Le muscle strié squelettique est un tissu richement vascularisé. Au delà de l'apport en oxygène et en nutriments, de nouvelles fonctions des vaisseaux ont été récemment identifiées, par le biais des interactions établies entre les cellules du vaisseau (cellules endothéliales) et les cellules du muscle, en particulier les cellules souches musculaires (cellules satellites). Celles-ci interagissent étroitement avec les cellules endothéliales pour leur expansion et leur différenciation, puis avec les cellules péri-endothéliales pour leur auto-renouvellement et leur retour à la quiescence. Les vaisseaux participent ainsi au contrôle de l’homéostasie du muscle squelettique. Grâce à ces interactions, les cellules vasculaires jouent donc un rôle central dans le remodelage tissulaire après un phénomène destructif, survenant par exemple au cours d’un trauma ou d’une myopathie. Pour étudier, les mécanismes de la plasticité vasculaire au cours du remodelage tissulaire, deux situations paradigmatiques de muscle en régénération chez l’enfant : la dermatomyosite juvénile (DMJ) et la dystrophie musculaire de Duchenne (DMD) ont été étudiées. Il existe, dans ces deux pathologies une souffrance musculaire associée à des cycles de nécrose/régénération. Elles se différencient par leur plasticité vasculaire et par leur évolution. En effet, la DMJ, la myopathie inflammatoire la plus fréquente de l’enfant est caractérisée par une vasculopathie avec perte en capillaires. L’évolution peut être favorable avec restitution ad integrum du muscle. La DMD est une myopathie génétique conduisant à une dégradation progressive de la force musculaire associée à une néovascularisation compensatrice. Le volet clinique/histologique incluant une analyse multiparamétrique des critères évolutifs cliniques et de réponse thérapeutique couplée à une réévaluation des données histologiques de la DMJ (analyse morphométrique des muscles DMJ) a permis de montrer qu’il existait des sous groupes phénotypiques homogènes de sévérité différente dans la DMJ. Le degré de sévérité clinique est relié à la gravité de la vasculopathie musculaire Par ailleurs, des marqueurs cliniques et histologiques simples permettant de repérer au diagnostic les patients nécessitant une escalade thérapeutique rapide (CMAS>34, atteinte gastrointestinale, fibrose endomysiale musculaire au diagnostic) ont été identifiés. Le volet cellulaire a permis l’identification in vitro des interactions cellulaires spécifiques et différentielles des myoblastes issues de patients DMD et DMJ sur les cellules endothéliales normales par l’analyse de leur rôle sur la prolifération, migration et différenciation des cellules vasculaires. Dans la DMD, les myoblastes entrainent une réponse angiogénique importante mais non efficace (néovascularisation anarchique). Dans la DMJ, les myoblastes participent efficacement à la reconstruction vasculaire notamment via la sécrétion de facteurs proangiogéniques. Ces résultats ont été renforcés par analyse transcriptomique effectuée à partir de cellules endothéliales et satellites isolées de muscles de patients confirmant le rôle central de la vasculopathie associée à un contexte inflammatoire spécifique lié à l’interféron dans la physiopathologie de la DMJ et montrant dans la DMD une dérégulation de l’homéostasie normale des interactions vaisseau-muscle avec mise en jeu d’un remodelage tissulaire non efficace. Ces données permettent d'identifier de nouvelles fonctions des cellules vasculaires dans le remodelage du muscle strié squelettique au cours des pathologies musculaires de l'enfant, et devraient ouvrir la voie à de nouvelles approches thérapeutiques. / Skeletal muscle is highly vascularised. Beyond oxygen and nutriment supply, new functions for vessels have been recently identified, through the interactions that vessel cells (endothelial cells) establish with muscle cells, particularly with muscle stem cells (satellite cells). These latter closely interact with endothelial cells for their expansion and their differentiation, then with periendothelial cells for their self-renewal and return to quiescence. During skeletal muscle regeneration endothelial cells reciprocally interact with myogenic cells by direct contact or by releasing soluble factors to promote both myogenesis and angiogenesis processes. Skeletal muscle regeneration typically occurs as a result of a trauma or disease, such as congenital or myopathies. To better understand the role of vessel plasticity in tissue remodeling, we took advantage of two muscular disorders that could be considered as paradigmatic situations of regenerating skeletal muscle in the child: Juvenile Dermatomyositis (JDM), the most frequent inflammatory myopathy and Duchenne Muscular Dystrophy (DMD), the most common type of muscular dystrophy. Although these two muscular disorders share, at the tissue level, similar mechanisms of necrosis-inflammation, they differ regarding the vessel domain. In JDM patients, microvascular changes consist in a destruction of endothelial cells assessed by focal capillary loss. This capillary bed destruction is transient. The tissue remodeling is efficient and muscle may progressively recover its function. By contrast, in DMD, despite an increase of vessels density in an attempt to improve the muscle perfusion, the muscle function progressively alters with age. We identified clinical and pathological markers of severity and predictive factors for poor clinical outcome in JDM by computing a comprehensive initial and follow-up clinical data set with deltoid muscle biopsy alterations controlled by age-based analysis of the deltoid muscle capillarization. We demonstrated that JDM can be divided into two distinctive clinical subgroups. The severe clinical presentation and outcome are linked to vasculopathy. Furthermore, a set of simple predictors (CMAS<34, gastrointestinal involvement, muscle endomysial fibrosis at disease onset) allow early recognition of patients needing rapid therapeutic escalation with more potent drugs. We studied in vitro the specific cell interactions between myogenic cells issued from JDM and DMD patients and normal endothelial cells to explore whether myogenic cells participate to the vessel remodeling observed in the two pathologies. We demonstrated that MPCs possessed angiogenic properties depending on the pathological environment. In DMD, MPCs promoted the development of establishment of an anarchic, although strong, EC stimulation, leading to the formation of weakly functional vessels. In JDM, MPCs enhanced the vessel reconstruction via the secretion of proangiogenic factors. This functional analysis was supported by the transcriptomic analysis consistent with a central vasculopathy in JDM including a strong and specific response to an inflammatory environment. On the contrary, DMD cells presented an unbalanced homeostasis with deregulation of several processes including muscle and vessel development with attempts to recover neuromuscular system by MPCs. To summarize, our data should allow the definition of new functions of vessel cells in skeletal muscle remodelling during muscle pathologies of the child that will open the way to explore new therapeutic options and to gain further insights in the pathogenesis of these diseases.

