key: cord-0764761-4ya9w0ay authors: Young, J.; Mercieca, L.; Ceci, M.; Pisani, D.; Betts, A.; Boffa, M.J. title: A case of bullous pemphigoid after the SARS‐CoV‐2 mRNA vaccine date: 2021-10-05 journal: J Eur Acad Dermatol Venereol DOI: 10.1111/jdv.17676 sha: d727ada1fe3b82ac5a6697e905143e6369cd0025 doc_id: 764761 cord_uid: 4ya9w0ay A 68-year-old, otherwise healthy, man-presented-to-our-dermatology department in late April 2021 with a history-of-a-blistering-eruption-which commenced three days after his first dose of the Pfizer BioNTech COVID-19 vaccine (2nd March 2021) and worsened after the second dose given three weeks later. The blisters-first-appeared-over-the sternal area and were accompanied by intense, generalised-pruritus-which-started-a-day before the blisters appeared. However, the blisters continued to increase in number and erupted over the right side of the chest and upper back particularly after the patient received the second dose of the Pfizer vaccine. At presentation to dermatology, the patient had several healing crusted areas scattered over the right chest and back but no intact blisters and was prescribed clobetasol propionate ointment and an emollient cream. Routine blood tests, epidermal basal membrane antibodies and prickle cell desmosomes antibodies were normal and negative respectively. At follow-up, 2 weeks later, there was a recently ruptured blister arising in an area of urticated erythema over his back (Fig 1a, b) and an ulcer situated on the left buccal mucosa (Fig 1c) . A biopsy taken from one of the truncal lesions revealed subepidermal blistering associated with a superficial dermal inflammatory infiltrate composed of eosinophils and hemosiderophages. The roof of the bulla consisted of thinned, viable epidermis whilst within the bulla, erythrocytes and scattered inflammatory cells including eosinophils were seen (Fig 1d) . Direct immunofluorescence showed linear basal deposition of IgG and C3 (Fig 1e, f) . All these findings were in keeping with a diagnosis of bullous pemphigoid (BP). He was advised to continue the previously prescribed topical treatment, and at follow-up 3 months after the first dose of COVID-19 vaccine, he was found to be completely asymptomatic with no new blisters present and only residual post-inflammatory hyperpigmentation present at previously affected sites. This case is intriguing since to our knowledge it is the first reported case of BP related to the SARS-CoV-2 mRNA vaccine. We acknowledge that a possible differential diagnosis for this case would be epidermolysis bullosa acquisita (EBA). However, the histological features, particularly the eosinophilic-predominant infiltrate, are not typical of EBA and are more in keeping with BP. A large number of cases of BP have been reported following other vaccines including the pneumococcal vaccine 1 and influenza vaccine. 2 However, the pathogenesis is not clear. It has been hypothesized that vaccine-induced inflammation could lead to disruption of the basement membrane architecture with subsequent generation of anti-basement membrane-specific antibodies, and such vaccines may also increase the antigenicity of BP antigens. However, there are no known similarities between the basement membrane protein and the implicated vaccines; therefore, it is unlikely that the vaccine coupled with its respective antibody response is the sole cause of this phenomenon. In fact, it has also been postulated that these vaccines may precipitate a heightened immune response in individuals having either subclinical BP or immunological deposition. 2 Interestingly, vaccine-induced-adult BP hasbeen seen mainly in the elderly. This in part may be explained by the phenomenon of immunosenescence which occurs as a result of age-induced thymic atrophy and can lead to autoimmune disease via breakdown of immune tolerance. 1 On further review of the literature, several articles document other cutaneous manifestations associated with the COVID-19 vaccines (Table 1 ). [3] [4] [5] [6] [7] [8] [9] In a large-scale study by McMahon et al., out of the 414 subjects, no cases of vaccine-induced BP were reported. In fact, the commonest cutaneous manifestations excluding local site reactions were urticaria, morbilliform drug eruptions and erythromelalgia. 10 Although it is possible that the appearance of BP after COVID vaccination in our patient was coincidental, the onset of symptoms so soon after the first dose, worsening after the second dose, complete resolution within a few weeks with only topical treatment, and no subsequent recurrence suggest a true association in this case. Case of pemphigoid with immunoglobulin G antibodies to BP180 C-terminal domain and laminin-c1 (p200) developed after pneumococcal vaccination Does influenza vaccination induce bullous pemphigoid? a report of four cases Persistent maculopapular rash after the first dose of Pfizer-BioNTech COVID-19 vaccine Pityriasis rosealike eruptions following vaccination with BNT162b2 mRNA COVID-19 Covid-19 vaccine induced Steven-Johnson syndrome Morbilliform rash after administration of Pfizer-BioNTech COVID-19 mRNA vaccine Widespread annular eruption after Ad26.COV2.S COVID-19 vaccine Lichen planus arising after COVID-19 vaccination SARS-CoV-2 mRNA vaccine-associated fixed drug eruption Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registrybased study of 414 cases The patient gave written informed consent to the publication of his case details. None. None. The data that support the findings of this study are available from the corresponding author upon reasonable request.