Muscular strength, bone density and body composition of a woman with systemic lupus erythematosus submitted to a resistance training program: A case report

Introduction. Physical activity can provide long-term benefits for systemic lupus erythematosus (SLE). Objective. This study sought to demonstrate the effects of progressive resistance training on the muscular strength, bone mineral density (BMD) and body composition of pre-menopausal women with SLE undergoing glucocorticoid (GC) treatment. Materials and Methods. This is the case report of a 43-year-old African-South American premenopausal woman with non-extensive SLE and low bone density. A six-month program with three bimonthly cycles of 70%, 80%, and 90% intensity according to the 10 maximum-repetition test was used. Dual-energy X-ray absorptiometry (DXA) was used to measure the BMD, T-scores and body composition, and indirect fluorescence was used to measure the levels of antinuclear antibodies. Student's t-test was used. Results. Statistical improvement was noted in all strength exercises, including the 45° leg press (Δ%=+50%, p<0.001) and knee extension (Δ%=+15%, p=0.003) to maintain the BMD of the L2-L4 lumbar (Δ%=+0.031%; p=0.46) as well as the trochanter (Δ%=+0.037%; p=0.31) and BMI (Δ%=-0.8, p=0.54). Conclusion. In this case study, the presented methodology had a positive effect on strength and contributed to the maintenance of BMD and body composition in a woman with SLE undergoing GC treatment. © 2012 Revista Andaluza de Medicina del Deporte.

Long-term cardiac changes in patients with systemic lupus erythematosus

Background: The aim of this study was evaluate the late-onset repercussions of heart alterations of patients with systemic lupus erythematosus (SLE) after a 13-year follow up. Methods. A historical prospective study was carried out involving the analysis of data from the charts of patients with a confirmed diagnosis of lupus in follow up since 1998. The 13-year evolution was systematically reviewed and tabulated to facilitate the interpretation of the data. Results: Forty-eight patient charts were analyzed. Mean patient age was 34.5 ± 10.8 years at the time of diagnosis and 41.0 ± 10.3 years at the time of the study (45 women and 3 men). Eight deaths occurred in the follow-up period (two due to heart problems). Among the alterations found on the complementary exams, 46.2% of cases demonstrated worsening at reevaluation and four patients required a heart catheterization. In these cases, coronary angioplasty was performed due to the severity of the obstructions and one case required a further catheterization, culminating in the need for surgical myocardial revascularization. Conclusion: The analysis demonstrated progressive heart impairment, with high rates of alterations on conventional complementary exams, including the need for angioplasty or revascularization surgery in four patients. These findings indicate the need for rigorous cardiac follow up in patients with systemic lupus erythematosus. © 2013 de Godoy et al.; licensee BioMed Central Ltd.

IL-2, IL-5, TNF-α and IFN-γ mRNA expression in epidermal keratinocytes of systemic lupus erythematosus skin lesions

OBJECTIVE: To analyze cytokine gene expression in keratinocytes from patients with systemic lupus erythematosus (SLE). INTRODUCTION: Keratinocytes represent 95% of epidermal cells and can secrete several cytokines. METHODS: Keratinocytes were obtained by laser microdissection from 21 patients with SLE (10 discoid and 11 acute lesions) at involved and uninvolved sites. All patients were receiving a low/moderate prednisone dose and 18 were receiving chloroquine diphosphate. IL-2, IL-5, TNF-α and IFN-γ gene expression was evaluated by real-time PCR and expressed as the ratio (R) to a pool of skin samples from 12 healthy volunteers. RESULTS: Heterogeneity in cytokine gene expression was found among patients with SLE. Eighteen of 38 valid SLE samples (47%) presented overexpression (R>1) of at least one cytokine. Lesional skin samples tended to show higher cytokine expression than samples from uninvolved skin (p = 0.06). IL-5 and IFN-γ were the most commonly overexpressed cytokines. Samples with cytokine overexpression corresponded to more extensive and severe lesions. Prednisone dose did not differ between samples without cytokine overexpression (15.71±3.45 mg/day) and those with overexpressed cytokines (12.68±5.41 mg/day) (p = 0.216). Samples from all patients not receiving diphosphate chloroquine had at least one overexpressed cytokine. CONCLUSIONS: The heterogeneous keratinocyte cytokine gene expression reflects the complex immunological and inflammatory background in SLE. Patients with severe/extensive skin lesions showed a higher frequency of cytokine gene overexpression. Increased IFN-γ and IL-5 expression suggests that Th1 and Th2 cells are involved in SLE skin inflammation. The possibility that prednisone and antimalarial drugs may have contributed to low cytokine gene expression in some samples cannot be ruled out.

