected
in immunouorescence analyses. Clinical and histopathological nd-
ings were considered as AGEP. She was treated with intravenous corti-
costeroids, oral antihistamines and topical corticosteroids. The patient’s
rashes decreased within the following 7days and then diminished with
desquamation.
How this report contributes to current knowledge: We report a
patient with AGEP after the use of mesalazine. It’s important to con-
sider AGEP in the dierential diagnosis of acute pustular rashes and
drugs should be investigated as causative agents. Knowledge of the
clinical features are necessary to be distinguished from other entities.
It’s the rst AGEP case due to 5-ASA derived mesalazine in the litera-
ture. As mesalazine has been oftenly using for inammatory bowel
diseases, clinicians should be aware of its potential about developing
AGEP and be careful about it.
Consent: Written informed consent was obtained from the patient.
P75
Changes ofblood plasmacytoid dendritic cells, myeloid dendritic
cells, andbasophils duringthe acute stage ofdrug reaction
witheosinophilia andsystemic symptoms (DRESS) andother drug
eruptions
Shao‑Hsuan Hsu, Yung‑Tsu Cho, Che‑Wen Yang, Kai‑Lung Chen, Chia‑Yu
Chu
Department of Dermatology, National Taiwan University Hospital
and National Taiwan University College of Medicine, Taipei, Taiwan
Correspondence: Shao‑Hsuan Hsu
Clinical and Translational Allergy 2016, 6(Suppl 3):P75
Background: Drug reaction with eosinophilia and systemic symptoms
(DRESS) is a severe cutaneous drug reaction characterized by exan-
thematous skin rash, fever, lymphadenopathies, eosinophilia, atypical
lymphocytosis and internal organ involvement. Reactivation of human
herpes virus (HHV)-6 and decreased plasmacytoid dendritic cell (pDC)
in the peripheral blood were putatively related to the disease, though
the causality remained inconclusive.
Materials and methods: We recruited 18 patients from July 2013 to
May 2014 with the diagnosis of drug eruptions including maculopapu-
lar eruptions (MPE), Stevens–Johnson syndrome (SJS), xed drug erup-
tion (FDE) and DRESS. The peripheral blood pDC (lin−CD123+CD11c−),
myeloid DC (mDC, lin−CD123−CD11c+) and basophils (lin−HLA-
DR−CD123+CD11c+) were simultaneously labeled and processed by
4-color assay method, with the frequencies of such cells counted by
ow cytometry. HHV-6 reactivation was determined by the presence
of viral DNA in the whole blood sample or the elevation of anti-HHV-6
IgG in the serum during the convalescent stage.
Results: Decreased frequencies of pDC were signicantly associ-
ated with the diagnosis of DRESS (p=0.004), presence of atypical
lymphocytosis (p=0.023) and HHV-6 reactivation (p=0.043), while
those of mDC and basophils were unrelated to the type of drug erup-
tion, presence of atypical lymphocytosis, eosinophilia or HHV-6 reac-
tivation. The reactivation of HHV-6 was only found in DRESS patients,
in which the pDC frequencies consistently showed a decreasing
trend.
Conclusions: In this study, we found that decreased pDC in the
peripheral blood during the acute stage is more common in DRESS
patients than the other drug eruptions, while only part of the patients
demonstrated measurable HHV-6 reactivation. mDC and basophils did
not show remarkable trend among dierent drug eruptions. The dec-
rement of peripheral blood pDC might be the preceding, or might be
the causative, event before HHV-6 reactivation.
Keywords: Drug reaction with eosinophilia and systemic symptoms;
Plasmacytoid dendritic cell; Myeloid dendritic cell; Basophil; Human
herpes simplex virus-6
P76
Characterization ofisoniazid/rifampicin‑specic t‑cell responses
inpatients withDRESS syndrome
Young‑Min Ye1, Gyu‑Young Hur2, Hae‑Sim Park1, Seung‑Hyun Kim1
1Department of Allergy & Clinical Immunology, Ajou University School
of Medicine, Suwon, South Korea; 2Department of Internal medicine, Col‑
lege of Medicine, Korea University, Seoul, South Korea
Correspondence: Seung‑Hyun Kim
Clinical and Translational Allergy 2016, 6(Suppl 3):P76
Background: Antituberculosis drugs (ATDs) including isoniazid,
rifampicin, pyrazinamide and ethambutol are commonly used for
the treatment of tuberculosis, but occasionally associated with drug-
induced hypersensitive reactions such as drug rash with eosino-
philia and systemic symptoms (DRESS) syndrome and hepatitis. The
culprit drug and mechanistic basis of the hypersensitive reaction has
Page 30 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
not been dened.The aim of this study was to nd whether drug-
responsive T cell response was detectable in patients with ATD-related
DRESS and characterize the mechanistic features of the T-cell response.
Materials and methods: A lymphocyte transformation test (LTT)
was performed using peripheral blood mononuclear cells (PBMCs)
from ATD-induced DRESS patients. Subsequently, drug-specic T-cell
clones were generated from the hypersensitive patients. We measured
the drug-specic proliferative responses and interferon-gamma (IFN-
γ) secretion. Anti-human class I and class II blocking antibodies were
used to analyze HLA-restricted T-cell response.
Results: Strong proliferative responses to isoniazid or rifampicin were
detectable in the patient with DRESS by LTT. Isoniazid/rifampicin-
specic T-cell clones were generated from blood of the patients, but
not pyrazinamide or ethambutol. The T cell clones proliferated and
secreted IFNγ when stimulated with isoniazid or rifampicin. They did
not cross-react with each other. T-cell responses were blocked in the
presence of anti-human class II antibodies.
Conclusions: This study identies isoniazid/rifampicin- responsive
T-cells in peripheral blood of certain patients with ATD-induced DRESS.
