Clasificación y manejo actual en dermatomiositis juvenil / Classification and current management in juvenile dermatomyositis

La Dermatomiositis Juvenil representa el 75-80% de las miopatías inflamatorias juveniles. Si bien, tiene baja incidencia y prevalencia, presenta importante morbilidad dada por sus manifestaciones cutáneas, musculares, pulmonares, gastrointestinales, cardiacas, entre otras. Corresponde a un desorden poligénico con múltiples factores gatillantes, que determina el desarrollo de una vasculopatía que lleva a atrofia muscular, inflamación y activación de vías del IFN-1. Actualmente su diagnóstico se basa en las guias EULAR/ACR (2017). En los últimos años, se han descubiertos distintos subtipos de la enfermedad, basados en el perfil de autoanticuerpos específicos de miositis, lo que ha permitido establecer pronóstico y estrategias terapéuticas personalizadas. El manejo farmacológico continúa basándose principalmente en el uso de corticoesteroides y DMARDs, así como también terapia biológica; en los últimos años, los inhibidores JAK han mostrado resultados promisorios, convirtiéndose en la más nueva alternativa terapéutica para el control de la enfermedad.

Juvenile Dermatomyositis represents 75-80% of juvenile inflammatory myopathies. Although it has a low incidence and prevalence, it presents significant morbidity due to its cutaneous, muscular, pulmonary, gastrointestinal and cardiac manifestations, among others. It corresponds to a polygenic disorder with multiple triggering factors, which determines the development of a vasculopathy that leads to muscle atrophy, inflammation and activation of IFN-1 pathways. Currently its diagnosis is based on the EULAR/ACR guidelines (2017). In recent years, different subtypes of the disease have been discovered, based on the profile of myositis-specific autoantibodies, which has made it possible to establish prognosis and personalized therapeutic strategies. Pharmacological management continues to be based mainly on the use of corticosteroids and DMARDs, as well as biological therapy; In recent years, JAK inhibitors have shown promising results, becoming the newest therapeutic alternative for disease control.

Autoimmune diseases are associated with an increased risk of schizophrenia: A nationwide population-based cohort study.

OBJECTIVES: Studies have suggested a possible autoimmune contribution in a subset of patients with schizophrenia. The purpose of this study was to determine if a history of autoimmune diseases (AD) is associated with an increased risk of later onset of schizophrenia. METHODS: Taiwan's National Health Insurance Research Database was used to identify a total of 64,817 AD patients and an equal number of age-matched control patients. The incidence rates of schizophrenia with a maximum follow-up period of 10 years between patients with and without AD were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). RESULTS: The main finding was the discovery of a higher incidence of subsequent schizophrenia in patients with AD (HR: 1.72, 95% CI: 1.23-2.4) after adjustment for other demographic characteristics. Specifically, the risk of schizophrenia was observed to be a significant increase in systemic lupus erythematosus (3.73, 2.07-6.72), rheumatoid arthritis (2.89, 1.97-4.23), dermatomyositis (5.85, 1.32-25.94) and autoimmune vasculitis (2.44, 1.17-5.06). Also, this study revealed some potential risk factors for developing schizophrenia, including younger age (less than or equal to 50 years) and some comorbidities (hypertension, chronic obstructive pulmonary disease, and alcohol use disorder). Conversely, this study found that steroid use was a potential protective factor for the development of schizophrenia. CONCLUSIONS: This study found that AD were associated with an increased risk of developing schizophrenia, suggesting that the abnormal autoimmune process was associated with an increase in the expression of psychiatric disturbances.

Biologic therapies for refractory juvenile dermatomyositis: five years of experience of the Childhood Arthritis and Rheumatology Research Alliance in North America.

BACKGROUND: The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA). METHODS: The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011-2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013-2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting. RESULTS: One hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups. CONCLUSIONS: Our CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future. Significance and Innovations This is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years. This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.

