Granulomatous lymphocytic interstitial lung disease (glild) associated with chronic lymphocytic leukemia

SESSION TITLE: Diffuse Lung Disease: Truly Unique Cases SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/11/2023 09:40 am - 10:25 am INTRODUCTION: Granulomatous lymphocytic interstitial lung disease (GLILD) is a rare form of interstitial lung disease (ILD) characterized pathologically by lymphocytic aggregates and granulomas and may be related to B-cell deficiency or dysregulation. GLILD is most commonly associated with common variable immunodeficiency (CVID) but can be seen in other primary and acquired immunodeficiencies. Patients with CVID-associated GLILD have increased mortality, with a median survival of 13.7 years, compared to 28.8 years in individuals without GLILD. The association between GLILD and other conditions is not well described. Treatment regimens are not well established but have generally included glucocorticoids and other immunosuppression, including rituximab or azathioprine. CASE PRESENTATION: A 75-year-old woman was found to have pulmonary nodules and infiltrates during workup for chronic lymphocytic leukemia (CLL). Her past medical history included chronic kidney disease, diabetes mellitus, and positive antinuclear and anti-centromere antibodies. Underlying autoimmune disease was suspected due these antibodies, as well as symptoms of dry eyes, dry mouth, and Raynaud's phenomenon of the hands. She had no history of chronic or recurrent infections.The patient underwent a CT-guided lung lesion biopsy that was inconclusive, demonstrating only mature lymphocytes, followed by an endobronchial ultrasound guided fine needle aspiration and transbronchial biopsies, which demonstrated lymphoid infiltration and granulomas. She then underwent video-assisted thoracoscopic surgery lung biopsy, which demonstrated lymphoid infiltration and granulomas. Notably, there was no evidence of lymphoma or infection in any of the samples.Post bronchoscopy treatment with corticosteroids (prednisone 20 mg daily) resulted in significant symptomatic improvement. After she was found to have low immunoglobulin levels, corticosteroids were stopped and intravenous immunoglobulin (IVIG) was initiated without further improvement, prompting resumption of prednisone at an outpatient follow-up appointment.Her treatment course is ongoing at time of this case report. DISCUSSION: While there are cases in the literature of GLILD associated with CVID, there is only one case series from 1988 reporting GLILD associated with CLL. In this case series, lung biopsies were performed on 9 patients with CLL and abnormal chest x-rays. 8 of these 9 patients had lymphocytic infiltration. A granulomatous reaction was found in 5 of the patients, with necrotizing granulomas in 2 of the samples. Other than this, there are no reports of the correlation between GLILD and CLL. This case represents a unique situation in which GLILD was found in a patient with CLL. The patient had suggestion of autoimmune condition but no clinical evidence of CVID. CONCLUSIONS: GLILD is a rare form of ILD most commonly found in patients with CVID and is associated with increased mortality. The pathophysiology is not clearly established, but is likely multifactorial, involving innate B-cell dysregulation and aberrant immune responses to antigens. Targets for therapy include corticosteroids and other immunosuppression, including rituximab. This patient did not have clinical evidence of CVID, but had been diagnosed with CLL and had features of autoimmune disease that did not meet criteria for a specific condition such as Sjögren syndrome. REFERENCE #1: Ng J, Wright K, Alvarez M, Hunninghake GM, Wesemann DR. Rituximab Monotherapy for Common Variable Immune Deficiency-Associated Granulomatous-Lymphocytic Interstitial Lung Disease. Chest. 2019;155(5):e117-e121. doi:https://doi.org/10.1016/j.chest.2019.01.034 REFERENCE #2: Cinetto F, Scarpa R, Carrabba M, et al. Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) in Common Variable Immunodeficiency (CVID): A Multicenter Retrospective Study of Patients From Italian PID Referral Centers. Frontiers in Immunology. 2021;12. doi:https://doi.org/10.3389/fimmu.2021.627423 REFERENCE #3: Rollins SD, Colby TV. Lung biopsy in chronic lymphocytic leukemia. Archives of Pathology & Laboratory Medicine. 1988;112(6):607-611. 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