Granulomatous-lymphocytic interstitial lung disease (GLILD) is a noninfectious interstitial lung disorder characterized by granulomatous inflammation and lymphoid proliferation. It is most frequently identified in individuals with common variable immunodeficiency (CVID) and has been reported less often in other primary immunodeficiencies. Characteristic histopathologic patterns include non-necrotizing granulomas, lymphocytic interstitial pneumonia, follicular bronchiolitis, and lymphoid hyperplasia. Accurate diagnosis requires multidisciplinary integration of clinical, radiologic, and pathological data to distinguish GLILD from other granulomatous or lymphoproliferative interstitial lung diseases.
A 20-year-old man with isolated IgA deficiency developed GLILD following a long-standing history of immune dysregulation. His initial presentation at age nine included severe thrombocytopenia and a direct Coombs-positive test without hemolysis, consistent with immune thrombocytopenia. He subsequently developed neutropenia and experienced significant infectious morbidity, including recurrent otitis media, recurrent sinusitis, dental abscesses, skin and soft-tissue infections, and multiple pneumonias. Immunologic studies consistently showed normal IgG and IgM levels, absence of IgA, intact T cell subsets, and repeatedly negative evaluations for autoimmune lymphoproliferative syndrome (ALPS).
He underwent extensive immunomodulatory therapy—including intravenous immunoglobulin (IVIG), corticosteroids, granulocyte colony-stimulating factor, mycophenolate mofetil (MMF), rituximab, eltrombopag, and sirolimus—with minimal sustained benefit. Splenectomy was performed due to massive splenomegaly and transfusion dependence; however, he presented a year later with widespread lymphadenopathy. Progressive respiratory symptoms and evolving radiographic abnormalities led to a lung biopsy, which demonstrated follicular bronchiolitis, a pattern compatible with GLILD-associated pathology. Multidisciplinary review of clinical, imaging, and histologic findings supported a diagnosis of GLILD. He is currently being treated with rituximab in combination with MMF.
This case highlights the diagnostic and therapeutic challenges encountered when GLILD develops in the context of a non-CVID primary immunodeficiency. As current understanding of GLILD is largely shaped by studies of CVID cohorts, evidence to guide diagnosis and management in non-CVID immune phenotypes remains limited. The patient’s course underscores the need for heightened clinical awareness of GLILD and supports the development of tailored diagnostic pathways and individualized immunomodulatory strategies outside the context of CVID.
