Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline

Abstract

Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure.Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability.Results: The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and 1 best practice statement. All evidence was very low quality.Conclusions: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available.

Keywords: cardiac sarcoidosis; endobronchial ultrasound biopsy; granuloma; pulmonary hypertension; rare lung disease.

Figure 1.

Comparison of pulmonary sarcoidosis granuloma histology to other granulomatous lung diseases. (A) Typical sarcoidosis histology with well-formed granulomas comprised of macrophage aggregates (G) and featuring multinucleated giant cells (white arrows, inset), with minimal surrounding lymphocytic inflammation (L). (B) Hypersensitivity pneumonitis featuring smaller granulomas (G) with more extensive surrounding lymphocytic alveolitis (L). (C) A large acellular necrotizing granuloma (NG) caused by pulmonary Histoplasma capsulatum infection.

Figure 2.

Typical ECG and radiographic features of cardiac sarcoidosis. (A) ECG demonstrates first-degree A-V block (P-R interval, 200 ms) and right bundle branch block. (B) Cardiac magnetic resonance showing multifocal abnormal late gadolinium enhancement involving the mid- to epicardial lateral ventricular wall (arrowheads). (C) Cardiac positron emission tomography demonstrates intense hypermetabolic uptake of ¹⁸F-fluorodeoxyglucose in the lateral left ventricular wall (arrow).

Figure 3.

Schematic of recommended diagnostic algorithm. The figure outlines a general approach to the diagnosis of sarcoidosis and refers to tables presented with this article. PICO = problem, intervention, comparison, outcome question format.