It highlights an important role of drug-responsive T-cell immune
responses in ATD-induced DRESS syndrome.
Keywords: Antituberculosis drugs; Drug rash with eosinophilia and
systemic symptoms; T cell response; HLA
P77
DRESS syndrome secondary tosulfasalazine withdelayed TEN: a
case presentation
Syed Ali1, Michaela Lucas2, Peter N. Hollingsworth3, Andrew P. C.
Mclean‑Tooke3
1Department of Immunology, Perth, Australia; 2Department of Immu‑
nology, Pathwest; QE2 Medical Centre; SMP, PALM, UWA; IIID, Murdoch
University, Perth, Australia; 3Department of Immunology, Pathwest; QE2
Medical Centre, Perth, Australia
Correspondence: Syed Ali
Clinical and Translational Allergy 2016, 6(Suppl 3):P77
Background: Drug reaction with eosinophilia and systemic symptoms
(DRESS) is a rare and potentially life threatening condition. DRESS pre-
ceding toxic epidermal necrolysis (TEN) has only been reported with
three cases to date.
Report: A 31 year old lady presented with a 3 day history of fever,
morbilliform rash, cervical lymphadenopathy and facial oedema.
5weeks prior she had been diagnosed with rheumatoid arthritis (RA)
and commenced on hydroxychloroquine and sulfasalazine. Investiga-
tions showed an eosinophilia, elevated liver function tests (LFTs) and
high inammatory markers. Infectious screen including viral tests was
negative. A clinical diagnosis of DRESS was made, all RA drugs were
ceased and she was started on high dose oral corticosteroids. During
admission she developed a marked lymphocytosis, neutrophilia and
eosinophilia with worsening LFTs and coagulopathy. The rash, LFTs
and leukocytosisgradually improved and she was discharged on day 9
to continue on high dose oral steroids.
She presented 3days later with worsening of her rash, high fevers and
right upper quadrant abdominal pain associated with worsening of LFTs,
anaemia and thrombocytopenia. 3 doses of IV methylprednisolone were
administered. Haemophagocytic lymphohistiocytosis was considered
given a high ferritin and hypobrinogenaemia although bone marrow
examination showed reactive changes but no evidence of haemophago-
cytosis. There was again improvement in rash, facial swelling and labora-
tory markers, and she was discharged to continue high dose steroids.
She re-presented 7days later with return of fevers, rash, jaundice
and deterioration in her LFTs. Cyclosporin was added but ceased
after 4days due to concerns regarding worsening LFTs. Liver biopsy
showed submassive central necrosis and prominent bile duct dam-
age. Ganciclovir was added following an equivocal PCR for HHV-6 on
the liver biopsy tissue and she was considered for liver transplant
if her liver failure worsened. On day 40 her LFTs had improved but
she developed mucosal ulceration involving the mouth, eyes and
genitals with bullous skin lesions involving 80% of the body surface
which was Nikolsky sign positive. Skin biopsy was consistent with
TEN. She was transferred to the ICU for aggressive management and
intravenous immunoglobulin but deteriorated and passed away the
next day.
How this report contributes to current knowledge: Here, we pre-
sent a fatal case of DRESS with fulminant liver failure followed by
extensive TEN despite immunosuppression and broad anti-microbial
cover.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P78
Drug rash witheosinophilia andsystemic symptoms (DRESS)
features according tothe culprit drug
Zohra Chadly, Nadia Ben Fredj, Karim Aouam, Haifa Ben Romdhane,
Naceur A. Boughattas, Amel Chaabane
Faculty of Medicine/University Hospital/University of Monastir, Monastir,
Tunisia
Correspondence: Karim Aouam
Clinical and Translational Allergy 2016, 6(Suppl 3):P78
Background: The aim of this study was to evaluate the clinical and
chronological Drug Rash with Eosinophilia and Systemic Symptoms
(DRESS) characteristics according to the culprit drug.
Materials and methods: We carried out a retrospective study includ-
ing all cases of DRESS notied to the Pharmacovigilance Unit of
Monastir during 11 years. Diagnosis of DRESS was based on Euro-
pean RegiSCAR criteria. Imputability was established according
to Begaud’s method. Skin tests were performed according ENDA
recommendations.
Results: Fourty seven cases of DRESS were included in our study:
27 men and 20 women, with a mean age of 47years± 19. Antie-
pileptics drugs (18 cases: 15 carbamazepine, 2 phenobarbital, and 1
lamorigine) were the most frequent responsible drugs in our study
followed by antibiotics (12: 6 betalactams, 4 glycopeptides, 1 cot-
rimoxazole and 1 ethambutol), allopurinol (10) and salazopyrin (7).
All patients had pruritic maculopapular rash involving more than
50% of their body surface area. Mucosal involvement was observed
mainly with antiepileptics drugs (ve cases) and allopurinol (four
cases). Lymphadenopathy was more frequent with salazopyrin
and antiepileptics drugs (55 % each). Eosinophilia was observed
in 90% of cases with allopurinol, 66% with antibiotics and antie-
pileptics drugs, and 57 % with salazopyrin. Atypical lymphocyto-
sis was observed only in eight cases. Liver was the most common
organ aected (74.5%) in our series. The most frequent type of liver
injury was: cytolytic with antibiotics and allopurinol (58 and 30 %
respectively) and mixed with salazopyrin and allopurinol (57 and
50% respectively). Renal failure was observed in all cases induced
by allopurinol. Pulmonary involvement was observed in ve cases
(three with salazopyrin and two with antiepileptic drugs). The mean
incubation period was similar in the four groups of incriminated
drugs. The outcome was favorable after drug withdrawal in 95.7%
of cases. Two patients with DRESS induced by allopurinol died
because of multiple organ failure. Skin tests (patch or intradermal
tests) were done in 33 cases. 75% of skin tests with antiepileptics
drugs and antibiotics were positive. Skin tests with salazopyrin and
allopurinol were all negative.
