Systemic drug-related intertriginous and flexural exanthema-like eruption after Oxford-AstraZeneca COVID-19 vaccine

Abstract

Systemic drug-related intertriginous and flexural exanthema (SDRIFE) is an adverse drug reaction which manifests as a symmetrical erythematous rash involving the skin folds after systemic drug exposure. A vast array of possible side effects associated with administration of different anti-SARS-CoV-2 vaccines have been reported in literature since the beginning of the COVID-19 pandemic, but only few times SDRIFE-like eruptions have been described in this context. We discuss here a case of SDRIFE-like eruption following the second dose of Oxford-Astrazeneca Vaxzevria vaccine.

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Bona Di et al. Clinical and Molecular Allergy (2022) 20:13
https://doi.org/10.1186/s12948-022-00179-8
the axillary fold. ere was no history of any other con-
stitutional symptom nor any mucosal involvement.
e patient started a treatment with cetirizine without
clinical benefit. She was also prescribed topical flucon-
azole due to suspicion of intertriginous fungal infection
by her general practitioner with no improvement. After
a few days, the patient consulted a dermatologist who
suggested a treatment with topical methylpredniso-
lone acetonate and emollient creams for 20 days, result-
ing in complete remission. No systemic symptoms were
reported throughout the skin rush.
e patient is affected by hypertension, asthma, rhini-
tis, and contact allergy to nickel and fragrance mix. She
didn’t take any drug in the days preceding the appearance
of the skin lesions except for her daily oral anti-hyper-
tensive medication (i.e., nebivolol/hydrochlorothiazide),
which was never stopped.
Laboratory tests, performed in September, including
inflammatory markers and complete blood count were
within the normal range. Skin tests (prick and intrader-
mal tests [ID]) with triamcinolone acetonide containing
To the editor,
A 67-year-old female patient visited our department for
an exanthem which occurred few days after receiving the
second dose of Vaxzevria (ChAdOx1 nCoV-19; Oxford-
AstraZeneca) vaccine.
After the first dose of the vaccine, administered on May
10th, 2021, the patient complained of fever and fatigue
for few days. ese symptoms showed up again after the
second dose which was administered on July 19; 5 days
after, she also reported a sharply demarcated pruritic ery-
thematous rash in the inguinal region bilaterally [Fig.1]
that subsequently involved the gluteal fold, the thighs,
the lower abdomen [Fig.2], the inframammary fold and
Clinical and Molecular Allergy
*Correspondence:
Eustachio Nettis
ambulatorio.allergologia@uniba.it
1Department of Emergency and Organ Transplantation, School of
Allergology and Clinical Immunology, University of Bari Aldo Moro,
Policlinico di Bari, Bari, Italy
2Unit of Allergology, Azienda Ospedaliero Universitaria Consorziale
Policlinico, Bari Piazza Giulio Cesare, 11., 70124 Bari, Italy
Abstract
Systemic drug-related intertriginous and flexural exanthema (SDRIFE) is an adverse drug reaction which manifests
as a symmetrical erythematous rash involving the skin folds after systemic drug exposure. A vast array of possible
side effects associated with administration of different anti-SARS-CoV-2 vaccines have been reported in literature
since the beginning of the COVID-19 pandemic, but only few times SDRIFE-like eruptions have been described
in this context. We discuss here a case of SDRIFE-like eruption following the second dose of Oxford-Astrazeneca
Vaxzevria vaccine.
Systemic drug-related intertriginous
and exural exanthema-like eruption after
Oxford-AstraZeneca COVID-19 vaccine
Danilo Di Bona1,2, Andrea Miniello1,2 and Eustachio Nettis2*

