Phenotyping Sarcoidosis from a Pulmonary Perspective

RATIONALE: Sarcoidosis is known as a disease with high heterogeneity in clinical severity and inflammatory activity. On the basis of radiologic criteria, John Guyette Scadding developed a classification system, which is widely used, but is insufficient for clinical decision making. Therefore, biomarkers and genetic markers that predict outcome are urgently needed. OBJECTIVES: To obtain a classification system based on clinical criteria to evaluate biomarker and genetic markers. METHODS: We developed a protocol for classification of various disease courses (sarcoid clinical activity classification SCAC) based on clinical criteria with three categories: (1) whether the disease was acute or nonacute in onset, (2) whether treatment was required, and (3) whether there was need for long-term treatment. MEASUREMENTS AND MAIN RESULTS: In total, we evaluated 225 patients with sarcoidosis, applying both classification protocols retrospectively. The described SCAC protocol based on clinical criteria was retrospectively able to stratify patients according to disease outcome. The classes of patients with chronic disease differed significantly regarding pulmonary function test parameters and bronchoalveolar lavage fluid cell composition. Most interestingly, concentrations of soluble IL-2 receptor and neopterin were particularly increased in patients with acute disease who required long-term treatment. A moderate but significant increase in soluble IL-2 receptor and neopterin was also observed in patients with nonacute disease who needed long-term treatment. In contrast to the clinical classification system, the system based on radiologic criteria separated the patients with the need for long-term therapy insufficiently, but identified patients with advanced fibrotic remodeling. CONCLUSIONS: The described SCAC protocol is practicable and gives additional information not yet acquired by radiologic typing and seems suitable for studies evaluating genetic influence and biomarkers.