key: cord-0896729-0klbjvrj
authors: Kreuter, A.; Licciardi‐Fernandez, M. J.; Burmann, S.‐N.; Burkert, B.; Oellig, F.; Michalowitz, A.‐L.
title: Induction and exacerbation of subacute cutaneous lupus erythematosus following mRNA‐based or adenoviral vector‐based SARS‐CoV‐2 vaccination
date: 2021-09-13
journal: Clin Exp Dermatol
DOI: 10.1111/ced.14858
sha: a5a5fefc2850c9336e56f899054e75bd9c814b88
doc_id: 896729
cord_uid: 0klbjvrj

Evidence is accumulating that COVID‐19 vaccines might induce or exacerbate autoimmune rheumatic diseases. The currently available COVID‐19 vaccines include mRNA and recombinant adenoviral vector vaccines, both encoding SARS‐CoV‐2 spike protein production as the primary target for neutralizing antibodies. We report a case of subacute cutaneous lupus erythematosus (SCLE) following mRNA vaccination with the Pfizer mRNA vaccine BNT162b2, and summarize the current literature on CLE occurring after COVID‐19 vaccination.[Image: see text]

Induction and exacerbation of subacute cutaneous lupus erythematosus following mRNA-based or adenoviral vector-based SARS-CoV-2 vaccination doi: 10.1111/ced.14858

Dear Editor, Evidence is accumulating that COVID-19 vaccines might induce or exacerbate autoimmune rheumatic diseases. The currently available COVID-19 vaccines include mRNA and recombinant adenoviral vector vaccines, both encoding SARS-CoV-2 spike protein production as the primary target for neutralizing antibodies. 1 We report a case of subacute cutaneous lupus erythematosus (SCLE) following mRNA vaccination with the Pfizer mRNA vaccine BNT162b2, and summarize the current literature on CLE occurring after COVID-19 vaccination.

A 79-year-old man was admitted to our department with a widespread annular and papulosquamous exanthema on his trunk and lower legs, occurring concomitantly with mild malaise and fatigue (Fig. 1a-c) . There were no potential trigger factors for his skin lesions such as recent (viral or bacterial) infections, ultraviolet light exposure or new drug intake. However, he had received the first dose of BNT162b2 mRNA vaccine 10 days before onset of the exanthema.

Histopathogical examination of a skin biopsy taken from the patient's chest revealed features of CLE, including vacuolar interface dermatitis, dense dermal lymphocytic infiltrates, and mild mucin deposition (Fig. 1d ,e).

Laboratory investigations showed normal blood cell count and serum chemistry, but increased titres (1 : 320; normal < 1 : 160) for antinuclear antibodies (ANA), positivity for anti-Ro/SSA (60 kDa) and anti-La/SSB antibodies, and a slightly increased rheumatoid factor (18 U/mL; normal < 14 U/mL). All other extractable nuclear antigens were negative, and review of organ systems (chest radiography, abdominal ultrasonography, heart echography) was unremarkable.

Based on these findings, a diagnosis of vaccine-induced SCLE was made, and treatment with hydroxychloroquine 200 mg twice daily and tapered intravenous glucocorticosteroid therapy beginning at 150 mg daily was initiated, resulting in a complete clearance of all skin lesions within 4 weeks.

SCLE is a distinct subtype of CLE with typical clinical (annular and/or papulosquamous cutaneous lesions symmetrically located in sun-exposed areas) and serological (anti-Ro/SSA antibodies) characteristics. Various external factors including drugs and vaccines are known to induce disease flares in CLE, especially in SCLE. 2 To our knowledge, three similar cases of post-vaccination CLE have been reported. [3] [4] [5] All were classified clinically as SCLE, and all occurred within 10 days after application of the first vaccination dose and rapidly responded to treatment with systemic corticosteroids (Table 1) . Both mRNA and adenoviral vaccines elicit immunity to SARS-CoV-2 by production of high levels of spike proteins. Additionally, they trigger innate sensors by intrinsic adjuvant activity, resulting in production of type 1 interferons (IFNs), 1 which play an important role in the pathogenesis of various autoimmune rheumatic diseases through elevated levels of nuclear antigen-containing immune complexes. The elevated levels of nuclear antigen-containing immune complexes might enhance production of type 1 IFNs, which in turn further disturbs B-and T-cell tolerance mechanisms, promoting production of ANAs. 6 The type 1 IFN pathway is also a major component of CLE pathogenesis, and correlates with disease activity. 2 Interestingly, among ANA-positive clinically asymptomatic patients, anti-Ro/SSA and/or anti-La/ SSB antibodies were associated with an elevated IFN signature and the lupus-risk variant IRF5. 6 These findings might explain why all of the reported post-vaccination lupus cases had Ro/SSA-positive SCLE (Table 1) .

A recently published register-based study on 414 skin reactions following mRNA-based COVID-19 vaccination revealed that most cutaneous adverse effects were large local reactions and local injection site reactions as well as urticarial and morbilliform eruptions. Less frequently seen reactions included chilblains, cosmetic filler reactions, herpes zoster or herpes simplex flares, and pityriasis rosea-like reactions. Only two patients had cutaneous vasculitis. Lupus-like skin lesions or lupus deterioration were not reported. 7 Strong agreement exists that all patients with autoimmune rheumatic diseases should be vaccinated against COVID-19. However, SARS-CoV-2 vaccination should be considered as a potential trigger of disease flares, especially in individuals with certain ANA constellations (e.g. anti-Ro/SSA and anti-La/SSB antibodies) predisposing for CLE. 

COVID-19 vaccines: modes of immune activation and future challenges

An update on the pathogenesis of cutaneous lupus erythematosus and its role in clinical practice

Prompt onset of Rowell's syndrome following the first BNT162b2 SARS-CoV-2 vaccination

Exacerbation of subacute cutaneous lupus erythematosus following vaccination with BNT162b2 mRNA vaccine

Transition of cutaneous into systemic lupus erythematosus following adenoviral vector based SARS-CoV-2 vaccination

Presence of an interferon signature in individuals who are anti-nuclear antibody positive lacking a systemic autoimmune rheumatic disease diagnosis

Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases