Skeletal muscle major histocompatibility complex class I and II expression differences in adult and juvenile dermatomyositis

OBJECTIVE: To analyze major histocompatibility complex expression in the muscle fibers of juvenile and adult dermatomyositis. METHOD: In total, 28 untreated adult dermatomyositis patients, 28 juvenile dermatomyositis patients (Bohan and Peter's criteria) and a control group consisting of four dystrophic and five Pompe's disease patients were analyzed. Routine histological and immunohistochemical (major histocompatibility complex I and II, StreptoABComplex/HRP, Dakopatts) analyses were performed on serial frozen muscle sections. Inflammatory cells, fiber damage, perifascicular atrophy and increased connective tissue were analyzed relative to the expression of major histocompatibility complexes I and II, which were assessed as negatively or positively stained fibers in 10 fields (200X). RESULTS: The mean ages at disease onset were 42.0 +/- 15.9 and 7.3 +/- 3.4 years in adult and juvenile dermatomyositis, respectively, and the symptom durations before muscle biopsy were similar in both groups. No significant differences were observed regarding gender, ethnicity and frequency of organ involvement, except for higher creatine kinase and lactate dehydrogenase levels in adult dermatomyositis (p<0.050). Moreover, a significantly higher frequency of major histocompatibility complex I (96.4% vs. 50.0%, p<0.001) compared with major histocompatibility complex II expression (14.3% vs. 53.6%, p = 0.004) was observed in juvenile dermatomyositis. Fiber damage (p = 0.006) and increased connective tissue (p<0.001) were significantly higher in adult dermatomyositis compared with the presence of perifascicular atrophy (p<0.001). The results of the histochemical and histological data did not correlate with the demographic data or with the clinical and laboratory features. CONCLUSION: The overexpression of major histocompatibility complex I was an important finding for the diagnosis of both groups, particularly for juvenile dermatomyositis, whereas there was lower levels of expression of major histocompatibility complex II than major histocompatibility complex I. This finding was particularly apparent in juvenile dermatomyositis.

Incidence of adverse events associated with percutaneous muscular biopsy among healthy and diseased subjects

The development of the percutaneous muscle biopsy technique is recognized as one of the most important scientific contributions in advancing our understanding of skeletal muscle physiology. However, a concern that this procedure may be associated with adverse events still exists. We reported the incidence of adverse outcomes associated with percutaneous muscle biopsy in healthy and diseased subjects. Medical records of 274 volunteers (496 muscle biopsies) were reviewed. This included 168 healthy subjects (330 muscle biopsies) as well as 106 chronically ill patients (166 muscle biopsies). This latter group encompassed patients with type II diabetes (n=28), osteoarthritis (n=39), inclusion body myositis (n=4), polymyositis (n=4), and chronic heart failure (n=31). The most common occurrences were pain (1.27%), erythema (1.27%), and ecchymosis (1.27%). Panic episode, bleeding, and edema were also reported (0.21%, 0.42%, and 0.84%, respectively), while infection, hematoma, inflammation, denervation, numbness, atrophy, and abnormal scarring were not verified. The percent of incidents did not differ between healthy and ill individuals. In conclusion, the incidence of complications associated with percutaneous muscle biopsy is scarce and of minor clinical relevance. Additionally, the rate of adverse events is comparable between healthy and chronically ill subjects.