Chronic active disease pattern predicts early damage in juvenile systemic lupus erythematosus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pancreatitis subtypes survey in 852 childhood-onset systemic lupus erythematosus patients: a multicenter cohort

Pancreatitis is a rare and a life-threatening SLE manifestation in childhood-onset systemic lupus erythematosus (c-SLE). The objective of this study was to systematically classify pancreatitis in c-SLE according to the International Study Group of Pediatric Pancreatitis (INSPPIRE) and determine the overall prevalence, clinical features, laboratory and first episode outcomes. A multicenter cohort study in 10 Pediatric Rheumatology centers, including 852 cSLE patients. Pancreatitis was diagnosed in 22/852 (2.6%) cSLE patients. It was classified as acute pancreatitis in 20 (91%), acute recurrent pancreatitis in 2 (9%) and none of them had chronic pancreatitis. None of them had gallstones, traumatic pancreatitis or reported alcohol/tobacco use. The comparison of patients with pancreatitis (first episode) and without this complication revealed a shorter disease duration [1(0-10) vs. 4(0-23) years, p < 0.0001] and higher median of SLEDAI-2K [21(0-41) vs. 2(0-45), p < 0.0001]. The frequencies of fever (p < 0.0001), weight loss (p < 0.0001), serositis (p < 0.0001), nephritis (p < 0.0001), arterial hypertension (p < 0.0001), acute renal failure (p < 0.0001), macrophage activation syndrome (p < 0.0001) and death (p = 0.001) were also higher in patients with pancreatitis. The frequencies of intravenous methylprednisolone use (p < 0.0001) and the median of prednisone dose [55(15-60) vs. 11(1-90)mg/day, p < 0.0001] were significantly higher in patients with pancreatitis. Of note, the two patients with acute recurrent pancreatitis had two episodes, with pain-free interval of 1 and 4 years. This was the first study characterizing pancreatitis using the INSPPIRE standardized definitions in patients with cSLE showing that the predominant form is acute pancreatitis seen in association with glucocorticoid treatment and active severe disease.

Juvenile onset systemic lupus erythematosus: a possible role for vitamin D in disease status and bone health

Purpose: In juvenile onset systemic lupus erythematosus (JoSLE), evidence for the association between vitamin D status, lupus activity, and bone health is very limited and not conclusive. The aim of this study was, therefore, to assess in JoSLE patients the possible relevance of vitamin D deficiency in disease and bone parameters. Methods: Fifty-seven JoSLE patients were initially compared to 37 age, race and body mass index (BMI) -matched healthy controls. The serum concentration of 25 hydroxyvitamin D (25OHD) was determined by radioimmunoassay. Patients with 25OHD deficiency (acurrency sign20 ng/mL) were compared to those with levels > 20 ng/mL. Disease activity was evaluated by SLE Disease Activity Index (SLEDAI). Bone mineral density (BMD) and body composition (BC) were measured using dual-energy X-ray absorptiometry (DXA). Results: 25OHD levels were similar in patients and controls (21.44 +/- 7.91 vs 22.54 +/- 8.25 ng/mL, p = 0.519), regardless of supplementation (65% of patients and none in controls). Thirty-one patients with 25OHD deficiency (acurrency sign20 ng/mL) were further compared to the 26 JoSLE patients with levels > 20 ng/mL. These two groups were well-balanced regarding vitamin D confounding variables: age (p = 0.100), ethnicity (p = 1.000), BMI (p = 0.911), season (p = 0.502), frequency of vitamin D supplementation (p = 0.587), creatinine (p = 0.751), renal involvement (p = 0.597), fat mass (p = 0.764), lean mass (p = 0.549), previous/current use of glucocorticoids(GC) (p = 1.0), immunosuppressors (p = 0.765), and mean current daily dose of GC (p = 0.345). Patients with vitamin D deficiency had higher SLEDAI (3.35 +/- 4.35 vs 1.00 +/- 2.48, p = 0.018), lower C4 levels (12.79 +/- 6.78 vs 18.38 +/- 12.24 mg/dL, p = 0.038), lower spine BMD (0.798 +/- 0.148 vs 0.880 +/- 0.127 g/cm2, p = 0.037) and whole body BMD (0.962 +/- 0.109 vs 1.027 +/- 0.098 g/cm2, p = 0.024). Conclusion: JoSLE vitamin D deficiency, in spite of conventional vitamin D supplementation, affects bone and disease activity status independent of therapy and fat mass reinforcing the recommendation to achieve adequate levels. Lupus (2012) 21, 1335-1342.

