Vancomycine-induced DRESS syndrome in a female patient

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Short Communication
Pharmacology 2008;82:138–141
DOI: 10.1159/000142729
Vancomycin-Induced DRESS Syndrome in
a Female Patient
Laetitia Vauthey a Ilker Uçkay a, b Sophie Abrassart a Louis Bernard c, d
Mathieu Assal a Tristan Ferry b Marina Djordjevic e Constantinos Roussos a
Pierre Vaudaux b
a Orthopaedic Surgery Ser vice and
b Service of Infectious Diseases, University Hospitals of Geneva, Geneva ,
Switzerland;
c Service of Infectious Diseases, Raymond Poincaré University Hospital, and
d Public Assistance,
Hospitals of Paris, Garches , France;
e Clinical Center Nis, Nis , Serbia
can be a cause of DRESS syndrome. A high index of suspicion
is warranted in order not to miss this potentially lethal dis-
ease. Copyr ight © 2008 S. Karger AG, B asel
Introduction
Adverse cutaneous reactions to antibacterial agents
are frequently encountered [1, 2] ; however, life-threaten-
ing adverse events, especially in response to glycopep-
tides, are rare
[2] . The DRESS syndrome (drug rash with
eosinophilia and systemic symptoms) occurs roughly in
1 over 10,000 exposures, and is characterized by high
fever, facial edema, maculopapular eruptions, general-
ized lymphadenopat hy, eosinophilia , mononucleosis-like
lymphocytosis
[3] and multiorgan involvement [4] . The
mortality rate can reach 10%
[3, 4] . Common triggering
agents are antiepileptic drugs or allopurinol
[4] . Antibiot-
ics are seldom a cause, and the clinical presentation may
Key Words
DRESS syndrome ⴢ Vancomycin ⴢ Drug rash ⴢ Drug
hypersensitivity ⴢ Eosinophilia
Abstract
Background: DRESS syndrome (drug rash with eosinophilia
and systemic symptoms) is a hypersensitivity reaction with
skin rashes, eosinophilia, fever, lymph node enlargement
and internal organ involvement. Case Report: A 60-year-old
diabetic woman was hospitalized at the University Hospitals
of Geneva for mid-leg amputation due to peripheral arterial
occlusive disease. No drug allergy was reported. Because of
a wound infection by methicillin-resistant Staphylococcus
aureus , treatment with vancomycin (2 g/day) in continuous
perfusion was initiated. Approximately 2 week s later, she de -
veloped a toxidermia with fever, a progressive maculopapu-
lar skin rash, eosinophilia and acute renal insufficiency. The
skin biopsy revealed a necrosis with lymphocytic and eo-
sinophilic infiltrations, supporting the suspicion of DRESS
syndrome. A cure was achieved by the withdrawal of vanco-
mycin and the administration of methylprednisolone (1 g/
day), antihistaminics and topical mometasone, without the
introduction of other antibiotics. Conclusion: Vancomycin
Recei ved: February 22, 200 8
Accepted : March 3, 2008
Publis hed online: July 8, 200 8
Pierre Vaudaux, PhD
Ser vice of Infectious Disease, University Hospitals of Gene va
24 Rue Micheli-du-Crest
CH–1211 Geneva 14 (Switzerland)
Tel. +41 22 372 9826, Fax +41 22 372 9 8 30, E-Mail pierre.vaudaux@hc uge.ch
© 200 8 S. Karger AG, Basel
0031–701 2/08/0 822– 0138$24 .50/0
Accessible online at:
www.karger.com/pha
Parts of the manuscript have been presented as a poster on 14 June
2007 at the Annual Meeting of the Swiss Society for Infectious Dis-
eases in Zurich, Switzerland.
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Vancomycin-Induced DRESS Syndrome Pharmacology 2008;82:138–141
139
be confounded with the sepsis the antibiotics were ad-
ministered for.
Since Geneva has a high prevalence of nosocomial
methicillin-resistant Staphylococcus aureus (MRSA) [5] ,
vancomycin is often used for prophylactic and therapeu-
tic purposes. We describe a case of a va ncomycin-induced
DRESS syndrome, and recall the hallmarks of this poten-
tially fatal disease.
