What is the recommended treatment for sarcoidosis with multiple organ involvement?

Treatment of Sarcoidosis with Multiple Organ Involvement

For sarcoidosis with multiple organ involvement, a stepped treatment approach is recommended, starting with prednisone 20-40 mg daily for 3-6 months, followed by addition of 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

First-Line Treatment

• Prednisone 20-40 mg daily is the preferred initial treatment for symptomatic sarcoidosis with multiple organ involvement, allowing 3-6 months to demonstrate responsiveness 1, 2
• For pulmonary sarcoidosis with high risk of mortality or permanent disability, start with prednisone 20 mg daily for 2-6 weeks, followed by maintenance with 5-10 mg daily or every other day 3, 4
• Taper prednisone to the lowest tolerable dose (≤10 mg) after initial response, while monitoring for bone density loss, hypertension, and hyperglycemia 1, 3
• The reported rate of disease relapse upon glucocorticoid withdrawal after 2 years of initial therapy ranges from 20% to 80% 1
• Prolonged prednisone may be required to stabilize disease, with at least half of patients remaining on treatment 2 years later 3, 5

Second-Line Treatment

• Add methotrexate (10-15 mg weekly) to prednisone if there is:
  • Disease progression despite adequate glucocorticoid treatment 1
  • Unacceptable side effects from glucocorticoids 1, 3
  • Inability to wean prednisone to a lower dose 1, 4
• Alternative second-line agents include:
  • Azathioprine 1, 6
  • Mycophenolate mofetil 3, 7
  • Leflunomide 3, 6
• For cardiac sarcoidosis specifically, consider early initiation of steroid-sparing medications due to significant morbidity of long-term glucocorticoid use 3, 8

Third-Line Treatment

• Add infliximab for patients with continued disease despite glucocorticoids and second-line agents 1
• Discontinuation of infliximab after 6-12 months is associated with disease relapse in more than half of cases 1
• For cutaneous sarcoidosis, infliximab can be considered for patients with continued active skin disease despite glucocorticoids/immunosuppressives 3
• Repository corticotrophin injection or concomitant levofloxacin, ethambutol, azithromycin, rifampin (CLEAR) therapy may be considered in refractory cases, though consensus on these approaches is lacking 1

Organ-Specific Considerations

Pulmonary Sarcoidosis

• Monitor treatment response with pulmonary function tests, especially FVC 1, 5
• For patients with pulmonary hypertension (which occurs in up to 70% of advanced cases), consider phosphodiesterase inhibitors and prostacyclin analogues 4, 5

Cardiac Sarcoidosis

• Glucocorticoids with or without immunosuppressives are strongly recommended for patients with functional cardiac abnormalities 3, 8
• Low-dose prednisone/methotrexate combination may be as effective as standard-dose prednisone with better quality of life due to reduced side effects 8

Neurosarcoidosis

• First-line treatment is glucocorticoids, with methotrexate as second-line and infliximab as third-line 3
• For pituitary sarcoidosis, high-dose corticosteroids are used in about 90% of patients, with steroid-sparing therapy subsequently used in 57% 1

Cutaneous Sarcoidosis

• For cosmetically important active skin lesions not controlled by local treatment, oral glucocorticoids are suggested 1
• Hydroxychloroquine 200-400 mg once daily with periodic ocular exams can be considered as an alternative treatment 3

Sarcoidosis-Associated Fatigue

• First-line treatment is a pulmonary rehabilitation program and/or inspiratory muscle strength training for 6-12 weeks 3
• Second-line treatment includes consideration of D-methylphenidate or armodafinil for 8 weeks to test effect on fatigue and tolerability 3

Treatment Duration and Monitoring

• Continue therapy for at least 3-6 months if there is improvement in symptoms, pulmonary function tests, and radiographic findings 3, 5
• Re-evaluate the need for continued successful treatment every 1-2 years 1
• Monitor for adverse effects of immunosuppressive therapy, including appropriate microbial prophylaxis for Pneumocystis jiroveci and herpes zoster when indicated 5
• Despite different treatments, relapse rates range from 13% to 75% depending on the stage of sarcoid, number of organs involved, socioeconomic status, and geography 4