What are the steps to diagnose sarcoidosis?

Diagnosing Sarcoidosis

The diagnosis of sarcoidosis requires three essential criteria: compatible clinical presentation, histopathologic evidence of non-caseating granulomas in at least one organ, and exclusion of alternative causes of granulomatous disease. 1, 2

Step 1: Clinical Evaluation

Clinical Presentation Assessment

• Identify highly probable clinical features:
  • Löfgren's syndrome (bilateral hilar adenopathy with erythema nodosum and/or periarticular arthritis)
  • Characteristic skin lesions (lupus pernio)
  • Ocular manifestations (uveitis, optic neuritis)
  • Erythema nodosum
  • Seventh cranial nerve paralysis 1, 2

Organ-Specific Symptoms to Evaluate

• Pulmonary (most common, 90% of cases):
  • Persistent dry cough
  • Dyspnea
  • Chest pain 1
• Extrapulmonary manifestations:
  • Skin: Maculopapular, erythematous, or violaceous lesions
  • Eyes: Uveitis, scleritis, retinitis
  • Neurological: Cranial nerve palsies, especially facial nerve
  • Cardiac: Arrhythmias, cardiomyopathy
  • Constitutional: Fatigue, weight loss, night sweats 1, 2

Step 2: Diagnostic Imaging

Chest Imaging

• Chest radiography (initial test):

  • Look for bilateral hilar adenopathy (highly specific)
  • Upper lobe or diffuse infiltrates
  • Peribronchial thickening 1, 2

• Chest CT:

  • Perilymphatic nodules
  • Perilobular and fissural distribution with upper and posterior predominance 1

Advanced Imaging for Extrapulmonary Involvement

• Cardiac MRI: For suspected cardiac involvement (preferred over echocardiography)
• PET scan: For suspected extrapulmonary involvement, shows increased inflammatory activity
• CNS MRI with gadolinium: For neurological involvement (highly specific)
• X-ray, CT, or MRI: For osseous involvement (osteolysis, cysts, trabecular pattern) 1, 2

Step 3: Laboratory Testing

• Basic laboratory tests:

  • Serum calcium and vitamin D levels (look for hypercalcemia/hypercalciuria)
  • Liver function tests (elevated alkaline phosphatase >3x upper limit)
  • Complete blood count
  • Renal function tests 2

• Specialized tests:

  • Angiotensin-converting enzyme (ACE) level (supportive if >50% of upper limit of normal)
  • Bronchoalveolar lavage (BAL): Look for lymphocytosis or elevated CD4:CD8 ratio 1, 2

Step 4: Histopathologic Confirmation

• Biopsy of the most accessible involved organ:
  • Look for non-caseating granulomas
  • Endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal/hilar lymph nodes
  • Transbronchial lung biopsy for pulmonary involvement 1, 2

Step 5: Exclusion of Alternative Diagnoses

• Rule out other granulomatous diseases:

  • Infections: Tuberculosis, fungal infections
  • Malignancy: Lymphoma
  • Berylliosis: Consider blood lymphocyte proliferation test
  • Vasculitides: Check for MPO/PR3 antineutrophil cytoplasmic antibodies
  • IgG4-related disease: Pathology examination
  • Common variable immunodeficiency 1, 2

• Consider medication-induced granulomatous reactions:

  • Immune checkpoint inhibitors
  • Anti-TNF-α agents 1

Common Pitfalls to Avoid

• Over-reliance on ACE levels (supportive but not diagnostic)
• Failure to exclude other granulomatous diseases
• Incomplete evaluation of extrapulmonary involvement
• Missing cardiac or neurological involvement (can be life-threatening)
• Assuming all granulomas are sarcoidosis (histopathologic features alone cannot distinguish sarcoidosis from other granulomatous diseases) 1, 2

Special Diagnostic Scenarios

• For suspected cardiac sarcoidosis:

  • Baseline ECG for all patients with extracardiac sarcoidosis
  • Cardiac MRI is preferred; if unavailable, use dedicated PET 2

• For suspected pulmonary hypertension:

  • Initial testing with transthoracic echocardiography
  • If suggested, proceed to right heart catheterization 2

• For highly characteristic presentations (e.g., Löfgren's syndrome, lupus pernio), histological confirmation may not be required 1, 2