Conclusions: Throughout this study, we point out the variability of
DRESS clinical characteristics according to the culprit drug in one hand
and the usefulness of skin tests with salazopyrin and allopurinol in the
other hand.
P79
Drug reaction witheosinophilia andsystemic symptoms induced
byallopurinol: not always easy todiagnose
Marina Lluncor Salazar1, Beatriz Pola1, Ana Fiandor2, Teresa Bellón3, Elena
Ramírez4, Javier Domínguez Ortega2, Santiago Quirce5, Rosario Cabañas2
1Allergy Department, La Paz Hospital Institute for Health Research
(IdiPAZ), Madrid, Spain; 2Allergy Department, La Paz Hospital Institute
for Health Research (IdiPAZ), Consorcio Piel en RED, Madrid, Spain;
Page 31 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
3Immunology Department, La Paz Hospital Institute for Health Research
(IdiPAZ), Consorcio Piel en RED, Madrid, Spain; 4Department of Clinical
Pharmacology, Hospital La Paz Health Research Institute (IdiPAZ), School
of Medicine, Universidad Autónoma de Madrid, Madrid, Spain. Consorcio
Piel en RED, Madrid, Spain; 5Allergy Department, La Paz Hospital Institute
for Health Research (IdiPAZ), Madrid, Spain
Correspondence: Marina Lluncor Salazar
Clinical and Translational Allergy 2016, 6(Suppl 3):P79
Background: DRESS is a life threatening hypersensitivity reaction.
Allopurinol is a frequent cause. Lymphocyte transformation test
(LTT) and epicutaneous tests with allopurinol are usually negative.
We report a case with positive LTT to allopurinol and its metabolite,
oxypurinol.
Materials and methods: A 37-year-old female attended the emer-
gency room complaining of asthenia, cough, and generalized
edema. She had a history chronic renal insufficiency stage 4 sec-
ondary to focal segmental glomerulosclerosis, high blood pressure
and migraine. She was admitted with respiratory infection, acute
kidney injury, and desquamative skin lesions that had appeared
20days before. Initially she had erythema and face swelling, diffi-
culty swallowing, painful papular lesions on face, scalp and upper
trunk, abdomen and thighs. She had been treated with antihista-
mines, topical and systemic low dose corticosteroids with clinical
improvement. She was on treatment with omeprazole, valsartan,
prednisone, acetazolamide, allopurinol and ezetimibe/simvastatin.
DRESS was suspected. A team of specialists (dermatologist, aller-
gologist, pharmacologist, nephrologist) evaluated the patient.
Laboratory tests and herpes virus serology were performed. After
discharge she was evaluated on Allergy Unit. LTT was performed
2months later according to Pichler etal. LTT is positive if stimula-
tion index (SI) ≥2
Results: Tests revealed WBC 11,400, 700eosinophils/mm3 (6.2%),
creatinine 4.38mg/dl (baseline 2.8mg/dl), CRP 498, GPT 483, GGT
1264 and hyperamilasemia. Serology was only positive for herpes
6(1/320). According to Kardaun score, “probable” DRESS diagno-
sis was established (four points). She was included in Piel en Red
Registry. Causality assessment according the Spanish Pharmacovig-
ilance System Algorithm (SFEV) results were: allopurinol +7(prob-
able) and Conditional (Unrelated) the other drugs. Allopurinol
treatment was stopped. She received a bolus of metylprednisolone
intravenously three consecutive days, antihistamines and antibiot-
ics with improvement. She was discharged 15days later with corti-
costeroid treatment (reducing dose) during 14weeks. Patch tests
were negative with allopurinol, ezetimibe and simvastatine. LTT
was positive to allopurinol and to its metabolite oxypurinol at dif-
ferent concentrations with the highest stimulation index for oxypu-
rinol (SI 14.84)
Conclusions: We report a case of DRESS by allopurinol in which the
diagnosis was dicult to establish. LTT has been useful to identify the
etiological agent.
Keywords: DRESS; Allopurinol; Oxypurinol; LTT
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P80
Drug reaction witheosinophilia andsystemic symptoms
syndrome induced bytwo drugs simultaneously: a case report
Krasimira Baynova, Marina Labella, Manuel Prados
HUVR Seville, Seville, Spain
Correspondence: Krasimira Baynova
Clinical and Translational Allergy 2016, 6(Suppl 3):P80
Background: Drug reaction with eosinophylia and systemic symp-
toms (DRESS) is a severe potentially life-threatening drug hypersensi-
tivity reaction with delayed onset (2–8weeks after beginning a drug
intake). It is characterized by rash, fever, blood abnormalities and/
or internal organ involvement. Most frequently implicated drugs in
DRESS are anti-epileptic drugs. We present a case of DRESS induced by
carbamzepine and paracetamol simultaneously.
Report: A 84year-old Caucasian woman with no previous drug hyper-
sensitivity history, complained of generalized maculopapular itchy
purplish rash (trunk, abdomen, upper and lower extremities), peeling
skin, fever and general weakness. A month before she was diagnosed
of trigeminal neuralgia and started a treatment with pregabalin, car-
bamazepine and paracetamol. Previously the patient had used par-
acetamol without adverse reactions. Pregabalin and carbamazepine
were used for the rst time. Symptoms disappeared when the three
drugs were interrupted and oral corticoid treatment was established.
Peripheral blood test was done when patient was symptomatic. Skin
patch test and lymphocyte activation test (LAT)with paracetamol, car-
bamazepine and pregabalin were performed 4weeks after complete
recovering. In blood test was observed eosinophylia (1000/mm3) and
leucocytosis (>11,000/mm3). Kidney and liver function were normal.