Le muscle strié squelettique est un tissu richement vascularisé. Au delà de l'apport en oxygène et en nutriments, de nouvelles fonctions des vaisseaux ont été récemment identifiées, par le biais des interactions établies entre les cellules du vaisseau (cellules endothéliales) et les cellules du muscle, en particulier les cellules souches musculaires (cellules satellites). Celles-ci interagissent étroitement avec les cellules endothéliales pour leur expansion et leur différenciation, puis avec les cellules péri-endothéliales pour leur auto-renouvellement et leur retour à la quiescence. Les vaisseaux participent ainsi au contrôle de l’homéostasie du muscle squelettique. Grâce à ces interactions, les cellules vasculaires jouent donc un rôle central dans le remodelage tissulaire après un phénomène destructif, survenant par exemple au cours d’un trauma ou d’une myopathie. Pour étudier, les mécanismes de la plasticité vasculaire au cours du remodelage tissulaire, deux situations paradigmatiques de muscle en régénération chez l’enfant : la dermatomyosite juvénile (DMJ) et la dystrophie musculaire de Duchenne (DMD) ont été étudiées. Il existe, dans ces deux pathologies une souffrance musculaire associée à des cycles de nécrose/régénération. Elles se différencient par leur plasticité vasculaire et par leur évolution. En effet, la DMJ, la myopathie inflammatoire la plus fréquente de l’enfant est caractérisée par une vasculopathie avec perte en capillaires. L’évolution peut être favorable avec restitution ad integrum du muscle. La DMD est une myopathie génétique conduisant à une dégradation progressive de la force musculaire associée à une néovascularisation compensatrice. Le volet clinique/histologique incluant une analyse multiparamétrique des critères évolutifs cliniques et de réponse thérapeutique couplée à une réévaluation des données histologiques de la DMJ (analyse morphométrique des muscles DMJ) a permis de montrer qu’il existait des sous groupes phénotypiques homogènes de sévérité différente dans la DMJ. Le degré de sévérité clinique est relié à la gravité de la vasculopathie musculaire Par ailleurs, des marqueurs cliniques et histologiques simples permettant de repérer au diagnostic les patients nécessitant une escalade thérapeutique rapide (CMAS>34, atteinte gastrointestinale, fibrose endomysiale musculaire au diagnostic) ont été identifiés. Le volet cellulaire a permis l’identification in vitro des interactions cellulaires spécifiques et différentielles des myoblastes issues de patients DMD et DMJ sur les cellules endothéliales normales par l’analyse de leur rôle sur la prolifération, migration et différenciation des cellules vasculaires. Dans la DMD, les myoblastes entrainent une réponse angiogénique importante mais non efficace (néovascularisation anarchique). Dans la DMJ, les myoblastes participent efficacement à la reconstruction vasculaire notamment via la sécrétion de facteurs proangiogéniques. Ces résultats ont été renforcés par analyse transcriptomique effectuée à partir de cellules endothéliales et satellites isolées de muscles de patients confirmant le rôle central de la vasculopathie associée à un contexte inflammatoire spécifique lié à l’interféron dans la physiopathologie de la DMJ et montrant dans la DMD une dérégulation de l’homéostasie normale des interactions vaisseau-muscle avec mise en jeu d’un remodelage tissulaire non efficace. Ces données permettent d'identifier de nouvelles fonctions des cellules vasculaires dans le remodelage du muscle strié squelettique au cours des pathologies musculaires de l'enfant, et devraient ouvrir la voie à de nouvelles approches thérapeutiques. / Skeletal muscle is highly vascularised. Beyond oxygen and nutriment supply, new functions for vessels have been recently identified, through the interactions that vessel cells (endothelial cells) establish with muscle cells, particularly with muscle stem cells (satellite cells). These latter closely interact with endothelial cells for their expansion and their differentiation, then with periendothelial cells for their self-renewal and return to quiescence. During skeletal muscle regeneration endothelial cells reciprocally interact with myogenic cells by direct contact or by releasing soluble factors to promote both myogenesis and angiogenesis processes. Skeletal muscle regeneration typically occurs as a result of a trauma or disease, such as congenital or myopathies. To better understand the role of vessel plasticity in tissue remodeling, we took advantage of two muscular disorders that could be considered as paradigmatic situations of regenerating skeletal muscle in the child: Juvenile Dermatomyositis (JDM), the most frequent inflammatory myopathy and Duchenne Muscular Dystrophy (DMD), the most common type of muscular dystrophy. Although these two muscular disorders share, at the tissue level, similar mechanisms of necrosis-inflammation, they differ regarding the vessel domain. In JDM patients, microvascular changes consist in a destruction of endothelial cells assessed by focal capillary loss. This capillary bed destruction is transient. The tissue remodeling is efficient and muscle may progressively recover its function. By contrast, in DMD, despite an increase of vessels density in an attempt to improve the muscle perfusion, the muscle function progressively alters with age. We identified clinical and pathological markers of severity and predictive factors for poor clinical outcome in JDM by computing a comprehensive initial and follow-up clinical data set with deltoid muscle biopsy alterations controlled by age-based analysis of the deltoid muscle capillarization. We demonstrated that