Sarcoidosis Workup

Updated: Feb 09, 2022
  • Author: Nader Kamangar, MD, FACP, FCCP, FCCM; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Laboratory Studies

Serum markers such as serum amyloid A (SAA), soluble interleukin-2 receptor (sIL-2R), lysozyme, angiotensin-converting enzyme (ACE), and the glycoprotein KL-6 have been reported to be markers of sarcoidosis. [43]

Hypercalcemia or hypercalciuria may occur (noncaseating granulomas [NCGs] secrete 1,25 vitamin D). Hypercalcemia is seen in about 10-13% of patients, whereas hypercalciuria is 3 times more common.

Elevated 1, 25-dihydroxyvitamin D levels are associated with protracted treatment in sarcoidosis. In one study, serum 1, 25-dihydroxyvitamin D levels were associated with patients requiring repeated regimens of systemic immunosuppressive therapy or longer than 1 year of therapy. The majority (71%) of the patients with levels higher than 51 pg/mL required long-term immunosuppressive therapy. [44]

An elevated alkaline phosphatase level could suggest hepatic involvement. One study has shown that the severity of liver function test abnormalities is significantly related with the degree of fibrosis and extensiveness of the granulomatous inflammation in sarcoidosis. [45]

ACE levels may be elevated. NCGs secrete ACE, which may function as a cytokine. Serum ACE levels are elevated in 60% of patients at the time of diagnosis. Serum ACE levels may correlate with total body granuloma load. Levels may be increased in fluid from bronchoalveolar lavage or in cerebrospinal fluid. Sensitivity and specificity as a diagnostic test is limited (60% and 70%, respectively). There is no clear prognostic value. Serum ACE levels may decline in response to therapy. Decisions on treatment should not be based on the ACE level alone.


Imaging Studies

A chest radiograph is central to evaluation. [46]

Air trapping is a common feature in sarcoidosis that can be supported with imaging studies and correlates with evidence of small airways disease on pulmonary function testing. [47]

Routine chest CT scanning adds little to diagnosis. High-resolution CT (HRCT) scanning of the chest may identify active alveolitis or fibrosis and correlates with yield of biopsy.

Some studies have suggested that whole body F(18)-fluorodeoxyglucose positron emission tomography (FDG-PET) scanning appears to be of additional value to assess inflammatory activity in patients with persistent symptoms in the absence of signs of serological inflammatory activity and to detect extrathoracic lesions. [48] Whole-body FDG-PET scanning is of value in identifying occult and reversible granulomas in patients with sarcoidosis. [49, 50]

Prior to the ease and availability of bronchoscopy, gallium scanning was occasionally used as a diagnostic test. It may still be helpful in a subset of patients in whom the clinical picture remains confusing despite histologic evidence of noncaseating granulomas (NCGs) (eg, differentiating chronic hypersensitivity pneumonitis from sarcoidosis).


Other Tests

Pulmonary function tests and a carbon monoxide diffusion capacity test of the lungs for carbon monoxide (DLCO) may be performed. They are used routinely in evaluation and follow-up. The most common abnormality is an isolated decrease in DLCO. A restrictive pattern is seen in patients with more advanced pulmonary disease. Approximately 15-20% of patients have obstruction.

Patients with DLCO of less than 60% predicted and oxygen desaturation of less than 90% on the 6-minute walk test have a high likelihood of pulmonary hypertension and should undergo further evaluation for the presence of this disorder. [51] In one study, patients with a saturation of less than 90% during a 6-minute walk test were 12 times more likely to have pulmonary hypertension. [51]

Cardiopulmonary exercise testing is a sensitive test for identifying and quantifying the extent of pulmonary involvement. Cardiopulmonary exercise testing also may suggest cardiac involvement that otherwise is not evident.

Attenuated heart rate recovery after exercise is thought to be a marker of reduced parasympathetic activity. Impaired heart rate recovery during the first minute following exercise has been shown to be an independent predictor for cardiovascular and all-cause mortality. [1, 52] Considering its prognostic significance, the heart rate recovery index may have clinical use in identifying patients with sarcoidosis who are at high risk for ventricular arrhythmias and sudden death. [2]

In accordance with the position statement of the American Thoracic Society, all patients should have an annual ECG. If patients report palpitations, this should prompt a thorough evaluation.



Diagnosis requires biopsy in most cases. If therapy is to be given for sarcoidosis, tissue confirmation is essential. Watchful waiting is indicated only for patients who exhibit a classic presentation, are asymptomatic, and with whom one can ensure close follow-up.

Transbronchial biopsy via fiberoptic bronchoscopy has a high diagnostic yield. Results may be positive, even in the setting of normal chest radiography findings.

Standard transbronchial needle aspiration allows successful lymph node sampling in nearly all patients with sarcoidosis and is associated with high diagnostic yield regardless of disease stage. [53]

Endobronchial biopsy is performed during bronchoscopy and increases the yield of the procedure. In a study of 34 subjects, endobronchial biopsy findings were positive in 61.8% of patients with a yield comparable to transbronchial biopsy, which showed nonnecrotizing granulomas in 58.8% of subjects. The addition of endobronchial biopsy increased the yield of fiberoptic bronchoscopy by 20.6%. [54]

At least one study has shown that the diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration for stage I and II sarcoidosis is even higher than standard transbronchial lung biopsy. [55]

In at least one study, the CD4/CD8 ratio and tumor necrosis factor (TNF)–α levels in induced sputum correlated with those in bronchoalveolar lavage fluid (BALF) and paralleled changes with treatment. Induced sputum may therefore be a surrogate for BALF for certain markers in patients with sarcoidosis. [56] In another study, the differential cell count in BALF demonstrated a significantly lower percentage of neutrophils and a significantly higher percentage of macrophages than in induced sputum. The profiles of T-cell subsets, however, showed the same pattern in both groups. A CD4/CD8 ratio of 2.5 or greater had a sensitivity of 100% and a specificity of 81.2%, with a positive predictive value of 81.2%, to distinguish sarcoidosis from nongranulomatous interstitial lung diseases. [57]


Histologic Findings

The central histologic finding is the presence of noncaseating granulomas (NCGs) with special stains negative for fungus and mycobacteria.