D1.357 - Atypical case of common variable immune deficiency with granulomatous lymphocytic interstitial lung disease

Background: Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency, characterized by hypogammaglobulinemia and heterogeneous clinical presentation. A significant subset develops interstitial lung disease, particularly Granulomatous–lymphocytic interstitial lung disease (GLILD), a rare non-infectious complication with limited evidence guiding diagnosis and management. We report an unusual case of CVID with GLILD in an elderly patient with minimal symptoms and no treatment.

Case presentation: A 76-year-old woman with a decades-long history of mild productive cough and otherwise minimal infections was evaluated after a pulmonary nodule was detected on chest imaging (Figure 1). Surgical enucleation by video-assisted thoracoscopic surgery revealed necrotizing granulomatous inflammation with lymphocytic infiltration. Subsequent evaluation demonstrated profoundly decreased serum immunoglobulins (IgG <3,2 g/l, IgM <0.25 g/l, IgA <0.25 g/l) and poor vaccine antibody response, with persistent mild lymphocytosis. Imaging and laboratory workup suggested granulomatous lung disease consistent with GLILD in the context of CVID. Immunoglobulin replacement therapy and further immunologic investigations were recommended but declined by the patient. Despite persistently severe hypogammaglobulinemia and absence of substitution therapy, the patient has remained clinically stable, physically active, and largely asymptomatic over follow-up (being 84 years old), reporting only occasional cough.

Discussion: CVID is typically diagnosed in adulthood and often presents with recurrent infections, autoimmunity, or lymphoproliferative disease. GLILD is associated with increased morbidity and mortality and is usually evaluated with chest CT, pulmonary function testing, bronchoscopy, and lung biopsy. Management commonly includes immunoglobulin replacement and, when indicated, immunosuppressive therapy. However, clinical heterogeneity is substantial, and rare patients may demonstrate indolent disease courses with minimal symptoms.

Conclusion: This case highlights an atypical presentation of CVID with GLILD marked by late recognition, profound hypogammaglobulinemia, and unexpectedly benign clinical evolution without therapy. Individualized management and further studies are needed to better define prognosis and treatment strategies in uncommon phenotypes of CVID-associated GLILD.