Skin patch test (interpretation in 48 and 96h) and lymphocyte activa-
tion testwere positive to paracetamol and carbamazepine, and nega-
tive to pregabalin.
Pregabalin treatment was continued without adverse reactions. A
few months later our patient took a pill of paracetamol and experi-
enced eosinophylia and maculopapular rush in abdomen and lower
extremities.
How this report contributes to current knowledge: DRESS is a
type IV drug hypersensitivity reaction and is commonly induced by
aromatic anticonvulsants as carbamazepine. Nevertheless any drug
intake could induce this severe reaction, including “innocuous” drugs
as paracetamol. The allergy work-out should be carried out 4–6weeks
after the complete recovering and should include all involved drugs.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P81
The drug reaction witheosinophilia andsystemic symptoms
(DRESS) induced bythe second‑line antituberculosis drugs
andEpstein–Barr virus infection
Agne Ramonaite, Ieva Bajoriuniene, Brigita Sitkauskiene, Raimundas
Sakalauskas
Department of Pulmonology and Immunology, Lithuanian University
of Health Sciences, Kaunas, Lithuania
Correspondence: Agne Ramonaite
Clinical and Translational Allergy 2016, 6(Suppl 3):P81
Background: Drug reaction with eosinophilia and systemic symp-
toms (DRESS) is a severe drug-induced reaction that involves both
skin and viscera. Antiepileptic agents, allopurinol and sulfonamides
are the most frequently reported causes. Other causal factors such as
drug metabolites, genetic factors and viral infections have been also
reported.
Report: 31-year-old female was admitted to the hospital for the treat-
ment of multidrug-resistant pulmonary tuberculosis. She was treated
with second-line antituberculosis drugs: moxioxacin, kanamycin,
cycloserine, prothionamide, para-aminosalicylic acid. After 3 weeks
of therapy she developed high fever (>39°C), lymphadenopathy in
the cervical and axillary regions and pruritic maculopapular eruption
all over the body. Hematologic abnormalities such as leukocytosis
with eosinophilia (1.81×109/l) and monocytosis (1.85×109/l) were
detected in peripheral blood of the patient. Hepatitis was asymp-
tomatic and detected using the liver function tests: serum aspartate
aminotransferase (AST 1379IU/l) and alanine aminotransferase (ALT
1221 IU/l) levels were increased by approximately 30–40-fold above
the normal limits. The positive diagnosis of Epstein–Barr infection
was based on an increase in the anti Epstein–Barr immunoglobulin G
titer, implicating an Epstein–Barr virus reactivation. Based on the clinic
and laboratory ndings diagnosis of DRESS was suspected, and all the
drugs were discontinued. Patient’s condition improved after 8weeks.
The skin patch tests with moxioxacin, kanamycin, cycloserine, pro-
thionamide and para-aminosalicylic acid were done 2 months after
the hypersensitivity syndrome resolved. The patch tests showed a pos-
itive reaction to prothionamide and para-aminosalicylic acid.
How this report contributes to current knowledge: This case reports
the development of DRESS caused by late type of hypersensitivity to
Page 32 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
second-line antituberculosis drugs (prothionamide and para-amino-
salicylic acid) in association with Epstein–Barr virus infection.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
Poster Walk 10: Miscellaneous drug hypersensitivity (P82–P91)
P82
A case ofcycloserine‑induced lichenoid drug eruption conrmed
witha lymphocatye transformation test
Jae‑Woo Kwon1, Shinyoung Park2
1Department of Allergy and Clinical Immunology, Kangwon National
University School of Medicine, Chuncheon, Korea; 2The Research Depart‑
ment, Kangwon Regional Cancer Center, Kangwon National University
Hospital, Chuncheon, Korea
Correspondence: Jae‑Woo Kwon
Clinical and Translational Allergy 2016, 6(Suppl 3):P82
Background: LDE (Lichenoid drug eruption) is a rare form of delayed
type drug eruptions. Among anti-Tb (antituberculosis) drugs, etham-
butol is one of the most common causative drugs to induce LDEs and
cycloserine has been reported known as a rare causative drug of the
LDEs.
Report: 38 years old man presented with pururitus, lichenoid skin
lesion on whole body, and blood eosinophilia (16,824/µl). He had been
treated with isoniazid, rifampicin, ethambutol, and pyrazinamide for
2months and then with ethambutol, levooxacin, cycloserine for next
2months because of elevated liver enzymes. Mild pruritus developed
at the start of anti-Tb medications and aggravated with develop-
ment of lichenoid skin lesion 1month ago. Pruritus, skin lesions, and
eosinophilia were improved sinceanti-Tb medications were stopped.
Patch test showed mild reaction for ethambutol and strong reaction
forcycloserine. Thenwe performed an LTT (lymphocyte transformation
test)and successfully conrmed cycloserine as the oending drug.
How this report contributes to current knowledge: This suggests
that the cycloserine should be considered as a possible causative drug
of LDE and an LTT could be an option for the diagnosis of lichenoid
drug eruption due to cycloserine.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P83
Allergic reaction totopical eye drops: 5years’ retrospective study
ina drug allergy unit
Diana Silva1, Leonor Carneiro Leão1, Fabricia Carolino2, Eunice Castro2,
Josefina Cernadas2
1Allergy and Clinical Immunology Department, São João Medical Center;
Laboratory of Basic & Clinical Immunology, Faculty of Medicine, Porto
University, Porto, Portugal; 2Allergy and Clinical Immunology Depart‑
ment, São João Medical Center, Porto, Portugal
Correspondence: Diana Silva
Clinical and Translational Allergy 2016, 6(Suppl 3):P83
Background: Ophthalmic products are widely used and long-term
application is frequently needed. This might lead to ocular surface
changes and increase the frequency of adverse reactions. However,
the underlying mechanisms and the causal agent are usually dicult
to ascertain. We aimed to evaluate the patients referred to our drug
allergy unit with suspected hypersensitivity reaction to topical eye
drops.
