What are the management strategies for patients with interstitial lung disease (ILD) or autoimmune diseases starting long-term steroid treatment?

Management of Patients with ILD or Autoimmune Diseases Starting Long-Term Steroids

Before Starting Steroids: Disease-Specific Contraindications

For systemic sclerosis-ILD (SSc-ILD), glucocorticoids are strongly contraindicated as first-line therapy due to high risk of scleroderma renal crisis, particularly at prednisone doses >15 mg daily. 1, 2

• For all other systemic autoimmune rheumatic disease-ILD (SARD-ILD) including inflammatory myopathy-ILD, mixed connective tissue disease-ILD, rheumatoid arthritis-ILD, and Sjögren's-ILD, short-term glucocorticoids may be used as part of initial therapy. 2

Baseline Evaluation Before Initiating Steroids

Screen for infections and alternative diagnoses before starting high-dose steroids, as infections and lymphoproliferative disorders can mimic ILD progression. 2, 3

• Obtain baseline glucose, blood pressure, bone density assessment, and ophthalmologic evaluation for glaucoma/cataracts. 1
• Check for latent tuberculosis and hepatitis B status before immunosuppression. 1
• Assess thiopurine methyltransferase activity or genotype if azathioprine is being considered as steroid-sparing agent to prevent life-threatening leukopenia. 1

Initial Steroid Dosing Regimens

For Rapidly Progressive or Severe ILD (Non-SSc)

Pulse dose 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. 2, 3, 4

For Moderate-Severe Symptomatic ILD (Non-SSc)

Standard dosing is prednisone 0.5-1.0 mg/kg daily based on clinical context and disease severity. 1

For SSc-ILD at Any Stage

Avoid glucocorticoids entirely; initiate mycophenolate mofetil as first-line therapy instead. 1, 2

Concurrent Steroid-Sparing Immunosuppression

Mycophenolate mofetil is the preferred first-line steroid-sparing agent for all SARD-ILD types and should be initiated when long-term steroid use is contemplated. 1, 2, 3

• Azathioprine is an acceptable alternative first-line steroid-sparing agent for myositis-ILD, MCTD-ILD, RA-ILD, and Sjögren's-ILD. 1, 2, 3
• Rituximab should be considered for patients with inflammatory arthritis or myositis. 3
• Cyclophosphamide is reserved for severe, rapidly progressive cases and requires Pneumocystis jirovecii prophylaxis. 2, 3

Monitoring During Steroid Treatment

Inpatient Monitoring

Daily assessment of respiratory status, oxygen requirements, and pulse oximetry at rest and with activity. 3

• Monitor for hyperglycemia and hypertension daily. 2, 3
• Serial pulmonary function tests as clinically indicated during hospitalization. 3

Outpatient Monitoring

Pulmonary function tests every 3-6 months, especially in the first 1-2 years. 2, 3

• Monitor for short-term steroid complications: glucose intolerance, avascular necrosis, fluid retention, hypertension, myopathy, psychological effects (hyperactivity, insomnia, psychosis), pancreatitis, truncal obesity, acne, leukocytosis, ecchymosis. 1
• Monitor for long-term steroid complications: osteoporosis, diabetes, adrenal insufficiency, peptic ulcer disease, hepatic steatosis, glaucoma, cataracts, hyperlipidemia. 1

Steroid Tapering Strategy

Taper steroids to the lowest effective dose or discontinue entirely while continuing steroid-sparing agents as maintenance therapy. 3

• For alternate-day therapy (when appropriate): transition to alternate-day dosing once control is established, potentially tripling or quadrupling the daily maintenance dose given every other day rather than doubling. 5
• Avoid dexamethasone and betamethasone for alternate-day therapy due to prolonged adrenal suppression. 5
• Short-acting corticosteroids (methylprednisolone, hydrocortisone, prednisone, prednisolone) are preferred for alternate-day therapy as they produce adrenocortical suppression for only 1.25-1.5 days. 5

Management of Disease Progression on Steroids

For SARD-ILD with progression despite first-line therapy, conditionally recommend against adding glucocorticoids; for SSc-ILD progression, strongly recommend against adding glucocorticoids. 1, 2

• Switch to or add mycophenolate, rituximab, or cyclophosphamide for progressive disease. 1
• Consider adding nintedanib for SARD-ILD progression (except SSc-ILD where it may be first-line). 1
• For RA-ILD progression, consider adding pirfenidone. 1

Critical Pitfalls to Avoid

Never use long-term glucocorticoids in SSc-ILD due to scleroderma renal crisis risk. 1, 2

• Be aware of drug-induced lung disease from TNF-alpha inhibitors, sulfasalazine, cyclophosphamide, rituximab, leflunomide, methotrexate, and sulfonamides. 2
• Do not use azathioprine without checking thiopurine methyltransferase status due to risk of severe leukopenia. 1
• Recognize that patients on chronic steroids have suppressed HPA axis and are vulnerable to stress; may require stress-dose steroids during acute illness or surgery. 5
• Provide Pneumocystis jirovecii prophylaxis when using cyclophosphamide. 2