Management of Sarcoidosis
Treatment Decision Framework
Treatment should be initiated when there is risk of death, permanent organ damage, or significant quality of life impairment—not simply based on the presence of granulomas or radiographic findings alone. 1, 2
The decision to treat depends on two critical factors:
- Risk for mortality or irreversible organ failure (particularly pulmonary, cardiac, neurologic, renal, or ocular involvement) 1, 2
- Significant impairment of quality of life (including troublesome fatigue, symptomatic organ involvement, or cosmetically important skin lesions) 1
Approximately 5-7% of sarcoidosis patients die from the disease, with pulmonary and cardiac involvement being the leading causes of death. 1, 3
First-Line Treatment: Glucocorticoids
For symptomatic sarcoidosis requiring treatment, oral prednisone 20-40 mg daily is the first-line therapy. 1, 2, 4
Initial Dosing and Duration
- Start prednisone 20-40 mg daily for 3-6 months 2, 5
- Reassess at 3-6 months for treatment response (symptom improvement, pulmonary function tests, radiographic changes) 2, 5
- If improvement occurs, taper over 4-8 weeks to the lowest effective dose 2, 5
- Treatment duration often requires at least 2 years, with 25% of patients needing longer-term therapy 5, 3
Common Pitfall
Prolonged glucocorticoid use (≥10 mg/day for extended periods) causes significant toxicity including diabetes, osteoporosis, and psychosis—this necessitates early consideration of steroid-sparing agents. 1, 5, 4
Second-Line Treatment: Methotrexate
For patients on glucocorticoids with continued disease, unacceptable steroid side effects, or anticipated need for prolonged high-dose steroids, add methotrexate as the preferred steroid-sparing agent. 1, 2
Indications for Adding Methotrexate
- Inadequate response to glucocorticoids alone 1, 2
- Glucocorticoid toxicity or high risk for toxicity 2, 5
- Need for prednisone ≥10 mg/day for extended periods 3
- Expectation of prolonged treatment (>6 months) 5
Evidence
Methotrexate improves and/or preserves forced vital capacity (FVC) and quality of life in pulmonary sarcoidosis, though the evidence quality is very low. 1 Regular laboratory monitoring for hepatotoxicity is required. 2
Third-Line Treatment: Infliximab
For refractory disease despite glucocorticoids and methotrexate (or other second-line agents), add infliximab—the preferred anti-TNF biologic with the strongest evidence. 1, 2
Specific Indications by Organ System
Pulmonary: For continued symptomatic disease despite glucocorticoids ± methotrexate, infliximab improves FVC and quality of life. 1, 2
Cutaneous: For cosmetically important active skin lesions unresponsive to glucocorticoids and/or other immunosuppressives, infliximab reduces skin lesions. 1, 2
Neurologic: For neurosarcoidosis failing glucocorticoids and second-line agents (methotrexate, azathioprine, mycophenolate), infliximab is recommended. 1, 2
Caveat
Discontinuation of infliximab after 6-12 months results in relapse in more than 50% of cases, suggesting prolonged therapy may be necessary. 5
Organ-Specific Management
Cardiac Sarcoidosis
For any evidence of functional cardiac abnormalities (heart block, dysrhythmias, cardiomyopathy), glucocorticoids with or without other immunosuppressives are strongly recommended—this is a STRONG recommendation despite very low quality evidence due to high mortality risk. 1, 5
Cardiac involvement causes death in up to 80% of sarcoidosis-related deaths in Japan and is a leading cause worldwide. 3 New-onset third-degree AV block in young/middle-aged adults is highly suggestive of cardiac sarcoidosis. 5
Neurosarcoidosis
For clinically significant neurosarcoidosis, glucocorticoids are strongly recommended as first-line treatment. 1
Treatment escalation algorithm:
- Glucocorticoids (strong recommendation) 1
- Add methotrexate if continued disease on glucocorticoids 1
- Add infliximab if continued disease on glucocorticoids + second-line agent 1
Cutaneous Sarcoidosis
For cosmetically important active skin lesions not controlled by local treatment, oral glucocorticoids should be considered. 1
Hydroxychloroquine may be added for skin disease or hypercalcemia. 2
Pulmonary Sarcoidosis
For symptomatic pulmonary disease with risk of mortality or permanent disability, glucocorticoids are strongly recommended. 1, 2
Treatment is indicated for:
- Symptomatic disease (cough, dyspnea) with parenchymal infiltrates and abnormal pulmonary function tests 3, 6
- Risk factors for progression: pulmonary hypertension, reduced lung function, pulmonary fibrosis 1
- Scadding Stage III-IV disease (only 10-40% chance of spontaneous resolution for Stage III; 0% for Stage IV) 3
Sarcoidosis-Associated Fatigue
For troublesome fatigue, pulmonary rehabilitation and/or inspiratory muscle strength training for 6-12 weeks is recommended first. 1
If fatigue persists and is not related to active disease activity, after consideration of exercise/rehabilitation:
- D-methylphenidate or armodafinil for 8 weeks to test effect and tolerability 1
Important Exclusions
Rule out other causes of fatigue before attributing to sarcoidosis: diabetes, thyroid dysfunction, depression, sleep apnea, small fiber neuropathy, vitamin D deficiency, heart failure. 1
Treatment Response Monitoring
Assess response at 3-6 month intervals using:
- Pulmonary function tests (FVC, DLCO) 2
- Chest imaging for radiographic changes 2
- Quality of life measures and symptom resolution 2
Treatment may be discontinued if disease has been stable for 2-3 years, though relapse rates range from 13-75% depending on stage, organ involvement, and other factors. 2, 3
Critical Caveat
Serum ACE levels should NOT guide treatment decisions—low or normal ACE does not exclude active disease requiring treatment. 5 Treatment decisions must be based on clinical symptoms, organ involvement risk, functional parameters, and radiographic findings. 5
Special Populations and Considerations
Hepatic Involvement
For hepatic sarcoidosis with symptoms (abdominal pain, jaundice) or risk of cholestasis/portal hypertension, prednisone is first-line treatment. 7 Consider azathioprine as steroid-sparing agent for hepatic involvement. 5 Monitor liver function tests regularly and consider ursodeoxycholic acid for cholestatic features. 5
Advanced Fibrocystic Disease (Stage IV)
Patients with Stage IV disease have the highest mortality risk (>40% at 5 years) and may develop precapillary pulmonary hypertension in up to 70% of cases. 3 These patients may respond to targeted pulmonary arterial hypertension medications and should be considered for lung transplantation if eligible. 3, 6