A Rare Clinical Association of Type I Hereditary Angioedema and Acquired Epidermolysis Bullosa: A Case Report

Introduction. Both hereditary angioedema (HAE) and acquired epidermolysis bullosa (AEB) are extremely rare disorders, and their coexistence in a single patient is unique. Awareness of this exceptional association can aid in timely diagnosis and guide safe, individualized treatment strategies. Case Report. We present a case of a 38-year-old female with co-occurring type I HAE, associated with a heterozygous SERPING1 variant c.425T>C (p.Leu142Ser) of uncertain significance previously reported in individuals with angioedema, and a rare autoimmune subepidermal blistering disorder mediated by autoantibodies against type VII collagen – AEB. Since adolescence, the patient had experienced recurrent limb edema and atypical dermatological manifestations, including macules, vesicles, and bullae, predominantly in areas exposed to mechanical stress and frequently resulting in scar formation. The disease course later progressed with an episode of acute laryngeal edema following a dental procedure. Laboratory evaluation confirmed a critically low level of C1-inhibitor and an almost complete depletion of C4 in plasma, indicating chronic activation of the classical complement pathway. Given the frequent exacerbations and severe clinical course, long-term prophylactic therapy with intravenous C1-INH (1,000 IU twice weekly) was initiated. This treatment regimen led to sustained clinical remission, resolution of angioedema episodes, notable improvement in dermatologic symptoms of AEB, and a substantial enhancement in overall quality of life. Conclusions. The coexistence of HAE and AEB is exceptionally rare, with no prior cases identified. Complement dysregulation may link these conditions, underscoring the importance of considering autoimmune blistering disorders in HAE patients with atypical skin manifestations. This case highlights a potential role for complement-targeted therapies, warranting further clinical investigation.