What are the treatment options for sarcoidosis?

Treatment Options for Sarcoidosis

For symptomatic pulmonary sarcoidosis, the recommended first-line treatment is oral prednisone at 20-40 mg daily for 3-6 months, followed by tapering to the lowest effective dose, with methotrexate as the preferred second-line agent when glucocorticoids are ineffective or cause unacceptable side effects. 1, 2

Treatment Algorithm Based on Disease Severity

First-Line Treatment

• Nearly half of sarcoidosis patients never require systemic treatment as the disease may resolve spontaneously 2
• For symptomatic pulmonary sarcoidosis with high risk of mortality or permanent disability, initiate prednisone 20-40 mg daily for 3-6 months 3, 1, 2
• For patients with worsening quality of life but lower risk, consider initial low-to-medium dose glucocorticoid treatment (5-10 mg daily) 3, 1
• For patients not at risk for morbidity/mortality and without significant quality of life impairment, no glucocorticoid treatment may be preferred due to high prevalence of adverse events 3, 1
• Aim to taper prednisone to lowest tolerable dose, ideally ≤10 mg daily 3

Second-Line Treatment

• Add methotrexate (10-15 mg weekly) if there is:
  • Disease progression despite adequate glucocorticoid treatment
  • Unacceptable side effects from glucocorticoids
  • Need for steroid-sparing therapy 3, 1
• Methotrexate is the most widely studied and best-tolerated second-line agent 3, 1
• Alternative second-line agents include azathioprine, leflunomide, or mycophenolate mofetil 1, 4

Third-Line Treatment

• Add infliximab for patients with continued disease despite glucocorticoids and second-line agents 3, 1
• Infliximab has multiple clinical trials supporting its use in various manifestations of sarcoidosis 3, 1
• For advanced disease not responding to standard therapies, consider repository corticotrophin injection (RCI) or concomitant levofloxacin, ethambutol, azithromycin, rifampin (CLEAR) therapy 3

Organ-Specific Treatment Considerations

Pulmonary Sarcoidosis

• Treatment decisions should be based on three key factors: risk of mortality or permanent disability, significant impairment of quality of life, and presence of symptoms 1, 2
• Inhaled glucocorticoids added to oral glucocorticoids do not provide significant benefits 3, 2
• Monitor treatment response with pulmonary function tests and radiographic findings 1, 5

Cardiac Sarcoidosis

• Glucocorticoids with or without other immunosuppressives are strongly recommended for patients with functional cardiac abnormalities 1
• Consider early initiation of steroid-sparing medications due to significant morbidity of long-term glucocorticoid use 1

Neurosarcoidosis

• First-line treatment is glucocorticoids, with second-line treatment being the addition of methotrexate if disease continues 1
• Third-line treatment is the addition of infliximab if disease continues despite glucocorticoids and second-line agents 1

Cutaneous Sarcoidosis

• Infliximab can be considered for patients with continued active skin disease despite glucocorticoids/immunosuppressives 1
• Alternative treatment is hydroxychloroquine 200-400 mg once daily with periodic ocular exams 1, 6

Treatment Duration and Monitoring

• Continue therapy for at least 3-6 months if there is improvement 3, 1
• Re-evaluate the need for continued successful treatment every 1-2 years 1, 2
• At least half of patients started on glucocorticoids may still be on treatment 2 years later 1, 2
• Monitor for glucocorticoid side effects including weight gain, hypertension, diabetes, and osteoporosis 1, 2
• For patients on methotrexate, monitor complete blood count, liver function tests, and renal function 1

Common 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 3, 2
• Inadequate treatment may result in permanent pulmonary and extrapulmonary organ dysfunction 7
• Inappropriate labeling of patients as "corticosteroid failures" may lead to unnecessary exposure to other potentially toxic drugs 7
• Failure to recognize when to transition from active treatment to supportive care in patients with irreversible fibrotic changes 8
• Underutilization of steroid-sparing agents, leading to unnecessary glucocorticoid-related adverse effects 3, 1

Risk Stratification

• Prioritize treatment for patients at risk for mortality or permanent disability 3, 1
• Risk factors for cardiac sarcoidosis include age >50 years, left ventricular ejection fraction <40%, ventricular tachycardia, and cardiac inflammation on imaging 1
• Risk factors for pulmonary sarcoidosis include pulmonary hypertension, reduced lung function, and pulmonary fibrosis 1, 5