What is the treatment for sarcoidosis?

Treatment of Sarcoidosis

Glucocorticoids are the first-line treatment for symptomatic sarcoidosis, with prednisone 20-40 mg daily recommended as initial therapy, followed by methotrexate as the preferred steroid-sparing agent for chronic disease, and infliximab reserved for refractory cases. 1, 2, 3

When to Treat vs. Observe

Treatment decisions hinge on two critical factors: risk of death or permanent organ damage and impact on quality of life. 1, 2

Indications for immediate treatment include: 1, 2, 4

• Cardiac involvement (can cause sudden death from arrhythmias or heart block)
• Neurologic involvement (risk of permanent disability)
• Eye involvement threatening vision
• Hypercalcemia or renal dysfunction
• Symptomatic pulmonary disease with declining lung function
• Severe constitutional symptoms impairing quality of life

Observation is appropriate for: 2, 5, 6

• Asymptomatic patients with stable radiographic findings
• Stage I disease (hilar lymphadenopathy alone) without symptoms
• Patients where spontaneous remission is likely (up to 2 years of observation is reasonable)

Critical pitfall: African-American patients tend to have more severe, prolonged disease with higher relapse rates compared to white patients, warranting earlier and more aggressive treatment. 5

First-Line Treatment: Glucocorticoids

Prednisone 20-40 mg daily is the initial dose for symptomatic disease. 2, 3, 7, 4 The FDA label confirms prednisone is indicated for symptomatic sarcoidosis. 7

Treatment duration and tapering: 2, 3, 4

• Continue initial dose for 3-6 months
• Taper over 4-8 weeks if improvement occurs
• Minimum treatment duration of 1 year is recommended
• Reassess at 3-6 month intervals with pulmonary function tests and imaging

Dose adjustments required for: 2

• Diabetes (higher risk of hyperglycemia)
• Psychosis (may exacerbate psychiatric symptoms)
• Osteoporosis (increased fracture risk)

Major caveat: Relapse rates range from 13-75% upon glucocorticoid withdrawal, with relapses occurring in over 50% of patients after discontinuation. 2, 5, 4 Prolonged low-dose prednisone (10-15 mg daily) may be necessary to prevent relapses. 5

Second-Line Treatment: Steroid-Sparing Agents

Methotrexate is the preferred steroid-sparing agent. 1, 2, 3, 8

Indications for adding methotrexate: 2, 3

• Inadequate response to glucocorticoids after 3-6 months
• Glucocorticoid toxicity or intolerance
• Requirement for prednisone ≥10 mg/day for prolonged periods
• Expectation of needing treatment for >2 years

Alternative second-line agents: 2, 4, 8

• Azathioprine (particularly for hepatic and pulmonary involvement)
• Mycophenolate (for interstitial lung disease)
• Hydroxychloroquine (specifically for hypercalcemia and cutaneous disease)

Important monitoring: Regular laboratory monitoring is required for methotrexate toxicity, including liver function tests and complete blood counts. 2

Third-Line Treatment: Biologic Agents

Infliximab is the preferred anti-TNF agent for refractory sarcoidosis. 2, 3, 8

Indications for infliximab: 2, 3

• Failure of glucocorticoids and methotrexate
• Refractory pulmonary disease
• Severe small-fiber neuropathy unresponsive to other treatments
• Cardiac or neurologic involvement not responding to conventional therapy

Critical limitation: Discontinuation of infliximab after 6-12 months results in relapse in more than 50% of cases, suggesting prolonged therapy may be necessary. 2

Alternative biologic: Adalimumab can be used for refractory cases, particularly for small-fiber neuropathy. 2

Organ-Specific Treatment Considerations

Pulmonary sarcoidosis: 1, 3, 4

• Glucocorticoids strongly recommended for symptomatic disease with risk of mortality or disability
• Stage IV fibrocystic disease with >20% fibrosis on HRCT carries >40% 5-year mortality
• Pulmonary hypertension develops in up to 70% of advanced cases and may respond to targeted pulmonary arterial hypertension medications

Cardiac sarcoidosis: 1, 2

• New-onset third-degree AV block in young/middle-aged adults is highly suggestive
• Requires aggressive treatment due to high mortality risk
• Cardiac involvement is the leading cause of sarcoidosis death in Japan (>70% of deaths)

Neurologic sarcoidosis: 1, 2

• Central nervous system involvement can cause permanent disability
• Requires prompt glucocorticoid therapy
• May need prolonged immunosuppression

Small-fiber neuropathy: 2

• Mild symptoms: topiramate, tramadol, α-lipoic acid, or topical therapies (lidocaine, capsaicin)
• Severe symptoms: GABA analogues or antidepressants
• Persistent symptoms: IVIg or TNF inhibitors

Cutaneous and hypercalcemia: 2, 3

• Hydroxychloroquine may be added to glucocorticoids
• Particularly effective for skin manifestations and calcium metabolism abnormalities

Monitoring Treatment Response

Assess response using: 3

• Pulmonary function tests (FVC and DLCO)
• Chest imaging (radiographs or CT)
• Symptom improvement and quality of life measures
• Organ-specific functional assessments

Treatment discontinuation: Consider stopping therapy if disease has been stable for 2-3 years, but remain vigilant for relapse. 3

Prognosis and Long-Term Outcomes

Mortality: Approximately 5-7% of sarcoidosis patients die from the disease over 5 years. 1, 4 Up to 80% of sarcoidosis deaths are from advanced cardiopulmonary failure (pulmonary hypertension and respiratory infections). 4

Radiographic stages and prognosis: 4

• Stages I-II: 30-80% radiographic remission
• Stage III: 10-40% resolution
• Stage IV: No chance of resolution, highest mortality risk

Chronic disease: At least 25% of patients require treatment for more than 2 years, and some may need lifelong therapy. 2