Claudia Tereza Lobato Borges

Resistance Training with Vascular Occlusion in Inclusion Body Myositis: A Case Study

UNLABELLED Inclusion body myositis (IBM) is a rare idiopathic inflammatory myopathy that produces remarkable muscle weakness. Resistance training with vascular occlusion has been shown to improve muscle strength and cross-sectional area in other muscle wasting conditions. PURPOSE We evaluated the efficacy of a moderate-intensity resistance training program combined with vascular occlusion by examining functional capacity, muscle morphology, and changes in the expression of genes related to muscle protein synthesis and proteolysis in a patient with IBM. METHODS A 65-yr-old man with IBM resistant to all proposed treatments underwent resistance training with vascular occlusion for 12 wk. Leg press one-repetition maximum; thigh cross-sectional area; balance, mobility, and muscle function; quality of life; and blood markers of inflammation and muscle damage were assessed at baseline and after the 12-wk program. The messenger RNA (mRNA) expression levels of mechanogrowth factor, mammalian target of rapamycin, atrogin-1, and muscle RING finger-1 were also quantified. RESULTS After the 12-wk training program, the patients leg press one-repetition maximum, balance and mobility function, and thigh cross-sectional area increased 15.9%, 60%, and 4.7%, respectively. All Short Form-36 Health Survey Questionnaire subscales demonstrated improvements as well, varying from 18% to 600%. mRNA expression of mechanogrowth factor increased 3.97-fold, whereas that of atrogin-1 decreased 0.62-fold. Muscle RING finger-1 and mammalian target of rapamycin mRNA levels were only slightly altered, 1.18- and 1.28-fold, respectively. Importantly, the exercise did not induce disease flare. CONCLUSIONS We describe a novel, and likely the first, nonpharmacological therapeutic tool that might be able to counteract the muscle atrophy and the declining strength that usually occur in IBM.

Association of Interferon‐ and Transforming Growth Factor β–Regulated Genes and Macrophage Activation With Systemic Sclerosis–Related Progressive Lung Fibrosis

Systemic sclerosis (SSc)–related interstitial lung disease (ILD) is one of the leading causes of mortality. We undertook this study to analyze the gene expression of lung tissue in a prospective cohort of patients with SSc‐related ILD and to compare it with that in control lungs and with 2 prospective clinical parameters in order to understand the molecular pathways implicated in progressive lung disease.

Centrilobular Fibrosis: An Underrecognized Pattern in Systemic Sclerosis

Background: The impressive association of lung involvement and gastroesophageal reflux in scleroderma raises the possibility of a cause-effect relationship. Objectives: To determine clinical, radiological and histopathological features of systemic sclerosis (SSc) patients according the presence or absence of centrilobular fibrosis (CLF). Methods: Twenty-eight SSc patients with lung involvement were submitted to open lung biopsy and the specimens classified for the presence of CLF (bronchocentric distribution of the lesions and intraluminal matter according to the classification of idiopathic interstitial pneumonia). HRCT, pulmonary function tests and esophageal analysis were also performed. Subsequently, cyclophosphamide was introduced for the nonspecific interstitial pneumonia subgroup and antireflux treatment was intensified for isolated CLF patients. Results: Isolated CLF was found in 21% of the biopsies and also found associated to nonspecific interstitial pneumonia in 84% of these patients. The other 3 cases had usual interstitial pneumonia, pulmonary hypertension and respiratory bronchiolitis-associated interstitial lung disease. The histopathological analysis revealed that all 6 patients with isolated CLF had the bronchocentric distribution and intraluminal basophilic content, with foreign bodies detected in one third of them. The central distribution of lung involvement on HRCT was found in 67% of these patients with a consistent patchy distribution (100%). Ground glass (67%) and consolidation (33%) were the predominant patterns found. The constant clinical finding in all isolated CLF cases was dyspnea, esophageal abnormalities and a moderate lung impairment (FVC: 63.83 ± 16.31%; DLCO: 61.66 ± 18.84%). Lung function parameters in isolated CLF patients remained stable after 1 year of exclusively intensive antireflux treatment (FVC, p = 0.23; DLCO, p = 0.59). Conclusions: The novel description of CLF pattern in SSc lung disease with peculiar histological, tomographic and clinical features will certainly contribute to a more appropriate therapeutic approach.

