The prognosis of patients with pediatric rheumatic diseases has substantially improved. However, there has been an increasing concern with mid- or long-term adverse effects associated with its treatment as well as the disease itself and functional capacity of the patients (1,6). In this respect, exercise training has emerged as a potential therapeutic strategy to counteract the decline in physical function and aerobic capacity in pediatric rheumatic disease (3).
In fact, our group (8) and others (9,10) have recently showed that regular exercise training can benefit patients with juvenile dermatomyositis, juvenile fibromyalgia, and juvenile idiopathic arthritis. To our knowledge, there is no evidence that exercise can be effective and safe in juvenile systemic lupus erythematosus (JSLE).
JSLE patients commonly present a low aerobic level, reduced exercise capacity, fatigue, and poor functioning (5). Theoretically, exercise might alleviate such symptoms (3). Herein, we report for the first time on the effects of exercise training in a 15-yr-old boy with JSLE and antiphospholipid syndrome (APS).
A 10-yr-old boy had a seizure episode, which improved after phenytoin therapy. Two months later, he was hospitalized with bronchopneumonia with pleural effusion associated to autoimmune hemolytic anemia. At that moment, his laboratorial exams were as follows: hemoglobin = 9.5 g·dL−1, hematocrit = 32%, white blood cell count = 5600 mm−3 (63% neutrophils, 17% lymphocytes, 19% monocytes, and 1% eosinophils), platelets: 300,000 mm−3, positive Coombs test, erythrocyte sedimentation rate = 35 mm for the first hour (reference value: <20 mm for the first hour), C-reactive protein = 32 mg·L−1 (reference value = <5 mg·L−1), urea = 42 mg·dL−1 (reference value = 13–36 mg·dL−1), creatinine = 0.4 mg·dL−1 (reference value = 0.6–0.9 mg·dL−1), urinalysis (14,000 leukocytes and 8400 erythrocytes), and proteinuria = 0.3 g·d−1. Immunological tests were positive for the following serum antibodies: antinuclear antibodies = 1:80, anti–double-stranded DNA = 117 IU·mL−1, and anticardiolipin (immunoglobulin M = 60 IgM phospholipid units/mL and immunoglobulin G = 45 IgG phospholipid units/mL). Therefore, the diagnosis of JSLE was established according to the American College of Rheumatology’s classification criteria (4), and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 21. He was treated with intravenous methylprednisolone (1 g·kg−1·d−1 for 3 d), intravenous immunoglobulin (2 g·kg−1 per dose), and intravenous cyclophosphamide (500 mg·m−2·month−1 for six consecutive months). Maintenance treatment included phenytoin, prednisone, and chloroquine diphosphate. Four months later, he had recurrent seizures, and convulsive therapy was replaced with carbamazepine and nitrazepam. Concomitantly, deep-vein thrombosis in the right lower limb and inferior caval vein was observed, and diagnosis of APS was established according to previously defined classification criteria (7). Anticoagulation was introduced with low–molecular weight heparin and thereafter with warfarin (international normalized ratio = 2.9) along with azathioprine and prednisone, which were progressively tapered (5 mg·d−1).
In 2009, the 15-yr-old patient underwent a 12-wk aerobic exercise training program to improve his physical capacity and functioning. At that time, the SLEDAI-2K score was 4, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score was 2. Training sessions were performed twice a week and consisted of a 5-min treadmill warm-up followed by a 30- to 50-min treadmill aerobic training. Aerobic training intensity was monitored by an HR monitor (HR correspondent to the ventilatory anaerobic threshold (VAT)). All of the sessions were performed in a hospital gymnasium and monitored by two fitness professionals. Before and after the 12-wk exercise program, the patient was submitted to incremental cardiopulmonary tests to determine V˙O2peak, peak exercise intensity (i.e., treadmill speed and treadmill slope), exercise intensity at VAT, and time to exhaustion. In addition, a 6-min square-wave test was performed. In brief, this is a submaximal test with a fixed load, which enables the evaluation of the metabolic response during exercise. Metabolic data were obtained at 2-, 4-, and 6-min intervals of the test. Functioning was assessed by using the visual analog scale (VAS) (adolescent self-reporting, parent proxy reporting, and physician proxy reporting). Laboratory parameters of inflammation were assessed at baseline and 48 h after the last training session. This trial was approved by the local ethical committee, and the informed written consent was given by the subjects’ parents.
