Sarcoidosis is a multisystemic disorder of unknown etiology, characterized by granuloma formation. Tissue biopsy is the primary test used to diagnose sarcoidosis; other laboratory tests, including CBC and chemistry panels, are not specific for the diagnosis but may be useful in assessing disease severity.

  • Diagnosis
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

Lymphadenopathy on chest x-ray or other appropriate clinical signs and symptoms consistent with diagnosis of sarcoidosis

Criteria for Diagnosis

  • Clinical and radiological presentation
  • Noncaseating granulomas
  • No evidence of other disease

Laboratory Testing

  • General testing
    • Diagnosis of exclusion
      • Rule out other granulomatous diseases – consider stains, cultures, and serologies for fungi, acid fast bacteria, and tuberculosis
    • Nonspecific testing
      • Chemistry panel – nonspecific test; may demonstrate
      • CBC – also nonspecific but may show leukopenia with lymphopenia
    • Angiotensin converting enzyme (ACE) – may have elevated level (2x normal), but this is not diagnostic for disease
  • Type specific testing
    • Pulmonary sarcoidosis
      • Fiber optic bronchoscopy with bronchoalveolar lavage (BAL), transbronchial biopsy, or endobronchial biopsy
      • BAL
        • Winterbauer criteria – CD4/CD8 >2; ≤1% neutrophils; ≤1% eosinophils
        • Triad has 59% sensitivity, 94% specificity
          • Positive predictive value 73%; negative predictive value 90%
          • Most centers use >3.5 as definitive (Costabel, 2010)
      • Transbronchial biopsy
        • Has better yield if 4-5 specimens are obtained – yield increased when endobronchial biopsy combined with transbronchial biopsy
        • If Winterbauer criteria are met and clinical presentation is consistent with sarcoidosis, absence of granulomas on biopsy does not negate the diagnosis of sarcoidosis
        • If results are negative and high suspicion remains, consider surgical biopsy with mediastinoscopy procedure of choice
    • Neurosarcoidosis
      • Cerebrospinal fluid (CSF) findings are nonspecific – lymphocyte pleocytosis, increased protein, decreased glucose, increased opening pressure
      • Rule out meningitis first
      • ACE – elevated level supports diagnosis of neurosarcoidosis but is not diagnostic
        • Specific (~90%) but not sensitive (<60%)
      • ~30% have no abnormalities
      • Elevated CD4/CD8 frequent
    • Ocular sarcoidosis
      • Histology positive or ACE positive with ocular signs and symptoms


  • Presence of noncaseating granulomas
    • Tissue obtained by bronchoscopy if pulmonary signs and symptoms
    • May be obtained from other organ sites – skin, lymph node, parotid are most common
    • Special stains for acid fast and fungi should be performed to rule out other diseases

Imaging Studies

  • Pulmonary disease
    • Chest x-ray – hilar lymphadenopathy or parenchymal disease (nodules or fibrosis)
      • Necessary for staging
    • High resolution computed tomography (CT) – produces better diagnostic yield than a chest x-ray
      • Classically shows widespread micronodules with perilymphangitic distribution in middle and upper lobes (unnecessary test for most patients)
  • Central nervous system (CNS) disease
    • Gadolinium-enhanced magnetic resonance imaging (MRI)
      • Involvement of leptomeninges in ~40%
    • CT – not as accurate as MRI but can be used if MRI is contraindicated
  • Gallium 67 scan
    • Classic uptake – parotid and lacrimal glands (Panda sign)
    • Paratracheal and bilateral hilar uptake (Lambda sign)

Other Testing

  • Pulmonary function testing
    • May show restriction abnormalities, airflow obstruction, and/or reduced diffusing capacity of the lung for carbon monoxide (DLCO)
  • Electrocardiogram (ECG)
    • Obtained at baseline, with further testing (eg, echocardiogram) for abnormal result
  • Cardiac MRI
    • Test of choice for diagnosis of cardiac sarcoidosis

Differential Diagnosis

  • Serial angiotensin converting enzyme (ACE) – may be useful in monitoring disease activity
  • Serial pulmonary function tests – useful in monitoring pulmonary disease


  • Incidence – 10-20/100,000 in U.S. (Heinle, 2014)
    • 40/100,000 among African Americans and in some North European countries
  • Age – peak incidence in 20s-40s; rare in children <15 years
  • Sex – M<F
  • Ethnicity – most prevalent in Swedes, Danes, and African Americans


  • Certain alleles have been noted to be associated with sarcoidosis presentations, although not with enough consistency to be considered in the clinical workup
    • HLA-DRB1*03 – higher rate of spontaneous resolution at 2 years if positive
    • HLA-DRB1*14/*15 – disease tends to be chronic
    • HLA-DRB1*0401 – associated with ocular involvement
    • HLA-DRB1*0101 – associated with abnormal calcium metabolism
    • HLA-DRB1*0301, HLA-DRB1*0101 – associated with T-cell expansion
    • HLA- DQB1*0601 – associated with cardiac sarcoidosis

Risk Factors

  • Family member with sarcoidosis (5-fold increased risk)
  • HLA-DRB1*1101, HLA-DPB1*0101 alleles


  • Result of chronic immunological response associated with a genetic susceptibility and exposure to specific infections or environmental factors
    • Exaggerated immune response to antigens not yet identified
  • Accumulation of activated T cells and macrophages at site of disease activity
  • Lymphocytes are CD4 type
  • Macrophages release cytokines that drive inflammation, granuloma formation, and eventual fibrosis

Disease Stages

  • Stage 0 – normal
  • Stage I – bilateral hilar lymphadenopathy
  • Stage II – bilateral hilar lymphadenopathy with lung infiltration
  • Stage III – parenchymal infiltration
  • Stage IV – advanced parenchymal disease, including overt pulmonary fibrosis

