What is the best diagnostic test for sarcoidosis?

From the Guidelines

The best test for diagnosing sarcoidosis is a tissue biopsy showing non-caseating granulomas, typically obtained from the most accessible involved organ, such as endobronchial or skin biopsy, as stated in the european position paper on rhinosinusitis and nasal polyps 2020 1.

Key Points to Consider

• A positive biopsy is the definitive test for sarcoidosis, with the classic appearance of non-caseating granulomas composed of epithelioid cells, giant cells, and lymphocytes 1.
• Blood tests, such as serum angiotensin-converting enzyme (ACE) levels, may be elevated in sarcoidosis but are not diagnostic, with a sensitivity of 60% and specificity of 70% 1.
• Other tests, such as pulmonary function tests, perfusion studies, and bronchoalveolar lavage, may support the diagnosis but are not definitive.
• Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a less invasive option with good diagnostic yield, particularly in patients with mediastinal and/or hilar adenopathy, with a pooled diagnostic accuracy of 79% 1.

Diagnostic Approach

• Patients suspected of having sarcoidosis should undergo a thorough clinical evaluation, including chest imaging and laboratory studies.
• A tissue biopsy should be obtained from the most accessible involved organ, with endobronchial or skin biopsy being common approaches.
• EBUS-TBNA may be considered as a less invasive option, particularly in patients with mediastinal and/or hilar adenopathy.
• The diagnosis of sarcoidosis requires correlation of clinical, radiological, and histopathological findings, as well as exclusion of other granulomatous diseases.
• The use of serum soluble interleukin-2 (sIL-2R), angiotensin converting enzyme (ACE) and lysozyme levels can be useful tools in the diagnosis of sarcoidosis and for evaluating disease activity, in addition to fluorodeoxyglucose-positron emission tomography (FDG-PET) 1.

From the Research

Diagnostic Approaches for Sarcoidosis

• The diagnosis of sarcoidosis is based on a combination of clinical presentation, histologic findings, and exclusion of alternative diseases 2.
• There is no single reliable diagnostic test for sarcoidosis, and diagnosis relies on three criteria: compatible clinical and radiologic presentation, pathologic evidence of noncaseating granulomas, and exclusion of other diseases with similar findings 3.
• A Sarcoidosis Diagnostic Score (SDS) has been developed to summarize the clinical features of patients with possible sarcoidosis, with a sensitivity of 90.6% and specificity of 88.5% for an SDS clinical score ≥ 3 4.

Imaging and Histopathologic Features

• High-resolution computed tomographic (HRCT) scans are superior to chest X-rays in assessing the extent of disease, and some CT features may discriminate an active inflammatory component from fibrosis 5.
• Typical findings on HRCT include micronodules, perilymphatic and bronchocentric distribution, perihilar opacities, and varying degrees of fibrosis 5.
• Histopathological examination is essential for verifying the diagnosis of sarcoidosis, with typical findings of noncaseating granulomas 6, 3.

Clinical Features and Diagnostic Certainty

• The presence of specific clinical features, especially multiorgan involvement, can enhance the diagnostic certainty of sarcoidosis 4, 2.
• Clinical features such as persistent dry cough, eye and skin manifestations, weight loss, fatigue, night sweats, and erythema nodosum are commonly associated with sarcoidosis 6.
• The diagnostic approach to sarcoidosis requires knowledge of the varied presentations of the disease and other alternative conditions, as well as histologic examination of an affected tissue in most instances 2.