JDM can be divided into two distinctive clinical subgroups. The severe clinical presentation and outcome are linked to vasculopathy. Furthermore, a set of simple predictors (CMAS<34, gastrointestinal involvement, muscle endomysial fibrosis at disease onset) allow early recognition of patients needing rapid therapeutic escalation with more potent drugs. We studied in vitro the specific cell interactions between myogenic cells issued from JDM and DMD patients and normal endothelial cells to explore whether myogenic cells participate to the vessel remodeling observed in the two pathologies. We demonstrated that MPCs possessed angiogenic properties depending on the pathological environment. In DMD, MPCs promoted the development of establishment of an anarchic, although strong, EC stimulation, leading to the formation of weakly functional vessels. In JDM, MPCs enhanced the vessel reconstruction via the secretion of proangiogenic factors. This functional analysis was supported by the transcriptomic analysis consistent with a central vasculopathy in JDM including a strong and specific response to an inflammatory environment. On the contrary, DMD cells presented an unbalanced homeostasis with deregulation of several processes including muscle and vessel development with attempts to recover neuromuscular system by MPCs. To summarize, our data should allow the definition of new functions of vessel cells in skeletal muscle remodelling during muscle pathologies of the child that will open the way to explore new therapeutic options and to gain further insights in the pathogenesis of these diseases.

Introdução: A dermatomiosite juvenil (DMJ) é uma doença autoimune idiopática caracterizada pela presença de lesão cutânea, perda de massa muscular, fraqueza muscular proximal, fadiga e redução da aptidão física. Nesse contexto, a suplementação de creatina emerge como estratégia terapêutica não farmacológica para atenuar os sintomas ocasionados pela disfunção muscular e perda de massa muscular em diversas condições, como nas doenças reumatológicas pediátricas; Objetivo: O objetivo deste estudo foi avaliar a eficácia e a segurança da suplementação de creatina em pacientes com DM de início juvenil; Métodos: Trata-se de um estudo duplo-cego, crossover, balanceado e controlado por placebo. Todos os voluntários (n = 15) receberam dois tratamentos, a saber: creatina (0,1 g/kg/dia) ou dextrose (placebo - 0,1 g/kg/dia). Para cada tratamento, o período de suplementação foi de 12 semanas, interpassadas por um período de washout de oito semanas. A ordem dos tratamentos foi determinada de forma aleatória e contrabalanceada. Tanto nos períodos pré-suplementação, como nos períodos pós-suplementação foram avaliadas a força e função musculares (desfechos primários), além da composição corporal, densidade mineral óssea, marcadores bioquímicos do remodelamento ósseo, citocinas inflamatórias, aptidão aeróbia, qualidade de vida, parâmetros relacionados à atividade da doença, consumo alimentar e conteúdo intramuscular de fosforilcreatina. Nos mesmos períodos de tempo, a segurança da intervenção foi avaliada por parâmetros laboratoriais e por clearance de 51Cr-EDTA. Os eventos adversos foram registrados durante todo o estudo; Resultados: Não houve diferença significativa no conteúdo intramuscular de fosforilcreatina entre as condições, antes e após as intervenções (Creatina - Pré: 21,4 ± 5,3/Pós: 20,6 ± 2,7, delta escore = -0,3 ± 2,5 mmol/kg peso úmido; Placebo - Pré: 20,4 ± 3,7/Pós: 20,7 ± 3,6, delta escore = -0,1 ± 4,2 mmol/kg peso úmido, p = 0,45 da interação entre as condições). Também, não houve diferença significativa entre as condições placebo e creatina para função muscular, capacidade aeróbia, composição corporal, densidade mineral óssea e qualidade de vida. Além disso, não houve alteração na função renal após a suplementação de creatina e nenhum efeito adverso foi observado; Conclusão: O protocolo de suplementação de creatina (0,1 g/kg/d) por 12 semanas foi bem tolerado e livre de efeitos adversos. Entretanto, a suplementação de creatina não foi capaz de aumentar o conteúdo intramuscular de fosforilcreatina, o que se traduziu em ausência de melhora da função muscular, aptidão aeróbia, composição corporal e parâmetros de qualidade de vida em pacientes com DM de início juvenil / Introduction: Juvenile dermatomyositis (JDM) is an autoimmune idiopathic disease characterized by skin rashes, insidious loss of muscle mass, symmetrical proximal muscle weakness, decreased physical capacity, and fatigue. In this context, creatine supplementation has emerged as a promising non-pharmacological therapeutic strategy to counteract muscle dysfunction and low lean mass in a variety of conditions, including in pediatric and rheumatic diseases. Objective: To examine the safety and efficacy of creatine supplementation in Juvenile Dermatomyositis (JDM) patients; Methods: JDM patients (n = 15) received placebo or creatine supplementation (0.1 g/kg/d) in a randomized, crossover, double-blind design. Subjects were assessed at baseline and after 12 weeks, with an 8-week washout period. Primary outcome was muscle function. Secondary outcomes included body composition, bone mineral density, biochemical markers of bone remodeling, inflammatory cytokines, aerobic conditioning, health-related quality of life, disease-related parameters, dietary intake and muscle phosphorylcreatine (PCR) content. Safety was assessed by laboratory parameters and kidney function measurements such as 51Cr-EDTA clearance; Results: Intramuscular PCR content was not significantly different between creatine and placebo before or after the intervention (Creatine - Pre: 21.4 ± 5.3, Post: 20.6 ± 2.7, delta score = -0.3 ± 2.5 mmol/kg wet muscle, ES = -0.15; Placebo - Pre: 20.4 ± 3.7, Post: 20.7 ± 3.6, delta score = -0.1 ± 4.2 mmol/kg wet muscle, ES = -0.15; 95% CI for delta score = -2.8 ± 2.4, p = 0.45 for interaction between intervention). No significant changes between placebo and creatine for muscle function and aerobic conditioning, body composition, bone mineral density, and quality of life were detected, probably due to the lack of change in intramuscular PCR content. Kidney function was not changed after creatine supplementation and no side effects were noticed; Conclusion: a 12-week creatine supplementation protocol is well tolerable and free of adverse effects but did not affect intramuscular PCR, muscle function, body composition, bone mineral density or quality of life in JDM patients

