Sex: M
Vaccine: COVID19
Symptoms: Condition aggravated, Dermatitis bullous, Immunology test, Investigation, SARS-CoV-2 test
Clinical narrative: Autoimmune bullous disorder flares following severe acute respiratory syndrome coronavirus 2 vaccination; Autoimmune bullous disorder flares following severe acute respiratory syndrome coronavirus 2 vaccination; The initial case was missing the following minimum criteria: [Unspecified product]. Upon receipt of follow-up information on [29Sep2023], this case now contains all required information to be considered valid.  This is a literature report.  An 88-year-old male with history of bullous pemphigoid (BP) presented with diffuse pruritus approximately 24 h after receiving the second dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine. He was diagnosed in 2016 by indirect Immunofluorescence (IIF) with a positive enzyme-linked immunosorbent assay (ELISA) for BP230 and was moderately well controlled on 5-10 mg of prednisone daily and topical triamcinolone acetonide 0.1% cream as needed. IIF/ELISA results at diagnosis were ELISA (2020): BP180, negative; BP230 15.8 units. He had previously declined treatment with steroid-sparing immunosuppressive agents including mycophenolate mofetil and methotrexate. Since the onset of the pandemic, the patient had never displayed symptoms concerning for COVID-19 nor been tested. Examination demonstrated numerous erythematous, urticarial papules and confluent plaques on the torso and extremities, with admixed tense vesicles and erosions. IIF/ELISA results with current flare were ELISA: BP180, negative; BP230 10 units IIF: 1:10, 240 BMZ (basement membrane zone) IgG (ME (monkey esophagus)), 1:2,560 (roof, HSS (human split skin)). After discussion of treatment options, the patient was prescribed an oral prednisone taper, starting at 40 mg and reduced by 10 mg weekly, until returning to his baseline 5-10 mg daily. After 5 weeks, his pruritus completely resolved, and his skin lesions were well healed. SARS-CoV-2 infection status was negative. Reference ranges: IIF: positive: > 1:10 (ME, IHS, HSS); borderline/indeterminate: 1:10 BMZ IgG (ME, HSS), 1:10 cell surface IgG4 (ME and IHS); negative: < 1:10 (ME, HIS, HSS); ELISA: BP180 and BP230: > 9 units; Dsg-1: > 20 units; borderline/indeterminate: Dsg-1: 9-20 units; negative: Dsg-1: < 9 units.  Discussion: Autoimmune bullous disorder (ABD) may precipitate from a variety of mediators that are often challenging to definitively pinpoint. Given the dysregulation of the immune system in BP and PF, there is concern for the potential to exacerbate disease activity after inducing an immune response with administration of the SARS-CoV-2 vaccine. In a single-institution academic dermatology clinic, we identified three patients with ABD who flared after receiving the COVID vaccine. Of the cases identified, two opted to use systemic steroids, while topical steroid application was sufficient for the remaining patient. All three patients significantly improved or returned to baseline by their follow-up appointments ranging between 5 weeks and 10 weeks after the initial visit. Subsequently, using a deidentified medical record search query with ICD codes L10.X, L12.X, and L13.X, we identified 160 ± 3 patients (the search query program outputs inexact numbers to maintain confidentiality in cases of rare disease that may make the data identifiable) who were seen in our dermatology clinics between 1 January2021 and 20 July 2021; no additional cases of ABD flare after vaccination were identified. Individual data, including the fraction of 160 ± 3 patients who received COVID-19 vaccination, are unknown. Identifying a potential causal relationship between vaccination and disease flare is important for appropriately assessing risk and counseling patients. Notably, in case 3, a potential relapse in disease due to discontinuation of rituximab is less likely given that it was stopped in June2019, while her PF flare occurred shortly after vaccination in March of 2021. This observation supports the hypothesis that her increased PF activity was vaccine related, highlighting a potential association between the vaccine and the perturbation of disease. This study was also limited by the timeline of antibody titer testing, as disease activity levels may have measured higher if antibody titers were tested closer to onset of symptoms rather than during or after treatment of the flare. Importantly, all cases of pemphigoid and pemphigus eruptions following vaccination were readily treated and patients improved without the need for prolonged changes in baseline medications. Prompt amelioration of symptoms suggests the unintended vaccine response is mild and transient and is corroborated by low IIF and disease-specific ELISA antibody titers in two of the cases. The precise mechanism by which the vaccine may have exacerbated BP or PF in these patients has not been elucidated. It is possible that the intentional immune response triggered to induce immunity to SARS-CoV-2 may also upregulate inflammatory mediators known to be elevated during an acute COVID-19 illness, including interleukin (IL)-1B, IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, CXCL10, and CCL2, leading to changes in T-regulatory (CD4+, CD25+ , FOXP3) cells. Of these inflammatory molecules, IL-1B, IL-6, IL-8, and IL-10 are also upregulated in ABD.  A previous study demonstrates no significant change in autoantibody titers following booster vaccination for SARS-CoV-2, though whether or not the patients had a flare of their disease was not reported. Such widespread activation of the immune system, coupled with activation of overlapping inflammatory pathways, may provoke preexisting ABD through increased autoantibody production. Recent reports have described flares of hereditary bullous disorders and acquired ABD following the administration of the COVID-19 vaccination. Alternatively, evidence suggests that anti-SARS-CoV-2 antibodies do not directly cross-react pemphigus or pemphigoid autoantibodies, though whether SARS-CoV-2 infection indirectly augments the immune system, therein precipitating ABD and other autoimmunity, remains unclear. This study is therefore inherently limited by the lack of laboratory data for these patients, as it pertains to autoantibody titer levels during their disease flare. Further studies are needed to elucidate autoantibody titer changes in the context of possible vaccine-related ABD activity. Importantly, the potential adverse event following immunization (AEFI) should be described as rare and tractable, and clinicians may safely and confidently encourage patients to receive COVID-19 vaccination.; Sender's Comments: Based on the limited information provided in this case, a contributory role of the suspect product BNT162b2 (COMIRNATY) to the reported events cannot be excluded. Events are considered Related conservatively. There is very limited information provided in this report. Case will be reassessed upon receipt of additional information.,Linked Report(s) : US-PFIZER INC-PV202300163568 Same article/ drug/event and different patient;