Increased IgE serum levels are unrelated to allergic and parasitic diseases in patients with juvenile systemic lupus erythematosus

OBJECTIVE: The aim of this study was to assess the IgE serum levels in juvenile systemic lupus erythematosus patients and to evaluate possible associations with clinical and laboratory features, disease activity and tissue damage. METHODS: The IgE serum concentrations in 69 consecutive juvenile systemic lupus erythematosus patients were determined by nephelometry. IgG, IgM and IgA concentrations were measured by immunoturbidimetry. All patients were negative for intestinal parasites. Statistical analysis methods included the Mann-Whitney, chi-square and Fisher's exact tests, as well as the Spearman rank correlation coefficient. RESULTS: Increased IgE concentrations above 100 IU/mL were observed in 31/69 (45%) juvenile systemic lupus erythematosus patients. The mean IgE concentration was 442.0 +/- 163.4 IU/ml (range 3.5- 9936.0 IU/ml). Fifteen of the 69 patients had atopic disease, nine patients had severe sepsis and 56 patients presented with nephritis. The mean IgE level in 54 juvenile systemic lupus erythematosus patients without atopic manifestations was 271.6 +/- 699.5 IU/ml, and only nine of the 31 (29%) patients with high IgE levels had atopic disease. The IgE levels did not statistically differ with respect to the presence of atopic disease, severe sepsis, nephritis, disease activity, or tissue damage. Interestingly, IgE concentrations were inversely correlated with C4 levels ( r = -0.25, p = 0.03) and with the SLICC/ACR-DI score (r = -0.34, p = 0.005). The IgE concentration was also found to be directly correlated with IgA levels (r = 0.52, p = 0.03). CONCLUSIONS: The present study demonstrated for the first time that juvenile systemic lupus erythematosus patients have increased IgE serum levels. This increase in IgE levels was not related to allergic or parasitic diseases. Our results are in line with the hypothesis that high IgE levels can be considered a marker of immune dysregulation.

Functional single-nucleotide polymorphisms in the DEFB1 gene are associated with systemic lupus erythematosus in Southern Brazilians

Systemic lupus erythematosus (SLE) is an autoimmune disease that results in inflammation and tissue damage. The etiology of SLE remains unknown, but recent studies have shown that the innate immune system may have a role in SLE pathogenesis through the secretion of small cationic peptides named defensins. The aim of the study was to determine the possible involvement in SLE of three functional single nucleotide polymorphisms (SNPs) (c.-52G>A, c.-44C>G and c.-20G>A) in the 5'UTR region of DEFB1 gene, by analyzing them in a population of 139 SLE patients and 288 healthy controls. The c.-52G>A SNP showed significant differences in allele and genotype frequency distribution between SLE patients and controls (p = 0.01 and p = 0.02 respectively) indicating protection against SLE (A allele, OR = 0.68, AA genotype OR = 0.51). Significant differences were also observed for c.-44C>G SNP, the C/G genotype being associated with susceptibility to SLE (OR = 1.60, p = 0.04). Moreover, statistically significant differences between patients and controls were found for two DEFB1 haplotypes (GCA and GGG, p = 0.01 and p = 0.02 respectively). When considering DEFB1 SNPs and SLE clinical and laboratory manifestations, significant association was found with neuropsychiatric disorders, immunological alterations and anti-DNA antibodies. In conclusion, our results evidence a possible role for the c.-52G>A and c.-44C>G DEFB1 polymorphisms in SLE pathogenesis, that can be considered as possible risk factors for development of disease and disease-related clinical manifestations. Additional studies are needed, to corroborate these results as well as functional studies to understand the biological role of these SNPs in the pathogenesis of SLE. Lupus (2012) 21, 625-631.