Le muscle strié squelettique est un tissu richement vascularisé. Au delà de l'apport en oxygène et en nutriments, de nouvelles fonctions des vaisseaux ont été récemment identifiées, par le biais des interactions établies entre les cellules du vaisseau (cellules endothéliales) et les cellules du muscle, en particulier les cellules souches musculaires (cellules satellites). Celles-ci interagissent étroitement avec les cellules endothéliales pour leur expansion et leur différenciation, puis avec les cellules péri-endothéliales pour leur auto-renouvellement et leur retour à la quiescence. Les vaisseaux participent ainsi au contrôle de l’homéostasie du muscle squelettique. Grâce à ces interactions, les cellules vasculaires jouent donc un rôle central dans le remodelage tissulaire après un phénomène destructif, survenant par exemple au cours d’un trauma ou d’une myopathie. Pour étudier, les mécanismes de la plasticité vasculaire au cours du remodelage tissulaire, deux situations paradigmatiques de muscle en régénération chez l’enfant : la dermatomyosite juvénile (DMJ) et la dystrophie musculaire de Duchenne (DMD) ont été étudiées. Il existe, dans ces deux pathologies une souffrance musculaire associée à des cycles de nécrose/régénération. Elles se différencient par leur plasticité vasculaire et par leur évolution. En effet, la DMJ, la myopathie inflammatoire la plus fréquente de l’enfant est caractérisée par une vasculopathie avec perte en capillaires. L’évolution peut être favorable avec restitution ad integrum du muscle. La DMD est une myopathie génétique conduisant à une dégradation progressive de la force musculaire associée à une néovascularisation compensatrice. Le volet clinique/histologique incluant une analyse multiparamétrique des critères évolutifs cliniques et de réponse thérapeutique couplée à une réévaluation des données histologiques de la DMJ (analyse morphométrique des muscles DMJ) a permis de montrer qu’il existait des sous groupes phénotypiques homogènes de sévérité différente dans la DMJ. Le degré de sévérité clinique est relié à la gravité de la vasculopathie musculaire Par ailleurs, des marqueurs cliniques et histologiques simples permettant de repérer au diagnostic les patients nécessitant une escalade thérapeutique rapide (CMAS>34, atteinte gastrointestinale, fibrose endomysiale musculaire au diagnostic) ont été identifiés. Le volet cellulaire a permis l’identification in vitro des interactions cellulaires spécifiques et différentielles des myoblastes issues de patients DMD et DMJ sur les cellules endothéliales normales par l’analyse de leur rôle sur la prolifération, migration et différenciation des cellules vasculaires. Dans la DMD, les myoblastes entrainent une réponse angiogénique importante mais non efficace (néovascularisation anarchique). Dans la DMJ, les myoblastes participent efficacement à la reconstruction vasculaire notamment via la sécrétion de facteurs proangiogéniques. Ces résultats ont été renforcés par analyse transcriptomique effectuée à partir de cellules endothéliales et satellites isolées de muscles de patients confirmant le rôle central de la vasculopathie associée à un contexte inflammatoire spécifique lié à l’interféron dans la physiopathologie de la DMJ et montrant dans la DMD une dérégulation de l’homéostasie normale des interactions vaisseau-muscle avec mise en jeu d’un remodelage tissulaire non efficace. Ces données permettent d'identifier de nouvelles fonctions des cellules vasculaires dans le remodelage du muscle strié squelettique au cours des pathologies musculaires de l'enfant, et devraient ouvrir la voie à de nouvelles approches thérapeutiques. / Skeletal muscle is highly vascularised. Beyond oxygen and nutriment supply, new functions for vessels have been recently identified, through the interactions that vessel cells (endothelial cells) establish with muscle cells, particularly with muscle stem cells (satellite cells). These latter closely interact with endothelial cells for their expansion and their differentiation, then with periendothelial cells for their self-renewal and return to quiescence. During skeletal muscle regeneration endothelial cells reciprocally interact with myogenic cells by direct contact or by releasing soluble factors to promote both myogenesis and angiogenesis processes. Skeletal muscle regeneration typically occurs as a result of a trauma or disease, such as congenital or myopathies. To better understand the role of vessel plasticity in tissue remodeling, we took advantage of two muscular disorders that could be considered as paradigmatic situations of regenerating skeletal muscle in the child: Juvenile Dermatomyositis (JDM), the most frequent inflammatory myopathy and Duchenne Muscular Dystrophy (DMD), the most common type of muscular dystrophy. Although these two muscular disorders