Granulomatous Interstitial Lung Disease (GL-ILD) in Common Variable Immune Deficiency (CVID)

Abstract

INTRODUCTION: Granulomatous interstitial lung disease (GL-ILD) develops in a subset of patients with common variable immunodeficiency (CVID) and is commonly confused with sarcoidosis. Little is known about the treatment options and their efficacies in GL-ILD. It is also unclear whether all patients with GL-ILD in the setting of CVID need treatment. CASE PRESENTATION: An 18-year-old Caucasian male presented with failure to thrive, splenomegaly, and poor exercise tolerance. His past medical history was significant for Evan's syndrome (autoimmune hemolytic anemia and thrombocytopenia) at age 11, which was treated with corticosteroids and rituximab. He later developed lymphadenopathy, poor exercise tolerance, and pan-hypogammaglobinemia and was diagnosed with Common Variable Immune Deficiency (CVID). Intravenous immune globulin was administered monthly. The patient underwent a pulmonology evaluation including complete pulmonary function tests, computed tomography (CT) of the chest with intravenous contrast, bronchoscopy with bronchoalveolar lavage, and lung biopsy. Pulmonary function tests showed moderate to severe restriction with decreased diffusion capacity. CT chest showed diffuse ground glass opacity with multiple semi-solid nodules bilaterally. Cylindrical bronchiectasis with diffuse mediastinal lymphadenopathy was also seen. Lung biopsy was suggestive of atypical follicular hyperplasia. Immunostaining studies were performed and the majority of lymphocytes stained positive for CD3. There was also a CD20 highlighted focal nodular collection. Molecular clonality was negative. The patient also showed an expansion of his T cell compartment in the peripheral circulation (CD3 T cell count: 4980 cells/mL; normal range: 865-3618 cells/mL), CD4 T cells: 2877 cells/mL, normal range: 497-2267 cells/mL), CD8 T cells: 1895 cells/mL, normal range : 243-1303 cells/mL). Advanced T cell phenotyping showed an expansion of activated CD4 T cells. The patient was treated with rituximab (375mg/m2) IV once a week for 4 weeks and daily azathioprine (Chase et al1).After 3 months of treatment, the patient is clinically improved based on symptoms and improved exercise tolerance. Repeat CT scans and full pulmonary function tests are planned when the patient returns for follow up in 6 months (Oct 2013). DISCUSSION: This is one of the first patients at our institution with GL-ILD in the setting of CVID who has been treated with combination chemotherapy. Most patients with GL-ILD associated with CVID show a progressive decline in their pulmonary status. This new modality of treatment offers some hope to decrease the progression and possible reversal of the lung inflammation in patients with CVID. CONCLUSIONS: Pulmonologists should be aware of the disease entity of GL-ILD in CVID and should consider treatment options for symptomatic patients.