Sjögren's Syndrome-Associated Interstitial Lung Disease: Etiology and Clinical Course

Introduction to Sjögren's-Associated ILD

Sjögren's-associated ILD is an autoimmune-mediated inflammatory process resulting from lymphocytic infiltration of the lung parenchyma, occurring as part of the systemic autoimmune exocrinopathy that characterizes Sjögren's syndrome 1, 2

ILD prevalence increases over time: 10% within the first year of Sjögren's diagnosis and 20% after 5 years 1, 2, 3

Nonspecific interstitial pneumonia (NSIP): 45% - the most common pattern 1, 2, 3
Respiratory bronchiolitis: 25% 1, 2, 3
Usual interstitial pneumonia (UIP): 16% 1, 2, 3
Lymphoid interstitial pneumonia (LIP): 15% - highly typical for Sjögren's but occurs in only a few cases 1, 2, 3
Organizing pneumonia: 7% 1, 2, 3
Amyloid: 6% 1, 2, 3
Lymphoma: 4% 1, 2, 3

Cystic lung disease occurs more commonly in Sjögren's compared with other connective tissue diseases 1, 2, 3, 4
Associated with older age, secondary Sjögren's, and elevated anti-SSA (Ro) antibody 1, 2, 3, 4
Higher frequency of anti-SSB (La) antibody has also been reported 1, 2, 3, 4

Most ILDs in Sjögren's follow an indolent course 1, 2, 3, 4
UIP pattern portends worse prognosis and can be progressive 1, 2, 3, 4
Acute exacerbations of NSIP and UIP can precipitate respiratory failure and death 1, 2, 3, 4
Mortality correlates with decreased baseline PaO2 and presence of microscopic honeycombing 1, 2, 3, 4

Medications used to treat Sjögren's can themselves cause drug-induced ILD, including TNF-alpha inhibitors 5, Sulfasalazine 5, Cyclophosphamide 5, Rituximab 6, Leflunomide 5, Methotrexate 5, and Sulfonamides 5
While the risk is approximately 1% for most agents, drug-induced ILD must be considered in patients who are progressive or refractory to therapies 6, 7, 5

The European Respiratory Society recommends excluding identifiable causes of ILD, including environmental exposures and drug toxicity, when diagnosing ILD in patients with potential Agent Orange exposure 8, 9, 10
The diagnostic approach should investigate environmental exposures, including occupational exposures and mineral particles, to exclude known causes of ILD 8, 9, 10
The American Thoracic Society and European Respiratory Society suggest that connective tissue diseases, including Sjögren's syndrome, rheumatoid arthritis, and systemic sclerosis, should be considered when evaluating ILD 8, 9, 10
Drug-induced lung disease from immunosuppressive medications, such as methotrexate, TNF-alpha inhibitors, cyclophosphamide, rituximab, leflunomide, and sulfasalazine, must be considered in Sjögren's patients with ILD 11, 12, 13
Confirming Sjögren's syndrome diagnosis through serologic testing and minor salivary gland biopsy if needed is crucial in patients with ILD 8, 9, 10

Monitoring for drug-induced ILD is essential if immunosuppressive therapy is initiated in patients with Sjögren's-associated ILD 11, 13