Erythema multiforme in COVID-19 patients and following COVID-19 vaccination: manifestations, associations and outcomes.

Abstract

Dear Editor: Erythema multiforme (EM) is a delayed-type hypersensitivity reaction linked to infectious agents in 90% of cases and medications or vaccination in less than 10% of cases. A 19-year-old male presented with a 48-h history of an itchy rash. Examination revealed erythematous papules and plaques with central dusky erythema and crusting on the bilateral upper extremities. There was no involvement of the palms, soles or oral mucosa. He had no fever, cough or medications. Prednisone 20 mg and cetirizine 10 mg daily were started. After 3 days, he developed fever, shortness of breath and dry cough; and a SARS-CoV-2 test was positive. He was started on remdesivir and dexamethasone. After 5 days, the rash started to improve, and after 2 weeks, it completely resolved. EM in patients with COVID-19 has been reported in 23 publications (Fig. 1), including 36 cases with 19 males (53%). Four articles reported EM after COVID-19 vaccination (Fig. 1). The details of these manuscripts are summarized in Table 1. Among patients with EM and COVID-19, 16.7% (6/36) patients were less than 18-year old, 19.4% (7/36) patients were 18–40 years old and 63.9% (23/36) patients were more than 40 years old. Eleven patients (30.6%) took no medications before EM; however, 25 patients (69.4%) reported exposure to medications before. Drugs to which patients were exposed before EM were HCQ in 20 cases (55.5%), azithromycin in 14 cases (38.9%) with 13 of them receiving HCQ in addition to azithromycin and lopinavir/ritonavir in 12 patients (33.3%), all in combination with HCQ. EM occurred before any classic COVID-19 symptoms only in 5/36 patients (13.9%), four of them under 23 years. Three patients (8.3%) presented with EM and COVID-19 symptoms simultaneously. However, in most of the patients (78%), EM started after COVID-19 symptoms. Four patients (11.1%) had only mucosal involvement, five patients (13.9%) had mucosal and skin involvement, but most of the patients (27 patients, 75%) had only skin lesions. Thirty-five of 36 patients survived, and only a 72-year-old woman died. Interestingly, her skin lesions were the first manifestation of infection.1 Therefore, we believe EM is not associated with worse outcomes. EM following vaccination is rare, with eight reported cases: three after Moderna (37.5%), four after Pfizer (50%) and one after CoronaVac (12.5%) (Table 1). In another study, three of 414 cases of dermatological presentations were EM after the first dose of the Moderna vaccine.2 This rarity makes it hard to establish a causal link. Infection with SARS-CoV-2 may have a role in the pathogenesis of EM.3 The underlying mechanism is not clear.4 EM may result from the interaction with the virus itself, antiviral immune response and medications. EM can rarely be the presenting sign of COVID-19, and EM is not associated with worse outcomes. Further studies are needed to elucidate the exact relationship between infection, medications and erythema multiforme in the setting of COVID-19. Elbows, knees, thighs, arms, forearms, legs, ankles, dorsal feet, dorsal hands HCQ, azithromycin and oseltamivir trunk and upper limbs, without mucosal involvement Mycoplasma pneumoniae and HSV were negative. HIV antibodies were negative, CMV and EBV serologies only found IgG, and mycoplasma pneumoniae was negative. A full sepsis work-up Was negative. Mycoplasma pneumoniae, EBV, HSV 1 and 2, adenovirus and parvovirus B19 were negative. Entire trunk with a transition to the shoulders and buttocks Parenteral glucocorticosteroids Time from hospital admission to EM onset was 14 days. Generalized targetoid lesions, and facial oedema Time from hospital admission to EM onset was 28 days. Time from hospital admission to EM onset was 23 days. Time from hospital admission to EM onset was 24 days. Age: 60 (40–78) 2 of 4 were F Topical corticosteroids and oral antihistamines Within 12 h of receiving the first BNT162b2 vaccine. A similar eruption occurred 24 h after receiving the second BNT162b2 vaccine. Not declared. None. The data that support the findings of this study are available from the corresponding author upon reasonable request.