Common variable immunodeficiency without known genetic defect

Common variable immunodeficiency (CVID) without known genetic defect is a primary immunodeficiency disorder characterized by significantly reduced levels of immunoglobulins (IgG, often with low IgA and/or IgM) and impaired antibody responses to infections and vaccinations. This subtype represents the majority of CVID cases in which no specific causative genetic mutation has been identified, despite the condition likely having a complex genetic basis. CVID is the most common symptomatic primary immunodeficiency in adults. The disease primarily affects the immune system, leading to recurrent and often severe bacterial infections, particularly of the respiratory tract (sinusitis, bronchitis, pneumonia) and gastrointestinal tract. Over time, recurrent lung infections can lead to bronchiectasis and chronic lung disease. Many patients also develop non-infectious complications, including autoimmune disorders (especially autoimmune cytopenias such as immune thrombocytopenia and autoimmune hemolytic anemia), granulomatous disease affecting the lungs, liver, or spleen, lymphoid hyperplasia, splenomegaly, and an increased risk of lymphoma and other malignancies. Gastrointestinal manifestations, including chronic diarrhea, malabsorption, and inflammatory bowel-like disease, are also common. The mainstay of treatment is lifelong immunoglobulin replacement therapy (administered intravenously or subcutaneously), which significantly reduces the frequency and severity of infections. Prophylactic antibiotics may be used in some patients. Autoimmune and inflammatory complications are managed with immunosuppressive agents, corticosteroids, or targeted therapies as needed. Regular monitoring for complications, including pulmonary function testing and cancer surveillance, is essential. Early diagnosis and appropriate management have substantially improved outcomes and quality of life for affected individuals.

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