What is the recommended treatment regimen, follow-up imaging, and follow-up intervals for a patient with proven sarcoidosis (biopsy of hilar lymphadenopathy) and symptomatic disease?

Treatment Regimen for Symptomatic Sarcoidosis with Biopsy-Proven Hilar Lymphadenopathy

For patients with symptomatic sarcoidosis confirmed by biopsy of hilar lymphadenopathy, oral prednisone at an initial dose of 20 mg daily is recommended as first-line therapy, with treatment evaluation after 3-6 months and subsequent tapering to the lowest effective dose (5-10 mg daily or every other day). 1, 2

Initial Treatment Approach

First-Line Therapy

• Prednisone/prednisolone:
  • Initial dose: 20 mg once daily 1, 2
  • Duration: Allow 3-6 months to demonstrate responsiveness 1, 2
  • Monitoring: Blood pressure, serum glucose, weight, bone density 1
  • Target: Improvement in symptoms, pulmonary function tests (FVC), and quality of life 1

Recent evidence from the SARCORT trial showed that higher initial doses (40 mg) did not provide superior outcomes compared to 20 mg daily, while having similar adverse effect profiles 3.

Treatment Adjustments Based on Response

1. If improving: Taper to lowest effective dose (5-10 mg daily or every other day) 1, 2
2. If stable: Decrease to maintenance level 2
3. If worsening or experiencing unacceptable side effects: Add second-line therapy 1, 2

Second-Line and Escalation Therapy

Second-Line Options (when prednisone is insufficient or poorly tolerated)

• Methotrexate: 10-15 mg once weekly 1
  • Monitoring: Complete blood count, hepatic and renal function tests 1
  • Recent evidence suggests methotrexate may be as effective as prednisone for first-line therapy with a different side effect profile 4

Third-Line Options (for refractory disease)

• Infliximab: 3-5 mg/kg initially, 2 weeks later, then every 4-6 weeks 1
  • Screen for prior tuberculosis before initiating
  • Contraindicated in severe CHF, prior malignancy, demyelinating neurologic disease, active TB, deep fungal infections 1

Alternative Second-Line Options

• Leflunomide: 10-20 mg once daily 1
• Azathioprine: 50-250 mg once daily 1
• Mycophenolate mofetil: 500-1500 mg twice daily 1

Follow-Up Protocol

Imaging Follow-Up

• Chest X-ray at baseline and at 3-6 month intervals during initial treatment to assess response 1, 5
• Consider additional imaging based on organ involvement and symptoms

Clinical Follow-Up Intervals

• Every 1-3 months during initial treatment phase
• Every 3-6 months during maintenance phase
• Reassess need for continued therapy every 1-2 years 1

Monitoring Parameters

1. Pulmonary function tests: FVC is a critical marker of response 1, 5
2. Symptom assessment: Cough, dyspnea, chest pain, fatigue 5
3. Quality of life measures 1, 2
4. Medication-specific monitoring:
   • For prednisone: Blood pressure, blood glucose, weight, bone density 1
   • For methotrexate: CBC, liver and kidney function tests 1
   • For biologics: Signs of infection, allergic reactions 1

Important Considerations

Duration of Therapy

• Relapse rates upon withdrawal of therapy after 1-2 years range from 20-80% 1
• Withdrawal of methotrexate after 2 additional years was associated with 80% reinstitution of systemic therapy 1
• Discontinuation of infliximab after 6-12 months was associated with relapse in more than 50% of cases 1

Treatment Algorithm Based on Disease Phenotype

• Acute phenotype: Start with prednisone 20 mg daily, evaluate after 3-6 months
• Chronic phenotype: Add methotrexate if disease progression or steroid toxicity occurs
• Advanced phenotype: Consider escalation to infliximab if inadequate response to methotrexate 1

Cautions

• Monitor closely for medication side effects
• Weigh benefits against risks, particularly with long-term corticosteroid use
• Consider prophylaxis for Pneumocystis jiroveci and herpes zoster when using combination immunosuppressive therapy 5