Exercise training in juvenile dermatomyositis

Objective. To investigate the effects of a supervised exercise training program on health parameters, physical capacity, and health-related quality of life in patients with mild and chronic juvenile dermatomyositis (DM). Methods. This was a prospective longitudinal study following 10 children with mild and chronic juvenile DM (disease duration >1 year). The exercise program consisted of twice-a-week aerobic and resistance training. At baseline and after the 12-week intervention, we assessed muscle strength and function, aerobic conditioning, body composition, juvenile DM scores, and health-related quality of life. Results. Child self-report and parent proxy-report Pediatric Quality of Life Inventory scores were improved after the intervention (-40.3%; P = 0.001 and -48.2%; P = 0.049, respectively). Importantly, after exercise, the Disease Activity Score was reduced (-26.9%; P = 0.026) and the Childhood Muscle Assessment Scale was improved (+2.5%; P = 0.009), whereas the Manual Muscle Test presented a trend toward statistical significance (+2.2%; P = 0.081). The peak oxygen consumption and time-to-exhaustion were increased by 13.3% (P = 0.001) and 18.2% (P = 0.003), respectively, whereas resting heart rate was decreased by 14.7% (P = 0.006), indicating important cardiovascular adaptations to the exercise program. Upper and lower extremity muscle strength and muscle function were also significantly improved after the exercise training (P < 0.05). Both the whole-body and the lumbar spine bone mineral apparent density were significantly increased after training (1.44%; P = 0.044 and 2.85%; P = 0.008, respectively). Conclusion. We showed for the first time that a 12-week supervised exercise program is safe and can improve muscle strength and function, aerobic conditioning, bone mass, disease activity, and health-related quality of life in patients with active and nonactive mild and chronic juvenile DM with near normal physical function and quality of life.

High frequency of osteoporosis and fractures in women with dermatomyositis/polymyositis

Bone mass was only previously studied in juvenile dermatomyositis/polymyositis (DM/PM) patients. Therefore, the objective this study was to evaluate the prevalence of osteoporosis and fractures in adult DM/PM. Forty female DM/PM and 78 age-, gender-, and BMI-matched healthy controls were studied. Medical charts and clinical interviews of all patients were evaluated for demographic and clinical data, including disease activity, cumulative doses of glucocorticoid, menarche and menopause age, and fractures. Bone mineral density (BMD) using dual X-ray absorptiometry (DXA) were measured at lumbar spine (L1-L4) and hip. A decreased BMD in lumbar spine [0.902 (0.136) vs. 0.965 (0.141) g/cm(2), P = 0.022] and femoral neck [0.729 (0.12) vs. 0.784 (0.127) g/cm(2), P = 0.027] was observed in patients compared to controls. In addition, osteoporosis was more frequent in patients than in controls in both lumbar spine (20 vs. 3.8%, P = 0.007) and the femoral neck (27.5 vs. 10.3%, P = 0.016). Moreover, a high prevalence of fractures was found in patients in comparison to healthy subjects (17.9 vs. 5.1%, P = 0.040; OR = 3.92; CI 95%: 1.07-14.33). Comparing DM/PM patients with (n = 17) and without (n = 23) osteoporosis/fractures, significant differences were observed regarding age [56.8 (11.9) vs. 48.3 (13.2) years, P = 0.042], weight [62.05 (13.56) vs. 71.51 (11.46) kg, P = 0.022] and frequency of post menopausal women (94.1 vs. 65.2%, P = 0.0002). No differences were observed concerning height, lean mass, total fat mass, disease activity, mean value of creatine kinase, cumulative glucocorticoid dose, or bisphosphonate use. Logistic regression analysis revealed a negative association between the presence of osteoporosis/fractures and weight (OR: 0.92, 95% CI: 0.85-0.98; P = 0.016). This is the first study that analyzed bone mass in adult DM/PM patients and it demonstrated that about one quarter of these patients have osteoporosis/fracture.

Adalimumab induced-inflammatory myopathy in rheumatoid arthritis

The application of immunobiologics for the rheumatoid arthritis treatment may present as a rare complication the development of inflammatory myopathy. Until this moment, there have been described in literature only seven cases of inhibitors of tumor necrosis factor induced-myositis. In this paper, we report the case of the patient with 39 years-old with eight years of arthritis rheumatoid and that due to refractory to various immunosuppressive drugs, the adalimumab was introduced, and evolved to dermatomyositis status.