Juvenile systemic lupus erythematosus and dermatomyositis associated with urticarial vasculitis syndrome: a unique presentation

To report a case of triple association of juvenile systemic lupus erythematosus (SLE), juvenile dermatomyositis and urticarial vasculitis as well as a review of the relevant literature. A 12-year-old male patient diagnosed with overlap syndrome between SLE and juvenile dermatomyositis since 2004 evolved with erythematous plaques, which were compatible with an urticarial rash. Clinical, laboratory and histopathological findings indicated a diagnosis of urticarial vasculitis. The patient previously had a C1q deficiency. Using the established treatment with methylprednisolone (1 g/day for 3 days), increasing doses of deflazacort and introduction of a dapsone, as well as mycophenolate mofetil regimen, with the suspension of azathioprine resulted in complete resolution of skin lesions. Urticarial vasculitis can present in various diseases. In SLE, presentation of urticarial vasculitis in children is rarely found. The triple association of juvenile-onset SLE, juvenile dermatomyositis and urticarial vasculitis is unusual, and this is the first case described in literature.

Hydroxychloroquine reduces low-density lipoprotein cholesterol levels in systemic lupus erythematosus: a longitudinal evaluation of the lipid-lowering effect

The influence of antimalarials on lipids in systemic lupus erythematosus (SLE) has been identified in several studies but not in many prospective cohorts. The aim of this study was to longitudinally determine the effect of antimalarials on the lipoprotein profile in SLE. Patients and methods: Fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein cholesterol (LDL) plasma levels were determined at entry and after 3 months of hydroxychloroquine (HCQ) treatment in a longitudinal evaluation of 24 patients with SLE. Results: a significant decrease in TC (198 +/- 33.7 vs. 183 +/- 30.3 mg/dl, p = 0.023) and LDL levels (117 +/- 31.3 vs. 101 +/- 26.2 mg/dl, p = 0.023) were detected after the 3 months of HCQ therapy. The reduction of 7.6% in TC (p = 0.055) and 13.7% in LDL levels (p = 0.036) determined a significant decrease in the frequency of dyslipidemia (26% vs. 12.5%, p = 0.013) after HCQ therapy. Conclusion: This longitudinal study demonstrated the beneficial effect of antimalarials on lipids in SLE since this therapy induced a reduction of atherogenic lipoproteins. Lupus (2012) 21, 1178-1182.

Invasive aspergillosis: a severe infection in juvenile systemic lupus erythematosus patients

Infections are an important cause of morbidity and mortality in juvenile systemic lupus erythematosus (JSLE). Among them, invasive aspergillosis (IA), which is usually related to immunosuppressed patients, has been rarely reported in JSLE. From 1983 to 2011, 5604 patients were followed at our institution and 283 (5%) met the American College of Rheumatology (ACR) classification criteria for SLE. Six (2.1%) of our JSLE patients had IA. One of them was previously reported and five will be described herein. Four of them were female. The median age at JSLE diagnosis was 12 years (8-16) and the median interval between diagnosis of JSLE and IA was 6 months (1-38). All had pulmonary involvement and three of them had systemic involvement. The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was 19 (7-22). Diagnosis of IA was performed by isolation of Aspergillus spp., two in bronchoalveolar lavage culture and by way of autopsy in the others. All of them were treated with corticosteroids and/or immunosuppressive drugs at IA diagnosis (azathioprine and/or intravenous cyclophosphamide). They all required treatment in the pediatric intensive care unit with mechanical ventilation and antifungal therapy (fluconazole, amphotericin B, itraconazole and/or voriconazole); nonetheless, none of them survived. In conclusion, this was the first report that evaluated the prevalence of IA in a large population of JSLE patients from a tertiary pediatric hospital, and clearly showed the severity of the outcome, especially in patients with active disease and treated with immunosuppressive agents. This study reinforces the importance of early diagnosis and treatment with certain antifungals, especially in critically ill patients. Lupus (2012) 21, 1011-1016.