C a s e R e p o r t
A 60-year-old diabetic Caucasian woman, without a known
drug allergy, was
ho sp it a li ze d in Ap ri l 2 0 06 at th e U ni ve rs it y H os -
pitals of Geneva for mid-leg amputation due to peripheral arte-
rial occlusive disease. Because of wound infection due to MRSA,
treatment with vancomycin (2 g/day) was initiated. Eighteen days
later, she developed fever (40
° C), periorbital edema and an ery-
thematous maculopapular rash involving the palms and sparing
the mucosa. The granulocyte count was 3.6 ! 10 9 /l with 13%
nonsegmented neutrophils and 152,000 ! 10 9 /l thrombocytes.
The maximal eosinophil and C-reactive protein (CRP) values
were 1,251 ! 10 9 /l (9%) and 336 mg/l, respectively. Creatinine
clearance dropped from normal values to 30 ml/min mostly due
to dehydratation without elements for interstitial nephritis. There
was no oral, o cular, genital or ung ular involvement and no ly mph-
adenopathy. ␥ -Glutamyltranspeptidase (224 U/l) was the only el-
evated hepatic parameter.
Two skin biopsies from the abdominal wall showed necrosis
with ly mphocytic and e osinophilic infilt rations ( f ig. 1 ). Immuno-
globulin depots were absent. Vancomycin was the only persistent
new medication, and dermatological and pharmacological con-
sultations identified it as the most probable cause. No history of
vancomycin administration in previous hospitalizations had
been reported. Its cumulative dose had reached 36 g, and serum
levels had oscillated between 20.4 and 30.8 mg/l on continuous
perfusion before onset of the rash. A cure was achieved by the im-
mediate withdrawal of vancomycin and administration of meth-
ylprednisolone (1 g/day), antihistaminics and topical mometa-
sone. All other medication was kept in place. The patient left the
ho spi ta l 2 mo nth s l ate r. No s ki n pat ch o r ly mp hoc y te t ra ns for ma-
tion testing were necessary.
Discussion
Vancomycin may cause adverse skin reactions ranging
from the ‘red man syndrome’, a histamine deliberation
provoked by rapid infusion
[6] , to thrombocytopenia [7] ,
agranulocytosis
[8] , allergic exanthema [2] , anaphylaxis
[6, 9] , linear IgA bullous disease [10] , vasculitis [11] , ery-
thema multiforme
[12] and Stevens-Johnson syndrome/
toxic epidermal necrolysis
[13, 14] . In contrast, a vanco-
mycin-induced DRESS syndrome is extremely rare, al-
though a underreporting bias might exist.
To the best of our knowledge, we are reporting the
fifth case worldwide. Table 1 summaries key characteris-
tics of published reports. Briefly, DRESS syndrome oc-
curred within 2–5 weeks after starting vancomycin treat-
ment
[4, 15] , which is later than most reactions to drugs
[2, 3] . Vancomycin was the only causative agent, except
in 1 case where teicoplanin was attributed to the relapse
of DRESS syndrome
[17] . Cross-reactivity between van-
comycin and teicoplanin has also been reported in other
adverse events
[8, 11, 12, 16] . All patients survived after
the immediate withdrawal of the glycopeptides and ad-
ministration of intravenous corticosteroids.
A skin biopsy may help to diagnose DRESS syndrome,
but it is usually not specific and often shows a nonspe-
cific lymphocytic infiltrate on the papillary dermis,
which contains eosinophils and is denser than in other
drug reactions
[4] .
The pathogenesis of DRESS syndrome is not fully un-
derstood and may be multifactorial, involving hypogam-
maglobulinemia
[18] , human herpesvirus 6 activation [3,
17] , immunological mechanisms and drug detoxification
pathways; this is underlined by the association of slow
acetylation with an increased risk of DRESS syndrome
[4] . As for vancomycin, the cumulative dose or exceed-
ingly high serum levels did not seem to be related to
DRESS syndrome, but may prolong the established dis-
ease because of accumulation
[15] and is a subject of de-
bate
[4] .
Fig. 1. Histolog y of a skin biopsy from the abdominal wall (hema-
toxylin). Central pustule with spongiosis, lymphocytosis, eosino-
phils and necrotic keratinocytes.
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Vauthey et al.
