What syndrome is most frequently associated with interstitial lung disease?

Systemic Sclerosis is Most Frequently Associated with Interstitial Lung Disease

Systemic sclerosis (SSc) represents the connective tissue disease with the highest prevalence of ILD, occurring in nearly 50% of patients, and accounts for approximately 31% of all CTD-ILD cases. 1, 2, 3

Epidemiology of CTD-ILD by Disease

The distribution of ILD across connective tissue diseases follows a clear hierarchy:

• Rheumatoid arthritis (RA-ILD): Accounts for 39% of CTD-ILD cases, making it the most common CTD-ILD in absolute numbers, though individual patient prevalence is lower than SSc 2, 3
• Systemic sclerosis (SSc-ILD): Accounts for 31% of CTD-ILD cases, but affects nearly 50% of individual SSc patients—the highest individual disease prevalence 1, 2, 3
• Idiopathic inflammatory myopathies (polymyositis/dermatomyositis): Frequently associated with ILD, particularly in antisynthetase syndrome 3, 4
• Sjögren syndrome (SS-ILD): Occurs in 9-30% of patients 1
• Mixed connective tissue disease (MCTD-ILD): Affects 40-80% of patients 5
• Systemic lupus erythematosus (SLE-ILD): Only 2-10% prevalence, making it the least common CTD-ILD 1

Clinical Significance and Mortality Impact

SSc-ILD carries particularly high morbidity and mortality, contributing to significant early death in this population. 1 The disease demonstrates:

• Irreversible loss of lung function that can be silent and significant in early stages 1
• Variable clinical course ranging from subclinical abnormalities to respiratory failure 1
• ILD may precede or follow the onset of rheumatic symptoms 1

SS-ILD, while less prevalent, demonstrates a fourfold increased risk of 10-year mortality compared to SS without pulmonary manifestations, with a 5-year survival rate of only 85%. 1

Histopathologic Patterns by Disease

The predominant patterns vary by underlying CTD:

• Nonspecific interstitial pneumonia (NSIP): Most common in SSc, polymyositis/dermatomyositis, MCTD, and Sjögren syndrome 1, 4, 6, 7, 8
• Usual interstitial pneumonia (UIP): More frequent in rheumatoid arthritis than other CTDs 4, 6
• Organizing pneumonia, DAD, and lymphoid interstitial pneumonia: Can occur across various CTDs 4, 6, 7, 8

Critical Screening Recommendations

All patients with systemic sclerosis should undergo baseline HRCT and pulmonary function tests (spirometry and DLCO) at diagnosis, with PFTs repeated every 6 months and HRCT annually for the first 3-4 years. 1, 5

For other high-risk CTDs:

• MCTD with SSc phenotype: Follow SSc screening intervals 1
• Sjögren syndrome with risk factors: Annual PFTs and chest radiography, with HRCT if abnormalities detected 1

Common Pitfalls to Avoid

• Failing to screen asymptomatic SSc patients: Irreversible fibrosis can develop silently before symptoms appear 1
• Relying on chest radiography alone: Will not detect mild disease; HRCT is mandatory for accurate assessment 1
• Missing drug-induced ILD: Immunosuppressive agents used to treat CTD (methotrexate, TNF-alpha inhibitors, leflunomide) can themselves cause ILD in approximately 1% of cases 3
• Overlooking environmental exposures: 47% of apparently idiopathic ILD cases are actually hypersensitivity pneumonitis when thoroughly evaluated 2, 3