What are the latest guidelines for sarcoidosis management?

Latest Guidelines for Sarcoidosis Management

The European Respiratory Society recommends a stepped treatment approach for sarcoidosis, starting with prednisone 20-40 mg daily for 3-6 months, followed by methotrexate as a second-line agent if disease continues or steroid side effects become unacceptable, and infliximab as a third-line agent for refractory cases. 1, 2

Treatment Decision Framework

• Treatment decisions should be based on risk of mortality or organ failure, with pulmonary and cardiac disease being the most common causes of death from sarcoidosis (approximately 5% of patients die from the disease) 3, 2
• Quality of life impairment, including fatigue and symptomatic manifestations, should also be considered when making treatment decisions 3, 2
• Pattern of organ involvement is another important factor in determining the treatment approach 2

First-Line Treatment

• Prednisone 20-40 mg daily is the preferred initial treatment for symptomatic sarcoidosis, allowing 3-6 months to demonstrate responsiveness 1, 2
• For pulmonary sarcoidosis with symptoms (cough, dyspnea, chest pain), parenchymal infiltrates, and abnormal pulmonary function tests, oral prednisone should be started at 20-40 mg daily for 2-6 weeks 4
• Taper prednisone over 6-18 months if symptoms, pulmonary function tests, and radiographs improve 4, 5
• The reported rate of disease relapse upon glucocorticoid withdrawal after 2 years of initial therapy ranges from 20% to 80% 3, 1

Second-Line Treatment

• Add methotrexate (10-15 mg weekly) to prednisone if there is disease progression despite adequate glucocorticoid treatment or unacceptable side effects from glucocorticoids 1, 2
• Recent evidence from a 2025 study shows methotrexate may be noninferior to prednisone as first-line treatment for pulmonary sarcoidosis, with different side effect profiles that may inform treatment decisions 6
• Alternative second-line agents include azathioprine, mycophenolate mofetil, and leflunomide, although evidence for these is not as strong 1, 5

Third-Line Treatment

• Add infliximab for patients with continued disease despite glucocorticoids and second-line agents 1, 2
• Discontinuation of infliximab after 6-12 months is associated with disease relapse in more than half of cases 3, 1

Organ-Specific Considerations

• For cardiac sarcoidosis, glucocorticoids with or without immunosuppressives are strongly recommended for patients with functional cardiac abnormalities 1
• For neurosarcoidosis, first-line treatment is glucocorticoids, with methotrexate as second-line and infliximab as third-line 1
• For cutaneous sarcoidosis, oral glucocorticoids are suggested for cosmetically important active skin lesions not controlled by local treatment 1
• Hydroxychloroquine 200-400 mg once daily with periodic ocular exams can be considered as an alternative treatment for cutaneous sarcoidosis 1, 2

Treatment Duration and Monitoring

• Continue therapy for at least 3-6 months if there is improvement in symptoms, pulmonary function tests, and radiographic findings 1, 2
• Re-evaluate the need for continued successful treatment every 1-2 years 1
• Monitor pulmonary function tests, including FVC and DLCO, to assess treatment response 2, 4
• Follow radiographic changes using chest imaging and track symptom improvement using quality of life measures 2

Special Considerations

• For patients with pulmonary sarcoidosis and precapillary pulmonary hypertension (which occurs in up to 70% of patients with advanced disease), phosphodiesterase inhibitors and prostacyclin analogues should be considered 4, 5
• Stage IV fibrocystic sarcoidosis with significant pulmonary physiologic impairment, >20% fibrosis on HRCT, or pre-capillary pulmonary hypertension have the highest risk of mortality (>40% at 5 years) 5
• Despite different treatments, relapse rates range from 13% to 75% depending on disease stage, number of organs involved, socioeconomic status, and geography 5