Influenza Vaccine as a Potential Trigger for Urticarial Phase Bullous Pemphigoid: A Case Report

Introduction

Bullous pemphigoid (BP) is a chronic autoimmune subepidermal blistering condition with a strong predisposition for older adults.¹ Autoantibodies to hemidesmosome proteins BP180 (type XVII collagen) and BP230, major constituents of the dermal–epidermal junction, mediate this condition.² These antibodies (predominantly IgG) initiate the inflammatory cascade and complement activation, resulting in tense bullae and erythematous plaques.¹ Widespread tense blisters on normal or erythematous skin are the typical clinical presentation. In some cases, a prodromal phase of urticarial plaques and pruritus occurs, often under-recognized and delaying diagnosis.³ BP has multiple triggers, including medication (diuretics and antibiotics), infection, physical trauma, and vaccination.^4,5

Urticarial phase BP requires histopathological analysis, including immunofluorescence, to distinguish it from pruritic dermatoses.⁶ Vaccinations have been recognized to play a role in autoimmune disease pathogenesis, including BP, and both influenza and COVID 19 vaccines are potential triggers.^7,8 Although rare, post-vaccination BP cases indicate a complex interplay between immune activation and autoimmunity. Garcia Doval et al⁹ show an association between higher influenza vaccination rates and BP incidence, and systematic reviews likewise have reported BP after COVID 19 vaccination.^10,11 This report presents a case of urticarial phase BP after influenza vaccination to discuss diagnosis and treatment and highlight the association between vaccination and autoimmune susceptibility.

Case Presentation

A 58-year-old male patient presented with a two-month history of widespread pruritic, erythematous plaques. His medical history included well-controlled hypertension and diabetes mellitus managed with oral hypoglycemic agents (dipeptidyl peptidase-4 inhibitors). Additional comorbidities included dyslipidemia, bronchial asthma, and gastroesophageal reflux disease. He reported no recent changes in diet or exposure to new environmental allergens.

Symptoms began approximately two weeks following influenza vaccination, initially localized to the abdomen and back as intensely pruritic plaques. Over the following weeks, these lesions spread to the upper and lower extremities. The patient described the itching as debilitating, significantly disrupting his sleep and daily activities. Notably, no vesicles, bullae, mucosal, or erosions were observed during the early phase, contributing to diagnostic difficulty. Upon clinical examination, multiple well-defined annular plaques with erythematous borders and post-inflammatory hyperpigmentation were observed on the trunk, arms, and legs (Figure 1). Crucially, there was no indication of vesiculation, bullae development, mucosal involvement, or actual erosions such crusting, exudation, or epidermal denudation. Furthermore, there was no evidence of systemic involvement or secondary infection was detected.

Figure 1 (A and B) Multiple well-defined annular erythematous plaques over the trunk and post-inflammatory hyperpigmented patches.

A punch biopsy from the abdomen was performed two weeks after the presentation. The biopsy findings were consistent with the urticarial phase of BP, demonstrating a spongiotic epidermis and dense eosinophilic infiltration predominantly localized to the upper dermis. Direct immunofluorescence (DIF) revealed characteristic linear IgG and C3 deposition along the basement membrane zone, a hallmark of BP (Figure 2). These findings confirmed the autoimmune nature of the condition.

Figure 2 (A) Hematoxylin/eosin stain, Original Magnification 200X). (B) Direct Immunofluorescence, Original Magnification 400X. A Photomicrograph of a skin punch biopsy shows spongiosis and acanthosis, with an underlying eosinophilic infiltrate mainly around the basement membrane; direct immunofluorescence (DIF) study reveals linear positivity of IgG and C3.

The patient was initially prescribed oral prednisolone at 30 mg daily, which provided partial symptomatic relief. However, upon tapering the dose over five days, symptoms recurred, necessitating an increase to 40 mg daily with a slower tapering regimen. Topical corticosteroids, including clobetasol and mometasone, were applied to affected areas twice daily. Antihistamines (loratadine 10 mg daily) were added to control pruritus. Over six weeks, the patient showed marked improvement, with resolution of active lesions and reduced pruritus. Post-inflammatory hyperpigmentation persisted but was managed conservatively. Follow-up at three months revealed sustained remission with a maintenance dose of prednisolone at 5 mg daily and continued use of topical corticosteroids.

Discussion

The urticarial phase of BP is a diagnostic entity of critical significance because it may present with a nonspecific appearance resembling chronic urticaria and/or eczema. This is an under-recognized phase that can delay diagnosis, unnecessarily prolong drug treatment, and worsen patient discomfort. Because this phase lacks blisters—the hallmark of BP—it requires a high clinical suspicion, especially in patients over 50 or with a personal or family history of autoimmune disease. Although DIF remains necessary for immunopathological confirmation of urticarial phase BP and to distinguish it from other dermatological conditions,¹ DIF may not be essential for all patients with tense blisters if the diagnosis can be made with a skin biopsy.

Vaccinations such as influenza and COVID-19 are now considered risk factors for BP.^12,13 Molecular mimicry, which gives rise to a vaccine antigen similar to a self-antigen and induces an autoimmune response, is likely involved in the pathogenesis. Secondly, adjuvants and intense antigenic stimulation may also cause immune dysregulation, which could thus exacerbate preexisting immune predispositions. In addition, eosinophil-rich hypersensitivity reactions are evidence of a vaccine-triggered mechanism.¹⁴ When influenza vaccination and symptom onset occur in the same time frame, as in this case, this temporal relationship fits with what has been found in other studies.⁹

As shown in Table 1, there have been multiple documented cases where the vaccine acts as the trigger and have comparable clinical and histological characteristics. Baroero et al⁴ described a pediatric case of BP as a vaccine side effect induced by hepatitis B vaccination and attributed pathogenesis to robust immune responses. Fournier et al⁵ similarly described adult cases linked to influenza vaccines with similar histological findings. While the occurrence of BP post-COVID-19 vaccination has been recently reviewed,^10,11 a shared mechanism across vaccines has been elaborated (Table 1). According to Bar-Ilan et al, BP after immunization has also been observed in younger adults and newborns, despite the fact that the majority of reported instances involve elderly patients.⁶

Table 1 Comparison of This Case with Previous Case Reports

Awareness of vaccine‑triggered BP is essential for dermatologists and general practitioners. Early recognition, thorough evaluation, and appropriate diagnostics such as DIF can prevent disease progression and support effective management. Patients with new-onset urticarial plaques or pruritus should be asked about recent vaccinations, especially if they are at higher autoimmune risk. Although vaccines may rarely trigger BP, the danger posed by severe infections like influenza or COVID‑19 remains far greater. Thus, maintaining vaccination programs while equipping healthcare providers to manage uncommon complications is crucial. Further research should clarify how vaccines contribute to BP, identify genetic or immunologic susceptibilities, and evaluate vaccine safety in predisposed individuals. Exploring alternative formulations or adjuvants may also reduce rare adverse events.

Conclusion

This case highlights the importance of recognizing BP as a potential post‑vaccination manifestation. The patient’s presentation, supported by histopathology and immunofluorescence, underscores the need for awareness of this underreported form of BP, particularly in individuals predisposed to autoimmune disease who develop new pruritic plaques. The report emphasizes vaccination as a possible trigger and calls for further research into the immunopathogenesis of vaccine‑associated BP, including mechanisms such as molecular mimicry or immune dysregulation. Improved understanding will enhance diagnosis, management, and vaccine safety for at‑risk populations.