Spontaneous pneumomediastinum and dermatomyositis may be a not so rare association: report of a case and review of the literature

One patient with dermatomyositis (DM) who developed spontaneous pneumomediastinum (SPnM) is described. A review of 15 previously reported cases shows that this is a complication of DM but not of polymyositis. It occurs in young patients with recent onset of disease characterized by cutaneous vasculopathy, and patients treated with immunosuppressive drugs have, in general, better outcomes. We suggest that the onset of SPnM in DM patients must alert to possible vasculitic activity and that immunosuppressive agents with progressive tapering of corticosteroids are part of the most reasonable approach in these cases.

miR-155 in the progression of lung fibrosis in systemic sclerosis

BackgroundMicroRNA (miRNA) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from patients with SSc-ILD. A chronic lung fibrotic murine model was used.MethodsRNA was isolated from lung tissue of 12 patients with SSc-ILD and 5 controls. High-resolution computed tomography (HRCT) was performed at baseline and 2–3 years after treatment. Lung fibroblasts and peripheral blood mononuclear cells (PBMC) were isolated from healthy controls and patients with SSc-ILD. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DNA Intelligent Analysis (DIANA)-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin.ResultsLung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q < 0.25). DIANA-miRPath revealed 57 Kyoto Encyclopedia of Genes and Genomes pathways related to the most dysregulated miRNA. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts only mildly expressed miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and weaker lung induction of several genes after bleomycin exposure compared to wild-type mice.ConclusionsmiRNA are dysregulated in the lungs and PBMC of patients with SSc-ILD. Based on mRNA-miRNA interaction analysis and pathway tools, miRNA may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD.

Myositis in mixed connective tissue disease: a unique syndrome characterized by immunohistopathologic elements of both polymyositis and dermatomyositis

OBJECTIVE To characterize the inflammatory cells, the expression pattern of adhesion molecules (ICAM-1 and VCAM-1), membrane attack complex (C5b-9), and major histocompatibility complex (MHC) antigens in muscle biopsy of mixed connective tissue disease (MCTD). METHOD We studied 14 patients with MCTD, and compared to 8 polimyositis (PM) patients, 5 dermatomyositis (DM) and 4 dystrophies. Inflammatory cells were examined for CD4+, CD8+, memory and naive T cells, natural killer cells, and macrophages. Expression of MHC-I and -II, ICAM-1, VCAM-1 and C5b -9 were characterized on muscle fibers and vessels. RESULTS Morphological analysis displayed a pattern of PM. Immunohistochemical study revealed a decreased number of capillaries, predominance of CD4+ and B cells in perivascular regions and predominance of CD8+ and CD45RO+ in endomysial regions. The expression of MHC-I on vessels and on degenerated muscle fibers, MHC-II expression on vessels and perifascicular muscle fibers, and the expression of ICAM-1 / VCAM-1 on endothelial cells indicated both vascular and cellular-immune mediated processes causing the muscular lesion. CONCLUSION Our findings revealed a mixed mechanism in MCTD, both vascular involvement as DM, and cell-mediated like PM.

Diffuse systemic sclerosis and autoimmune hepatitis: a unique association

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology characterized by continuing hepatocellular necrosis and inflammation that afflicts 100,000 to 200,000 persons in the United States. It is a rare manifestation of systemic sclerosis. Only about nine reports of this association have been previously reported in the literature. Importantly, all cases had the limited clinical form of systemic. The authors describe herein the first report of a patient with diffuse systemic sclerosis who was diagnosed with AIH with positive antimitochondrial antibody and had an excellent response to immunosuppressive drugs. We also briefly review the literature regarding this issue.

The effect of intravenous zoledronic acid on glucocorticoid-induced multiple vertebral fractures in juvenile systemic lupus erythematosus

Glicocorticoides sao farmacos comumente usados no tratamento de pacientes lupicos, porem apresentam efeitos adversos importantes, principalmente a osteoporose e fraturas. O tratamento da osteoporose em pacientes jovens deve ser eficaz e nao prejudicial ao crescimento e remodelamento osseo. Os bisfosfonatos sao drogas que reduzem a incidencia de fraturas, mas seu uso em criancas e adolescentes ainda e controverso, devido a seus possiveis efeitos adversos no esqueleto em crescimento. Estudos recentemente publicados demonstraram que o crescimento linear se manteve normal com o uso de bisfosfonatos, nao havendo supressao excessiva do remodelamento osseo ou defeitos de mineralizacao. O acido zoledronico e um novo bisfosfonato endovenoso aprovado pelo FDA para o uso na hipercalcemia das neoplasias e parece ser um tratamento eficaz para a osteoporose pos-menopausica. Os autores descrevem um caso de uma adolescente lupica que desenvolveu multiplas fraturas vertebrais induzidas pelo glicocorticoide e obteve importante melhora clinica e densitometrica apos o tratamento com o acido zoledronico.Glucocorticoids are widely used in the treatment of lupus patients, and adverse effects, which include osteoporosis and associated fractures, are frequent. Treatment of osteoporosis of young patients should be effective and not harmful to bone growth and remodeling. Bisphosphonates are drugs that decrease the incidence of bone fractures, but their use in juvenile patients is still controversial because of their possible side effects on the growing skeleton. However, recently published studies showed that linear growth continued normally after treatment with these drugs, and there was no excessive suppression of bone remodeling or mineralization defects. Zoledronic acid is a new intravenous bisphosphonate that has been approved by the US FDA for use with hypercalcemia of malignancies and might be an effective treatment for postmenopausal osteoporosis. The authors report a case of a young girl with systemic lupus who developed multiple vertebral collapses due to glucocorticoid therapy, and zoledronic acid was used producing significant clinical and densitometric improvement.

