Treatment of Sarcoidosis
For patients with symptomatic pulmonary sarcoidosis at risk of mortality or permanent disability, initiate glucocorticoid therapy with prednisone 20-40 mg daily for 3-6 months, then taper based on response. 1, 2
Initial Assessment and Risk Stratification
Before initiating treatment, perform baseline evaluation including:
- Spirometry with FVC, FEV1, and DLCO measurements 1, 3
- Chest radiography and high-resolution CT in clinically significant pulmonary disease 1
- Transthoracic echocardiography if chronic exercise intolerance or suspected pulmonary hypertension 1
- 6-minute walk distance testing 1
High-risk patients requiring treatment include those with:
- Reduced lung function (FVC and DLCO) 3
- Moderate to severe pulmonary fibrosis 3
- Precapillary pulmonary hypertension 3
- Stage III-IV disease with >20% fibrosis on HRCT 4
First-Line Treatment: Glucocorticoids
Prednisone 20-40 mg daily is the initial treatment for symptomatic disease. 2, 5, 4
Treatment Duration and Tapering
- Continue initial dose for 2 weeks to 2 months 4
- Taper over 6-18 months if symptoms, spirometry, and radiographs improve 4
- Prolonged therapy may be required to stabilize disease, with at least half of patients remaining on treatment 2 years later 6
- Relapse rates upon glucocorticoid withdrawal after 2 years range from 20-80% 6
Evidence for Glucocorticoid Efficacy
Glucocorticoids demonstrate short-term efficacy with:
- 2.44-fold increased clinical improvement at 3-6 months 1
- 1.35-fold increased radiographic improvement 1
- Significant pulmonary function improvement in patients with initial lung involvement 1
Second-Line Treatment: Methotrexate
Add methotrexate 10-15 mg weekly if disease progresses despite adequate glucocorticoids or unacceptable steroid side effects develop. 1, 2, 6
Methotrexate is the preferred second-line agent as a steroid-sparing medication for chronic disease. 2
Alternative second-line agents include azathioprine, mycophenolate mofetil, and leflunomide, though evidence is weaker. 6
Third-Line Treatment: Infliximab
For patients failing glucocorticoids and methotrexate, add infliximab. 1, 2, 6
Infliximab is the preferred anti-TNF agent with the strongest evidence. 2
Discontinuation of infliximab after 6-12 months is associated with disease relapse in more than half of cases. 6
Organ-Specific Treatment Approaches
Cardiac Sarcoidosis
For patients with functional cardiac abnormalities (heart block, dysrhythmias, or cardiomyopathy), glucocorticoids with or without other immunosuppressives are strongly recommended. 1
Cardiac involvement occurs in 25% of sarcoidosis patients but causes clinical problems in only 5%, yet may be suddenly fatal. 7
Neurosarcoidosis
Glucocorticoids are strongly recommended as first-line treatment. 1
- Add methotrexate for continued disease despite glucocorticoids 1
- Add infliximab for disease refractory to glucocorticoids and second-line agents 1
Cutaneous Sarcoidosis
For cosmetically important active skin lesions not controlled by topical treatment, oral glucocorticoids are suggested. 1
- Topical glucocorticoids should be attempted first 1
- Hydroxychloroquine 200-400 mg daily with periodic ocular exams is an alternative 6
- For refractory disease after glucocorticoids and other immunosuppressives, add infliximab 1
Only 20% of lupus pernio patients achieve complete resolution with systemic glucocorticoids alone, requiring an average daily prednisone dose of 16 mg. 1
Treatment Response Monitoring
Assess response using:
- Pulmonary function tests (FVC and DLCO) 2
- Chest imaging for radiographic changes 2
- Quality of life and symptom resolution measures 2
Re-evaluate the need for continued treatment every 1-2 years. 6
Treatment may be discontinued if disease has been stable for 2-3 years. 2
Critical Pitfalls to Avoid
Do not withhold treatment in high-risk patients: Stage IV fibrocystic sarcoidosis with significant physiologic impairment, >20% fibrosis on HRCT, or precapillary pulmonary hypertension carries >40% mortality at 5 years. 4
Screen all patients for cardiac involvement: Cardiac sarcoidosis may be asymptomatic but suddenly fatal. 7
Screen all patients for eye involvement: Asymptomatic patients may have eye involvement causing permanent vision impairment. 7
Minimize prolonged high-dose glucocorticoid exposure: Corticosteroid toxicity causes significant morbidity and mortality. 8
Anticipate high relapse rates: Relapse rates range from 13-75% depending on stage, organs involved, socioeconomic status, and geography. 4