Clinical Presentation

  • Asymptomatic (30-50%) routine chest x-ray with abnormalities of hilar adenopathy typically leads to diagnosis
  • Nonspecific (30%) – fever, weight loss, fatigue
  • Pulmonary (30%)
    • Löfgren syndrome – bilateral hilar adenopathy, ankle arthritis, fever, myalgia, weight loss, and erythema nodosum
    • Dyspnea, wheezing
  • Musculoskeletal – arthralgias
  • Dermatologic – maculopapular rashes, plaques and nodules (lupus pernio), erythema nodosum, and lupus pernio
  • Renal – nephrolithiasis, nephrocalcinosis, renal failure
  • Cardiac – conduction disorders, infiltrative cardiomyopathy with heart failure, pericarditis
  • Ophthalmic – anterior uveitis
  • Hepatic/splenic – granulomas, but dysfunction is rare
  • Endocrine – hypercalcemia with nephrolithiasis
  • Central nervous system – neurosarcoidosis is an uncommon but serious manifestation of sarcoidosis, affecting about 5-10% of patients
    • Most common manifestations include myelopathy, cranial neuropathy, and encephalopathy
      • Most common nerves are cranial nerves (CN) VII and II
    • Untreated patients may develop acute neurologic emergencies, including seizures, cord compression, and increased intracranial pressure
    • Heerfordt syndrome – uveitis, parotid gland enlargement, fever, and cranial neuropathy (usually CN VII)
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Calcium, Serum or Plasma 0020027
Method: Quantitative Spectrophotometry

Alkaline Phosphatase, Serum or Plasma 0020005
Method: Quantitative Enzymatic

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Angiotensin Converting Enzyme, Serum 0080001
Method: Quantitative Enzymatic


Antihypertensive medications such as ACE inhibitors, ACE receptor blockers, and diuretics may interfere with test results

Test is a nonspecific indicator of response to treatment; not specific for diagnosis

In neurosarcoidosis, serum ACE concentrations are less likely to be elevated than cerebrospinal fluid (CSF) ACE concentrations


Further tissue biopsy and evaluation for granulomas is necessary to confirm the diagnosis 

Angiotensin Converting Enzyme, CSF 0098974
Method: Quantitative Spectrophotometry


Antihypertensive medications such as ACE inhibitors, ACE receptor blockers, and diuretics may interfere with test results

Test is a nonspecific indicator of response to treatment and is not specific for sarcoidosis

Lymphocyte Subset Panel 4 - T-Cell Subsets Percent and Ratio, Bronchoalveolar Lavage 0093420
Method: Flow Cytometry

General References

Bargagli E, Mazzi A, Rottoli P. Markers of inflammation in sarcoidosis: blood, urine, BAL, sputum, and exhaled gas. Clin Chest Med. 2008; 29(3): 445-58, viii. PubMed

Carmona EM, Kalra S, Ryu JH. Pulmonary Sarcoidosis: Diagnosis and Treatment. Mayo Clin Proc. 2016; 91(7): 946-54. PubMed

Costabel U, Bonella F, Ohshimo S, Guzman J. Diagnostic modalities in sarcoidosis: BAL, EBUS, and PET. Semin Respir Crit Care Med. 2010; 31(4): 404-8. PubMed

Hamzeh N. Sarcoidosis. Med Clin North Am. 2011; 95(6): 1223-34. PubMed

Heinle R, Chang C. Diagnostic criteria for sarcoidosis. Autoimmun Rev. 2014; 13(4-5): 383-7. PubMed

Keir G, Wells AU. Assessing pulmonary disease and response to therapy: which test? Semin Respir Crit Care Med. 2010; 31(4): 409-18. PubMed

Nunes H, Bouvry D, Soler P, Valeyre D. Sarcoidosis. Orphanet J Rare Dis. 2007; 2: 46. PubMed

O'Regan A, Berman JS. Sarcoidosis. Ann Intern Med. 2012; 156(9): ITC5-1 through ITC5-15; quiz ITC5-16. PubMed

Rose AS, Tielker MA, Knox KS. Hepatic, ocular, and cutaneous sarcoidosis. Clin Chest Med. 2008; 29(3): 509-24, ix. PubMed

Soto-Gomez N, Peters JI, Nambiar AM. Diagnosis and Management of Sarcoidosis. Am Fam Physician. 2016; 93(10): 840-8. PubMed

Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet P, Müller-Quernheim J. Sarcoidosis. Lancet. 2014; 383(9923): 1155-67. PubMed

Wells AU. The clinical utility of bronchoalveolar lavage in diffuse parenchymal lung disease. Eur Respir Rev. 2010; 19(117): 237-41. PubMed

Winterbauer RH, Lammert J, Selland M, Wu R, Corley D, Springmeyer SC. Bronchoalveolar lavage cell populations in the diagnosis of sarcoidosis. Chest. 1993; 104(2): 352-61. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Erickson A, Cousin R, Wu JT, Ashwood ER. Quantitative spectrophotometric microplate assay for angiotensin-converting enzyme in cerebrospinal fluid. Clin Chem. 2003; 49(6 Pt 1): 970-2. PubMed

Krasowski MD, Savage J, Ehlers A, Maakestad J, Schmidt GA, La'ulu SL, Rasmussen NN, Strathmann FG, Genzen JR. Ordering of the Serum Angiotensin-Converting Enzyme Test in Patients Receiving Angiotensin-Converting Enzyme Inhibitor Therapy: An Avoidable but Common Error Chest. 2015; 148(6): 1447-53. PubMed

Medical Reviewers

Content Reviewed: 
January 2018

Last Update: February 2018