Antinuclear Matrix Protein 2 Autoantibodies and Edema, Muscle Disease, and Malignancy Risk in Dermatomyositis Patients.

OBJECTIVE: Dermatomyositis (DM) patients typically present with proximal weakness and autoantibodies that are associated with distinct clinical phenotypes. We observed that DM patients with autoantibodies recognizing the nuclear matrix protein NXP-2 often presented with especially severe weakness. The aim of this study was to characterize the clinical features associated with anti-NXP-2 autoantibodies. METHODS: There were 235 DM patients who underwent testing for anti-NXP-2 autoantibodies. Patient characteristics, including muscle strength, were compared between those with and without these autoantibodies. The number of cancer cases observed in anti-NXP-2-positive subjects was compared with the number expected in the general population. RESULTS: Of the DM patients, 56 (23.8%) were anti-NXP-2-positive. There was no significant difference in the prevalence of proximal extremity weakness in patients with and without anti-NXP-2. In contrast, anti-NXP-2-positive patients had more prevalent weakness in the distal arms (35% versus 20%; P = 0.02), distal legs (25% versus 8%; P < 0.001), and neck (48% versus 23%; P < 0.001). Anti-NXP-2-positive subjects were also more likely to have dysphagia (62% versus 35%; P < 0.001), myalgia (46% versus 25%; P = 0.002), calcinosis (30% versus 17%; P = 0.02), and subcutaneous edema (36% versus 19%; P = 0.01) than anti-NXP-2-negative patients. Five anti-NXP-2-positive subjects (9%) had cancer-associated myositis, representing a 3.68-fold increased risk (95% confidence interval 1.2-8.6) compared to the expected prevalence in the general population. CONCLUSION: In DM, anti-NXP-2 autoantibodies are associated with subcutaneous edema, calcinosis, and a muscle phenotype characterized by myalgia, proximal and distal weakness, and dysphagia. As anti-NXP-2-positive patients have an increased risk of cancer, we suggest that they undergo comprehensive cancer screening.

Increased subsequent risk of acute coronary syndrome for patients with dermatomyositis/polymyositis: a nationwide population-based retrospective cohort study.

OBJECTIVES: The aim of this study was to explore the possible association between dermatomyositis/polymyositis (DM/PM) and subsequent acute coronary syndrome (ACS) risk. METHOD: We used data from the National Health Insurance (NHI) system of Taiwan to address the research topic. The exposure cohort contained 2029 patients with new diagnoses of DM/PM. Each patient was randomly frequency-matched according to sex and age with four participants from the general population who did not have a history of ACS at the index date (control group). Cox proportional hazard regression analyses were conducted to estimate the relationship between DM/PM and subsequent ACS risk. RESULTS: Among patients with DM/PM, the overall risk for developing subsequent ACS was significantly higher than that of the control group [adjusted hazard ratio (aHR) 1.98, 95% confidence interval (CI) 1.17-3.35]. Further analysis indicated a higher risk in patients who were male, older, or diagnosed with comorbidities. CONCLUSIONS: The findings from this population-based retrospective cohort study suggest that DM/PM is associated with an increased subsequent ACS risk.

The autoimmune disease complex interstitial pneumonia/dermatomyositis in the light of endocrinology and cancer epidemiology.

The autoimmune disease interstitial pneumonia/dermatomyositis complex (ID) is classified as a paramalignancy since it is associated with a variety of malignancies at a high incidence in aged patients. We found a striking resemblance of pathophysiological features between ID and immunoendocrinopathy syndromes (IES) with depressed adrenocortical function. Drip infusion of megadose vitamin C, dehydroepiandrosterone and cortisol (an adrenocortical secretion substitute) was found to be effective for the control of ID. It has also been indicated that ID is a disease of adrenocortical insufficiency. Evidence is presented to indicate that ID in its clinical course is linked to environmental stress. The nature of paramalignant ID is discussed in the light of cancer epidemiology.

Presente y futuro de la terapia biológica en Dermatología / Present and future of biologic therapy in dermatology

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