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, but nearly half of patients never need systemic treatment as the disease may resolve spontaneously. 1

When to Treat vs. Observe

The decision to initiate treatment hinges on three critical factors 1:

• High risk of mortality or permanent organ disability - This includes cardiac involvement, neurosarcoidosis, sight-threatening ocular disease, or progressive pulmonary fibrosis 1, 2
• Significant impairment of quality of life - Debilitating symptoms affecting daily function 1
• Presence of symptoms with organ dysfunction - Cough, dyspnea, chest pain with abnormal pulmonary function tests 3

For asymptomatic patients without organ dysfunction risk or quality of life impairment, observation without treatment is preferred due to the high prevalence of glucocorticoid adverse events. 1, 2

First-Line Treatment Protocol

Standard Dosing

• Start prednisone 20-40 mg once daily for 3-6 months to assess therapeutic response 4, 1
• After the initial period, taper to maintenance dose of 5-10 mg daily or every other day 4, 2
• Continue tapering over 6-18 months if symptoms, pulmonary function tests, and radiographs improve 5, 3

Modified Dosing for Lower-Risk Disease

• For patients with 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

Dose Reductions for Comorbidities

• Reduce the starting dose in patients with diabetes, psychosis, or osteoporosis 1, 6

Essential Monitoring

• Bone density, blood pressure, and serum glucose throughout treatment 4
• Baseline serum calcium to screen for abnormal calcium metabolism 6
• Evaluate response at 3 months with clinical assessment, organ-specific testing, and imaging 6

When to Add Second-Line Therapy

Add methotrexate 10-15 mg once 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 the most extensive evidence base 1, 7. It requires monitoring with complete blood count, hepatic, and renal serum testing, and should be avoided in significant renal failure 4.

Alternative second-line agents include azathioprine (50-250 mg once daily), leflunomide (10-20 mg once daily), or mycophenolate mofetil (500-1500 mg twice daily), though these have less experience in sarcoidosis 4, 2.

Third-Line Treatment

Add infliximab for patients with continued disease despite glucocorticoids and second-line agents 1, 2. Infliximab is dosed at 3-5 mg/kg initially, 2 weeks later, then every 4-6 weeks 4. It has multiple clinical trials supporting its use across various sarcoidosis manifestations 1.

Critical screening before infliximab: Screen for prior tuberculosis, monitor for allergic reactions, and note contraindications including severe congestive heart failure, prior malignancy, demyelinating neurologic disease, active tuberculosis, and deep fungal infections 4.

Treatment Duration and Re-evaluation

• Continue therapy for at least 3-6 months if there is improvement 1, 2
• Re-evaluate the need for continued treatment every 1-2 years 1
• At least half of patients started on glucocorticoids remain on treatment 2 years later 1, 2
• If disease worsens during treatment, add or increase adjunctive therapy and re-evaluate the diagnosis 6

Critical Pitfalls to Avoid

Prolonged prednisone monotherapy ≥10 mg daily causes significant toxicity including weight gain, diabetes, hypertension, osteoporosis, cataracts, glaucoma, and reduced quality of life, even at low doses 4, 6. This represents cumulative toxicity that worsens over time 4.

Do not add inhaled glucocorticoids to oral glucocorticoids - three randomized trials showed no significant benefit from this combination 1, 6, 2.

Lack of response over 3-6 months indicates need for alternative strategy - continuing ineffective treatment delays appropriate escalation 6.

Organ-Specific Considerations

Cardiac Sarcoidosis

• Glucocorticoids with or without other immunosuppressives are strongly recommended for functional cardiac abnormalities 2
• Consider early initiation of steroid-sparing medications due to significant morbidity of long-term glucocorticoid use 2
• Cardiac MRI is suggested for suspected cardiac involvement 6

Neurosarcoidosis

• First-line: glucocorticoids 2
• Second-line: add methotrexate if disease continues 2
• Third-line: add infliximab if disease continues despite glucocorticoids and methotrexate 2

Cutaneous Sarcoidosis

• Hydroxychloroquine 200-400 mg once daily is an alternative treatment option with periodic ocular exams 4, 2
• Note: hydroxychloroquine has minimal impact on cardiac and neurologic disease 4

Supportive Care

Provide prophylaxis during prolonged steroid use, including calcium and vitamin D supplementation to prevent osteoporosis 6.