share, at the tissue level, similar mechanisms of necrosis-inflammation, they differ regarding the vessel domain. In JDM patients, microvascular changes consist in a destruction of endothelial cells assessed by focal capillary loss. This capillary bed destruction is transient. The tissue remodeling is efficient and muscle may progressively recover its function. By contrast, in DMD, despite an increase of vessels density in an attempt to improve the muscle perfusion, the muscle function progressively alters with age. We identified clinical and pathological markers of severity and predictive factors for poor clinical outcome in JDM by computing a comprehensive initial and follow-up clinical data set with deltoid muscle biopsy alterations controlled by age-based analysis of the deltoid muscle capillarization. We demonstrated that JDM can be divided into two distinctive clinical subgroups. The severe clinical presentation and outcome are linked to vasculopathy. Furthermore, a set of simple predictors (CMAS<34, gastrointestinal involvement, muscle endomysial fibrosis at disease onset) allow early recognition of patients needing rapid therapeutic escalation with more potent drugs. We studied in vitro the specific cell interactions between myogenic cells issued from JDM and DMD patients and normal endothelial cells to explore whether myogenic cells participate to the vessel remodeling observed in the two pathologies. We demonstrated that MPCs possessed angiogenic properties depending on the pathological environment. In DMD, MPCs promoted the development of establishment of an anarchic, although strong, EC stimulation, leading to the formation of weakly functional vessels. In JDM, MPCs enhanced the vessel reconstruction via the secretion of proangiogenic factors. This functional analysis was supported by the transcriptomic analysis consistent with a central vasculopathy in JDM including a strong and specific response to an inflammatory environment. On the contrary, DMD cells presented an unbalanced homeostasis with deregulation of several processes including muscle and vessel development with attempts to recover neuromuscular system by MPCs. To summarize, our data should allow the definition of new functions of vessel cells in skeletal muscle remodelling during muscle pathologies of the child that will open the way to explore new therapeutic options and to gain further insights in the pathogenesis of these diseases.

Objetivo. Investigar os efeitos e a segurança de um programa de exercícios físicos supervisionados em parâmetros da doença, capacidade física e qualidade de vida relacionada à saúde em pacientes com dermatomiosite juvenil (DMJ). Métodos. Estudo longitudinal e prospectivo com 10 pacientes com DMJ crônica e com atividade leve. O programa de exercícios consistiu de treinos aeróbios e de resistência duas vezes por semana. Nos momentos inicial e 12 semanas após a intervenção foram avaliadas força e função musculares, condicionamento aeróbio, composição corpórea, escores da DMJ e qualidade de vida relacionada à saúde. Resultados. Pediatric Quality of Life Inventory do paciente e dos pais melhoraram após a intervenção (8,3%; p=0,0008 e 8,7%; p=0,027, respectivamente). Disease Activity Score reduziu (-30,6%; p=0,021) e Childhood Muscle Assessment Scale melhorou (2,5%; p=0,009), enquanto Manual Muscle Testing apresentou uma tendência à significância estatística (2,2%; p=0,081). O pico de consumo de oxigênio e o tempo para exaustão aumentou em 13,3% (p=0,001) e 18,2% (p=0,003), respectivamente, enquanto a frequência cardíaca de repouso diminuiu em 14,7% (p=0,006), indicando importantes adaptações cardiovasculares ao exercício. A força muscular dos membros superiores e inferiores e a função muscular também melhoraram significantemente após o programa (p < 0,05). A densidade mineral aparente do corpo total e da coluna lombar aumentaram significantemente após os treinos (1,44%; p=0,044 e 2,85%; p=0,008, respectivamente). Conclusão. Pela primeira vez na literatura foi mostrado que um programa de exercícios físicos supervisionados por 12 semanas é seguro e capaz de melhorar força e função musculares, condicionamento aeróbio, massa óssea, atividade da doença, e qualidade de vida relacionada à saúde em pacientes com DMJ crônica e leve, em atividade ou em remissão / Objective. To investigate the effects and safety 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 (8,3%; P = 0.0008 and 8,7%; P = 0.027, respectively). Importantly, after exercise, the Disease Activity Score was reduced (-30.6%; P = 0.021) and the Childhood Muscle Assessment Scale was improved (2.5%; P = 0.009), whereas the Manual Muscle Testing 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 also improved significantly 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 non-active mild and chronic juvenile DM with near normal physical function and quality of life