Pharmacology 2008;82:138–141
140
The only undisputed way to treat DRESS syndrome is
the withdrawal of the suspected drug
[3, 4] . The use of
systemic corticosteroids is common, but remains contro-
versial
[3, 4] . Randomized trials are lacking, and the con-
troversy may be partly related to the confusion between
DRESS syndrome and other severe drug reactions, such
as toxic epidermial necrolysis. Most experts favor steroid
use which is supported by the fact that relapses of DRESS
syndrome often occur after tapering of steroid treatment
[4, 15] . Therapies aimed at eliminating the causative drug
deserve further study
[4] . Desensitization protocols,
which already exist for the ‘classical’ vancomycin-in-
duced allergy
[6, 9] , have not been evaluated for DRESS
syndrome, and this should not be attempted in the pres-
ence of alternative medication
[4] .
C o n c l u s i o n s
DRESS syndrome is a rare, but severe, adverse drug
reaction. When antibiotics are the potential cause, the
decision to stop them is particularly difficult, because the
clinical worsening may be confounded with the underly-
ing sepsis the antibiotic was given for. Vancomycin may
be such a potential agent. With its increasing use due to
emergence of MRSA and resistant coagulase-negative
staphylococci, a high index of suspicion and rapid diag-
nosis are necessary to save the patient’s life
[1] . Finally,
people with a history of DRESS syndrome need an ‘al-
lergy’ passport to maximize preventive efforts.
A c k n o w l e d g m e n t s
We are indebted to Dr. P. Chavaz for assistance with the his-
tological analyses, and to the team of the septic orthopedic ward
for clinical support.
Tab le 1. Cases of vancomycin-induced DRESS syndrome in the literature
Author Sex Age
years
Indication for
vancomycin
Delay
between
vancomycin
and DRESS
syndrome
days
Comorbidities
related to
internal
organs
Maximal
eosino-
philia
mm3
Rash Fever Other
features
Daily treatment
doses
Outcome
remarks
Zuliani
et al. [19]
f 45 staphylococcal
endocarditis
34 hepatitis;
nephritis
1,474 erythemato-
squamous
inter-
mittent
eosino-
philuria
4 ! 100 mg
methylpredni-
solone; 2 !
100 mg cyclo-
sporine
survival;
steroid resistant
response to
cyclosporine;
relapsing
Tamagawa-
Mineoka
et al. [17]
f 52 MRSA ear
infection after
tympanoplasty
14 hepatitis 1,832 maculo-
papular
‘high’ generalized
lymphadeno-
pathy
methylpredni-
solone
survival;
reactivation of
human herpes-
virus-6
Kwon
et al. [16]
m 50 osteomyelitis
with epidural
abscess
18 pneumonitis;
nephritis;
hepatitis
1,605 maculo-
papular
39.0° C – 120 mg
methylpredni-
solone
survival;
recrudescence
with teicoplanin
Yazganoğlu
et al. [15]
f 56 MRSA
bacteremia
20 hepatitis 1,396 maculo-
papular
39.4° C pharyngitis 80 mg methyl-
prednisolone
survival;
recrudescence
after steroid
tapering
Present
article
f 60 MRSA wound
infection
18 hepatitis 1,251 maculo-
papular
40° C – 1 g methyl-
prednisolone;
topical mome-
tasone
survival
References 1 Bachot N, Roujeau JC: Di fferential diagnosis
of severe cutaneous drug eruptions. Am J
Clin Dermatol 2003;
4: 561–572.
2 L ee CE, Zembower TR , Fotis MA, Postel nick
MJ, Greenberger PA, Peterson LR, Noskin
GA: The incidence of anti microbial allergies
in hospitalized patients: implications re-
garding prescribing patterns and emerging
bacterial resistance. Arch Intern Med 2000;
160: 2819–2822.
Downloaded by:
Universität Zürich
130.60.110.15 - 5/3/2022 1:36:59 PM

Vancomycin-Induced DRESS Syndrome Pharmacology 2008;82:138–141
141
3 Ghislain PD, Roujeau JC: Treatment of se-
vere drug reactions: Stevens-Johnson syn-
drome, toxic epidermal necrolysis and hy-
persensitivity syndrome. Dermatol Online J
2002;
8: 5.
4 Tas S, Simonar t T: Management of dr ug rash
with eosinophilia and systemic symptoms
(DRESS syndrome): an update. Dermatolo-
gy 2003;
206: 353–356.