Caspase-mediated cleavage of the exosome subunit PM/Scl-75 during apoptosis

Recent studies have implicated the dying cell as a potential reservoir of modified autoantigens that might initiate and drive systemic autoimmunity in susceptible hosts. A number of subunits of the exosome, a complex of 3'→5' exoribonucleases that functions in a variety of cellular processes, are recognized by the so-called anti-PM/Scl autoantibodies, found predominantly in patients suffering from an overlap syndrome of myositis and scleroderma. Here we show that one of these subunits, PM/Scl-75, is cleaved during apoptosis. PM/Scl-75 cleavage is inhibited by several different caspase inhibitors. The analysis of PM/Scl-75 cleavage by recombinant caspase proteins shows that PM/Scl-75 is efficiently cleaved by caspase-1, to a smaller extent by caspase-8, and relatively inefficiently by caspase-3 and caspase-7. Cleavage of the PM/Scl-75 protein occurs in the C-terminal part of the protein at Asp369 (IILD369↓G), and at least a fraction of the resulting N-terminal fragments of PM/Scl-75 remains associated with the exosome. Finally, the implications of PM/Scl-75 cleavage for exosome function and the generation of anti-PM/Scl-75 autoantibodies are discussed.

Dermatomiosite recém-diagnosticada em idosos como preditiva de malignidade

OBJETIVO: Os sintomas da dermatomiosite (DM) podem ser um indício da existência de um câncer oculto. Melhorar a detecção precoce é essencial, porém não há estudos avaliando em curto prazo os fatores preditivos para a doença. MÉTODO: Estudo retrospectivo, monocêntrico, incluindo pacientes com DM definida (pelo menos quatro dos cinco critérios de Bohan e Peter, 1975), no período entre 1991 e 2011. A presença de malignidade foi limitada a um período de até 12 meses após o diagnóstico da doença. RESULTADOS: Houve 12 casos de neoplasias em 139 pacientes (pele, trato gastrintestinal, próstata, tireoide, mama, pulmão e trato geniturinário). Os pacientes com neoplasia tiveram maior média de idade que os controles (56,8 ± 15,7 vs. 40,3 ± 13,1 anos, respectivamente, P = 0,004; odds ratio 1,09; intervalo de confiança de 95%: 1,04-1,14). Não foram observadas diferenças estatísticas em relação a gênero, etnia, frequência de sintomas constitucionais, envolvimento de órgãos e sistemas e/ou alterações laboratoriais. CONCLUSÃO: Na DM recém-diagnosticada, a idade tardia ao diagnóstico foi um fator preditivo de malignidade.

Dermatomiosite em adulto: experiência de um centro terciário brasileiro

OBJETIVOS: Relatamos os resultados de um estudo de coorte retrospectivo envolvendo 139 pacientes com dermatomiosite, conduzido de 1991 a 2011. MÉTODOS: Todos os pacientes preenchiam pelo menos quatro dos cinco critérios de Bohan and Peter (1975). RESULTADOS: A média de idade dos pacientes no início da doença foi de 41,7 ± 14,1 anos, e a duração da doença foi de 7,2 ± 5,2 anos. A amostragem constitui-se de 90,2% de indivíduos brancos, 79,9% do gênero feminino. Sintomas constitucionais foram detectados em menos da metade dos casos. Envolvimentos cutâneo e articular ocorreram em 95,7% e 41,7% dos pacientes, respectivamente. Em 48,2% dos pacientes foram apresentadas pneumopatia incipiente, opacidades em "vidro fosco" e/ou fibrose pulmonar. Todos os pacientes receberam prednisona (1 mg/kg/dia) e 51,1% receberam também metilprednisolona intravenosa (1 g/dia por três dias). Vários imunossupressores foram usados como poupadores de corticosteroide de acordo com tolerância, efeitos colaterais e/ou refratariedade. Houve recidiva de doença (clínica e/ou laboratorial) em 53,2% dos casos; 76,3% permaneceram em remissão no momento do estudo. A taxa de infecção grave foi de 35,3%, com o predomínio de herpes zoster. Houve 15 (10,8%) casos de câncer, dos quais 12 foram confirmados em um período de um ano após o diagnóstico da doença. Houve ainda 16 óbitos (11,5%) cujas causas principais foram sepse/choque séptico (27,5%), pneumopatia atribuída à doença (31,3%), neoplasias (31,3%) e eventos cardiovasculares (12,5%). CONCLUSÕES: No presente trabalho, os dados clínico-laboratoriais foram semelhantes aos de outros grupos populacionais descritos na literatura, com diferenças mínimas quanto à frequência e às características das manifestações extramusculares.