Materials and methods: A cross-sectional, retrospective analysis of
the clinical les of all patients studied in the Drug Allergy Unit of a Uni-
versity Hospital, in the last 5years (January 2010 to December 2015)
was made. Those with a suspected hypersensitivity reaction to topical
eye drops were selected. Demographic, clinical history and diagnostic
procedures data were collected.
Results: Four patients, two children (2 and 11years of age) and
two adults (49 and 72years), were referred due to a suspicion of
hypersensitivity reaction to topical eye drops. Both children reacted
after atropine conjunctival application. The two adults reacted with
each of the following topical drugs: timolol and moxifloxacin with
tobramycin. All showed local symptoms of conjunctival erythema
and ocular/facial edema immediately after drug administration.
The patient who reacted to timolol presented dyspnea. For diag-
nostic study, the 2-year-old child performed conjunctival provoca-
tion test (CPT) with increasing doses of atropine (1; 5 and 10mg/
ml), with positive reaction with facial erythema at 10mg/ml dose;
the 11-year-old child was submitted to skin prick and intradermal
tests with atropine, which were negative, and waits for CPT to com-
plete the study. The two adult patients performed only diagnostic
CPT. The 49-year-old woman, which reacted with timolol, did CPT
with spirometry control, without a significant change in FEV1 or
any clinical symptoms; the 72-year-old male performed two sepa-
rate CPT with moxifloxacin and tobramycin, both with negative
results.
Conclusions: Hypersensitivity reactions to topical eye drops are prob-
ably underreported in our clinical practice. In three out of four patient’s
hypersensitivity reaction was excluded after diagnostic work-up. Facial
erythema is a frequent dose-dependent adverse eect to topical atro-
pine, graded conjunctival challenge is important for establishing the
diagnosis. Awareness should be increased for unneeded avoidance of
topical eye drops.
Keywords: Drug allergy; Ocular allergy
P84
Allergy toheparins
Diana Perez‑Alzate, Natalia Blanca‑López, Maria Luisa Somoza Alvarez,
Maria Garcimartin, Maria Vazquez De La Torre, Francisco Javier Ruano
Pérez, Elisa Haroun, Gabriela Canto Diez
Hospital Universitario Infanta Leonor, Madrid, Spain
Correspondence: Diana Perez‑Alzate
Clinical and Translational Allergy 2016, 6(Suppl 3):P84
The published version of this abstract can be found at [1].
Reference
1. Javier Ruano Perez F, Perez Alzate D, Blanca‑Lopez N, Somoza ML, Vazquez
de la Torre M, Garcimartin MI, Haroun E, Canto G. Allergy to heparins. J
Allergy Clin Immunol. 2016;137(2, Supplement):AB46.
P85
Allopurinol‑induced adverse drug reactions
Katinka Ónodi‑Nagy1, Ágnes Kinyó2, Lajos Kemény1, Zsuzsanna
Bata‑Csörgo1
1Department of Dermatology and Allergology, Szeged, Hungary;
2Department of Dermatology, Venereology and Oncodermatology, Pécs,
Hungary
Correspondence: Katinka Ónodi‑Nagy
Clinical and Translational Allergy 2016, 6(Suppl 3):P85
Background: Allopurinol, a xanthine oxidase inhibitor, is the most
widely administered urate lowering drug in the long-term manage-
ment of chronic hyperuricemia and gout. In 2% of the treated patients
adverse drug reactions, life-threatening cutaneous and systemic
symptoms can develop. Human leukocyte antigen (HLA) genes play
central role in immune reactions. Important association between HLA-
B*5801 allele and allopurinol-induced severe cutaneous adverse drug
reactions have been reported.
Materials and methods: In the past few years an increase in allopu-
rinol-induced adverse drug reaction have been experienced among
patients at our clinic (University of Szeged). Therefore we decided to
investigate the clinical characteristics of these patients.
Results: Between 2002 and 2008, 81 patients were sent to our labo-
ratory center with suspected allopurinol hypersensitivity for Lympho-
cyte Transformation Test (LTT). This number rose to 222 between 2009
and 2015. LTT was positive in four cases out of the 81 patients and in
20 cases out of the 222 patients respectively, indicating 4.9 and 9%
sensitivity. Of all these patients we were able to obtain a complete
Page 33 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
clinical history of 35 patients (mean age 68years), 4 patients in the rst
period and 31 patients in the second period. They presented general-
ized maculopapular exanthems in 37.14%, drug reaction with eosino-
philia and systemic symptoms in 31.43%, Stevens–Johnson syndrome
in 8.57%, erythema multiforme in 5.71%, vasculitis in 5.71%, bullous
drug exanthems in 2.86%, toxic epidermal necrolysis in 2.86%, acute
generalized exanthematous pustulosis in 2.86 % and erythroderma
in 2.86%. The primary indication of the treatment was asymptomatic
hyperuricemia in 88.6% of the patients. We concluded that the con-
comitant use of allopurinol and certain diuretics, furosemide and/or
hydrochlorothiazide in 28 cases of our 35 patients, and impaired renal
function enhance allopurinol toxicity increasing the risk of adverse
drug reaction developments. Evaluation of the HLA-B*5801 studies are
in progress.
Conclusions: Our data show that the use of allopurinol and thus the
number of the resulting hypersensitivity reactions is increasing. The
more and more common hypersensitivity reactions may be the result
of the improper drug prescription, indication and advanced age.
Based on our results LTT is not sensitive enough in proving allopurinol-
induced adverse drug reactions.
