What is the recommended steroid treatment for interstitial lung disease (ILD)?

Steroid Treatment for Interstitial Lung Disease

For most forms of systemic autoimmune rheumatic disease-associated ILD (SARD-ILD), glucocorticoids should NOT be used as first-line monotherapy; instead, use mycophenolate or other immunosuppressants as primary treatment, with steroids reserved for rapidly progressive disease or as short-term adjunctive therapy. 1, 2

Critical Disease-Specific Steroid Recommendations

Systemic Sclerosis-ILD (SSc-ILD)

• Strongly avoid long-term glucocorticoids in SSc-ILD due to high risk of triggering scleroderma renal crisis, particularly at prednisone doses >15 mg daily 1, 2
• This is a strong recommendation with high-quality evidence—the most definitive contraindication in ILD management 1
• Even for progressive SSc-ILD despite first-line treatment, long-term glucocorticoids remain strongly contraindicated 1

Other SARD-ILD Types (RA-ILD, IIM-ILD, MCTD-ILD, Sjögren's-ILD, SLE-ILD)

• Short-term glucocorticoids (≤3 months) are conditionally recommended as part of initial combination therapy, not as monotherapy 2, 3
• For chronic/stable disease: Use oral prednisone at low doses (typically starting 1 mg/kg/day for 4 weeks, then taper to ≤10 mg daily) combined with steroid-sparing agents 1, 4
• Goal is to minimize chronic exposure to <7.5 mg/day prednisone equivalent and withdraw when possible 3

Rapidly Progressive or Acute ILD

Pulse Steroid Protocol

• For rapidly progressive SARD-ILD or acute respiratory failure: Use pulse IV methylprednisolone 1000 mg daily for 3 days, followed by moderate-to-high dose oral prednisone (up to 60 mg daily) with slow taper over weeks to months 1, 2, 5
• This approach showed multidimensional improvement in lung function (FVC improved from 77.8% to 94.6%, DLCO from 66.1% to 75.1% at 12 months) when combined with tacrolimus 6
• Alternative dosing: Methylprednisolone 250-1000 mg daily for 1-3 days is acceptable 3

Critical Caveat

• Always exclude infections or lymphoproliferative disorders before initiating high-dose steroids 2
• In acute exacerbation of non-IPF ILD, higher corticosteroid doses (>1 mg/kg prednisolone) improved outcomes compared to lower doses, but this benefit was NOT seen in IPF patients 7

First-Line Treatment Strategy (Non-Acute Disease)

Preferred Approach

• Mycophenolate mofetil is the preferred first-line immunosuppressive agent for all SARD-ILD types (1000-1500 mg twice daily) 1, 2, 5, 3
• Combine with short-term low-dose steroids rather than using steroids as monotherapy 2, 3
• Alternative first-line steroid-sparing agents: azathioprine (50 mg daily, gradually increasing to 2-3 mg/kg/day), rituximab, or cyclophosphamide 1, 2, 5

Specific Disease Considerations

• IIM-ILD: Calcineurin inhibitors (CNIs, particularly tacrolimus) are conditionally recommended as first-line options, especially for MDA-5 antibody-positive or severe disease at presentation 1
• SLE-ILD: Glucocorticoids combined with mycophenolate, azathioprine, rituximab, or cyclophosphamide as first-line therapy 3

Progressive Disease Despite First-Line Treatment

Steroid Recommendations

• For SSc-ILD progression: Strongly recommend AGAINST long-term glucocorticoids 1
• For other SARD-ILD progression: Conditionally recommend AGAINST long-term glucocorticoids 1, 2
• Instead, switch to or add: mycophenolate, rituximab, cyclophosphamide, or nintedanib 1, 3

Evidence Supporting Steroid Avoidance

• Long-term glucocorticoids increase morbidity without proven efficacy for chronic ILD management 2, 3
• A study comparing high-dose versus low-dose prednisone (10 mg daily) with cyclophosphamide showed the low-dose group achieved better improvement in radiologic lesions and Warrick index 4

Monitoring During Steroid Treatment

Inpatient Monitoring

• Daily assessment of respiratory status, oxygen requirements, and pulse oximetry at rest and with activity 5
• Monitor for steroid-related complications: hyperglycemia, hypertension, mood disturbances, osteoporosis, avascular necrosis 1, 5

Outpatient Monitoring

• Pulmonary function tests (FVC, DLCO) every 3-6 months to assess disease progression 2, 3
• High-resolution CT at baseline and annually (or with significant PFT changes) 3
• CBC with differential and LFTs when using steroid-sparing agents 1

Steroid Tapering Strategy

• After pulse therapy, taper prednisone dose by 5 mg every 2 weeks down to 10 mg daily 1, 4
• Prompt initiation of immunomodulatory agents expedites glucocorticoid tapering 3
• Continue steroid-sparing agents as maintenance therapy while tapering steroids to lowest effective dose or off 5

Common Pitfalls to Avoid

1. Never use long-term high-dose glucocorticoids as maintenance monotherapy—they substantially increase morbidity without proven long-term efficacy 1, 2, 3
2. Do not use any dose of chronic steroids in SSc-ILD due to scleroderma renal crisis risk 1, 2
3. Do not start steroids without ruling out infection first in immunocompromised patients 2
4. Avoid corticosteroid monotherapy for idiopathic pulmonary fibrosis (IPF) except in acute exacerbation context 5, 7
5. Provide Pneumocystis jirovecii prophylaxis when using cyclophosphamide 2
6. Be aware of drug-induced lung disease from TNF-alpha inhibitors, sulfasalazine, leflunomide, methotrexate, and sulfonamides 2