Pulmonary manifestations in late versus early systemic lupus erythematosus: A systematic review and meta-analysis☆
Introduction
Systemic lupus erythematosus (SLE) is a pleomorphic autoimmune disease that often begins in early life. Presentation ranges from rashes and arthralgia to life-threatening lung and kidney involvement. Late-onset SLE is a distinct classification that begins in patients ≥50 years old. Prior meta-analyses report significant differences in the clinical manifestations between late- and early-onset SLE patients, including fewer cutaneous manifestations and more sicca symptoms [1], [2]. A recent meta-analysis demonstrated increased pulmonary manifestations in adult-onset lupus patients compared to childhood-onset patients, suggesting a higher risk with increasing age [3]. Late-onset lupus patients were not included in this study, however. Other studies have suggested increased pulmonary involvement in late-onset patients as well [4], but conclusions have been limited by sample size. In the multiethnic prospective LUMINA cohort (n = 626), age was an independent risk factor for development of pulmonary damage in patients with SLE [5].
Moreover, in non-lupus populations, lung fibrosis increases with advanced age, raising our interest in examining these relationships in lupus [6]. Pulmonary involvement is common in SLE, and pulmonary features are the presenting symptom in 5% of patients [7]. The most common pulmonary manifestation, pleuritis, occurs in up to 50% of all lupus patients. Chronic interstitial lung disease (ILD) occurs in up to 13% of lupus patients, typically later in the disease course [8]. Other pulmonary manifestations of SLE including acute pneumonitis, diffuse alveolar hemorrhage, pulmonary hypertension, shrinking lung syndrome, and pulmonary embolism are less common and often difficult to classify independently from antiphospholipid antibody syndrome or medication complications [8]. Although some studies have suggested more pulmonary disease in the late-onset group [4], [9], we found no large dedicated meta-analysis that quantified the relative odds of lung involvement in late- versus early-onset SLE. Such information could have important implications for the diagnosis, screening, and prognosis in older adults with SLE.
We aimed to conduct a systematic review and meta-analysis to compare the odds of pulmonary involvement, including serositis, pleuritis, ILD, pulmonary embolism (PE), and pulmonary hypertension in late- versus early-onset lupus patients.
Section snippets
Literature search inclusion criteria
We performed a systematic review of the literature to identify articles comparing clinical manifestations of patients with late- versus early-onset lupus as described in our previous work [2]. We included the studies used in our prior meta-analysis that had data on pulmonary manifestations. Additionally we performed an electronic search of the literature in PubMed, CINAHL, and EMBASE using keyword subject headings “late-onset systemic lupus erythematosus” then “systemic lupus erythematosus,”
Results
The PubMed, CINAHL, and EMBASE literature search for our meta-analysis yielded 1568 potential articles of which 97 articles merited full-text review for application of exclusion criteria. Ultimately, we included 39 studies in this meta-analysis, encompassing 35 cohort and 4 case–control studies (see Fig. 1).
See Table 1 listing the 39 studies included in the systematic review and meta-analysis [4], [9], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26]
Discussion
Results of our meta-analysis indicate that late-onset SLE patients are more likely than early-onset patients to develop pulmonary manifestations. Older-onset SLE patients had a nearly three-fold increased odds of ILD, similar to age trends in idiopathic ILD. Overall, findings were consistent with prior SLE cohort studies [4], [9], [21] and a prior 1989 meta-analysis [1] which included 170 late-onset cases compared with our 1645 late-onset cases. It is known that idiopathic ILD is strongly
Conclusions
Our pooled analysis demonstrates increased odds of pulmonary manifestations, especially ILD, in late-onset SLE patients compared to their younger peers. Factors that likely contribute to this discovery are increased age, tobacco exposure, immune senescence, and the potential role of an SLE-SS overlap disease phenotype in older patients. Clinicians should recognize that late-onset patients are more likely to have ILD, and screen for the condition when appropriate. Future studies should
Acknowledgments
Authors would like to thank Sara Fitz, MD for help with original study selection, and Natalie Wietfeldt, Zaher Karp, Aimée Wattiaux, and Amanda Perez for help with manuscript preparation.
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2022, Handbook of Systemic Autoimmune DiseasesCitation Excerpt :Results of a recent systematic review of the literature and meta-analysis indicated that late-onset SLE patients, defined as ≥50 years of age, are more likely than early-onset patients to develop pulmonary manifestations. In fact, older-onset SLE patients had a nearly threefold increased odds of ILD, similar to age trends in idiopathic ILD [13]. From the clinical point of view, SLE patients with ILD may present with chest pain, nonproductive cough, and dyspnea resulting in decreased exercise tolerance.
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Funding: Bartels received K23 time support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number AR062381 during this project. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Bartels currently receives unrelated institutional grant funding from Independent Grants for Learning and Change (Pfizer). All other authors have no direct financial, consultant, or institutional conflict of interest pertaining to this manuscript.