Keywords: Allopurinol; Adverse reactions; Clinical characteristics
P86
Analysis ofa population withimmediate hypersensitivity
tocorticosteroids: an 11year review
Joana Sofia Pita1, Emília Faria1, Rosa Anita Fernandes1, Ana Moura1, Nuno
Sousa2, Carmelita Ribeiro1, Carlos Loureiro1, Ana Todo Bom1
1Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 2Centro
Hospitalar de Leiria, Leiria, Portugal
Correspondence: Joana Sofia Pita
Clinical and Translational Allergy 2016, 6(Suppl 3):P86
Background: Due to their anti-inammatory and immunomodula-
tory properties, corticosteroids are highly prescribed. The prevalence
of hypersensitivity (HS) reactions is estimated at <1%. The aim of our
study was to characterize a population of patients referred to our out-
patient clinic for suspected immediate HS to corticosteroids.
Materials and methods: Retrospective analysis including 61 patients
sent to our Drug Allergy consultation for suspected corticosteroid HS,
from January 2005 to December 2015. We proceeded to the patients’
clinical evaluation and analysis of the results of skin prick (SPT) and
intradermal tests (IDT) of the following drugs: prednisolone succi-
nate 125mg/ml, dexamethasone sodium phosphate 5 mg/ml, meth-
ylprednisolone sodium succinate 40mg/ml, hydrocortisone 100 mg/
ml, betamethasone dipropionate 5mg/ml. IDT were performed with
the following dilutions: 1:1000, 1:100 and 1:10. The tests were read at
20min, and at 24–48h.
Results: We analysed 61 patients with suspected immediate HS to cor-
ticosteroids, in which 77% was female, with a median age of 47years.
Twelve patients had positive tests results (19 %). The population
with positive results was mainly female, 58%, with a median age of
39 (±16 years). Half of this population had associated atopic disease
(asthma and/or rhinitis). The clinical manifestations after the drug
administration were: anaphylactic reactions in 50 %, urticaria and/
or angioedema in 41% and syncope in 8%. In these 12 patients we
obtained 6% of positive SPT, and 12% of positive IDT. Thir ty percent of
positive reactions occurred with methylprednisolone, followed by dex-
amethasone (26%), prednisolone (17%), hydrocortisone (13%) and
betamethasone (13 %). Eight patients (66 %) presented HS to more
than one corticosteroid.
Conclusions: We obtained 19% positive prick and intradermal tests to
corticosteroids, being anaphylaxis the most common reaction in these
patients. There was a high frequency of sensitization to methylpredni-
solone and dexamethasone. 66% of patients had HS to more than one
corticosteroid, which probably correlates with the presence of cross-
reactivity among these drugs.
Keywords: Hypersensitivity; Corticosteroids; Skin tests
P87
Anaphylaxis againstmivacurium ina 12‑months old boy
atrst‑time exposure
Wolfgang Pfützner
Department of Dermatology and Allergology, Philipps University Mar‑
burg, Marburg, Germany
Correspondence: Wolfgang Pfützner
Clinical and Translational Allergy 2016, 6(Suppl 3):P87
Background: Since sensitization against an allergen is an important
requirement for the development of anaphylaxis, drug hypersensitiv-
ity reactions are very uncommon in infants. We report on a 12-months
old boy who experienced a severe anaphylactic reaction during perio-
perative anaesthesia.
Materials and methods: About 5min after receiving fentanyl, propo-
fol and mivacurium for the induction of anaesthesia, a persistent rush
was noticed, followed by a fall of blood pressure down to 70/40mm
Hg, tachycardia (f = 150/min) and respiratory distress. Emergency
treatment was initiated by i.v.-application of epinephrine, after which
thelittle boy fully recovered. Two months laterhe was referred to our
department for allergological evaluation, including both laboratory
analysis and skin tests with dierent drugs.
Results: Total IgE was 25.5kU/l with no allergen-specic IgE-antibodies
detectable against pholcodine, latex, egg white and soja, and basal serum
mast cell tryptasewas 2.77µg/l (Thermo Fisher, Germany). Skin prick tests
revealed a positiveresult to mivacurium but showed negative reactions
against fentanyl, remifentanyl, propofol, rocuronium, and cis-atracurium.
Thus, diagnosis of drug allergy against mivacurium was established,
together with cross-reactive sensitization against another neuromuscular
blocking agent (NMBA), cis-atracurium. Surgery was rescheduled utilizing
rocuronium for muscle relaxation, which was well tolerated.
Conclusions: NMBAs are the major cause of perioperative anaphylaxis,
accounting for about 70% of all cases, with IgE-antibodies directed
against quaternary ammonium compounds (QAC). Hypersensitiv-
ity reactions against NMBAs without prior exposure to this drug class
have been reported previously, suggesting sensitization induced by
other QAM-containing substances like disinfectants, food or industrial
materials. However, we are not aware about reports of anaphylaxis
against NMBAs ininfants of such a young age. Thus, this case under-
lines both the risk of allergic reactions against NMBAs at rst exposure
and the necessity of comprehensively testing these drugs even in very
small children with the history of perioperative anaphylaxis.
Keywords: Anaphylaxis; Mivacurium; Infant; Anaesthesia
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P88
Antihistamine‑exacerbated chronic spontaneous urticaria: a
paradox?
Nadine Marrouche, Clive Grattan
Norfolk and Norwich University Hospital, Norwich, United Kingdom
Correspondence: Nadine Marrouche
Clinical and Translational Allergy 2016, 6(Suppl 3):P88
Background: Histamine released from mast cells plays a key role in
the pathogenesis of chronic spontaneous urticaria (CSU). However,
it is unlikely that histamine alone is the only mediator of the disease.
From clinical experience we know that H1-antihistamines, even at high
doses, are ineective in at least 30% of patients. Antihistamine hyper-
sensitivity has been reported in the literature but CSU exacerbation by
multiple antihistamines in the same patient is rare.
