Sarcoidosis Diagnosis and Treatment
The diagnosis of sarcoidosis requires a compatible clinical and radiologic presentation, histopathologic evidence of noncaseating granulomas, and exclusion of alternative diagnoses that can mimic sarcoidosis. 1
Diagnostic Criteria for Sarcoidosis
Clinical Features Supporting Diagnosis
Highly Probable Features
- Löfgren's syndrome (bilateral hilar adenopathy with erythema nodosum and/or periarticular arthritis) 1
- Characteristic physical findings including:
- Lupus pernio (violaceous facial lesions)
- Uveitis
- Optic neuritis
- Erythema nodosum 1
- Distinctive imaging findings such as:
- Bilateral hilar adenopathy on chest X-ray, CT, or PET
- Perilymphatic nodules on chest CT
- Gadolinium enhancement on CNS MRI
- Bone lesions (osteolysis, cysts, trabecular pattern)
- Parotid uptake on gallium or PET scans 1
- Laboratory abnormalities like hypercalcemia or hypercalciuria with abnormal vitamin D metabolism 1
Probable Features
- Seventh cranial nerve paralysis
- Treatment-responsive renal failure
- Cardiac manifestations (cardiomyopathy, AV node block)
- Skin lesions (maculopapular, erythematous, violaceous)
- Ocular findings (scleritis, retinitis)
- Elevated ACE levels (>50% above upper limit of normal) 1
Diagnostic Algorithm
- Identify compatible clinical presentation - Look for multisystem involvement with pulmonary predominance (>90% of cases) 2
- Obtain appropriate imaging - Chest X-ray and/or CT scan to identify characteristic patterns 1
- Perform tissue biopsy - Obtain histopathologic confirmation of noncaseating granulomas 3
- Exclude alternative diagnoses - Rule out infections, malignancy, and other granulomatous diseases 1
Key Diagnostic Tests
- Chest imaging (X-ray, CT) - First-line diagnostic test; may show bilateral hilar lymphadenopathy and/or parenchymal infiltrates 1
- Tissue biopsy - Essential for confirming noncaseating granulomas; site selection based on accessibility and clinical manifestations 3
- Bronchoalveolar lavage (BAL) - Can show lymphocytosis or elevated CD4:CD8 ratio; useful for excluding infections or malignancy 1
- Serum ACE levels - May be elevated but has limited sensitivity and specificity 1
- Pulmonary function tests - To assess functional impairment 4
- Specialized testing based on suspected organ involvement:
- Cardiac MRI/PET for cardiac sarcoidosis
- Ophthalmologic examination for ocular involvement
- Neurologic evaluation including MRI for neurosarcoidosis 2
Differential Diagnosis Considerations
- Infections - Tuberculosis, fungal infections, other mycobacterial diseases 1
- Malignancies - Lymphoma, metastatic disease 1
- Other granulomatous disorders - Berylliosis, hypersensitivity pneumonitis 1
- Medication-induced granulomatous reactions - From immune checkpoint inhibitors, anti-TNF agents 1
Treatment of Sarcoidosis
Indications for Treatment
Treatment is indicated when there is:
- Risk of mortality or permanent disability
- Significant impact on quality of life 2
First-Line Treatment
- Oral corticosteroids (prednisone 20-40 mg daily) for symptomatic disease 4
- Initial treatment for 2 weeks to 2 months, followed by tapering over 6-18 months if improvement occurs 4
- Indicated for symptomatic pulmonary disease with abnormal PFTs or significant extrapulmonary involvement 5
Second-Line/Steroid-Sparing Agents
- Methotrexate - First-choice steroid-sparing agent 2
- Azathioprine - Particularly useful for hepatic and pulmonary involvement 2
- Mycophenolate - Alternative for interstitial lung disease 2
Third-Line Therapy
- TNF inhibitors (infliximab, adalimumab) - For refractory cases 2
- Intravenous immunoglobulin (IVIg) - May be considered for persistent small-fiber neuropathy 2
Treatment Duration and Monitoring
- Relapse rates of 13-75% have been reported after treatment discontinuation 4
- Prolonged therapy may be required; at least 25% of patients need treatment for more than 2 years 2
- Regular monitoring of symptoms, organ function, and medication side effects is essential 4
Treatment Challenges
- High relapse rates (20-80%) upon glucocorticoid withdrawal 2
- Medication toxicity with prolonged corticosteroid use 2
- Progressive disease despite treatment in some cases, potentially requiring organ transplantation 3
Prognosis
- Overall mortality rate approximately 7% over 5 years 4
- Mortality causes - 60% due to sarcoidosis itself, with up to 80% from advanced cardiopulmonary failure 4
- Stage-dependent outcomes - Stages I and II have 30-80% chance of radiographic remission, Stage III only 10-40%, and Stage IV has no chance of resolution 4
- Poor prognostic factors - Advanced fibrocystic disease, pulmonary hypertension, cardiac involvement 4
Common Pitfalls to Avoid
- Inadequate exclusion of alternative diagnoses, particularly infections 1
- Overreliance on ACE levels for diagnosis (limited sensitivity/specificity) 1
- Insufficient monitoring for extrapulmonary manifestations 2
- Premature discontinuation of therapy leading to relapse 2
- Failure to recognize cardiac involvement, which carries significant mortality risk 2