Initial Treatment for Sarcoidosis
Start oral prednisone 20-40 mg daily for 3-6 months as first-line treatment for symptomatic sarcoidosis with risk of organ dysfunction, followed by gradual tapering to the lowest effective dose. 1, 2
When Treatment Is Indicated
Treatment should be initiated when sarcoidosis meets any of these criteria: 1, 2
- High risk for mortality or permanent organ disability
- Significant impairment of quality of life from symptoms
Do not treat asymptomatic patients without organ dysfunction risk or quality of life impairment, as nearly half of sarcoidosis cases resolve spontaneously and glucocorticoid adverse events are highly prevalent. 2, 3
Initial Prednisone Dosing Protocol
For symptomatic disease with organ dysfunction risk: 1, 2
- Start prednisone 20-40 mg daily
- Continue this initial dose for 3-6 months to assess therapeutic response
- Prednisone is FDA-approved for symptomatic sarcoidosis 4
For quality of life impairment alone (without organ threat): 1
- Consider lower initial dose of 5-10 mg daily through shared decision-making
Reduce the starting dose in patients with diabetes, psychosis, or osteoporosis. 1, 2
Monitoring and Response Assessment
Evaluate treatment response at 3 months with: 1, 2
- Clinical symptom assessment
- Organ-specific testing (pulmonary function tests for lung involvement)
- Imaging studies (chest imaging, cardiac MRI if cardiac involvement suspected)
- Begin tapering prednisone gradually to the lowest dose maintaining symptom control and disease stability
- Target maintenance dose ≤10 mg daily or discontinuation if possible
- Total treatment duration should be 6-18 months from initiation if disease responds
Adding Second-Line Therapy: Methotrexate
Add methotrexate 10-15 mg weekly if any of the following occur: 1, 2, 3
- Disease progression despite adequate glucocorticoid treatment
- Unacceptable glucocorticoid side effects
- Unable to taper prednisone below 10 mg daily after 6 months
Methotrexate is the preferred second-line agent based on the most extensive evidence and best tolerability profile compared to alternatives (azathioprine, leflunomide, mycophenolate mofetil). 1, 2, 3
Third-Line Treatment: Infliximab
Add infliximab 3-5 mg/kg (initially, at 2 weeks, then every 4-6 weeks) for patients with continued disease despite glucocorticoids and methotrexate. 2, 3 Infliximab is particularly effective for severe manifestations including cardiac and neurologic sarcoidosis. 1, 2
Organ-Specific Considerations
- Obtain cardiac MRI for suspected cardiac involvement
- Consider early initiation of steroid-sparing medications due to significant morbidity of long-term glucocorticoid use
Neurosarcoidosis: 3
- First-line: glucocorticoids
- Second-line: add methotrexate if disease continues
- Third-line: add infliximab if disease continues despite glucocorticoids and methotrexate
Cutaneous sarcoidosis: 3
- Consider hydroxychloroquine 200-400 mg once daily with periodic ocular exams as alternative
- Infliximab for continued active skin disease despite glucocorticoids/immunosuppressives
Supportive Care During Glucocorticoid Therapy
Provide prophylaxis during prolonged steroid use: 1, 2
- Calcium and vitamin D supplementation
- Monitor blood pressure, serum glucose, and bone density
- Baseline serum calcium testing to screen for abnormal calcium metabolism
Critical Pitfalls to Avoid
Do not use inhaled corticosteroids as adjunctive therapy - three randomized trials showed no benefit when added to oral glucocorticoids. 1
Avoid prolonged prednisone monotherapy ≥10 mg daily - even low doses cause significant toxicity including weight gain, metabolic complications, and reduced quality of life. 1
Do not continue ineffective treatment - lack of response over 3-6 months indicates need for alternative strategy (add methotrexate). 1, 3
Managing Relapse
If relapse occurs during or after tapering: 1
- Restart prednisone at the last effective dose
- Add methotrexate as steroid-sparing agent