An 89-year-old woman with history of osteoporosis presented to the dermatology clinic with pruritic, crusted erosions on the scalp, face, chest, back, and upper extremities of 8-month duration (Figure 1a,b). These developed 5 days after her second dose of the SARS-CoV-2 mRNA vaccine. Fragile erythematous vesicles were observed on the trunk (Figure 1c), while mucous membranes were clear. Previous treatments included topical hydrocortisone 1% cream and clobetasol 0.05% cream, the latter which improved the lesions. Two 4-mm punch biopsies were obtained from vesicular lesions on the back (Figure 2). Histopathology revealed subcorneal vesicular dermatitis with acantholysis and scattered eosinophils. Direct immunofluorescence was positive for intercellular IgG deposits in the upper epidermis. The epidermis, dermis, and underlying vessels were negative for IgM, IgA, C3, C1q, and fibrinogen. Gram stain was negative for bacterial forms. Pemphigus foliaceus (PF) is a rare condition mediated by autoantibodies against desmoglein-1, which disrupt surface keratinocyte intercellular adhesions.1 PF is clinically characterized by scattered, crusted erosions in a seborrhoeic distribution that usually spare the mucous membranes; vesicles and bullae are generally not observed as they rupture easily.1 On histopathologic examination, subcorneal vesiculation with acantholysis and an eosinophilic infiltrate are commonly observed. Direct immunofluorescence classically shows intercellular IgG and C3 within the superficial layers of the epidermis, as was the case with our patient. Autoimmune bullous disorders have been reported in association with the SARS-CoV-2 mRNA vaccine, including PF2-4 and pemphigus vulgaris (PV).4-6 Acquired autoimmune blistering disease (AIBD), including PF and PV, have been described following vaccination with the SARS-CoV-2 vaccine. Here, we report a case of vaccine-associated PF following the second dose of the Pfizer/BioNtech vaccine. The patient was continued on high-potency topical corticosteroids for treatment of her scalp, trunk, and extremities, with clinical and symptomatic improvement. Ultimately, after several months she developed worsening of her disease, requiring an oral prednisone taper. The clinical differential diagnosis for PF includes PV, BP, bullous impetigo, cutaneous lupus erythematosus, IgA pemphigus, drug induced pemphigus, and subcorneal pustular dermatosis. Diagnosis of PF is contingent upon the clinical findings, histopathological analysis, and immunodermatology studies that could include perilesional skin for direct immunofluorescence, or serum for indirect immunofluorescence and ELISA testing.7 First-line treatment for PF may include topical or systemic corticosteroids, with more significant disease requiring intravenous rituximab or systemic steroid-sparing agents such as azathioprine, methotrexate, or mycophenolate mofetil as adjuvants.1 With respect to AIBD in association with the SARS-CoV-2 mRNA vaccine, multiple cases of PF and PV have been described (Table 1). Treatment included both topical and oral corticosteroids, as well as steroid-sparing agents including azathioprine and mycophenolate mofetil to mitigate the disease flares. In our case, the temporal onset of pruritus with rash and vaccination during the pandemic supports the association of PF with SARS-CoV-2 vaccination. Though a direct pathological relationship between the SARS-CoV-2 vaccine and the development of pemphigus has yet to be elucidated, there is typically a temporal association between the two events. In our case, the patient developed PF 5 days after her second dose of the vaccine. This is in keeping with previously described cases (Table 1), with all patients developing pemphigus within 1 month of vaccination and with an average time to onset of 13 days. Of note, the majority of patients (84.2%) did not have pre-existing pemphigus, as was the case in our patient. There are several proposed mechanisms for vaccine-induced autoimmune disease, including (1) molecular mimicry, whereby structural homology between pathogenic epitopes and human self-proteins leads to immune cross reactivity8; (2) epitope spread, wherein self-antigens released during a chronic inflammatory response promote an immune response to endogenous antigens and (3) bystander activation of immune cells.3 Additional mechanisms are under investigation. Treatment for vaccine-associated PF has thus far paralleled existing treatment algorithms for de novo pemphigus. Our patient initially responded to high-potency topical corticosteroids, which offers a potential treatment option for more limited disease. She eventually required a course of oral prednisone, which is common in other cases described in the literature (Table 1). As vaccinations and boosters for Covid-19 become part of our standard of care, dermatologists may play a critical role in determining the risk-benefit profile for our patients who are at risk of developing new or worsening vaccine-associated AIBD. Further study is needed to describe the natural history of these eruptions, best practices for treatment, and the balance of disease prevention on both personal and epidemiologic levels. Conception: Genevieve Kaunitz. Drafting manuscript: Nicollette Pepin. Critically revising manuscript for important intellectual content: Genevieve Kaunitz, Brian Hinds. Histology: Brian Hinds. Final approval of the version to be published: Nicollette Pepin, Genevieve Kaunitz, Brian Hinds. None. The authors declare no conflict of interest. The patient in this manuscript has given written informed consent for participation in the study and the use of their de-identified, anonymized, aggregated data and their case details (including photographs) for publication. Ethical Approval not applicable. Data sharing is not applicable to this article as no new data were created or analyzed in this study.
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Mar 25, 2024
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