D2.368 - Concurrent Hereditary Angioedema Type I and Common Variable Immunodeficiency Presenting as Suspected Antibiotic Hypersensitivity: Case Report and Literature Review

Hereditary angioedema (HAE) and common variable immunodeficiency (CVID) are rare disorders with heterogeneous clinical presentations that pose significant diagnostic challenges. HAE is characterized by recurrent episodes of subcutaneous or submucosal edema affecting the skin, gastrointestinal tract, or airway, whereas CVID presents with variable immune dysfunction, recurrent infections, and impaired vaccine responses. The clinical manifestations of these conditions can mimic allergic reactions, drug hypersensitivity, mast cell disorders, autoimmune diseases, and other immunodeficiencies, making careful differential diagnosis essential.

We present an exceptionally rare case of a patient with concurrent HAE type I and CVID, initially evaluated for suspected antibiotic hypersensitivity, highlighting the complexity of diagnosis and therapeutic decision-making. We report the case of a 34-year-old man with a family history of HAE type I, but no family history of CVID that addressed to our clinic with a persistent, irritating cough lasting over one month, following an acute upper respiratory tract infection treated with amoxicillin/clavulanic acid. After completing the antibiotic course, he experienced a severe episode of cough accompanied by dysphonia and inspiratory dyspnea, followed by a brief loss of consciousness, which resulted in a minor car accident.

Laboratory findings confirmed both conditions, showing low C1 inhibitor levels and activity, markedly reduced serum concentrations of immunoglobulin G (including subclasses G1, G2, and G4), immunoglobulin A, and immunoglobulin M, along with a poor specific antibody response to vaccines. Skin allergy and oral provocation tests were negative, effectively ruling out antibiotic hypersensitivity. HLA genotyping revealed HLA-B*35:01 and B*44:01, with homozygosity for HLA-C*04:01, alleles previously associated with increased susceptibility to CVID. Using this case as a framework, we review the literature on coexisting HAE and CVID, examining clinical presentations, diagnostic approaches, biomarker profiles, and reported HLA associations.

We highlighted the critical importance of a comprehensive and personalized therapeutic approach, combining prophylactic and on-demand treatment for HAE with individualized immunoglobulin replacement for CVID.

Integrating detailed clinical assessment with immunologic and genetic testing is essential for the management of rare, complex disorders, and further studies are needed to clarify potential immunogenetic links between HAE and CVID.