Use of combination chemotherapy for treatment of granulomatous and lymphocytic interstitial lung disease (GLILD) in patients with common variable immunodeficiency (CVID)

Abstract

Purpose: A subset of patients with common variable immunodeficiency (CVID) develops granulomatous and lymphocytic interstitial lung disease (GLILD), a restrictive lung disease associated with early mortality. The optimal therapy for GLILD is unknown. This study was undertaken to see if rituximab and azathioprine (combination chemotherapy) would improve pulmonary function and/or radiographic abnormalities in patients with CVID and GLILD.

Methods: A retrospective chart review of patients with CVID and GLILD who were treated with combination chemotherapy was performed. Complete pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) scans of the chest were done prior to therapy and >6 months later. HRCT scans of the chest were blinded, randomized, and scored independently (in pairs) by two radiologists. The differences between pre- and post-treatment HRCT scores and PFT parameters were analyzed.

Results: Seven patients with CVID and GLILD met inclusion criteria. Post-treatment increases were noted in both FEV1 (p=0.034) and FVC (p=0.043). HRCT scans of the chest demonstrated improvement in total score (p=0.018), pulmonary consolidations (p=0.041), ground-glass opacities (p=0.020) nodular opacities (p=0.024), and both the presence and extent of bronchial wall thickening (p=0.014, 0.026 respectively). No significant chemotherapy-related complications occurred.

Conclusions: Combination chemotherapy improved pulmonary function and decreased radiographic abnormalities in patients with CVID and GLILD.

Fig. 1

GLILD: Histologic findings. a Follicular bronchiolitis (thick arrow), with lymphocytic aggregates around an airway (thin arrow). (Lung, H&E, 100×, patient 2). b Focal lymphoid aggregates (thick arrow) within collagenized fibrous tissue (thin arrow). (Lung, H&E, 100×, patient 5). c Mediastinal biopsy reveals follicular hyperplasia with prominent germinal centers (thick arrow) and associated para-cortical hyperplasia. Interfollicular areas (thin arrow) are expanded. (Lymph node, H&E, 40×, patient 4)

Fig. 2

GLILD: Immunohistochemistry. a CD3 staining reveals frequent T cells. (Lung, 200×, patient 5). b CD20 staining demonstrates numerous B cells. (Lung, 200×, patient 5). c CD68 staining shows alveolar macrophages (thick arrow), and scattered dendritic cells (thin arrow) within lymphoid aggregates. (Lung, 200×, patient 5)

Fig. 3

High-resolution computed tomography (HRCT) scans: pre-/ post-treatment. a High resolution CT scan of the chest demonstrates typical features of GLILD prior to initiation of combination chemotherapy, including diffuse ground glass and nodular opacities. (Patient 7). b Improvement of parenchymal abnormalities 17 months post-combination chemotherapy. (Patient 7)

Fig. 4

HRCT scans of the chest, abdomen in a patient with CVID, GLILD and a mutation in TACI. a Pre-treatment HRCT scan of the chest demonstrates diffuse pulmonary ground glass and nodular opacities. (Patient 6). b Improvement in pulmonary parenchymal abnormalities post-chemotherapy (Patient 6). c Pre-treatment splenomegaly extends to the iliac crest. (Patient 6; note: maximal spleen length shown). d Marked decrease in splenomegaly post-chemotherapy. (Patient 6; note: maximal spleen length shown)