Alveolar hemorrhage: distinct features of juvenile and adult onset systemic lupus erythematosus

We compared outcomes of alveolar hemorrhage (AH) in juvenile (JSLE) and adult onset SLE (ASLE). From 263 JSLE and 1522 ASLE, the AH occurred in 13 (4.9%) and 15 (1.0%) patients, respectively (p < .001). Both groups had comparable disease duration (2.6 +/- 3.0 vs. 5.6 +/- 7.0 years, p = .151) and median SLEDAI scores [17.5 (2 to 32) vs. 17.5 (3 to 28), p = 1.000]. At AH onset, a higher frequency of JSLE were already on a high prednisone dose ( > 0.5 mg/kg/day) compared to ASLE (54% vs. 15%, p = .042). The mean drop of hemoglobin was significantly lower in JSLE (2.9 +/- 0.9 vs. 5.5 +/- 2.9 g/dL, p = .006). Although treatments with methylprednisolone, plasmapheresis, intravenous immunoglobulin and cyclophosphamide were similar in both groups (p > .050), regarding outcomes, there was a trend in high frequency of mechanical ventilation use (85% vs. 47%, p = .055) and also significant mortality (69% vs. 13%, p = .006) in JSLE compared to ASLE. The sepsis frequency was comparable in both groups (50% vs. 27%, p = .433). We have identified that AH in JSLE has a worse outcome most likely related to respiratory failure. The AH onset in JSLE already treated with high-dose steroids raises the concern of inadequate response to this treatment and reinforces the recommendation of early aggressive alternative therapies in this group of patients. Lupus (2012) 21, 872-877.

Using exercise training to counterbalance chronotropic incompetence and delayed heart rate recovery in systemic lupus erythematosus: a randomized trial

Objective. To evaluate the efficacy of a 3-month exercise training program in counteracting the chronotropic incompetence and delayed heart rate recovery in patients with systemic lupus erythematosus (SLE). Methods. A 12-week randomized trial was conducted. Twenty-four inactive SLE patients were randomly assigned into 2 groups: trained (T; n = 15, 3-month exercise program) and nontrained (NT; n = 13). A sex-, body mass index-, and age-matched healthy control (C) group (n = 8) also underwent the exercise program. Subjects were assessed at baseline and at 12 weeks after training. Main measurements included the chronotropic reserve (CR) and the heart rate (HR) recovery (Delta HRR) as defined by the difference between HR at peak exercise and at both the first (Delta HRR1) and second (Delta HRR2) minutes after the exercise test. Results. Neither the NT SLE patients nor the C group presented any change in the CR or in Delta HRR1 and Delta HRR2 (P > 0.05). The exercise training program was effective in promoting significant increases in CR (P = 0.007, effect size [ES] 1.15) and in Delta HRR1 and Delta HRR2 (P = 0.009, ES 1.12 and P = 0.002, ES 1.11, respectively) in the SLE T group when compared with the NT group. Moreover, the HR response in SLE patients after training achieved parameters comparable to the C group, as evidenced by the analysis of variance and by the Z score analysis (P > 0.05, T versus C). Systemic Lupus Erythematosus Disease Activity Index scores remained stable throughout the study. Conclusion. A 3-month exercise training program was safe and capable of reducing the chronotropic incompetence and the delayed Delta HRR observed in physically inactive SLE patients.