From the Guidelines
The workup for sarcoidosis should begin with a thorough history and physical examination, focusing on multi-system symptoms and findings, as outlined in the 2020 American Thoracic Society clinical practice guideline 1.
Initial Evaluation
The initial evaluation should include:
- Chest X-ray to evaluate for bilateral hilar adenopathy
- Pulmonary function tests to assess for restrictive lung disease
- Complete blood count and comprehensive metabolic panel to evaluate for systemic involvement
- Serum calcium and angiotensin-converting enzyme (ACE) levels to support the diagnosis
Imaging Studies
High-resolution CT scan of the chest is essential to evaluate for characteristic hilar lymphadenopathy and parenchymal changes, as recommended by the 2020 guideline 1.
- Cardiac MRI or PET scan may be considered to assess for extrapulmonary involvement, particularly cardiac sarcoidosis, as suggested by the 2016 American Heart Association scientific statement 1.
Definitive Diagnosis
Definitive diagnosis typically requires tissue biopsy showing non-caseating granulomas, commonly obtained via:
- Bronchoscopy with transbronchial biopsy
- Endobronchial ultrasound-guided lymph node sampling
Additional Testing
Additional testing should be directed by clinical presentation and may include:
- Ophthalmologic examination to evaluate for uveitis or other ocular involvement
- Electrocardiogram to evaluate for cardiac involvement
- Brain MRI to evaluate for central nervous system involvement
- Specialized testing like the Kveim-Siltzbach test is rarely used today
Differential Diagnosis
Tuberculosis and other granulomatous diseases must be excluded through appropriate cultures and stains, as outlined in the 2020 guideline 1.
- Laboratory abnormalities like hypercalcemia, elevated alkaline phosphatase, and elevated ACE levels can support the diagnosis but are not specific to sarcoidosis.
- The workup should be comprehensive yet targeted to the patient's specific presentation, as sarcoidosis can affect virtually any organ system, with pulmonary involvement being most common.
From the Research
Work-up for Sarcoidosis
- The work-up for sarcoidosis typically involves a combination of clinical presentation, radiographic imaging, and histopathologic examination 2, 3.
- Chest radiographs are often used as an initial screening tool, but high-resolution computed tomographic (HRCT) scans are superior in assessing the extent of disease and identifying active inflammatory components versus fibrosis 2, 4.
- HRCT findings in pulmonary sarcoidosis may include micronodules, perilymphatic and bronchocentric distribution, perihilar opacities, and varying degrees of fibrosis 2, 4.
- Pulmonary function tests (PFTs) are also an essential part of the work-up, with forced vital capacity (FVC) being a simple and accurate parameter to reflect the impact of pulmonary sarcoidosis 3.
- Cardiopulmonary exercise testing can help understand the mechanism behind dyspnea of uncertain origin, while endoscopic transbronchial needle aspiration and bronchoalveolar lavage (BAL) may be used as additional diagnostic tools 3, 5.
- Hematologic parameters, such as the neutrophil-to-lymphocyte ratio (NLR), may also be useful in evaluating the prognosis of sarcoidosis patients 6.
- A tissue biopsy is often necessary to confirm the diagnosis, with transbronchial or ultrasound-guided biopsy of mediastinal lymph nodes providing a high diagnostic yield with low complication rates 5.
- The diagnosis of sarcoidosis is ultimately one of exclusion, and a careful history, physical examination, and follow-up are required to be fully confident of the diagnosis 5.