Introdução: Alterações pulmonares estruturais e funcionais podem ocorrer na dermatomiosite juvenil (DMJ). O objetivo foi avaliar a função pulmonar de pacientes com DMJ e analisar correlações entre os valores encontrados e os escores: tomográfico, de atividade e dano cumulativo da doença e qualidade de vida. Métodos: Estudo prospectivo, transversal, com 20 pacientes com DMJ entre 6 e 18 anos. Realizados testes de espirometria, pletismografia, difusão de monóxido de carbono (DLCO), teste de caminhada de 6 minutos (TCam6min) e tomografia de tórax (TC). Avaliados também: escores de atividade da doença (DAS), força muscular (CMAS e MMT), dano cumulativo (MDI) e qualidade de vida (PedsQL). Resultados: Vinte pacientes foram incluídos (média de 11,6 anos). Houve obstrução leve ou moderada em 35% dos pacientes, redução da difusão em 20%. Anormalidades espirométricas e/ou da difusão em 45% dos pacientes. Na pletismografia: CPT reduzida em 25% dos pacientes, condutância em 50% e relação VR/CPT em 35%. Treze pacientes realizaram TC sendo 8 alteradas com padrão intersticial(n=6) e misto(n=2). As correlações significativas (p < 0,05) foram: VEF1/CV versus DAS, PedsQL, CMAS e TC; condutância versus DAS, MDI e PedsQl; TCam6Min versus CMAS; DLCO versus MDI e CMAS; TC versus MDI, FEF 25%-75%, condutância, CMAS, PedsQL e DAS. Conclusão: A pletismografia, DLCO e o TCam6min são testes complementares na detecção de distúrbios funcionais em pacientes com DMJ. A existência de correlações significativas entre os parâmetros funcionais, estruturais e de dano cumulativo demonstram que as anormalidades da função pulmonar podem ter relação com o controle, gravidade e atividade da doença e influenciar na qualidade de vida desses pacientes. O distúrbio funcional obstrutivo, por doença inflamatória das vias aéreas, pode ser uma alteração precoce da doença pulmonar na DMJ / Background: Structural and functional pulmonary changes may occur in juvenile dermatomyositis (JDM). The objective of this study was to assess the pulmonary function of patients with JDM and the correlations between pulmonary function and scores for chest tomography, disease activity, cumulative damage, and quality of life. Methods: This prospective, cross-sectional study evaluated 20 patients with JDM aged between 6 and 18 years. Spirometry, plethysmography, diffusing capacity of the lungs for carbon monoxide (DLCO), 6-minute walk test (6MWT), and chest tomography (CT) examinations were performed. Disease Activity (DAS), muscle strength (CMAS and MMT), cumulative damage (MDI), and quality of life (PedsQL) scores were also evaluated. Results: Twenty patients were included in the study (mean age of 11.6 years). Mild or moderate pulmonary obstruction was observed in 35% of patients, and decreased pulmonary diffusion was observed in 20% of patients. Spirometric and/or diffusion abnormalities occurred in 45% of patients. With regard to the plethysmography results: total lung capacity (TLC) decreased in 25% of patients, conductance decreased in 50% of patients, and the residual volume (RV)/TLC ratio decreased in 35% of patients. Thirteen patients underwent CT; of these, 8 cases involved interstitial changes (n=6) and mixed disorders (n=2). The significant correlations (p < 0.05) were: forced expiratory volume in one second (FEV1)/vital capacity (VC) versus DAS, PedsQL, CMAS, and CT; conductance versus DAS, MDI, and PedsQL; 6MWT versus CMAS; DLCO versus MDI and CMAS; CT versus MDI, forced expiratory flow between 25% and 75% of vital capacity (FEF25-75%), conductance, CMAS, PedsQL, and DAS. Conclusion: Plethysmography, DLCO, and 6MWT can be used as complementary tests for the detection of functional disorders in patients with JDM. The significant correlations between functional, structural, and cumulative damage parameters indicate that pulmonary function abnormalities may be associated with disease control, severity, and activity and can influence the quality of life of these patients. Obstructive functional disorder due to inflammatory disease of the airways may constitute an early change in lung disease in JDM

Objetivo. Analisar a frequência de síndrome metabólica em pacientes adultas jovens com dermatomiosite (DM) e a possível associação de síndrome metabólica com as características clínicas e laboratoriais da DM. Posteriormente, analisar os níveis séricos das adipocitocinas em pacientes com DM. Métodos. O presente estudo unicentro e transversal incluiu 35 pacientes com DM, de acordo com os critérios de Bohan e Peter, pareadas por idade e índice de massa corpórea com 48 controles saudáveis. A atividade da doença foi baseada nos parâmetros estabelecidos pelo International Myositis Assessment and Clinical Studies Groups (IMACS). A síndrome metabólica foi definida de acordo com critérios preconizados por Joint Interim Statement de 2009. Resultados. A média de idade foi comparável entre DM e o grupo controle (respectivamente, 33,2 ± 6,5 e 33,3 ± 7,6 anos), com duração média da doença de um ano. Quando comparadas aos indivíduos do grupo controle, as pacientes com DM tinham alta prevalência de síndrome metabólica (34,3 vs. 6,3%; P = 0,001), assim como altos níveis séricos de adiponectina e resistina, em contraste com baixos níveis de leptina. Estas adipocitocinas se correlacionavam com vários parâmetros da dislipidemia em pacientes com DM. Além disto, os casos de DM com síndrome metabólica (N = 12) apresentaram maior faixa etária (36,7 ± 5,6 vs. 31,5 ± 8,0 anos; P = 0,035) e maior atividade da doença do que os casos sem síndrome metabólica (N = 23). Entretanto, a distribuição de adipocitocinas foi similar entre os grupos. Conclusão. Quando comparadas ao grupo controle, as pacientes adultas jovens com DM apresentam maior prevalência de síndrome metabólica e maiores níveis séricos de adiponectina e resistina, em contraste com menores níveis séricos de leptina. Entre as pacientes, a síndrome metabólica correlacionou-se positivamente com a maior faixa etária e com a atividade da doença / Objective. To analyze the frequency of metabolic syndrome in young adult female dermatomyositis (DM) patients and to evaluate the possible association of metabolic syndrome with DM-related clinical and laboratory features. Secondarily, to analyze the serum adipocytokine levels in DM patients. Methods. The present cross-sectional single-center study included 35 DM patients according to the criteria of Bohan and Peter, who were