Interstitial lung disease in patients with common variable immunodeficiency disorders: several different pathologies?

Abstract

Various reports of disease-related lung pathologies in common variable immunodeficiency disorder (CVID) patients have been published, with differing histological and high-resolution computed tomography (HRCT) findings. Data were extracted from the validated OxfordPrimary Immune Deficiencies Database (PID) database (1986-2016) on adult, sporadic CVID patients with suspected interstitial lung disease (ILD). Histology of lung biopsies was studied in relation to length of follow-up, clinical outcomes, HRCT findings and chest symptoms, to look for evidence for different pathological processes. Twenty-nine CVID patients with lung histology and/or radiological evidence of ILD were followed. After exclusions, lung biopsies from 16 patients were reanalysed for ILD. There were no well-formed granulomata, even though 10 patients had systemic, biopsy-proven granulomata in other organs. Lymphocytic infiltration without recognizable histological pattern was the most common finding, usually with another feature. On immunochemistry (n=5), lymphocytic infiltration was due to T cells (CD4 or CD8). Only one patient showed B cell follicles with germinal centres. Interstitial inflammation was common; only four of 11 such biopsies alsoshowed interstitial fibrosis. Outcomes were variable and not related to histology, suggesting possible different pathologies. The frequent nodules on HRCT were not correlated with histology, as there were no well-formed granulomata. Five patients were asymptomatic, so it is essential for all patients to undergo HRCT, and to biopsy if abnormal HRCT findings are seen. Internationally standardized pathology and immunochemical data are needed for longitudinal studies to determine the precise pathologies and prognoses in this severe complicationof CVIDs, so that appropriate therapies may be found.