Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease characterized by a broad range of symptoms and serological manifestations caused by autoantibody production, complement activation, and immune complex deposition. This disease involves multiple organs and may present as a characteristic malar rash on the face, sicca symptoms, and profound fatigue. Epidemiologic studies show that SLE has an incidence of approximately 1 to 10 per 100,000 person-years and a prevalence varying from 4.3 to 150 people in 100,000 or about five million people worldwide. Women are mostly affected by this disease as 90% are females, and men and women can be affected at any age. This disease may cause debilitating fatigue and pain, mental deterioration, and other psychological symptoms; which, together with multiorgan and cutaneous problems, limit people’s ability to work and social participation.
The treatment for SLE depends on the organs and systems involved as well as disease severity. Thus, its treatment includes topical applications, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, immune suppressants, hydroxychloroquine, and biological agents. Furthermore, exercise is generally used as an adjunct to the management of this chronic disease. Regular exercise training may reduce inflammatory markers; thus, it could be a valuable long-term intervention in people with SLE, helping to reduce symptoms such as pain, redness, swelling, and fatigue; improving depression and quality of life; and preventing comorbidities such as osteoporosis and cardiovascular disease. This review investigated whether structured exercise as adjunctive therapy for adults with SLE is helpful and safe compared with usual pharmacological care, usual pharmacological care and placebo, and usual pharmacological care and non-pharmacological care.
This review is important for:
People with SLE who must coexist with chronic fatigue and pain, their loved ones/caregivers, health professionals caring for this population, general practitioners, researchers, and policymakers.
Outcomes of this review
This is a new Cochrane Systematic Review (CSR) published in 2023. The main outcomes analyzed fatigue, functional capacity, disease activity, quality of life, pain, serious adverse events, and withdrawals due to any reason. Minor outcomes analyzed were composite responder rate, aerobic capacity, depression, and anxiety. The CSR included 13 trials published and/or registered up to March 30, 2022, with 540 participants. The studies included a structured exercise program that lasted up to 12 weeks, and their usual care included disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids.
Results showed that whole-body vibration exercise plus usual care may make little to no difference in fatigue, functional capacity, and pain compared to whole-body placebo vibration exercise plus usual care. It is uncertain whether exercise resulted in more withdrawal compared to placebo. None of the studies looked at disease activity or quality of life. Exercise combined with usual care may make little or no difference in fatigue, functional capacity, and disease activity when compared to usual care alone. On the other hand, it is uncertain whether exercise improves pain. Lastly, exercise plus usual care may reduce fatigue and improve functional capacity and probably makes little or no difference in disease activity and pain when compared to another non-medicine intervention plus usual care. None of the studies reported any serious side effects of exercise during or following the intervention.
These results must be interpreted with caution because (i) there was heterogeneity between exercise interventions and measures of outcomes; (ii) much information about how the exercise was conducted was lacking; and (iii) the authors were unable to isolate and investigate heterogeneity by the type of exercise or supervision. (iv) Outcomes were not evaluated at a longer period of follow-up (greater than 12 months), which may be considered appropriate in a chronic progressive disease like SLE. (v) An analysis for each specific drug therapy (biological, DMARD, NSAID) combined with exercise was not performed. (vi) The number of participants was low, and most of them had minimal disease activity at baseline; therefore, the overall results could not be generalizable to the whole SLE population. (vii) The measures of subjective outcome are susceptible to great variation over time. (viii) As for the quality of life, the studies used the SF-36, which is a generic evaluation scale, thus it lacks characteristic details that are specific to SLE. (ix) The studies were at high risk of blinding bias due to the specific nature of the intervention, and high or unclear allocation concealment bias. (x) The content of usual care was not accurately described in some so the relative effect of drug dosage was not analyzed.
Author’s conclusion of the review
As the evidence was estimated to be low- to very low, strong conclusions cannot be drawn. Comparing exercise plus usual care to another non-pharmacological intervention and usual care, exercise may reduce fatigue, may improve functional capacity, probably result in little to no difference in disease activity, and may result in little to no difference in pain. It is uncertain whether exercise results in fewer or more withdrawals. It is uncertain whether exercise may cause any harm because of the limited number of studies reporting adverse events.
The authors were unable to determine the best dosage of exercise and its best mode of delivery. In clinical practice, exercise should be tailored to the individual according to their preferences and limitations, avoiding the sun when the ultraviolet index is high, and should be monitored by an exercise professional.
Future recommendations
The authors recommended that large-scale, multi-center studies are needed, particularly (a) to find out standardized measures of disease activity, damage indices, changes in serological markers, participant-reported fatigue, quality of life, pain, depression and anxiety, dynamic muscle strength, and aerobic fitness, and to systematically investigate adverse events. (b) Because SLE is a chronic progressive disease, longer periods of follow-up are necessary to analyze the long-term benefits as well as harms and withdrawals of structured exercise and if they are clinically relevant. Future trials should (c) accurately describe the intervention as dose, intensity, and application and (d) possibly adhere to the Consensus on Exercise Reporting Template, or the CONSORT Template for Intervention Description and Replication. (e) The authors also recommend including a more diverse pool of patients, mostly participants with higher disease activity and who may receive different therapies (non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, biological agents, and no treatment). (f) In addition, to minimize detection bias, consistent blinding of outcomes assessors is recommended, since the patient cannot be blinded to the intervention due to the nature of the intervention.
summary by Robin Kuruvila Sentinella