5 Blanc DS, Pittet D, Ruef C, Widmer A, Müh-
lemann K, Petignat C, Harbarth S, Aucken-
thaler R, Bille J, Frei R, Zbinden R, Moreillon
P, Sudre P, Francioli P: Mole cular epidemiol-
ogy of predominant clones and sporadic
strains of methicillin-resistant Staphylococ-
cus aureus in Switzerland and comparison
with European epidemic clones. Clin Micro-
biol Infect 2002;
8: 419–426.
6 K itazawa T, Ota Y, Kada N, Morisawa Y, Yo-
shida A, Koike K, Kimura S: Successful van-
comycin desensitization with a combination
of rapid and slow infusion methods. Intern
Med 2006;
45: 317–321.
7 Marraffa J, Guharoy R, Duggan D, Rose F,
Nazeer S: Vancomycin-induced thrombocy-
topenia: a case proven with rechallenge.
Pharmacotherapy 2003;
23: 1195–1198 .
8 Hsiao SH, Chang CM, Tsai JC, Lin CY, Liao
LH, Lin WL, Wu TJ: Glycopeptide-induced
neutropenia: cross-reactivity between van-
comycin and teicoplanin. Ann Pharmacoth-
er 2007;
41: 891–894.
9 Chopra N, Oppenheimer J, Derimanov GS,
Fine PL: Vancomycin anaphylaxis and suc-
cessful desensitization in a patient with end
stage rena l disease on hemod ialysis by mai n-
taining steady antibiotic levels. Ann Allergy
Asthma Immunol 2000;
84: 633–635.
10 Waldman MA, Black DR, Callen JP: Vanco-
mycin-induced linear IgA bullous disease
presenting as toxic epidermal necrolysis.
Clin Exp Dermatol 2004;
29: 633–636.
1 1 M ar s ha l l C , S t re et A, Ga l br ai t h K : G ly co p ep -
tide-induced vasculitis-cross-reactivity be-
tween vancomycin and teicoplanin. J Infect
1998;
37: 82–83.
12 Padial MA, Barranco P, Lopez-Serrano C:
Erythema multiforme to vancomycin. Al-
lergy 2000;
55: 1201.
13 Thestrup-Pedersen K, Hainau B, Al’Eisa A,
Al’Fadley A, Hamadah I: Fatal toxic epider-
mal necrolysis associated with ceftazidine
and vanc omycin therapy : a report of two cas -
es. Acta Derm Venereol 2000;
80: 316–317.
14 Bouaziz JD, Valeyrie-Allanore L, Damak H,
Faure H, Marinho E, Regnier B: Toxic epi-
dermal necrolysis after vancomycin in a pa-
tient with terminal renal insufficiency: in-
terest for intensive haemodialysis? J Eur
Acad Dermatol Venereol 2006;
20: 1011–
1013.
15 Yazganoğlu KD, Őzkaya E, Ergin-Őzcan P,
Çakar N: Vancomycin-induced drug hyper-
sensitivity syndrome. J Eur Acad Dermatol
Ven ere ol 2 005;
19: 638–659.
16 Kwon HS, C hang YS, Jeong YY, Lee SM, S ong
WJ, Ki m HB, Kim YK , Cho SH, Kim YY, Min
KU: A case of hypersensitivity syndrome to
both vancomycin and teicoplanin. J Korean
Med Sci 2006;
21: 1108–1110.
1 7 T a m a g a w a - M i n e o k a R , K a t o h N , N i s h i m u r a
Y, Yamamoto S, Kishimoto S: DRESS syn-
drome caused by teicoplanin and vancomy-
cin, associated with reactivation of human
herpesvirus-6. Int J Dermatol 2007;
46: 654–
655.
18 Boccara O, Valeyrie-Allanore L, Crickx B,
Descamps V: Association of hypogamma-
globulinemia with DRESS (Drug Rash with
Eosinophilia and Sy stemic Symptoms). Eur J
Dermatol 2006;
16: 666–668.
19 Zuliani E, Zwahlen H, Gilliet F, Marone C:
Vancomycin-induced hypersensitivity reac-
tion with acute renal failure: resolution fol-
l ow i n g c y cl o s p o r in e t r e at m e n t . C l i n N e ph r o l
2005;
64: 155–158.
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130.60.110.15 - 5/3/2022 1:36:59 PM