What is the initial treatment for sarcoidosis?

Initial Treatment for Sarcoidosis

For symptomatic sarcoidosis with risk of mortality or permanent disability, start oral prednisone 20-40 mg daily for 3-6 months, then taper to the lowest effective maintenance dose of 5-10 mg daily or every other day. 1, 2

When to Treat vs. Observe

Treatment decisions hinge on three factors: risk of mortality or permanent disability, significant quality of life impairment, and presence of symptoms. 1

• Do not treat patients without symptoms, organ dysfunction risk, or quality of life impairment—nearly half of sarcoidosis patients never require systemic treatment as the disease may resolve spontaneously. 1, 3
• Observe for 2 years if the patient is relatively asymptomatic before initiating treatment, as spontaneous remissions occur frequently. 4
• Initiate treatment for symptomatic disease with major organ involvement, progressive radiographic changes over 2+ years, or significant quality of life impairment. 5, 1

First-Line Treatment Protocol

Prednisone is the cornerstone of initial therapy and FDA-approved for symptomatic sarcoidosis. 6

• Standard dosing: Start prednisone 20-40 mg daily for 3-6 months to control inflammation. 1, 2
• Lower-risk patients: 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, 2
• Dose modifications: Reduce the starting dose in patients with diabetes, psychosis, or osteoporosis. 1, 3

Monitoring and Tapering Strategy

• Assess response at 3 months with clinical evaluation, pulmonary function tests, and chest imaging. 3
• If improved: Begin tapering to the lowest dose maintaining symptom control and disease stability, typically 5-10 mg daily or every other day. 5, 2
• Target duration: Continue therapy for at least 3-6 months if there is improvement; total treatment duration typically 6-18 months from initiation. 1, 3
• Monitor for toxicity: Check bone density, blood pressure, and serum glucose regularly. 5, 2

When to Add Second-Line Therapy

Add methotrexate 10-15 mg weekly if any of the following occur: 5, 1, 2

• Disease progression despite adequate glucocorticoid treatment
• Unacceptable glucocorticoid side effects
• Unable to taper prednisone below 10 mg daily after 6 months
• Continued symptomatic disease requiring prolonged high-dose steroids

Methotrexate is the preferred second-line agent based on the most extensive evidence and best tolerability profile among steroid-sparing medications. 1, 2

• Monitoring: Check complete blood count, hepatic, and renal function regularly. 5
• Duration: Continue methotrexate for at least 2 years if effective. 7
• Alternative second-line agents: Azathioprine, leflunomide, or mycophenolate mofetil can be considered if methotrexate is contraindicated. 2

Third-Line Treatment

Add infliximab 3-5 mg/kg initially, at 2 weeks, then every 4-6 weeks for patients with continued disease despite glucocorticoids and methotrexate. 5, 1, 2

• Infliximab has multiple clinical trials supporting its use in various manifestations of sarcoidosis, particularly severe extrapulmonary disease. 1
• Screen for prior tuberculosis before initiating; contraindicated in severe congestive heart failure, prior malignancy, demyelinating neurologic disease, active tuberculosis, and deep fungal infections. 5

Long-Term Management

• Re-evaluate treatment need every 1-2 years as relapse rates range from 13-75% depending on disease stage and organs involved. 1, 8
• At least half of patients started on glucocorticoids remain on treatment 2 years later. 1, 2
• Relapse management: If relapse occurs during or after tapering, restart prednisone at the last effective dose and add methotrexate as a steroid-sparing agent. 3

Common Pitfalls to Avoid

• Do not add inhaled corticosteroids to oral glucocorticoids—three randomized trials showed no benefit. 2, 3
• Avoid prolonged prednisone monotherapy ≥10 mg daily—even low doses cause significant toxicity including weight gain, metabolic complications, osteoporosis, cataracts, and reduced quality of life. 5, 3
• Do not continue ineffective treatment—lack of response over 3-6 months indicates need for alternative strategy with addition of second-line agents. 3
• Provide prophylaxis during prolonged steroid use: calcium and vitamin D supplementation to prevent osteoporosis. 3

Organ-Specific Considerations

• Cardiac sarcoidosis: Consider early initiation of steroid-sparing medications due to significant morbidity of long-term glucocorticoid use; obtain cardiac MRI for suspected involvement. 2, 3
• Neurosarcoidosis: Follow the same stepwise approach (glucocorticoids → methotrexate → infliximab). 2
• Cutaneous sarcoidosis: Hydroxychloroquine 200-400 mg once daily is an alternative for skin manifestations with periodic ocular exams. 5, 2