Report: A 38-year old female patient presented with a 1-year history
of recurrent itchy hives. The clinical history was suggestive of CSU.
She was prescribed various antihistamines including chlorphenamine,
loratadine, fexofenadine, and cetirizine. The patient noticed signicant
worsening of her urticaria within an hour of taking any antihistamine.
Her urticaria exacerbations responded well to systemic steroids. The
Page 34 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
patient was re-challenged with cetirizine when her CSU was in remis-
sion. Within 90min, she developed generalized itchy wheals which
lasted several days. A skin biopsy showed typical urticaria with unusual
prominence of eosinophils suggestive of urticaria with superimposed
drug reaction (Figure 1). The patient was subsequently challenged
with oral acrivastine and a similar reaction was observed.
How this report contributes to current knowledge: The underly-
ing mechanism of antihistamine hypersensitivity remains unclear. Our
patient had a positive oral challenge to multiple antihistamines with at
least a 90-min delay which suggests that the underlying mechanism is
likely non-immunological. In one case report it was suggested that, in
some patients, antihistamines could paradoxically shift the H1 hista-
mine receptor to the active conrmation leading to adverse reactions
after dosing [*]. Our case highlights the rare possibility of a drug most
commonly used to treat urticaria acting as the causal agent itself.
*Urticaria induced by antihistamines. González de Olano D, et al. J
Investig Allergol Clin Immunol. (2006)
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P89
Anti‑osteoporotic agents‑induced cutaneous adverse drug
reactions inAsians
Yu‑En Chen1, Chun‑Bing Chen2, Wen‑Hung Chung2, Yu‑Ping Hsiao3,
Chia‑Yu Chu4
1College of Medicine, Chung Shan Medical University Hospital
and Chung Shan Medical University, Taichung, Taiwan; 2Department
of Dermatology, Drug Hypersensitivity Clinical and Research Center,
Chang Gung Memorial Hospitals, Linkou, Taipei, Keelung, Taiwan;
3Department of Dermatology, Chung Shan Medical University Hospital
and Chung Shan Medical University College of Medicine, Taichung, Tai‑
wan; 4Department of Dermatology, National Taiwan University Hospital
and National Taiwan University College of Medicine, Taipei, Taiwan
Correspondence: Yu‑En Chen
Clinical and Translational Allergy 2016, 6(Suppl 3):P89
Background: New medications such as bisphosphonates and stron-
tium ranelate (a strontium salt of ranelic acid) have been introduced
in the market for the treatment of osteoporosis and there are few case
reports of severe cutaneous adverse reactions (SCAR) related to anti-
osteoporotic agents. Therefore, we tried to identify the association
between anti-osteoporotic agents and cutaneous adverse drug reac-
tion (cADR) and the appropriate selection of alternative drugs.
Materials and methods: We retrospectively analyzed cADRs, includ-
ing maculopapular exanthema (MPE),Stevens–Johnson syndrome
(SJS), drug rash with eosinophilia and systemic symptoms (DRESS),
related to use of anti-osteoporotic agents in Taiwan and Hong Kong
from 2011 to 2015. We analyzed the causative anti-osteoporotic
agents, clinical characteristics, outcomes and further assessed
patients’ tolerability to alternative anti-osteoporotic agents after
the development of anti-osteoporotic agents-related cADRs. We
also review the literatures of anti-osteoporotic agents-related SCAR
(Table2; Fig.3).
Results: There were 14 cases of anti-osteoporotic agents-related
cADRs, including 6 SJS, 1 DRESS and 7 MPE. The most common causa-
tive agents were strontium ranelate and bisphosphonates. Strontium
ranelate was found to be related to most SCAR cases, including six
SJS and one DRESS. For MPE, there were three cases caused by bis-
phosphonates, three cases caused by strontium ranelate and one
case caused by teriparatide. There was no mortality and long-term
sequelae of all SCAR cases. There was no cross hypersensitivity among
strontium ranelate, bisphosphonates, and denosumab (a monoclonal
antibody). Patients with strontium ranelate-related cADRs were toler-
ant of alternative bisphosphonates and denosumab. One case of bis-
phosphonate-induced MPE was also tolerant of denosumab.
Conclusions: Most of the anti-osteoporotic agents-related cADRs
are usually mild. In Asia, strontium ranelate seems to cause more SJS/
TEN than DRESS in comparison with that in Europe. No mortality was
reported among patient with SCARs. Owing to the structural dierence
in anti-osteoporotic agents, denosumab was well tolerated in patients
Table 2 Strontium ranelate–induced severe cutaneous
adverse reactions
Abbreviations: 1SR Strontium ranelate, 2PM OPO postmenopausal osteoporosis,
3SJS/TEN Stevens–Johnson syndrome/toxic epidermal necrolysis, 4DRESS drug
rash with eosinophilia and systemic symptoms
*data are n(%) of patients unless otherwise specied
a Eye involvement: corneal ulcer or symblepharon, bLiver involvement:
twofold increase from normal or baseline levels of serum glutamic oxaloacetic
transaminase (GOT),glutamic pyruvate transaminase (GPT) or total bilirubin
c Kidney involvement: >1.5-fold elevation of serum creatinine from the normal range
d Eosinophilia: eosinophils count >500/μL
References
1. Tan KW, Wang YS, Tay YK. Stevens–Johnson syndrome due to strontium
ranelate. Ann Acad Med Singap. 2011;40(11):510–1.
2. Lee HY, etal. Strontium ranelate-induced toxic epidermal necrolysis in a
patient with post-menopausal osteoporosis. Osteoporos Int. 2009;20(1):161–2.
3. Cacoub P, etal. Drug rash with eosinophilia and systemic symptoms (DRESS) in
patients receiving strontium ranelate. Osteoporos Int. 2013;24(5):1751–7.
