What is the initial treatment for extra pulmonary sarcoidosis?

Initial Treatment for Extrapulmonary Sarcoidosis

Oral prednisone at 20-40 mg daily for 3-6 months is the first-line treatment for symptomatic extrapulmonary sarcoidosis, followed by gradual tapering to the lowest effective dose. 1, 2

When to Initiate Treatment

Treatment is indicated when extrapulmonary sarcoidosis meets any of these criteria:

• High risk for mortality or permanent organ disability (cardiac, neurologic, or severe ocular involvement) 1
• Significant impairment of quality of life from symptoms 1
• Progressive organ dysfunction that threatens permanent damage 3

Do not treat patients without symptoms, organ dysfunction risk, or quality of life impairment due to high prevalence of glucocorticoid adverse events. 1

First-Line Treatment Protocol

Standard Dosing

• Start prednisone 20-40 mg daily for symptomatic disease with organ dysfunction risk 1, 2, 4
• For quality of life impairment alone without organ threat, consider lower initial dose of 5-10 mg daily through shared decision-making 1
• Continue initial dose for 3-6 months to assess therapeutic response 1, 2

Dose Modifications for Comorbidities

Reduce the starting dose in patients with: 1, 2

• Diabetes
• Psychosis
• Osteoporosis

Monitoring and Tapering

• Evaluate response at 3 months with clinical assessment, organ-specific testing, and imaging 5
• If improved, begin tapering to the lowest dose maintaining symptom control and disease stability 1, 2
• Target total treatment duration of 6-18 months from initiation if disease responds 2, 6
• Monitor every 3-6 months during taper with clinical assessment and organ-specific testing 5

When to Add Second-Line Therapy

Add methotrexate 10-15 mg weekly if any of the following occur: 1, 2

• Disease progression despite adequate glucocorticoid treatment
• Unacceptable glucocorticoid side effects
• Unable to taper prednisone below 10 mg daily after 6 months 2, 5
• High risk for steroid toxicity anticipated
• Long-duration therapy expected

Methotrexate is the preferred second-line agent based on the most extensive evidence and best tolerability profile. 1, 2 Oral administration is favored, with subcutaneous route reserved for gastrointestinal side effects. 1

Third-Line Treatment

Add infliximab for patients with continued disease despite glucocorticoids and methotrexate. 1, 2 This applies particularly to severe extrapulmonary manifestations including cardiac and neurologic sarcoidosis where disease control is critical for preventing mortality. 1

Organ-Specific Considerations

Cardiac Sarcoidosis

• This represents the highest mortality risk (>70% of sarcoidosis deaths in some populations) and demands aggressive treatment 6, 7
• Cardiac MRI is suggested for suspected cardiac involvement 1

Neurologic Sarcoidosis

• Requires aggressive treatment due to risk of permanent disability 3

Ocular Sarcoidosis

• Severe manifestations warrant systemic therapy to prevent vision loss 4

Hypercalcemia

• Baseline serum calcium testing is strongly recommended to screen for abnormal calcium metabolism 1

Common Pitfalls to Avoid

• Do not use inhaled corticosteroids as adjunctive therapy - three randomized trials showed no benefit when added to oral glucocorticoids 1
• Avoid prolonged prednisone monotherapy ≥10 mg daily - even low doses cause significant toxicity including weight gain, metabolic complications, and reduced quality of life 2, 5
• Do not continue ineffective treatment - lack of response over 3-6 months indicates need for alternative strategy 1, 8
• Recognize that at least half of patients started on glucocorticoids remain on treatment at 2 years - plan for steroid-sparing agents early 1, 8

Managing Disease Changes During Treatment

If Disease Worsens

• Add or increase adjunctive therapy (methotrexate) 1
• Re-evaluate diagnosis and treatment plan 1
• Do not taper steroids 5

If Disease Improves

• Decrease steroid dose gradually to lowest effective level 1, 2
• Do not increase steroid dose 1

If Disease Remains Stable

• Continue current dose or cautiously decrease 1
• Avoid complete withdrawal during early stabilization 5

Relapse Management

If relapse occurs during or after tapering, restart prednisone at the last effective dose and add methotrexate as steroid-sparing agent. 5 Relapse rates range from 13-75% depending on organ involvement and disease stage. 7

Supportive Care During Glucocorticoid Therapy

Provide prophylaxis during prolonged steroid use: 5

• Calcium and vitamin D supplementation
• Proton pump inhibitor for gastrointestinal protection
• Consider Pneumocystis jiroveci and herpes zoster prophylaxis with immunosuppressive combinations 6