age-, body mass index-matched to 48 healthy controls. The disease activity was based on parameter established by the International Myositis Assessment and Clinical Studies Groups (IMACS). Metabolic syndrome was diagnosed according to the criteria established 2009 Join Interim Statement. Results. The median age was comparable in both the DM and control groups (33.2 ± 6.5 and 33.3 ± 7.6 years, respectively), with median disease duration of 1 year. When compared to healthy control group, the DM patients had a higher prevalence of metabolic syndrome (34.3 vs. 6.3%; P = 0.001), as well high serum adiponectin and resistin levels, in contrast to low serum leptin levels. These adipocytokines correlated with various dyslipidemia parameters in DM patients. Additionally, DM cases with metabolic syndrome (N = 12) were older (36.7 ± 5.6 vs. 31.5 ± 8.0 years; P = 0.035) and have more disease activity index than cases without metabolic syndrome (N = 23). Nevertheless, adipocytokines distribution was similar in both groups. Conclusion. Compared to control group, Adult young female patients with DM show higher metabolic syndrome prevalence and a higher serum adiponectin and resistin levels, in contrast to lower serum leptin levels. Among the patients, the metabolic syndrome correlates positively with older age and with disease activity

Objetivos: Avaliar a influência da exposição a fatores ambientais inalatórios durante a gravidez e o diagnóstico de dermatomiosite juvenil (DMJ). Métodos: Um estudo caso-controle incluiu 20 casos de DMJ e 56 controles, pareados por idade e sexo, residentes na região metropolitana de São Paulo. Através de um questionário foram obtidos os dados demográficos e os dados de exposição ambiental durante a gravidez: a exposição ocupacional (poeira causada por demolições, construções ou pedreiras, poeira de giz, tintas, verniz, vapor de combustível e fluídos de bateria), a existência de fontes de poluentes inalatórios próximas à residência da mãe e a exposição materna ao tabaco. As concentrações diárias de material particulado (PM10), dióxido de enxofre (SO2), dióxido de nitrogenio (NO2), ozônio (O3) e monóxido de carbono (CO) inalados foram avaliadas durante o período gestacional. Resultados: A exposição ocupacional materna a poeira de giz escolar e a resíduo volátil de gasolina ou diesel no grupo de DMJ foi significantemente maior comparada ao grupo controle (50% vs. 2,3%, p=0,004). Mães fumantes e exposição passiva ao cigarro na residência durante a gravidez foram significantemente maior no grupo de DMJ (20% vs. 1,7%, p=0,01; 35% vs. 16%, p=0,07, respectivamente). No modelo de regressão logística univariada, o fumo materno durante a gravidez, a exposição ocupacional a agentes inalados e a exposição ao CO troposférico no tercil mais elevado (3.2-5.4 ppm) no terceiro trimestre foram significantemente associados com DMJ (p < 0,05). Na análise multivariada, o fumo materno (OR=13,26, IC 95% 1,21-144,29, p=0,03), a exposição ocupacional (OR=35,39, IC 95%1,97-632,80, p=0,01) e a exposição ao CO (terceiro tercil) no terceiro trimestre de gestação (OR=12,21, IC 95%1,28- 115,96, p=0,03) permaneceram como fator de risco para DMJ. Conclusão: A exposição a poluentes inalatórios ambientais e fumaça de cigarro durante o desenvolvimento fetal podem contribuir para o aparecimento de DMJ / Objective: To evaluate the influence of exposures to inhaled environmental factors during pregnancy on juvenile dermatomyositis (JDM) diagnosis. Methods: A case-control study included 20 JDM and 56 healthy controls matched by age and gender residents in the metropolitan region of São Paulo city. A questionnaire assessed demographic data and environmental inhalation exposure during pregnancy (occupational exposure to demolition, chalk, construction and/or quarry dust, paints, varnish, fuel vapor and/or battery fluids, stationary sources of inhaled pollution near the mother\'s home and maternal tobacco exposure). Daily concentrations of inhaled particulate matter (PM10), sulphur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO) were evaluated throughout the gestational period. Results: Maternal occupational exposure to chalk dust/gasoline vapor in JDM group was significantly higher compared to controls (50% vs. 2. 3%, p=0.004). Smoking mothers and secondhand smoke exposure at home during pregnancy were significantly higher in JDM group (20% vs. 1.7%, p=0.01; 35% vs. 16%, p=0.07; respectively). In univariate logistic regression models, maternal smoking, occupational exposure to inhaled agents and the higher tertile of trospospheric CO (3.2-5.4 ppm) in the third trimester were significantly associated with JDM (p < 0.05). In multivariate analysis, smoking mother (OR=13.26, 95% CI 1.21-144.29, p=0.03), occupational exposure (OR=35.39, 95% CI 1.97-632.80, p=0.01) and CO (third tertile) exposure in the third trimester of gestation (OR=12.21, 95% CI 1.28-115.96, p=0.03) remained risk factors for JDM. Conclusion: Inhaled pollutants and tobacco smoking during fetal development may contribute to JDM

