What laboratory tests are used to diagnose sarcoidosis?

Laboratory Tests for Diagnosing Sarcoidosis

The diagnosis of sarcoidosis requires a compatible clinical presentation, evidence of nonnecrotizing granulomatous inflammation in tissue samples, and exclusion of alternative causes, with baseline serum calcium testing strongly recommended for all patients regardless of symptoms. 1

Core Diagnostic Laboratory Tests

Essential Laboratory Tests

• Serum calcium: Strongly recommended for all patients with suspected sarcoidosis, even those without hypercalcemia symptoms 1, 2
• Serum creatinine: Conditionally recommended to screen for renal sarcoidosis 1
• Serum alkaline phosphatase: Conditionally recommended to screen for hepatic sarcoidosis 1
• Angiotensin-converting enzyme (ACE) levels: Often elevated in active sarcoidosis, though not specific 3

Additional Laboratory Tests

• Vitamin D assessment: Both 25-(OH) and 1,25-(OH)₂ vitamin D levels should be measured when vitamin D metabolism assessment is needed 1, 2
• Complete blood count: To evaluate for anemia, leukopenia, or other hematologic abnormalities
• Erythrocyte sedimentation rate: Often elevated in active disease 4
• Immunoglobulin levels: May be elevated in sarcoidosis 4

Diagnostic Algorithm

1. Initial laboratory evaluation:

   • Serum calcium (highest priority)
   • Serum creatinine
   • Serum alkaline phosphatase
   • ACE levels
   • Basic blood studies (ESR, immunoglobulins)

2. Radiologic evaluation:

   • Chest radiography (abnormal in 85-95% of patients) 5
   • High-resolution computed tomography (HRCT) when indicated 2

3. Tissue sampling:

   • Biopsy of involved tissues to demonstrate noncaseating granulomas
   • Note: In patients with highly characteristic clinical presentations (e.g., Löfgren's syndrome, lupus pernio, Heerfordt's syndrome), lymph node sampling may not be necessary 1, 6

4. Exclusion of alternative diagnoses:

   • Testing to rule out infections (especially tuberculosis)
   • Testing to rule out malignancy
   • Testing to rule out other granulomatous diseases

Special Considerations

Organ-Specific Testing

• Cardiac involvement: ECG, echocardiography, cardiac MRI, or PET-CT with FDG imaging 2
• Pulmonary involvement: Pulmonary function tests 5
• Ocular involvement: Ophthalmologic examination

Activity Assessment

• 67Gallium scintigraphy: Highly sensitive (94%) for detecting active sarcoidosis 3
• Serum ACE levels: Useful for monitoring disease activity but less sensitive than gallium scanning 3

Pitfalls and Caveats

• No single diagnostic test: The diagnosis relies on a combination of clinical, radiological, and histopathological findings 7
• False negatives: Up to 15% of patients may have normal chest radiographs despite active disease 4
• ACE level limitations: While often elevated in sarcoidosis, ACE levels lack specificity and can be elevated in other conditions
• Biopsy necessity: Despite characteristic clinical presentations, histological confirmation is often required to exclude other diseases 7
• Monitoring challenges: In patients with peripheral pulmonary lesions, chest radiography may fail to document disease activity in up to 32% of cases 3

Key Point

When evaluating for sarcoidosis, the combination of serum calcium, creatinine, alkaline phosphatase, and ACE levels provides the core laboratory assessment. However, the diagnosis ultimately requires integration of clinical, radiological, and histopathological findings to establish the presence of noncaseating granulomas and exclude alternative diagnoses.