Patients with late-onset systemic lupus erythematosus (SLE) are more likely to develop pulmonary manifestations of the disease than are patients with early-onset disease, a meta-analysis demonstrated.
Among patients whose SLE was diagnosed after age 50, the odds ratio for having interstitial lung disease was 2.56 (95% CI 1.27-5.16, I2=26%), according to Christie M. Bartels, MD, and colleagues from the University of Wisconsin in Madison.
Increased risks also were seen for patients with late-onset SLE for pleuritis (OR 1.53, 95% CI 1.19-1.96, I2=36%) and serositis (OR 1.31, 95% CI 1.05-1.65, I2=61%), the researchers reported online in Seminars in Arthritis & Rheumatism.
Most patients with SLE begin to develop the disease early in life, but a minority only become symptomatic after age 50. Previous studies have suggested that there are differences in clinical manifestations between late- and early-onset systemic lupus erythematosus, including fewer cutaneous manifestations such as malar rash and photosensitivity in the older group.
Lung manifestations in general are common in SLE, with pleuritis being seen in up to half of patients and interstitial lung disease in up to 13%.
One recent study found more pulmonary manifestations in patients with adult-onset disease compared with childhood-onset, but patients older than 50 were not included.
Pulmonary fibrosis in general becomes more common with increasing age, but it has not been established whether patients with late-onset lupus are more susceptible to lung manifestations.
Therefore, Bartels and colleagues conducted a systematic literature review and meta-analysis of cohort and case-control studies on pulmonary involvement in late- and early-onset SLE published through 2016.
They identified 39 studies, 35 of which were cohort studies and the remaining four being case-control studies. Heterogeneity was assessed with the I2 statistic; 25%, 50%, and 75% represented low, moderate, and high heterogeneity between studies, respectively.
The studies included 10,963 patients with early-onset lupus and 1,656 patients with late-onset disease. The cohorts included were geographically and ethnically diverse, and the mean quality score of the individual studies was 6.3 out of 9.
The number of patients with late-onset SLE in the studies ranged from seven to 131.
Although there were trends toward significance, the risks were not statistically significant in the older-onset group for pulmonary embolism (OR 2.73, 95% CI 0.78-9.60, I2=0%) and pulmonary hypertension (OR 1.72, 95% CI 0.22-13.49, I2=0%), but with significantly increased for a combined category of “any” pulmonary manifestation (OR 1.70, 95% CI 1.36-2.14, I2=60%).
When case-control studies were excluded from the analysis, the risks remained elevated in the older onset group for interstitial lung disease (RR 2.21, 95% CI 1.14-4.31) and pleuritis (RR 1.39, 95% CI 1.12-1.73).
Many potential factors may contribute to the increased pulmonary risks among late-onset lupus patients, including effects on both the innate and adaptive immune systems. For example, neutrophils in older individuals are less capable of killing phagocytosed pathogens but have increased apoptosis, and thymic production of naive T-cells declines, leading to proliferation of memory T cells and a resulting proinflammatory state.
An additional contributory factor for interstitial lung disease in older patients may be a possible SLE-Sjogren’s syndrome overlap syndrome, which has been reported by several groups. The prevalence of interstitial lung disease in Sjogren’s syndrome, at 9% to 75%, is much higher than in SLE, at 1% to 15%, so an overlap syndrome could explain the high incidence in older patients.
“In addition to a possible Sjogren’s overlap phenotype in late-onset SLE, factors such as duration of disease, environmental exposures, and smoking trends over time might also correlate with SLE interstitial lung disease,” the researchers observed.
“Clinicians should recognize that late-onset patients are more likely to have interstitial lung disease and screen for the condition when appropriate,” they concluded.
Strengths of the analysis included the large, multinational cohort and the high quality of the studies included.
Limitations included inconsistent methods of pulmonary diagnosis in the various studies and the possibility of misclassification of serositis.
The authors have received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and the Independent Grants for Learning and Change (Pfizer).