What is the management of sarcoidosis?

Management of Sarcoidosis

Treatment Decision Framework

Glucocorticoids are the first-line therapy for symptomatic sarcoidosis requiring treatment, with methotrexate as the preferred second-line steroid-sparing agent, and infliximab reserved for refractory disease. 1, 2

Treatment decisions must prioritize three key factors:

• Risk of mortality or organ failure (pulmonary and cardiac disease cause most sarcoidosis deaths) 2
• Quality of life impairment (fatigue, dyspnea, and other symptomatic manifestations) 2
• Pattern of organ involvement (different organs require specific approaches) 2

When to Treat vs. Observe

For Stage I disease with minimal symptoms, observation without treatment is appropriate given the 65-80% spontaneous remission rate within 2 years. 3

Spontaneous Resolution Rates by Stage:

• Stage I: 65-80% resolution within 2 years 3
• Stage II: 50-65% resolution 3
• Stage III: Only 10-30% resolution 3
• Löfgren's syndrome: 85% spontaneous remission 3

Indications for Treatment:

• Symptomatic disease with progressive pulmonary involvement 1, 2
• Significant extrapulmonary involvement (cardiac, neurologic, ocular) 1
• Gradual radiographic progression for ≥2 years even without major symptoms 4
• Risk of permanent organ damage or mortality 2

Critical pitfall: Do not start treatment prematurely in asymptomatic Stage I disease—allow 2 years of observation unless high-risk features develop. 4

First-Line Therapy: Glucocorticoids

Start prednisone 20-40 mg daily for symptomatic pulmonary sarcoidosis requiring systemic therapy. 1, 2, 5

Dosing Protocol:

• Initial dose: 20-40 mg prednisone daily 2, 6
• Duration: Continue for 3-6 months before tapering 1, 2
• Taper: Over 4-8 weeks if improvement occurs 2
• Minimum treatment duration: At least 1 year unless no improvement after 3 months 4
• Maintenance: Consider 10-15 mg daily long-term to prevent relapses 4

Monitoring Response:

• Pulmonary function tests (FVC, DLCO) every 6-12 months 2, 3
• Chest imaging for radiographic changes 2
• Symptom assessment and quality of life measures 2

Expected response: Average 9.6% increase in predicted FVC at 12 months 7

Critical pitfall: Avoid prolonged corticosteroid monotherapy beyond 6-12 months—this causes significant toxicity without adequately addressing disease progression. 7

Second-Line Therapy: Methotrexate

Add methotrexate when patients have inadequate steroid response, steroid toxicity, or require prolonged treatment (>3-6 months). 1, 2

Indications for Methotrexate:

• Continued disease despite glucocorticoids 1, 2
• Significant glucocorticoid side effects 1, 2
• Chronic disease requiring prolonged treatment 1, 4
• High risk for steroid toxicity 1

Methotrexate Protocol:

• Allow 3-6 months to assess therapeutic response before escalating 7
• Add folic acid supplementation to reduce side effects 7
• Regular laboratory monitoring for hepatotoxicity and bone marrow suppression 2

Evidence: Methotrexate is steroid-sparing and associated with improved lung function. 7

Alternative second-line agents: Azathioprine is equally effective as methotrexate for pulmonary sarcoidosis. 7, 8

Third-Line Therapy: Infliximab

For patients failing glucocorticoids and methotrexate, add infliximab as the preferred biologic agent. 1, 2

Infliximab Protocol:

• Dosing: 5 mg/kg at weeks 0,2, and 6, then maintenance therapy 7
• Combination therapy: Use with low-dose methotrexate to reduce autoantibody formation risk 7
• Mandatory screening: Tuberculosis testing before initiation 7
• Duration: Continue for 2-3 years in responders 7

Alternative biologic: Adalimumab may be used if infliximab fails or is not tolerated. 1

Organ-Specific Management

Cardiac Sarcoidosis

For functional cardiac abnormalities (heart block, dysrhythmias, cardiomyopathy), strongly recommend glucocorticoids with or without other immunosuppressives. 1

High-risk features requiring treatment: 1

• Ventricular tachycardia
• Cardiac inflammation on FDG-PET
• Abnormal global longitudinal strain on echo
• Interventricular septal thinning
• Elevated troponin or BNP

Retrospective data suggests adding methotrexate to prednisone improves ejection fraction and BNP after 5 years. 1

Critical consideration: Cardiac sarcoidosis has high mortality risk, especially with reduced left ventricular function—aggressive treatment is warranted despite limited evidence. 1

Neurosarcoidosis

For clinically significant neurosarcoidosis, strongly recommend glucocorticoids as first-line therapy. 1

Treatment escalation pathway: 1

1. Glucocorticoids (first-line)
2. Add methotrexate if continued disease despite glucocorticoids
3. Add infliximab if failing glucocorticoids and methotrexate

Important: Neurosarcoidosis causes death at younger age than pulmonary disease and significantly impacts quality of life. 1

Cutaneous Sarcoidosis

For cosmetically important cutaneous sarcoidosis, start with topical glucocorticoids, then escalate to systemic therapy if needed. 1

Treatment ladder: 1

1. Topical glucocorticoids
2. Oral prednisone/prednisolone
3. Hydroxychloroquine or chloroquine (particularly effective for skin)
4. Methotrexate
5. Infliximab for refractory cases

Hydroxychloroquine is particularly effective for cutaneous manifestations and hypercalcemia. 2, 7

Special Considerations

Hypercalcemia

Add hydroxychloroquine to the treatment regimen for patients with hypercalcemia or skin disease. 2

Infection Prophylaxis

• Pneumocystis pneumonia prophylaxis for patients on multiple immunosuppressive agents 7
• Ensure pneumococcal and influenza vaccination 7

Treatment Discontinuation

Consider discontinuing treatment after disease has been stable for 2-3 years. 2, 7

Warning: Relapses during tapering or after discontinuation are common (13-75% depending on stage, organs involved, and population), especially in African-American patients. 4, 6

Advanced/Refractory Disease

For Stage IV fibrocystic disease with >20% fibrosis on HRCT or precapillary pulmonary hypertension, mortality exceeds 40% at 5 years. 6

Management of End-Stage Disease:

• Lung transplantation for severe disease unresponsive to therapy, worsening pulmonary function, or pulmonary hypertension 7
• Targeted pulmonary arterial hypertension medications for precapillary pulmonary hypertension (occurs in up to 70% of Stage IV patients) 6
• Shift goals to optimal supportive care when irreversible fibrotic changes are present 4

Critical pitfall: Do not increase corticosteroid dosage or add toxic immunosuppressive agents when irreversible fibrotic changes dominate—focus on supportive care instead. 4

Key Pitfalls to Avoid

• Do not use prolonged corticosteroid monotherapy beyond 6-12 months without adding steroid-sparing agents 7
• Do not escalate treatment prematurely—allow 3-6 months to assess response before changing therapy 7
• Do not delay treatment in high-risk organ involvement (cardiac, neurologic) even with limited evidence 1
• Do not forget tuberculosis screening before starting anti-TNF therapy 7