Aspectos da saúde reprodutiva em homens com miopatia inflamatória idiopática: um estudo multicêntrico

OBJECTIVE: To evaluate reproductive health of males with idiopathic inflammatory myopathies (IIM), and comparing them with a control group. METHODS: Demographic data, urologic evaluation (including pubertal parameters and sexual/erectile function), testicular ultrasound, hormone profile, semen analysis, clinical features, and treatment of 25 IIM patients were evaluated. The control group was composed of 25 healthy males. RESULTS: Median age of IIM patients was similar to that of the control group (24 versus 27 years, P = 0.566). The frequency of sexual activity, number of partners with spontaneous pregnancies after the onset of the disease, and use of condom were significantly lower in IIM patients than in the control group (60% versus 96%, P = 0.004; 16% versus 60%, P = 0.0031; 40% versus 76%, P = 0.021, respectively). Moreover, the frequency of testicular atrophy (28% versus 4%, P = 0.049), elevated levels of FSH and/or LH (25% versus 0%, P = 0.05), and sperm abnormalities (40% versus 0%, P = 0.0006) were statistically higher in IIM patients than in the control group. Median age of onset of IIM and current age were significantly higher in IIM patients with sexual/erectile dysfunction than in patients without this dysfunction (41 versus 12.5 years, P = 0.014; 46 versus 21 years, P = 0.027, respectively). On the other hand, differences in the age of spermarche, parameters of gonadal function, disease activity, muscle enzymes, and treatment were not observed between IIM patients with or without sexual/erectile dysfunction. CONCLUSION: This is the first study to identify changes in reproductive health and gonadal dysfunction in male IIM patients. Rheumatologists should discuss sexual problems with their patients, counseling them on contraceptive methods.

Avaliação dos fatores reprodutivos em 117 pacientes com esclerose sistêmica forma limitada e 72 pacientes com artrite reumatóide

Recently, reproductive factors have been studied in diffuse Systemic Sclerosis patients and pregnancy was not likely to be a risk factor for disease development. This findings need to be confirmed in the limited form of the disease. OBJECTIVE: To compare reproductive factors in 372 limited systemic sclerosis (LSSc) and 240 rheumatoid arthritis (RA) pregnancies and their relative risk for developing LSSc. METHODS: One hundred and seventeen LSSc and 72 RA consecutive female patients were interviewed with a detailed questionnaire to estimate the relative risk of developing LSSc given a relevant reproductive variable. The odds ratio (OR) was calculated using as reference nulliparous women and no history of miscarriage. RESULTS: Diagnosis of LSSc and RA was made after pregnancy for most patients of both diseases (97% vs. 90%, respectively, p > 0.05). A similar mean age at diagnosis (40.8 years old vs. 38.4 years old) and mean age of first pregnancy (22.7 years old vs. 23.5 years old) were noted in LSSc and RA (p > 0.05), respectively. The number of pregnancies/patient (3.1 vs. 3.3), percentage of patients ever pregnant (84.6% vs. 88.8%) and miscarriage (19.8% vs. 21.6%) was similar in both groups (p > 0.05). Compared to nulliparous women, parous LSSc had an OR of 0.7, 95% CI 0.3-1.7 for developing LSSc and, for women who experienced a miscarriage, the [OR] was 0.9, 95% CI 0.5-1.6, compared with those LSSc patients with no miscarriage. In addition to that, the number of pregnancies was not associated with an increased risk for LSSc when compared to nulliparous controls. CONCLUSIONS: These data suggest that the overall reproductive history of LSSc is comparable to RA. Moreover, it indicates that pregnancy is unlikely to account for an increased risk or a protective effect to develop LSSc in comparison to RA.