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Comparar e caracterizar, por intermédio dos protocolos de avaliação da deglutição, os achados fonoaudiológicos na fase preparatória oral e oral da deglutição nos pacientes avaliados nos dois grupos de doenças (DM/PM e ES). Foram identificados 80 pacientes com diagnóstico de dermatopolimiosite e esclerose sistêmica, de ambos os sexos, atendidos no ambulatório de Colagenoses do serviço de Reumatologia do Hospital Universitário Pedro Ernesto (HUPE-UERJ). Foram excluídos os indivíduos abaixo de 18 anos e acima de 60 anos (24) e com outras doenças e/ ou comorbidades. Dos 56 pacientes restantes, 73,2% (41) apresentavam ES e 26,8% (15) DM/PM. Após a assinatura do termo de consentimento livre e esclarecido, os indivíduos foram submetidos à avaliação clínica estrutural e funcional da deglutição pelo pesquisador, que é fonoaudiólogo. O estudo revelou elevada prevalência de alterações oromiofuncionais e da deglutição na fase preparatória oral e oral propriamente dita nos pacientes com ES para a consistência sólida, que geram disfagia oral e alta, e não somente uma disfagia baixa como tem sido apresentado na literatura médica. O estudo reforçou que as mulheres são as mais acometidas pelas doenças autoimunes e que os homens são em menor número. O fonoaudiólogo deve ser parte integrante da equipe interdisciplinar que atende esses pacientes. / Compare and Characterize by means of evaluation protocols of swallowing, speech-language findings in oral and oral preparatory phase of swallowing in patients evaluated in both groups of diseases (DM / PM and SS). We identified 80 patients with dermatomyositis and systemic sclerosis, of both sexes, Collagen outpatient clinic of the Rheumatology Service of Hospital Universitário Pedro Ernesto (HUPE-UERJ). We excluded individuals below 18 years and above 60 years (24) and other diseases and / or comorbidities. Of the 56 remaining patients, 73.2% (41) had SS and 26.8% (15) DM / PM. After signing an informed consent, subjects underwent structural and functional clinical assessment of swallowing, the researcher who is a speech and audiologist therapist. The study revealed high prevalence of oromiofunctionals and oral phase swallowing in patients with SS to solid food dysphagia and oral generating not only a high and low dysphagia as has been shown in medical literature. The study reinforced that women are more affected by autoimmune diseases, and that men are fewer. The speech and audiology therapist must be part of the interdisciplinary team that deals with these patients

Objetivos: Avaliar a influência da exposição a fatores ambientais inalatórios durante a gravidez e o diagnóstico de dermatomiosite juvenil (DMJ). Métodos: Um estudo caso-controle incluiu 20 casos de DMJ e 56 controles, pareados por idade e sexo, residentes na região metropolitana de São Paulo. Através de um questionário foram obtidos os dados demográficos e os dados de exposição ambiental durante a gravidez: a exposição ocupacional (poeira causada por demolições, construções ou pedreiras, poeira de giz, tintas, verniz, vapor de combustível e fluídos de bateria), a existência de fontes de poluentes inalatórios próximas à residência da mãe e a exposição materna ao tabaco. As concentrações diárias de material particulado (PM10), dióxido de enxofre (SO2), dióxido de nitrogenio (NO2), ozônio (O3) e monóxido de carbono (CO) inalados foram avaliadas durante o período gestacional. Resultados: A exposição ocupacional materna a poeira de giz escolar e a resíduo volátil de gasolina ou diesel no grupo de DMJ foi significantemente maior comparada ao grupo controle (50% vs. 2,3%, p=0,004). Mães fumantes e exposição passiva ao cigarro na residência durante a gravidez foram significantemente maior no grupo de DMJ (20% vs. 1,7%, p=0,01; 35% vs. 16%, p=0,07, respectivamente). No modelo de regressão logística univariada, o fumo materno durante a gravidez, a exposição ocupacional a agentes inalados e a exposição ao CO troposférico no tercil mais elevado (3.2-5.4 ppm) no terceiro trimestre foram significantemente associados com DMJ (p < 0,05). Na análise multivariada, o fumo materno (OR=13,26, IC 95% 1,21-144,29, p=0,03), a exposição ocupacional (OR=35,39, IC 95%1,97-632,80, p=0,01) e a exposição ao CO (terceiro tercil) no terceiro trimestre de gestação (OR=12,21, IC 95%1,28- 115,96, p=0,03) permaneceram como fator de risco para DMJ. Conclusão: A exposição a poluentes inalatórios ambientais e fumaça de cigarro durante o desenvolvimento fetal podem contribuir para o aparecimento de DMJ / Objective: To evaluate the influence of exposures to inhaled environmental factors during pregnancy on juvenile dermatomyositis (JDM) diagnosis. Methods: A case-control study included 20 JDM and 56 healthy controls matched by age and gender residents in the metropolitan region of São Paulo city. A questionnaire assessed demographic data and environmental inhalation exposure during pregnancy (occupational exposure to demolition, chalk, construction and/or quarry dust, paints, varnish, fuel vapor and/or battery fluids, stationary sources of inhaled pollution near the mother\'s home and maternal tobacco exposure). Daily concentrations of inhaled particulate matter (PM10), sulphur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO) were evaluated throughout the gestational period. Results: Maternal occupational exposure to chalk dust/gasoline vapor in JDM group was significantly higher compared to controls (50% vs. 2. 3%, p=0.004). Smoking mothers and secondhand smoke exposure at home during pregnancy were significantly higher in JDM group (20% vs. 1.7%, p=0.01; 35% vs. 16%, p=0.07; respectively). In univariate logistic regression models, maternal smoking, occupational exposure to inhaled agents and the higher tertile of trospospheric CO (3.2-5.4 ppm) in the third trimester were significantly associated with JDM (p < 0.05). In multivariate analysis, smoking mother (OR=13.26, 95% CI 1.21-144.29, p=0.03), occupational exposure (OR=35.39, 95% CI 1.97-632.80, p=0.01) and CO (third tertile) exposure in the third trimester of gestation (OR=12.21, 95% CI 1.28-115.96, p=0.03) remained risk factors for JDM. Conclusion: Inhaled pollutants and tobacco smoking during fetal development may contribute to JDM