Sex: F
Vaccine: COVID19
Symptoms: Autoimmune disorder, Dermatitis bullous, Histology, Immunology test, Investigation
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; This is a literature report for the following literature source(s):  A 50-year-old female with a history of PF presented with a few itchy, crusted erosions 1 week after receiving her first dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine, which increased slightly following her second vaccination. Vaccines were administered in March 2021 and April 2021, respectively. Initial diagnosis of PF was confirmed by histopathology, including consistent DIF, in 2010. She was first managed with prednisone due to intolerance of azathioprine and mycophenolate mofetil. In 2019, she demonstrated a positive IIF for cell surface immunoglobulin G4 (IgG4) on monkey esophagus(titer >1:40) and intact human skin (titer > 1:40), and positive desmoglein-1 autoantibodies (84 units; positive > 20 units), and was subsequently treated with rituximab 1000 mg every 2 weeks for two doses in June 2019 with an excellent clinical and serologic response; erosions resolved and her IIF and ELISA were negative. Following discontinuation of prednisone in October 2019, she was maintained off treatment. Examination revealed four superficial, crusted erosions on the posterior neck, torso, and upper extremities. Repeat IIF for cell surface IgG4 was negative on monkey esophagus and borderline on intact human skin (titer 1:10); desmoglein-1 autoantibodies were slightly elevated (23 units; positive > 20 units). The patient started application of augmented betamethasone dipropionate 0.05% ointment but eventually required a low-dose oral prednisone taper (10 mg and reduced by 2.5 mg weekly) due to persistent erosions. Her symptoms returned to baseline by her follow-up visit 10 weeks later. Of note, patient 3 did have a successful immune response after vaccination as demonstrated by a positive spike receptor-binding domain (RBD) protein antibody titer.  Discussion: 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 was 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 January 2021 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 June 2019, 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 was mild and transient and was 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)-1ß, 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 [13]. Of these inflammatory molecules, IL-1ß, IL-6, IL-8, and IL-10 are also upregulated in ABD. A previous study by Solimani et al. 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. Conclusion: The author presents three cases of mild flares of preexisting ABD occurring shortly after receiving the COVID-19 vaccination. Clinicians should counsel patients as to the possible unintended effects of vaccinating for SARS-CoV-2 and how these effects may exacerbate preexisting BP and PF. Individuals with preexisting ABD and other autoimmune disease have been cautiously considered since the beginning of the pandemic, and the evidence presented here highlights the treatability of any AEFI resulting from the COVID-19 vaccine for this subpopulation of people with autoimmune disease.; Sender's Comments: Based on the available information in the case, an association between the reported events 'Flare up of autoimmune bullous disorder/ bullous dermatitis' and the suspect drug cannot be ruled out due to an established temporal association.The impact of this report on the benefit-risk profile of the Pfizer product and on the conduct of the study is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to regulatory authorities, Ethics Committees, and Investigators, as appropriate.,Linked Report(s) : US-PFIZER INC-PV202300163081 Same article/ drug/event and different patient;