Page 2 of 5Bona Di et al. Clinical and Molecular Allergy (2022) 20:13
Polisorbate 80 at the concentrations of 40mg/mL, and
0.4 mg/mL, 4.0 mg/mL, 40 mg/mL, respectively, were
negative. e ID tests were read at 15min and at 96h.
e patient refused skin patch testing and lymphocyte
transformation test (LTT), which could have possibly
strengthened the suspicion of delayed drug reaction [1],
and denied her consent for histological examination.
Based on the patient’s clinical history, the lack of
systemic symptoms, of medications taken before the
development of the skin lesions, and of response to
the anti-fungal agent fluconazole suggested a pos-
sible diagnosis (by exclusion) of systemic drug-related
intertriginous and flexural exanthema (SDRIFE)-like
eruption induced by the COVID-19 vaccine. We applied
the Naranjo algorithm for estimation of the probability
of adverse drug reaction (ADR), and our case scored 5
points, which is indicative of “probable ADR”. [2]
Cutaneous events associated with COVID-19 vaccina-
tion may manifest themselves in many different clinical
pictures, but they’re mostly self-limited and easily man-
ageable with topical or oral steroids [3–5]. SDRIFE is a
relatively uncommon cutaneous adverse drug reaction
mediated by a type IV/delayed hypersensitivity mecha-
nism with only a limited number of cases reported in
Fig. 1 Sharply demarcated erythema on the inguinal region, 12 days after Vaxzevria vaccine second dose

Page 3 of 5Bona Di et al. Clinical and Molecular Allergy (2022) 20:13
literature. It is most commonly triggered by antibiotics
(especially beta-lactams) [6], but it also been described
following the administration of iodinated radiocontrast
media and different drugs including antiasthma treat-
ments (aminophylline, terbutaline), allopurinol and
monoclonal antibodies (infliximab, golimumab) [7–11].
To date, since the start of the global vaccination cam-
paign, nine cases of SDRIFE-like eruption following
COVID-19 vaccines [Table1] have also been reported.
[4, 12–17]. Most of these cases occurred after the second
dose, with the exception of the case reported by Manaa
et al., which occurred after the third (booster) dose of
Pfizer–BioNTech vaccine, and the ones reported by Ore-
nay et al. and Bellinato et al., who did not specify how
many injections were administered before the onset of
symptoms. e case reported here lends further support
to the possible causal relationship between COVID-19
vaccine and SDRIFE.
Fig. 2 Confluent erythematous papules merging on the lower abdominal region, 14 days after Vaxzevria second dose

Page 4 of 5Bona Di et al. Clinical and Molecular Allergy (2022) 20:13
Acknowledgements
Not applicable.
Author contributions
DDB conceptualization; AM and DDB draft writing; EN and DDB final editing.
All authors read and approved the final manuscript.
Funding
This research did not receive any specific grant from funding agencies in the
public, commercial, or not-for-profit sectors.
Availability of data and materials
Not applicable.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
All the authors gave their consent for publication.
Competing interests
None of the author have any conflict of interests to declare.
Received: 1 June 2022 / Accepted: 5 October 2022
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Table 1 Reported cases of SDRIFE-like eruption secondary following COVID-19 vaccination
Reported case Vaccine type Age / sex
of patient
Onset after
injection
N° of vac-
cine doses
prior to
SDRIFE
Treatment
Orenay et al. (2021)12 CoronaVac 87 M 4 days N/A Oral prednisolone 40 mg/day (3 weeks including ta-
pering off ); topical corticosteroids; oral antihistamines
Lim & Wylie (2021)13 Vaxzevria (ChAdOx1
nCoV-19)
61 M 1 day 2 Oral prednisolone 30 mg/day (4 weeks including
tapering off ); topical corticosteroids and antifungals
Hai et al. (2021)14 Comirnaty (BNT162b2) 23 M 6 weeks 2 Topical corticosteroid
38 F 2 weeks 2 Oral prednisolone 40 mg/day (9 days including taper-
ing off); topical corticosteroid
Bellinato et al.
(2021)4Comirnaty (BNT162b2) 65 M 2 weeks N/A N/A
Hong et al. (2022)15 Vaxzevria (ChAdOx1
nCoV-19)
53 M 7 days 2 Oral prednisolone 30 mg/day (2 weeks including
tapering off )
Lahouel et al.
(2022)16 Comirnaty (BNT162b2) 52 F 5 days 2 None (spontaneous remission after 5 days)
CoronaVac 57 F 3 days 2 Topical corticosteroids; oral antihistamine
Manaa et al. (2022)17 Comirnaty (BNT162b2) 59 M 2 days 3 Oral prednisone 40 mg/day (1 month including taper-
ing off); cyclosporine 2.5 mg/kg/day (2.5 months
including tapering off ); topical corticosteroids
Our case Vaxzevria (ChAdOx1
nCoV-19)
67 F 5 days 2 Topical corticosteroids (20 days)

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