What is the recommended treatment for a patient with Sarcoidosis?

Treatment of Sarcoidosis

Glucocorticoids are the first-line treatment for symptomatic sarcoidosis with significant organ involvement, particularly when there is risk of mortality or permanent disability. 1

Treatment Algorithm by Organ System

Pulmonary Sarcoidosis

First-Line Treatment:

• Initiate oral glucocorticoids (prednisone 20-40 mg daily) for patients with major pulmonary involvement at higher risk of future mortality or permanent disability to improve and/or preserve forced vital capacity (FVC) and quality of life 1, 2
• Higher risk patients include those with reduced lung function, moderate to severe pulmonary fibrosis, or precapillary pulmonary hypertension 3
• Taper prednisone over 6-18 months if symptoms, spirometry, and radiographs improve 2

Second-Line Treatment:

• Add methotrexate for patients with continued disease despite glucocorticoids or those experiencing unacceptable glucocorticoid side-effects (particularly if requiring ≥10 mg/day prednisone long-term) 1, 2
• This is a conditional recommendation based on very low quality evidence, but methotrexate serves as an effective steroid-sparing agent 1, 4

Third-Line Treatment:

• Add infliximab for patients with continued disease despite glucocorticoids and other immunosuppressive agents to improve and/or preserve FVC and quality of life 1, 2
• Anti-TNF agents (infliximab or adalimumab) are reserved for refractory cases 4, 5

Cardiac Sarcoidosis

Immediate Treatment Required:

• Initiate glucocorticoids (with or without other immunosuppressives) for any patient with functional cardiac abnormalities including heart block, dysrhythmias, or cardiomyopathy 1
• This is a strong recommendation despite very low quality evidence, reflecting the high mortality risk of untreated cardiac involvement 1, 2

Neurosarcoidosis

Treatment Escalation:

• Start with glucocorticoids as first-line therapy for clinically significant neurosarcoidosis (strong recommendation) 1
• Add methotrexate if disease continues despite glucocorticoids 1
• Add infliximab if disease persists after glucocorticoids plus a second-line agent (methotrexate, azathioprine, or mycophenolate mofetil) 1

Cutaneous Sarcoidosis

Localized Disease:

• High-potency topical corticosteroids (clobetasol or halobetasol propionate) for localized lesions 6
• Intralesional triamcinolone acetonide injections may be more effective than topical preparations 6

Systemic Treatment:

• Oral glucocorticoids for cosmetically important active skin lesions that cannot be controlled by local treatment 1, 6
• Response occurs in up to two-thirds of patients, though effects are often limited to treatment duration 6
• Add infliximab for patients with continued cosmetically important active skin disease despite glucocorticoids and/or other immunosuppressive agents 1, 6

Alternative Agents:

• Hydroxychloroquine or chloroquine can be considered as first-line systemic therapy for cutaneous sarcoidosis 4
• Tofacitinib may be considered on a case-by-case basis only after failure of glucocorticoids, hydroxychloroquine, methotrexate, and infliximab 7

Sarcoidosis-Associated Fatigue

Non-Pharmacologic First:

• Pulmonary rehabilitation program and/or inspiratory muscle strength training for 6-12 weeks for patients with troublesome fatigue 1

Pharmacologic Options:

• D-methylphenidate or armodafinil for 8 weeks for fatigue not related to disease activity, after consideration of pulmonary exercise or rehabilitation program 1

Critical Treatment Considerations

Duration and Monitoring

• Re-evaluate the need for continued treatment every 1-2 years 1, 6
• Relapse rates range from 13-75% depending on disease stage, organ involvement, and socioeconomic factors 2
• Relapse occurs in 20-80% of patients upon glucocorticoid withdrawal after 2 years 1
• Discontinuation of methotrexate after 2 years is associated with 80% re-institution of systemic therapy 1
• Discontinuation of infliximab after 6-12 months leads to relapse more than half the time 1

Common Pitfalls to Avoid

• Do not delay treatment in cardiac or neurologic sarcoidosis - these require immediate glucocorticoid initiation due to high morbidity risk 1, 2
• Do not use ACE levels alone for diagnosis - they have limited sensitivity (approximately 60%) and can be elevated in other granulomatous conditions 6
• Do not use tofacitinib before exhausting standard therapies - it should never be used before methotrexate and infliximab 7
• Exercise extreme caution with tofacitinib in neurological involvement and avoid in cardiac sarcoidosis where it has not been studied 7

Prognosis Indicators

• Scadding stages I and II have radiographic remission in 30-80% of cases 2
• Stage III has only 10-40% chance of resolution 2
• Stage IV (fibrocystic disease) has no chance of resolution and up to 70% develop precapillary pulmonary hypertension 2
• Stage IV disease with >20% fibrosis on HRCT or precapillary pulmonary hypertension has >40% mortality at 5 years 2
• Overall 5-year mortality for sarcoidosis is approximately 7%, with 60% of deaths due to sarcoidosis itself (80% from advanced cardiopulmonary failure) 2