Region Asia Europe
Case series This study Tan et al. [1]/
Lee et al. [2] Cacoub et al.
[3]
Country Taiwan and
Hong
Kong
Singapore France etc.
Culprit anti‑osteoporotic
agent SR1SR SR
Indication to anti‑osteo‑
porotic agent OPO PM OPO2OPO
Patients’ profile
Ethnicity Chinese Chinese Caucasian
Gender F (83.3) F (100.0) F (100.0)
Average age (year) 64.7 69.5 68.7 (in DRESS
group)
No. of SCARs patients 7 2 52
Phenotype
SJS/TEN3
Total case no. 6 (85.7) 2 (100.0) 5 (9.6)
Average latent period
(days) 29.2 16 Not men‑
tioned
Eye involvementa1 (16.7) 1 (50) Not men‑
tioned
Orogenital involvement 5 (83.3) 2 (100.0) Not men‑
tioned
DRESS4
Total case No. 1 (14.3) 0 47(90.4)
Average latent period
(days) 90.0 0 33.5
Liver involvementb0 (0) 0 (0) 37 (79.0)
Kidney involvementc0 (0) 0 (0) 12 (25.0)
Eosinophiliad1 (100.0) 0 (0) 43 (91.0)
Clinical sequelae Nil Nil Persistent
DRESS
symptoms
(21.3) and
relapse of
DRESS (2.0)
Mortality rate 0 % 0 % 8.5 % (in
DRESS
group)
Page 35 of 35
Clin Transl Allergy 2016, 6(Suppl 3):31
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allergic to either strontium ranelate or bisphosphonates as alternative
drug.
Keywords: Severe cutaneous adverse reactions; Anti-osteoporotic
agents; Bisphosphonates; Strontium ranelate; Denosumab
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images.
P90
Diagnosis ofallergic reactions toeye drops
Maria Vazquez De La Torre, Natalia Blanca‑Lopez, Diana Perez‑Alzate,
Maria Isabel Garcimartin, Francisco Javier Ruano1, Maria Luisa Somoza,
Elisa Haroun, Gabriela Canto
Hospital Infanta Leonor, Madrid, Spain
Correspondence: Natalia Blanca‑Lopez
Clinical and Translational Allergy 2016, 6(Suppl 3):P90
The published version of this abstract can be found at [1].
Reference
1. Poster discussion session PDS 1. Allergy 2015;70:113–279. doi:10.1111/
all.12717.
P91
Diagnostic approach insuspected hypersensitivity reactions
tocorticosteroids
Fabrícia Carolino, Eunice Dias De Castro, Josefina R. Cernadas
Serviço de Imunoalergologia, Centro Hospitalar São João E.P.E., Porto,
Portugal
Correspondence: Fabrícia Carolino
Clinical and Translational Allergy 2016, 6(Suppl 3):P91
Background: Hypersensitivity reactions (HSR) to corticosteroids (CS)
are rare although there are a growing number of reports both to sys-
temic and topical CS. There are no standardized procedures for diag-
nostic skin testing with these drugs but a panel is recommended to
assess cross-reactivity between steroids. Incremental drug challenge is
still necessary for diagnostic or tolerance assessment purposes, but in
this point safety issues may overcome.
Materials and methods: Retrospective analysis of consecutive
patients evaluated in our Drug Allergy Unit for suspected CS HSR, dur-
ing a 5-years-period. Skin prick tests (SPT) and intradermal tests (IDT)
were performed with commercially available sterile CS formulations—
betamethasone (7mg/ml), budesonide (0.5mg/ml), dexamethasone
(4mg/ml), hydrocortisone (100mg/ml), methylprednisolone (62.5mg/
ml) and/or prednisolone (25 mg/ml). Oral solution of deazacort
(22.75 mg/ml) and nasal-spray suspension of uticasone (27.5 μg/
dose) were also used for SPT. Patch tests (PT) with a standard and/or
complementary CS series were performed. Drug challenges (DC) used
a selected-CS dose ranging between approximately 0.5 and 1.5mg/
kg/day.
Results: A total of 31 patients were assessed (74.2 % females,
mean ± SDage 36.8 ± 23.2 years) for suspected CS HSR. The main
implicated CS were oral deazacort (n=11) and oral betamethasone
(n=5). 45.2% had immediate reactions and 38.2% late-onset symp-
toms; 51.6 % presented skin/mucosal manifestations. IDT were per-
formed in 12 patients and were positive to at least one of the tested
drugs in four (two with anaphylaxis and two with late-onset skin/
mucosal involvement); two patients tested positively in IDT for more
than one CS (dexamethasone/hydrocortisone and methylpredniso-
lone/hydrocortisone). IDT were also performed in non-atopic controls.
Patch tests in 10 patients revealed positive results (including the sus-
pected CS) in two of them. DC was undertaken with the suspected sys-
temic CS in eight patients (no positive challenges and two doubtful);
the remaining patients were tested for an alternative CS.
Conclusions: Proper validated skin tests may provide the necessary
diagnostic evidence in drug allergy. They are particularly useful in
more severe index reactions when re-challenging is not an option.
The accuracy of skin tests needs to be further established with larger
studies.
Keywords: Drug hypersensitivity; Corticosteroids; Skin tests
Fig. 3 Clinical presentations of strontium ranelate‑induced severe
cutaneour adverse drug reactions. A case of Stevens–Johnson
syndrome (SJS) had necrotic erosive lesions on the lips and scattered
dusky red macules over the face and neck (a), and close up view of
the nape and back with dusky macules/patches and some necrotic
epidermal detachment (b). Another case of drug reaction with
eosinophilia and systems symptom presented with facial edema (c),
and extensive confluent infiltrative erythematous eruption dissemi‑
nated to the truck (d)
