When are corticosteroids indicated for interstitial lung disease (ILD), and what is the recommended dosing and tapering regimen?

Use of Corticosteroids in Interstitial Lung Disease

Critical First Principle: Distinguish ILD Subtype Before Prescribing Steroids

Corticosteroids are conditionally recommended for most systemic autoimmune rheumatic disease-associated ILD (SARD-ILD) but are strongly contraindicated in systemic sclerosis-ILD (SSc-ILD) and idiopathic pulmonary fibrosis (IPF). 1, 2

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When Corticosteroids ARE Indicated

SARD-ILD (Excluding SSc-ILD)

• Glucocorticoids are conditionally recommended as first-line treatment for rheumatoid arthritis-ILD, inflammatory myositis-ILD, Sjögren's disease-ILD, and mixed connective tissue disease-ILD 1
• Start oral prednisone at 0.5–1.0 mg/kg/day, not exceeding 60 mg/day for moderate-to-severe inflammatory ILD with significant pulmonary function test or HRCT abnormalities 3
• Historical practice used 40–100 mg daily for 2–4 months, though no comparative dosing studies exist 1

Rapidly Progressive ILD (RP-ILD) in SARD

• Pulse intravenous methylprednisolone is conditionally recommended as first-line treatment for rapidly progressive disease 1
• One effective regimen: methylprednisolone 1000 mg IV for 3 days per week for 2 weeks, followed by low-dose oral prednisone (10 mg/day) combined with tacrolimus, showed multidimensional improvement in CTD-ILD 4

Acute Exacerbations

• High-dose corticosteroids are recommended for acute exacerbations of ILD, particularly in non-IPF subtypes 2, 5
• Doses >1.0 mg/kg prednisolone improve outcomes in acute exacerbation of non-IPF-ILD but not in IPF exacerbations 5

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When Corticosteroids Are CONTRAINDICATED

Systemic Sclerosis-ILD (SSc-ILD)

• Strongly recommend AGAINST glucocorticoids as first-line treatment for SSc-ILD 1
• Strongly recommend AGAINST long-term glucocorticoids even for progressive SSc-ILD despite first-line treatment 1

Idiopathic Pulmonary Fibrosis (IPF)

• Corticosteroids are not recommended for routine IPF treatment except during acute exacerbations 2, 6
• High-dose corticosteroids are now contraindicated in stable IPF due to lack of benefit and substantial morbidity 6
• Long-term corticosteroid monotherapy is associated with glucose abnormalities, cataracts, osteoporosis, diabetes, and infections without proven survival benefit 2
• Only exception: low-dose prednisone (up to 10 mg daily) may alleviate incapacitating cough in IPF for symptom management only 2

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Mandatory Steroid-Sparing Strategy

Always Add Immunosuppression Early

• Mycophenolate mofetil is the preferred first-line steroid-sparing agent for all CTD-related ILD 3
  • Start 500–1000 mg twice daily, titrate to target of 1500 mg twice daily 3
• Azathioprine is an acceptable alternative for myositis-ILD, MCTD-ILD, RA-ILD, or Sjögren's-ILD (check TPMT activity first) 3
• Rituximab, cyclophosphamide, mycophenolate, and azathioprine are all conditionally recommended as first-line options for SARD-ILD 1

For Refractory Disease

• Add rituximab 1000 mg IV on days 1 and 15 for rapidly progressive disease 3
• Add cyclophosphamide 500–750 mg/m² IV every 4 weeks for refractory cases 3

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Tapering and Maintenance Regimen

Standard Taper Protocol

• If response occurs (usually within 3 months), begin gradual taper guided by objective clinical parameters—dyspnea scores, pulmonary function tests, HRCT 1
• One validated regimen: prednisone 0.5 mg/kg lean body weight daily for 4 weeks, then 0.25 mg/kg daily for 8 weeks, then taper to 0.125 mg/kg daily or 0.25 mg/kg every other day 2
• Chronic low-dose prednisone (15–20 mg every other day) may be adequate for maintenance in responders 1

Duration of Treatment

• Prolonged treatment for minimum 1–2 years is reasonable for patients with unequivocal responses, as corticosteroids rarely eradicate disease completely 1
• Subjective improvement alone is inadequate to gauge response due to placebo and mood-enhancing effects of corticosteroids 1

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Monitoring Requirements

Objective Assessment Every 3 Months

• Perform full pulmonary function tests every 3–6 months, especially during the first 1–2 years 3
• Obtain multidisciplinary HRCT review with thoracic radiologist 3
• Assess functional capacity, resting and exertional pulse oximetry 3
• Echocardiogram when pulmonary hypertension is suspected 3

Before Initiating Steroids

• Actively exclude infectious etiologies and lymphoproliferative disorders before starting immunosuppression 3

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Progressive Fibrotic Phenotype

When to Add Antifibrotics

• Nintedanib is FDA-approved for progressive fibrotic ILD and may be added when HRCT shows predominantly fibrotic pattern despite adequate immunosuppression 3
• Nintedanib is conditionally recommended for SSc-ILD as first-line treatment 1
• Antifibrotic therapy can be combined with ongoing mycophenolate or azathioprine without discontinuation 3

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Common Pitfalls to Avoid

Do Not Continue Steroids Without Objective Improvement

• Corticosteroid therapy should not be continued indefinitely without objective evidence of stabilization or improvement 2
• Relapses or deterioration warrant dose escalation or addition of immunosuppressive agent, not indefinite high-dose steroids 1

High-Risk Populations Require Extra Caution

• Patients >70 years, poorly controlled diabetes, hypertension, severe osteoporosis, or peptic ulcer disease are at high risk for corticosteroid complications 1, 2
• Consider cytotoxic agents (azathioprine or cyclophosphamide) earlier in these populations 1

Long-Term Glucocorticoids in Progressive SARD-ILD

• Conditionally recommend AGAINST long-term glucocorticoids for SARD-ILD progression despite first-line treatment (except as noted for SSc-ILD where it is a strong recommendation against) 1