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Year : 2022  |  Volume : 67  |  Issue : 6  |  Page : 810-812
ChAdOx1 COVID-19 vaccine-associated erythema multiforme major and erythema multiforme-like vasculitis: A tale of two cases

1 From the Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication23-Feb-2023

Correspondence Address:
Neetu Bhari
Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijd.ijd_849_22

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How to cite this article:
Mehta N, Gaurav V, Agarwal S, Bhari N. ChAdOx1 COVID-19 vaccine-associated erythema multiforme major and erythema multiforme-like vasculitis: A tale of two cases. Indian J Dermatol 2022;67:810-2

How to cite this URL:
Mehta N, Gaurav V, Agarwal S, Bhari N. ChAdOx1 COVID-19 vaccine-associated erythema multiforme major and erythema multiforme-like vasculitis: A tale of two cases. Indian J Dermatol [serial online] 2022 [cited 2023 Sep 24];67:810-2. Available from:


The coronavirus disease-2019 (COVID-19) pandemic has taken the world by storm. Widespread vaccination reduces the transmission and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Many cutaneous adverse events have been reported following COVID-19 vaccination. These include injection site reactions, morbilliform or maculopapular exanthems, urticaria, delayed inflammatory reactions to dermal hyaluronic acid fillers, pernio/chilblains, erythromelalgia, erythema multiforme (EM), lichen planus, varicella-zoster and herpes simplex reactivation, pityriasis rosea-like reactions and petechial/purpuric rash.[1] Awareness about these reactions is important for complete information and counselling before vaccination, as mass vaccination is necessary to achieve herd immunity and evade the pandemic. Herein, we report two cases of similar targetoid morphology following the COVID vaccine, highlighting the different approaches in managing them.

A 54-year-old female presented with genital and oral ulcers with haemorrhagic crusting, and painful erythematous targetoid papules over bilateral palms and soles for 10 days, 2 days after the second dose of ChAdOx1 nCoV-19 recombinant coronavirus vaccine (Covishield, manufactured at Serum Institute of India Pvt. Ltd., Pune, India) [Figure 1]a and [Figure 1]b. She denied having similar lesions in the past or after the first dose. Tzanck smear and routine haematological and biochemical investigations were normal. Biopsy from a targetoid papule showed extensive necrosis of the epidermis with epidermal regeneration, papillary dermal fibrosis and mild perivascular lymphocytic infiltrate suggestive of resolving EM [Figure 1]c and [Figure 1]d. A diagnosis of vaccine-associated EM major was made and the patient was initiated on oral prednisolone (0.75 mg/kg) for 7 days with which the lesions resolved without any sequelae.
Figure 1: ChAdOx1-associated erythema multiforme major (a) Targetoid lesions at palms (b) Erosions and haemorrhagic crusting at the lips (c) Histopathology showing epidermis necrosis, papillary dermal fibrosis and mild perivascular lymphocytic infiltrate (Haematoxylin and Eosin, 40X) (d) Epidermal necrosis, higher power view (Haematoxylin and Eosin, 100X)

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The second case was of a 35-year-old female who presented with sudden onset of multiple painful erythematous plaques with a targetoid appearance on bilateral legs, followed by blistering and ulceration, 2 days after the administration of the first dose of ChAdOx1 nCoV- 19 [Figure 2]a and [Figure 2]b. There was no history suggestive of any prior disease, mucosal or systemic involvement, preceding infection or drug intake. Investigations for internal organ involvement, including urinary protein, were negative. Skin biopsy showed perivascular infiltrate of neutrophils with erythrocyte extravasation and fibrinoid necrosis of the vessel wall [Figure 2]c and [Figure 2]d. A diagnosis of vaccine-associated skin-limited leucocytoclastic vasculitis (LCV) with an EM-like morphology was made, and the patient was treated with oral prednisolone 0.5 mg/kg for 2 months, which led to complete resolution with sequelae of post-inflammatory hyperpigmentation and cribriform scarring.
Figure 2: ChAdOx1-associated skin-limited leucocytoclastic vasculitis (a) Targetoid lesions at legs (b) Blistering and ulceration (c) Histopathology showing fibrinoid necrosis of small vessels in the upper dermis, neutrophils in the vessel walls and erythrocyte extravasation (Haematoxylin and Eosin, 200X) (d) Higher power view (Haematoxylin and Eosin, 400X)

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Vaccination is based on activation of the immune system, hence can lead to immune-complex mediated and delayed-type hypersensitivity reactions like EM and LCV. EM has been reported following vaccinations, including COVID-19 vaccination. Previously reported cases followed the first dose of the vaccine.[1] In our case, EM followed the second dose. LCV also has been observed with various vaccines, including COVID vaccines like ChAdOx1.[2] The different types of vasculitis occurring after COVID-19 vaccination include systemic types like antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis and IgA vasculitis; and skin-limited leukocytoclastic vasculitis and urticarial vasculitis. The time gap between vaccine administration and lesions ranged from 36 h to 5 days, similar to our case. Vaccines cause EM or LCV by stand-by activation (non-specific immune activation), molecular mimicry (by antigenic components or its adjuvant) or neo-antigen formation (self-antigen structural change or exposure). These mechanisms are similar to those proposed for infection-induced EM or LCV.[3] COVID vaccines alter the immune response of the body favouring the appearance of these reactions.

The second patient refused to be further vaccinated with the same vaccine. It is difficult to identify the specific component (COVID virus antigens, platform antigens or adjuvants) responsible for reactions in patients. The second patient had no recurrence when switched to a whole-virion inactivated Vero cell-based vaccine (Covaxin, Bharat Biotech, Hyderabad, India). Both doses of the new vaccine had to be given. Only about 43% of patients are reported to have a recurrence with the second dose.[4] Cutaneous reactions to the second dose, including vasculitis, appear earlier and with more severity as compared to the ones following the first dose.[2],[4] Since, most vaccine-related cutaneous reactions are mild, withholding the second dose is not recommended.[4] Switching to a vaccine based on a different platform and ideally with different or least cross-reacting additives can be opted if the patient is afraid of a severe recurrence.

We highlight two rare reactions to the ChAdOx-1 vaccine with similar morphology but different pathology and histopathology. LCV can present with EM-like targetoid lesions.[5] We also highlight the approach of changing the vaccines in select patients with severe reactions to the first dose and the need for further studies on this subject.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Sun Q, Fathy R, McMahon DE, Freeman EE. COVID-19 vaccines and the skin: The landscape of cutaneous vaccine reactions worldwide. Dermatol Clin 2021;39:653-73.  Back to cited text no. 1
Sandhu S, Bhatnagar A, Kumar H, Dixit PK, Paliwal G, Suhag DK, et al. Leukocytoclastic vasculitis as a cutaneous manifestation of ChAdO×1 nCoV-19 corona virus vaccine (recombinant). Dermatol Ther 2021;34:e15141.  Back to cited text no. 2
Segal Y, Shoenfeld Y. Vaccine-induced autoimmunity: The role of molecular mimicry and immune crossreaction. Cell Mol Immunol 2018;15:586-94.  Back to cited text no. 3
McMahon DE, Amerson E, Rosenbach M, Lipoff JB, Moustafa D, Tyagi A, et al. Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases. J Am Acad Dermatol 2021;85:46-55.  Back to cited text no. 4
Hughey LC. Approach to the hospitalized patient with targetoid lesions. Dermatol Ther 2011;24:196-206.  Back to cited text no. 5


  [Figure 1], [Figure 2]


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