Concurrent hereditary angioedema type I and common variable immunodeficiency presenting as suspected antibiotic...

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. Here, 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. 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. The genetic analysis identified a heterozygous pathogenic SERPING1 variant, c.498C > A (p.Asn166Lys), previously reported in 1 Romanian and 1 Czech case, confirming the diagnosis of HAE. Human leukocyte antigen (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. The review highlights 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.