As a result of the intervention, all the cardiopulmonary (Table 1) and metabolic parameters (Table 2) improved. The SLEDAI-2K and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index scores of 4 and 2, respectively, did not change after the intervention, and the inflammatory laboratory parameters remained within normal range (erythrocyte sedimentation rate, before intervention = 5 mm for the first hour vs after intervention = 9 mm for the first hour; C-reactive protein, before intervention = 3 mg·L−1 vs after intervention = 0.3 mg·L−1). Furthermore, no clinical evidence of excessive exhaustion, pain, osteoarticular injury, muscle soreness, or any other adverse event was noticed. The international normalized ratio remained unchanged throughout the exercise program period. VAS scores were improved according to the patients’ evaluation (before intervention = 8 vs after intervention = 10), parents’ evaluation (before intervention = 8 vs after intervention = 10), and physicians’ evaluation (before intervention = 6 vs after intervention = 9).
We showed that a 12-wk aerobic training program improves aerobic conditioning in a patient with JSLE and APS. To the best of our knowledge, this is the first report on the therapeutic effects of exercise in lupus with secondary autoimmune thrombosis.
In fact, JSLE patients often present reduced levels of aerobic fitness and poor exercise tolerance when compared with healthy subjects (5). Importantly, we observed substantial improvements in aerobic conditioning after the exercise training. This finding is of paramount relevance because aerobic capacity has been negatively and independently associated with all-cause mortality (2).
Interestingly, data from the square-wave test indicate that exercise training led to reductions in metabolic cost of movement, which means that less energy was required to complete a given physical effort. This may beneficially affect the physical functioning and the daily life activities of the patient. In support of this speculation, we also observed clinically relevant improvements in physical functioning, as assessed by VAS.
There has been an empirical concern that exercise could make disease activity flare up and could exacerbate inflammation in patients with autoimmune diseases (3). Trauma-induced bleeding could be considered an additional concern in a patient with APS taking anticoagulant drugs. Importantly, no adverse events were observed in this trial, allowing us to infer that a supervised short-term exercise program may be safe for a patient with JSLE and APS. Indeed, further controlled studies should investigate the efficacy and safety of exercise interventions in these diseases.
In conclusion, this is the first evidence that a 12-wk supervised aerobic training program can be safe and effective in improving aerobic conditioning and physical function in a patient with JSLE and APS. In light of these findings, the therapeutic effects of exercise training in pediatric rheumatic diseases merit further investigations.
The authors declare no competing interests. Danilo M. Prado, Bruno Gualano, Hamilton Roschel, and Clóvis A. Silva were significant article writers. Ana L. Sá-Pinto, Adriana M. Sallum, and Maria B. Perondi were significant article reviewers/revisers. Concept and design were by Danilo M. Prado, Bruno Gualano, Ana L. Sá-Pinto, Adriana M. Sallum, Maria B. Perondi, Hamilton Roschel, and Clóvis A. Silva. Data acquisition was performed by Danilo M. Prado, Adriana M. Sallum, and Clóvis A. Silva. Data analysis and interpretation were performed by Danilo M. Prado, Ana L. Sá-Pinto, Adriana M. Sallum, Bruno Gualano, Hamilton Roschel, and Clóvis A. Silva. This study was sponsored by Fundação de Amparo à Pesquisa do Estado de São Paulo (grant 2010/51428-2 to HR and grant 08/58238-4 to C.A.S.), Conselho Nacional de Desenvolvimento Científico (300248/2008-3 to C.A.S.), and Federico Foundation to C.A.S.
The authors inform that the results of the present study do not constitute endorsement by the American College of Sports Medicine.
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Keywords:©2011The American College of Sports Medicine
AEROBIC TRAINING; JUVENILE SYSTEMIC LUPUS ERYTHEMATOSUS; THERAPEUTIC EFFECTS; PEDIATRIC RHEUMATIC DISEASES