When the lung is at risk: diagnosis, manifestations, and complications of pulmonary sarcoidosis

Abstract

Sarcoidosis is a heterogeneous granulomatous disease of unknown origin; a subset of patients develops an advanced pulmonary disease phenotype, marked by progressive pulmonary fibrosis, airway involvement, and sarcoidosis-associated pulmonary hypertension, leading to high morbidity and mortality. In this review, we summarize key concepts in pulmonary sarcoidosis pathobiology, outline practical approaches to diagnosis and longitudinal monitoring, and highlight major pulmonary complications, including fibrotic sarcoidosis, chronic pulmonary aspergillosis, and sarcoidosis-associated pulmonary hypertension (SAPH). We also provide a pragmatic, stepwise treatment framework that incorporates corticosteroids and steroid-sparing immunosuppressants, escalation strategies for refractory disease, and supportive care. Recent data, including methotrexate as a potential first-line alternative to prednisone, and emerging antifibrotic and targeted immunomodulatory approaches, are discussed in the context of phenotype-driven decision-making. Future priorities include validated biomarkers that distinguish inflammation from fibrosis, improved risk stratification for progressive phenotypes, and trials designed around radiographic and clinical endotypes to optimize outcomes while minimizing treatment-related harm.