What is the diagnostic approach for sarcoidosis?

Diagnostic Approach for Sarcoidosis

The diagnosis of sarcoidosis requires three major criteria: a compatible clinical presentation, histopathologic evidence of noncaseating granulomas, and exclusion of alternative causes of granulomatous disease. 1, 2

Diagnostic Criteria and Initial Evaluation

• Sarcoidosis diagnosis is based on a combination of clinical, radiological, and histopathological findings, as there is no single definitive test 1, 3
• The diagnosis requires:
  • Compatible clinical and radiological presentation
  • Histopathologic evidence of noncaseating granulomas in one or more tissues
  • Exclusion of alternative causes of granulomatous disease 1, 4
• Certain clinical presentations are highly specific and may not require biopsy confirmation:
  • Löfgren's syndrome (bilateral hilar adenopathy with erythema nodosum and/or periarticular arthritis)
  • Lupus pernio (violaceous skin lesions)
  • Heerfordt's syndrome (uveoparotid fever) 1, 2

Initial Diagnostic Testing

• Chest imaging is essential as initial evaluation:
  • Chest X-ray and high-resolution CT scan to detect bilateral hilar adenopathy, perilymphatic nodules, and parenchymal infiltrates 2, 3
• Laboratory testing should include:
  • Serum calcium (strong recommendation) to screen for abnormal calcium metabolism 1, 2
  • Serum creatinine to screen for renal involvement 1, 2
  • Serum alkaline phosphatase to screen for hepatic involvement 1, 2
  • If vitamin D assessment is needed, measure both 25-OH and 1,25-OH vitamin D levels 1, 2
• Cardiac screening:
  • Baseline ECG for all patients to screen for cardiac involvement 1, 2
  • Cardiac MRI for patients with suspected cardiac involvement based on symptoms or ECG abnormalities 2, 5

Tissue Sampling for Histopathologic Confirmation

• Tissue sampling is recommended from the most accessible involved site to confirm noncaseating granulomas 2, 6
• In patients with high clinical suspicion for sarcoidosis (e.g., Löfgren's syndrome, lupus pernio, Heerfordt's syndrome), lymph node sampling may not be necessary, but close clinical follow-up is required 1, 2
• Bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy is commonly used for tissue diagnosis in pulmonary sarcoidosis 2, 4
• BAL lymphocytosis or elevated CD4:CD8 ratio can support the diagnosis but is not diagnostic alone 1, 4

Exclusion of Alternative Diagnoses

• Alternative causes of granulomatous inflammation must be excluded:
  • Infections (tuberculosis, fungal infections)
  • Berylliosis (consider blood lymphocyte proliferation test)
  • Hypersensitivity pneumonitis
  • Vasculitis
  • Drug-induced sarcoid-like reactions (especially immunotherapeutics and anti-TNF agents)
  • Malignancy-associated granulomatous reactions 1, 2

Organ-Specific Evaluation

Pulmonary Evaluation

• Pulmonary function tests to assess lung function and severity of disease 3, 4
• Consider 6-minute walk test to evaluate exercise capacity 3

Cardiac Evaluation

• Baseline ECG for all patients 1, 5
• For suspected cardiac involvement:
  • Cardiac MRI is the preferred first-line imaging modality 2, 5
  • PET scanning if cardiac MRI is unavailable 5
  • Echocardiography if pulmonary hypertension is suspected 5

Ocular Evaluation

• Refer to ophthalmologist for patients with ocular symptoms or signs (uveitis, optic neuritis, scleritis, retinitis) 2, 4

Neurological Evaluation

• Refer to neurologist for patients with neurological symptoms, especially cranial nerve palsies 2, 4

Hepatic and Renal Evaluation

• Serum alkaline phosphatase for hepatic involvement 1, 7
• Serum creatinine for renal involvement 1, 2
• Consider referral to specialists for significant abnormalities 2, 7

Diagnostic Pitfalls to Avoid

• Do not rely solely on ACE levels, as they lack sensitivity and specificity 2, 6
• Do not overlook cardiac involvement, which can be fatal and may require specific imaging beyond routine echocardiography 2, 5
• Consider drug-induced sarcoid-like reactions and review medications 2
• Do not diagnose sarcoidosis without excluding other causes of granulomatous disease 1
• Remember that the diagnosis of sarcoidosis is never fully secure due to lack of universally accepted measures to determine if each diagnostic criterion has been satisfied 1

Clinical Features Supporting Diagnosis

• Highly probable features:

  • Löfgren's syndrome
  • Lupus pernio
  • Uveitis
  • Optic neuritis
  • Erythema nodosum
  • Bilateral hilar adenopathy on imaging
  • Perilymphatic nodules on chest CT
  • Hypercalcemia with abnormal vitamin D metabolism 1, 4

• Probable features:

  • Seventh cranial nerve paralysis
  • Treatment-responsive renal failure
  • Maculopapular skin lesions
  • Upper lobe or diffuse infiltrates on imaging
  • Elevated ACE level 1, 4