What is the treatment for sarcoidosis?

Treatment of Sarcoidosis

First-Line Treatment: Glucocorticoids

For symptomatic pulmonary sarcoidosis at risk for mortality or permanent disability, oral prednisone 20-40 mg daily for 2-6 weeks is strongly recommended, followed by tapering to a maintenance dose of 5-10 mg daily. 1, 2, 3

When to Treat vs. Observe

• Nearly half of sarcoidosis patients never require systemic treatment as the disease may resolve spontaneously 4
• Treatment decisions should prioritize three factors: risk of mortality/permanent disability, significant quality of life impairment, and presence of symptoms 4
• For patients without risk of morbidity/mortality and no significant quality of life impairment, no glucocorticoid treatment is preferred due to high prevalence of adverse events 1, 4
• A period of observation for 2 years or more is warranted if the patient is relatively asymptomatic 5

Initial Dosing Protocol

• Start prednisone 20-40 mg daily for 3-6 months to demonstrate responsiveness 2, 4, 6
• For patients with worsening quality of life but lower risk, consider initial low-to-medium dose (5-10 mg daily) 1, 4
• Dose reductions are needed for patients with diabetes, psychosis, or osteoporosis 4
• Inhaled glucocorticoids added to oral glucocorticoids do not provide significant benefits and should not be used 1, 4

Maintenance and Duration

• Taper to the lowest effective maintenance dose (typically 5-10 mg daily or every other day) over 6-18 months if symptoms, pulmonary function, and radiographs improve 2, 6
• At least half of patients started on glucocorticoids remain on treatment 2 years later 2, 4
• Continue therapy for at least 3-6 months if there is improvement, and re-evaluate need for continued treatment every 1-2 years 7, 4
• The relapse rate upon glucocorticoid withdrawal after 2 years ranges from 20% to 80% 7
• A minimum of 1 year of treatment is recommended unless no improvement is noted after 3 months 5

Second-Line Treatment: Methotrexate

For patients with continued disease despite adequate glucocorticoids or unacceptable glucocorticoid side effects, add methotrexate 10-15 mg once weekly. 1, 2, 7, 4

• Methotrexate is the most widely studied and best-tolerated second-line agent 4
• This combination can improve/preserve lung function and quality of life 2
• Alternative second-line agents include azathioprine, leflunomide, or mycophenolate mofetil, though evidence is not as strong 2, 7
• Methotrexate should be administered for at least 2 years 8

Third-Line Treatment: Infliximab

For patients with continued disease despite glucocorticoids and second-line agents, add infliximab. 2, 7, 4

• Infliximab has multiple clinical trials supporting its use in various manifestations of sarcoidosis 4
• Discontinuation of infliximab after 6-12 months is associated with disease relapse in more than half of cases 7

Organ-Specific Treatment Approaches

Cardiac Sarcoidosis

• Glucocorticoids with or without other immunosuppressives are strongly recommended for patients with functional cardiac abnormalities 2, 7
• Consider early initiation of steroid-sparing medications due to significant morbidity of long-term glucocorticoid use 2

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

• For cosmetically important active skin lesions, oral glucocorticoids are suggested, though systemic treatment was associated with improvement in only up to two-thirds of patients 1, 7
• For lupus pernio specifically, only 20% of patients receiving systemic glucocorticoid alone achieved complete or near-complete resolution 1
• For patients with continued active skin disease despite glucocorticoids/immunosuppressives, add infliximab 1, 2
• Alternative: hydroxychloroquine 200-400 mg once daily with periodic ocular exams 2, 7
• Topical glucocorticoids (clobetasol or halobetasol propionate) may be used for limited and discrete papules and plaques 1
• Intralesional triamcinolone acetonide may be more effective than topical preparations 1

Pulmonary Hypertension

• Up to 70% of patients with advanced pulmonary sarcoidosis develop precapillary pulmonary hypertension, which is associated with a 5-year mortality rate of approximately 40% 6
• These patients should be treated with phosphodiesterase inhibitors and prostacyclin analogues 6

Sarcoidosis-Associated Fatigue

• First-line: pulmonary rehabilitation program and/or inspiratory muscle strength training for 6-12 weeks 2
• Second-line: consider D-methylphenidate or armodafinil for 8 weeks 2

Monitoring Treatment Response

• Assessment should include improvement in symptoms, pulmonary function tests, and radiographic findings 2
• For cardiac sarcoidosis: monitor left ventricular ejection fraction and brain natriuretic peptide 2
• For fatigue: evaluate functional improvement with 6-minute walk test 2
• Monitor bone density, blood pressure, and serum glucose during glucocorticoid therapy 2

Critical Pitfalls to Avoid

• Prolonged use of even low doses of prednisone can lead to significant toxicity, including weight gain, steroid-induced complications, and reduced quality of life 4
• Patients inappropriately labeled as "corticosteroid failures" may be subjected to other potentially toxic drugs or even lung transplantation 9
• When irreversible fibrotic changes are present, changing goals to optimal supportive care may represent better management than unrealistic expectations from increased corticosteroid dosage 5
• There is no data on mortality balance between benefits from long-term treatment and risks due to treatment-induced comorbidities 1