For an adult with an inflammatory interstitial lung disease such as cryptogenic organizing pneumonia, acute hypersensitivity pneumonitis, nonspecific interstitial pneumonia, connective‑tissue‑disease‑related ILD, or an acute exacerbation of a fibrotic disease, what is the recommended systemic corticosteroid regimen (dose, route, duration, taper) and monitoring, and when should additional immunosuppressive or antifibrotic therapy be added?

Corticosteroid Management in Inflammatory Interstitial Lung Disease

For adults with inflammatory ILD (cryptogenic organizing pneumonia, acute hypersensitivity pneumonitis, NSIP, CTD-ILD, or acute exacerbations), initiate high-dose IV methylprednisolone 1000 mg daily for 3 days followed by oral prednisone 0.5-1.0 mg/kg daily (maximum 60 mg), then taper slowly over 2-4 months while simultaneously starting mycophenolate mofetil as mandatory steroid-sparing therapy. 1

Initial High-Dose Steroid Phase

For acute exacerbations or rapidly progressive disease:

• Start pulse-dose IV methylprednisolone 1000 mg daily for 3 consecutive days 1
• Alternative dosing: IV methylprednisolone 1-2 mg/kg/day for severe cases 1
• Critical first step: Rule out infections and lymphoproliferative disorders before initiating steroids, as these are common mimics that will worsen with immunosuppression 2, 1

For symptomatic but non-critical disease:

• Begin oral prednisone 0.5-1.0 mg/kg daily, not exceeding 60 mg daily 2, 1
• This applies to moderate-severe disease with significant PFT/HRCT abnormalities 2

Structured Tapering Protocol

Weeks 1-4 (Maintenance Phase):

• Continue initial prednisone dose (40-60 mg daily) if clinical improvement occurs 1
• Monitor for symptomatic response, oxygen requirements, and functional status 2

Weeks 4-8 (Early Taper):

• If symptoms improve to mild or absent, reduce by 5-10 mg every 1-2 weeks 1
• Target dose of 20-30 mg daily by end of month 2 1

Months 3-4 (Late Taper):

• Continue tapering to 10-20 mg daily by month 3 1
• Taper to off or lowest effective dose over 2-4 months total 2, 1

If clinical worsening occurs during taper:

• Return immediately to previous effective dose 1
• Do not continue tapering until stability re-established 1

Mandatory Concurrent Steroid-Sparing Immunosuppression

You must initiate steroid-sparing agents at the same time as steroids, not wait to see if taper fails:

First-line agent (preferred for all CTD-ILD types):

• Mycophenolate mofetil: Start 500-1000 mg twice daily, target 1500 mg twice daily 2, 1
• This is the preferred first-line maintenance agent for all connective tissue disease-related ILD 1

Alternative first-line agents:

• Azathioprine: For myositis-ILD, MCTD-ILD, RA-ILD, or Sjögren's-ILD 2, 1
• Check TPMT activity/genotype before starting 2

Second-line agents for refractory/rapidly progressive disease:

• Rituximab 1000 mg IV on days 1 and 15 2, 1
• Cyclophosphamide 500-750 mg/m² IV every 4 weeks 2, 1
• These should be added to high-dose steroids for acute/subacute hypoxic respiratory failure despite initial therapy 2

Essential Supportive Prophylaxis

Infection prophylaxis:

• Trimethoprim-sulfamethoxazole (Pneumocystis jirovecii prophylaxis) for all patients receiving ≥20 mg prednisone equivalent for ≥4 weeks 1

GI and bone protection:

• Proton pump inhibitor for GI prophylaxis 1
• Calcium and vitamin D supplementation with all prolonged steroid use 1
• Bisphosphonate if anticipated steroid duration >3 months 1

Monitoring Schedule

Pulmonary function testing:

• Perform full PFTs every 3-6 months, especially in the first 1-2 years 2
• Frequency dictated by individual pace of disease progression 2

Clinical monitoring:

• Functional capacity assessment 2
• Pulse oximetry at rest and with activity 2
• Critical HRCT review with thoracic radiologist in multidisciplinary discussion 2
• Consider echocardiogram if pulmonary hypertension suspected 2

Critical Pitfalls to Avoid

Do not use long-term glucocorticoids (>3-6 months) as maintenance monotherapy - this is associated with poor outcomes and significant toxicity without steroid-sparing agents 1

Do not inappropriately prolong steroids after clinical improvement - taper as outlined above 1

Exercise extreme caution with high-dose steroids in systemic sclerosis-ILD - this population has unique risks 1

Do not use this approach for idiopathic pulmonary fibrosis (IPF/UIP) - steroids are harmful in IPF, with one study showing 50% survival in non-steroid treated IPF acute exacerbations versus 25% in those receiving immunosuppression 3. A recent 2024 study demonstrated increased in-hospital mortality with steroids in fibrotic ILD (OR 4.11, p=0.049), though non-IPF patients may have reduced long-term mortality compared to IPF patients 4. There is no evidence supporting corticosteroids in IPF 2, 5.

When to Add Antifibrotic Therapy

For progressive fibrotic ILD phenotype:

• Nintedanib is FDA-approved for progressive fibrotic ILD 2
• Consider adding antifibrotic therapy when HRCT demonstrates predominantly fibrotic pattern despite immunosuppression 2
• Continue mycophenolate or azathioprine alongside antifibrotic agents 2

For organizing pneumonia patterns:

• A small study showed all 30 patients with organizing pneumonia at 6 weeks post-discharge improved with prednisone 0.5 mg/kg for 3 weeks, demonstrating significant symptomatic, physiological, and radiologic improvement 2