What is the initial treatment for sarcoidosis?

Initial Treatment for Sarcoidosis

Oral prednisone at 20-40 mg daily for 3-6 months is the first-line treatment for symptomatic sarcoidosis requiring therapy, followed by gradual tapering to the lowest effective dose. 1, 2

When to Initiate Treatment

Treatment decisions should be based on three critical factors 1:

• High risk for mortality or permanent organ disability (cardiac involvement, neurosarcoidosis, severe pulmonary disease with declining function)
• Significant impairment of quality of life from symptoms (dyspnea, cough, chest pain)
• Presence of organ dysfunction on functional testing or imaging

Nearly half of sarcoidosis patients never require systemic treatment as the disease may resolve spontaneously, so observation for 2 years or more is warranted if the patient is relatively asymptomatic. 1, 3

Do not treat patients without symptoms, organ dysfunction risk, or quality of life impairment due to the high prevalence of glucocorticoid adverse events. 1, 2

First-Line Treatment Protocol

Standard Dosing

• Start prednisone 20-40 mg daily for symptomatic disease with risk of organ dysfunction 1, 2, 4
• Continue initial dose for 3-6 months to assess therapeutic response 1, 2
• Begin tapering if improved, targeting 5-10 mg daily or every other day as maintenance 5, 6
• Monitor bone density, blood pressure, and serum glucose throughout treatment 5, 6

Modified Dosing for Lower-Risk Disease

• For quality of life impairment alone without organ threat, consider initial low-dose glucocorticoid treatment at 5-10 mg daily through shared decision-making 1, 6
• Reduce the starting dose in patients with diabetes, psychosis, or osteoporosis 1, 2

Treatment Duration

• Minimum 1 year of treatment is recommended unless no improvement is noted after 3 months 3
• At least half of patients started on glucocorticoids remain on treatment 2 years later 1, 6
• Re-evaluate the need for continued treatment every 1-2 years 1

When to Add Second-Line Therapy

Add methotrexate 10-15 mg weekly if any of the following occur 1, 6, 2:

• Disease progression despite adequate glucocorticoid treatment
• Unacceptable glucocorticoid side effects
• Unable to taper prednisone below 10 mg daily after 6 months

Methotrexate is the most widely studied and best-tolerated second-line agent, with evidence supporting its ability to improve/preserve lung function and quality of life. 1, 6, 7

Monitoring for Methotrexate

• Complete blood count, hepatic, and renal serum testing 5
• Cleared by kidney—avoid in significant renal failure 5

Alternative Second-Line Agents

If methotrexate is contraindicated or not tolerated 6:

• Azathioprine 50-250 mg once daily
• Leflunomide 10-20 mg once daily
• Mycophenolate mofetil 500-1500 mg twice daily (less experience in sarcoidosis)

Third-Line Treatment

Add infliximab for patients with continued disease despite glucocorticoids and second-line agents, particularly for severe manifestations including cardiac and neurologic sarcoidosis. 1, 6, 2

• Dosing: 3-5 mg/kg initially, 2 weeks later, then every 4-6 weeks 5
• Screen for prior tuberculosis before initiation 5
• Contraindicated in severe congestive heart failure, prior malignancy, demyelinating neurologic disease, active tuberculosis, and deep fungal infections 5

Organ-Specific Considerations

Cardiac Sarcoidosis

Glucocorticoids with or without other immunosuppressives are strongly recommended for patients with functional cardiac abnormalities, with consideration of early initiation of steroid-sparing medications due to significant morbidity of long-term glucocorticoid use. 6

Neurosarcoidosis

Treatment follows the same stepwise approach: glucocorticoids first-line, methotrexate second-line, infliximab third-line. 6

Cutaneous Sarcoidosis

• Infliximab for continued active skin disease despite glucocorticoids/immunosuppressives 6
• Alternative: Hydroxychloroquine 200-400 mg once daily with periodic ocular exams 5, 6

Common Pitfalls to Avoid

Prolonged use of even low doses of prednisone can lead to significant toxicity, including weight gain, diabetes, hypertension, osteoporosis, cataracts, glaucoma, and reduced quality of life. 5, 1, 2

Do not add inhaled glucocorticoids to oral glucocorticoids—three randomized trials showed no significant benefits. 1, 6, 2

Avoid continuing ineffective treatment—lack of response over 3-6 months indicates need for alternative strategy. 2

Provide prophylaxis during prolonged steroid use, including calcium and vitamin D supplementation for bone health. 2

Monitoring Treatment Response

Evaluate response at 3 months with 2:

• Clinical assessment of symptoms
• Pulmonary function tests (forced vital capacity)
• Chest radiography or CT imaging
• Organ-specific testing as indicated

If disease worsens, add or increase adjunctive therapy (methotrexate) and re-evaluate diagnosis and treatment plan. 2

If disease improves, decrease steroid dose gradually to lowest effective level. 2

Managing Relapses

Relapses as treatment is withdrawn are frequent, especially in African-American patients who tend to have more severe and prolonged disease. 3

If relapse occurs during or after tapering, restart prednisone at the last effective dose and add methotrexate as steroid-sparing agent. 2

Repeated relapses may indicate the need for life-long treatment with continued low-dose prednisone at 10-15 mg daily to prevent further progression. 3