What is the diagnostic approach for sarcoidosis?

Diagnosing Sarcoidosis: A Comprehensive Approach

The diagnosis of sarcoidosis requires three major criteria: a compatible clinical presentation, histopathological evidence of nonnecrotizing granulomatous inflammation in tissue samples, and the exclusion of alternative causes of granulomatous disease. 1

Clinical Presentation and Initial Evaluation

• Sarcoidosis can present with various symptoms depending on organ involvement, with pulmonary manifestations being most common (90% of cases) 2
• Highly suggestive clinical presentations include:
  • Löfgren's syndrome (bilateral hilar adenopathy with erythema nodosum and/or periarticular arthritis) 1
  • Lupus pernio (violaceous skin lesions) 1
  • Heerfordt's syndrome (fever, parotid enlargement, uveitis, and facial nerve palsy) 1
• In patients with these highly suggestive presentations, lymph node sampling may not be necessary 1

Diagnostic Testing Algorithm

Step 1: Imaging Studies

• Chest X-ray and high-resolution CT scan to detect:
  • Bilateral hilar adenopathy
  • Perilymphatic nodules
  • Parenchymal infiltrates 3, 4
• These findings are highly characteristic of pulmonary sarcoidosis 1

Step 2: Laboratory Testing

• Serum calcium (strong recommendation) to screen for abnormal calcium metabolism 1
• Serum creatinine to screen for renal involvement 1
• Serum alkaline phosphatase to screen for hepatic involvement 1
• Consider measuring both 25-OH and 1,25-OH vitamin D levels if vitamin D assessment is needed 1
• Note: Angiotensin-converting enzyme (ACE) lacks sensitivity and specificity and should not be solely relied upon 3, 5

Step 3: Tissue Sampling for Histopathological Confirmation

• Biopsy from the most accessible involved site to demonstrate noncaseating granulomas 3, 2
• Bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy is commonly used for pulmonary involvement 3
• Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal lymph node sampling 1

Step 4: Cardiac Evaluation

• Baseline ECG for all patients to screen for cardiac involvement 1
• For suspected cardiac involvement:
  • Cardiac MRI is preferred 1, 3
  • If cardiac MRI is unavailable, consider PET imaging 1
• Do not routinely perform echocardiography or 24-hour Holter monitoring without cardiac symptoms 1

Step 5: Evaluation for Pulmonary Hypertension (if suspected)

• Initial testing with transthoracic echocardiography 1
• If echocardiogram suggests pulmonary hypertension, perform right heart catheterization for confirmation 1, 3

Organ-Specific Evaluation

• Pulmonary: High-resolution CT scan, pulmonary function tests, bronchoscopy with BAL 3, 6
• Cardiac: ECG, cardiac MRI, PET 1, 3
• Ocular: Ophthalmologic examination for uveitis, optic neuritis, scleritis 3, 2
• Cutaneous: Skin examination for lupus pernio, erythema nodosum, maculopapular lesions 1, 3
• Neurological: Neurological examination, MRI for cranial nerve palsies 3, 2
• Renal: Serum creatinine, urinalysis, calcium levels 1, 3
• Hepatic: Alkaline phosphatase, liver function tests 1, 3, 7

Exclusion of Alternative Diagnoses

• Consider other granulomatous diseases including:
  • Infections (tuberculosis, fungal infections)
  • Berylliosis (blood lymphocyte proliferation test is diagnostic) 1
  • Hypersensitivity pneumonitis
  • Vasculitis
  • Drug-induced sarcoid-like reactions (especially from immunotherapeutics and anti-TNF agents) 1, 3
• BAL fluid analysis can help exclude infections or malignancy 1

Diagnostic Pitfalls to Avoid

• Not obtaining tissue confirmation in atypical presentations 1
• Over-reliance on serum ACE levels for diagnosis 3, 5
• Failure to exclude alternative diagnoses 1, 3
• Missing cardiac involvement, which can be fatal 3
• Not considering drug-induced sarcoid-like reactions 1, 3

Remember that the diagnosis of sarcoidosis is never fully secure and should be revisited if the clinical course is atypical or if the patient fails to respond to therapy 1.