Systemic Autoimmune Diseases in Patients with Hereditary Angioedema with C1 Inhibitor Deficiency: A Serbian Case Series

Hereditary angioedema (HAE) is an autosomal dominant disease due to mutations in the SERPING1 gene, resulting in the deficiency of C1 inhibitor (C1-INH) that plays a regulatory role in the complement system, the contact system, and the intrinsic coagulation cascade. Occasional reports and a few studies link HAE with autoimmune conditions with controversial results. Although several autoimmune disorders have been reported, the prevalence of defined autoimmune diseases still remains unknown. According to the data published so far, the prevalence of systemic lupus erythematosus (SLE) and other lupus-like disorders in patients with C1-INH-HAE is 1% to 2%.

We present a case series of five (four females, one male) patients with the manifestations of systemic autoimmune disease. We reviewed the medical records and laboratory findings and performed physical examination of patients with C1-INH-HAE for the manifestations of autoimmune diseases.

Our database included 94 patients (45.7% female) with C1-INH-HAE from 48 unrelated families. The majority of patients (92.5%) had C1-INH-HAE type I. Autoimmune systemic disease was diagnosed in five (5.3%) patients. Four female patients were affected by type I HAE, while a male was affected by type II HAE. For all patients, a disease-causing mutation was found in the SERPING1 gene. A high concentration of anti-Ro/SSA antibodies was found in the sera of all five patients.

The decreased function of C1-INH with subsequent dysregulation of the classical and lectin complement pathways may lead to increased co-occurrence of autoimmune diseases in patients with C1-INH-HAE. Based on our findings, the prevalence of autoimmune diseases in patients with C1-INH-HAE is higher than previously reported. All patients were symptomatic for HAE before developing autoimmune disease. The occurrence of autoimmune conditions in HAE patients may worsen the disease severity, and optimal treatment regimens remain to be defined.