What are the diagnostic criteria and treatment options for sarcoidosis?

Diagnosis of Sarcoidosis

The diagnosis of sarcoidosis requires three major criteria: a compatible clinical presentation, evidence of noncaseating granulomatous inflammation in one or more tissue samples, and exclusion of alternative causes of granulomatous disease. 1, 2

Diagnostic Criteria

Clinical Presentation

• Highly specific clinical features that may not require tissue confirmation:
  • Löfgren's syndrome (erythema nodosum, bilateral hilar lymphadenopathy, periarticular arthritis)
  • Lupus pernio (violaceous facial lesions)
  • Heerfordt's syndrome (uveitis, parotitis, facial nerve palsy, fever)
  • Bilateral hilar adenopathy without B symptoms 1, 2

Tissue Sampling

• Tissue sampling is not recommended when there is high clinical suspicion with classic presentations like Löfgren's syndrome 1, 2
• For all other cases, tissue confirmation showing noncaseating granulomas is necessary
• Common sampling sites:
  • Mediastinal or hilar lymph nodes (via endobronchial ultrasound)
  • Lung parenchyma
  • Skin lesions
  • Affected organs 1

Exclusion of Alternative Diagnoses

• Rule out other causes of granulomatous inflammation:
  • Infections (mycobacterial, fungal)
  • Malignancy
  • Beryllium disease
  • Vasculitis
  • IgG4-related disease 2

Recommended Baseline Testing

Laboratory Tests

• Serum calcium (strong recommendation) 1
• Serum creatinine (conditional recommendation) 1
• Serum alkaline phosphatase (conditional recommendation) 1
• Consider 25-OH and 1,25-OH vitamin D levels before vitamin D replacement 1, 2

Cardiac Evaluation

• Baseline ECG for all patients with extracardiac sarcoidosis (conditional recommendation) 1, 2
• Routine baseline transthoracic echocardiography or 24-hour Holter monitoring is not recommended for screening in asymptomatic patients 1
• For suspected cardiac involvement:
  • Cardiac MRI with late gadolinium enhancement (first-line) 2
  • PET-CT with fluorodeoxyglucose as an alternative 2

Imaging Studies

• High-resolution computed tomography (HRCT) for chest imaging 2
  • Look for: bilateral hilar adenopathy, perilymphatic nodules, upper lobe or diffuse infiltrates
• MRI with gadolinium for suspected CNS involvement 2

Diagnostic Algorithm

1. Initial evaluation:

   • Assess for compatible clinical presentation
   • Perform chest imaging (preferably HRCT)
   • Conduct baseline laboratory tests (calcium, creatinine, alkaline phosphatase)
   • Perform baseline ECG

2. Decision for tissue sampling:

   • If highly specific clinical features present (Löfgren's syndrome, lupus pernio) → no tissue sampling needed
   • For all other presentations → proceed with tissue sampling from most accessible involved site

3. Exclusion of alternative diagnoses:

   • Mycobacterial and fungal cultures/stains
   • Imaging and cytological evaluation for malignancy
   • Beryllium lymphocyte proliferation test if occupational exposure
   • ANCA testing if vasculitis suspected
   • IgG4 levels if IgG4-related disease suspected

Common Pitfalls and Caveats

• Diagnosis is never fully secure - ongoing assessment is required 1, 2
• Reliance on serum ACE levels alone is not diagnostic 2
• Failure to exclude alternative diagnoses can lead to misdiagnosis
• Not all patients require treatment - many cases are self-limited and remit spontaneously 3
• Mortality risk is highest with advanced pulmonary disease, cardiac involvement, or neurologic complications 4

Treatment Considerations

• First-line: Corticosteroids (prednisone 20-40 mg daily) for symptomatic disease 4
• Second-line: Methotrexate, azathioprine as steroid-sparing agents 2, 4
• Third-line: Anti-TNF agents for refractory disease 4
• Regular follow-up is essential to monitor for disease progression, remission, or complications 3

Prognosis

• Variable depending on organ involvement and disease stage
• Scadding stages for pulmonary sarcoidosis correlate with outcomes:
  • Stages I and II: 30-80% chance of radiographic remission
  • Stage III: 10-40% chance of resolution
  • Stage IV: No chance of resolution 4
• Overall 5-year mortality rate approximately 7% 4