Abstract Introduction Common variable immunodeficiency (CVID) describes disorders that are characterized by hypogammaglobulinemia and immune dysregulation. CVID can also cause various lung pathologies. Of these, granulomatous-lymphocytic interstitial lung disease (GLILD) is particularly important because of its association with significant morbidity and mortality. GLILD can be challenging to diagnose due to its heterogeneous presentation which can overlap with other pulmonary disorders, especially sarcoidosis. We present a case of GLILD initially misdiagnosed as sarcoidosis. Case Report A 64 year-old female presents to sarcoidosis clinic for a second opinion regarding sarcoidosis treatment. Sarcoidosis was diagnosed in 2019 after hospitalization with a severe pneumonia. Follow-up chest CT showed hilar lymphadenopathy and diffuse pulmonary nodules. Transbronchial biopsies revealed non-caseating granulomas with negative stains for infectious organisms. She was treated with prednisone and then methotrexate, but developed recurrent infections including pneumonias requiring hospitalization and three cases of ocular shingles. Her immunosuppression was intermittently held, then fully stopped in 2024. Pulmonary function testing (PFT) in 2025 showed worsening lung function, and a chest CT demonstrated worsening ground glass opacities and pulmonary nodules. Given this history, immunoglobulins were checked. IgA and IgM were undetectable, and IgG was markedly low. A PPSV-23 vaccine generated no antibody response. She was diagnosed with GLILD, and treatment with intravenous immunoglobulins has improved her pulmonary symptoms. Discussion GLILD is estimated to affect between 8-20% of patients with CVID and is associated with 50% reduction in life expectancy. This case highlights the challenges in diagnosing GLILD due to similarities with other diseases like sarcoidosis, hypersensitivity pneumonitis, and infectious granulomatous diseases. These diseases can have significant overlap in symptomatology, histology, and imaging findings. CVID should be suspected in patients with recurrent severe or atypical infections, and initial workup includes assessing for low immunoglobulin levels and poor vaccine antibody response. Immunoglobulin levels are low in CVID, but high in sarcoidosis. Diagnosis of GLILD is supported by a lymphocytic bronchoalveolar lavage, and imaging showing nodularity, ground-glass opacities, consolidation, or interlobular septal thickening in the lower lung and peribronchovascular areas. It is critically important to distinguish GLILD from other disorders because immunosuppression without treatment of underlying CVID substantially increases the risk of severe infectious complications. Treatment consists of immunoglobulin replacement and sometimes immunosuppression or stem cell transplant in patients who fail to respond to IVIG alone. The impact of treatment on mortality is unclear, but patients can show improvements in symptoms, PFTs, and imaging with immunosuppression. This abstract is funded by: none
Obrien et al. (Fri,) studied this question.