What is the diagnosis and workup of sarcoidosis?

Diagnosis and Workup of Sarcoidosis

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

Clinical Presentation

Highly Probable Clinical Features

• Specific syndromes:
  • Löfgren's syndrome (bilateral hilar adenopathy, erythema nodosum, arthritis)
  • Lupus pernio (violaceous facial lesions)
  • Heerfordt's syndrome (parotid enlargement, uveitis, facial nerve palsy)
• Physical findings:
  • Uveitis
  • Optic neuritis
  • Erythema nodosum

Imaging Features Highly Suggestive of Sarcoidosis

• Bilateral hilar adenopathy on chest X-ray, CT, or PET
• Perilymphatic nodules on chest CT
• Gadolinium enhancement on CNS MRI
• Osteolytic bone lesions or cysts
• Parotid uptake on gallium scan or PET

Laboratory Findings

• Hypercalcemia or hypercalciuria with abnormal vitamin D metabolism

Diagnostic Algorithm

1. Initial Evaluation:

   • Thorough assessment for compatible clinical features
   • Chest imaging (X-ray and/or CT)
   • Basic laboratory testing:
     • Serum calcium (strongly recommended) 1
     • Serum creatinine 1
     • Serum alkaline phosphatase 1
     • Consider 25- and 1,25-OH vitamin D levels if vitamin D assessment needed 1
     • ECG for cardiac screening 1

2. Histopathological Confirmation:

   • Tissue biopsy showing nonnecrotizing granulomas
   • Target most accessible involved organ
   • Exception: In patients with highly specific clinical presentations (Löfgren's syndrome, lupus pernio, or Heerfordt's syndrome), biopsy may be unnecessary 1

3. Exclusion of Alternative Diagnoses:

   • Rule out infections (tuberculosis, fungal infections)
   • Rule out malignancy
   • Rule out other granulomatous diseases (berylliosis, hypersensitivity pneumonitis)
   • Consider drug-induced granulomatous reactions

Biopsy Considerations

When to Biopsy

• Atypical clinical presentation
• Suspected extrapulmonary involvement requiring confirmation
• Treatment decisions depend on definitive diagnosis

Biopsy Site Selection

• Target the most accessible involved organ
• Consider conjunctival biopsy as a first-line option (54% sensitivity, cost-effective, minimal complications) 2
• Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for hilar/mediastinal lymphadenopathy
• Skin lesions if present
• Peripheral lymph nodes if enlarged

Exclusion of Alternative Diagnoses

This is a critical step that requires:

• Microbiological studies to exclude infections
• Special stains for fungi and mycobacteria
• Blood lymphocyte proliferation test for berylliosis 1
• Bronchoalveolar lavage (BAL) to exclude infections, malignancy, or identify patterns suggestive of other interstitial lung diseases 1

Organ-Specific Screening

For patients with confirmed sarcoidosis:

• Cardiac: Baseline ECG, consider advanced cardiac imaging if abnormal 1
• Renal: Baseline serum creatinine 1
• Hepatic: Baseline serum alkaline phosphatase 1
• Metabolic: Serum calcium (mandatory) 1
• Ocular: Ophthalmologic examination

Pitfalls to Avoid

1. Diagnostic pitfalls:

   • Failure to exclude infections that mimic sarcoidosis 3
   • Over-reliance on nonspecific findings (e.g., elevated ACE levels)
   • Assuming single-organ involvement represents sarcoidosis without adequate exclusion of other causes

2. Biopsy pitfalls:

   • Inadequate sampling
   • Failure to perform special stains for microorganisms
   • Misinterpretation of minimal necrosis (some variants of sarcoidosis can have minimal necrosis) 1

3. Treatment pitfalls:

   • Initiating corticosteroids before excluding infections
   • Failure to recognize opportunistic infections in treated patients 3

Multi-technique Imaging

• Chest radiography: Initial screening tool
• High-resolution CT: Characterizes pulmonary involvement and identifies potential biopsy sites
• MRI: Valuable for cardiac and neurological sarcoidosis
• FDG-PET/CT: Useful for identifying occult disease activity and potential biopsy sites 4

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 as expected 1.