RESUMEN
The THαß host immunological pathway contributes to the response to infectious particles (viruses and prions). Furthermore, there is increasing evidence for associations between autoimmune diseases, and particularly type 2 hypersensitivity disorders, and the THαß immune response. For example, patients with systemic lupus erythematosus often produce anti-double stranded DNA antibodies and anti-nuclear antibodies and show elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 throughout the disease course. These cytokines and antibody isotypes are associated with the THαß host immunological pathway. Similarly, the type 2 hypersensitivity disorders myasthenia gravis, Graves' disease, graft-versus-host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjögren's syndrome have also been linked to the THαß pathway. Considering the potential associations between these diseases and dysregulated THαß immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferon α/ß could be explored for effective management.
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Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/complicaciones , Síndrome de Sjögren/inmunología , Enfermedad Injerto contra Huésped/inmunología , Enfermedades Autoinmunes/inmunología , Citocinas/inmunología , Miastenia Gravis/inmunología , Anemia Hemolítica Autoinmune/inmunología , Enfermedad de Graves/inmunología , Enfermedad de Graves/complicaciones , Dermatomiositis/inmunologíaRESUMEN
Juvenile dermatomyositis (JDM) is the leading cause of chronic idiopathic inflammatory myopathy of auto-immune origin in children.1 Seven patients with JDM found in the records from 1998-2019 of the Department of Dermatology Farhat Hached Hospital, Sousse, Tunisia. Our study concerned a total of six girls and one boy with a median age at disease onset of 8,16 years.2 The average time before diagnosis was 8,8 months. The onset of the disease was acute in 2 patients. All patients displayed skin manifestations at diagnosis, with proximal muscular weakness in 4 cases. Four patients had elevated muscle enzymes and all of them showed myopathic findings on electromyography. Oral corticosteroids were prescribed in 6 patients, in association with other systemic therapies. Three patients achieved a good outcome while two others relapsed. The two other patients showed corticosteroids resistance with a fatal outcome in one case. This study highlights the diagnostic features and management of juvenile dermatomyositis.
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Dermatomiositis , Humanos , Dermatomiositis/diagnóstico , Dermatomiositis/tratamiento farmacológico , Masculino , Femenino , Niño , Adolescente , Preescolar , Corticoesteroides/uso terapéutico , Estudios Retrospectivos , Electromiografía , Túnez , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificaciónRESUMEN
Dermatomyositis (DM) is a complex and rare autoimmune disease characterized by muscle weakness and distinctive skin rashes. Its pathogenesis involves a combination of genetic susceptibility, environmental triggers, and immunological factors, with interferon pathways and specific gene upregulations playing crucial roles. Diagnosis is based on clinical presentation, laboratory findings, and imaging, with particular emphasis on myositis-specific antibodies and characteristic muscle and skin changes. The clinical heterogeneity of DM, including variants such as clinically amyopathic DM and DM-associated interstitial lung disease, necessitates a personalized diagnostic and therapeutic approach. Current pharmacological treatments for DM include glucocorticoids, which remain the first-line therapy despite their long-term adverse effects. Immunosuppressants, such as azathioprine, methotrexate, and mycophenolate mofetil, are commonly used in combination with glucocorticoids to enhance efficacy and reduce steroid dependence. Biologics, such as rituximab and intravenous immunoglobulin, have shown effectiveness in refractory cases. Emerging therapies, particularly Janus kinase inhibitors, offer promise for treatment-resistant DM, although they present significant safety concerns, including increased risks of infections and cardiovascular events. Despite significant advancements, managing DM remains challenging due to its rarity and variability. Future research should prioritize the development of precision medicine approaches tailored to individual genetic and pathological features. Additionally, integrated treatment strategies combining pharmacological and non-pharmacological interventions are crucial to improving patient outcomes and quality of life. Understanding the etiology and pathogenesis of DM more deeply will be vital for developing more effective and targeted treatments, ultimately leading to better disease management and prognosis.
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Dermatomiositis , Inmunosupresores , Humanos , Dermatomiositis/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Glucocorticoides/uso terapéuticoRESUMEN
OBJECTIVE: To study the trajectories of changes in damage over time and explore associations with autoantibody defined subgroups using a large international cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: Data from the MYONET registry, including patients who were tested for autoantibodies and had at least one assessment of damage using the Myositis Damage Index (MDI), were analyzed. Patients were sub-grouped according to their autoantibody profiles (myositis-specific, myositis-associated, or seronegative). The index date was defined as the time point for the first registered MDI assessment. The longitudinal trajectories of damage with autoantibody status as the main predictor were analyzed using linear mixed models. RESULTS: A total of 757 adult patients were included in this study. Each year of disease duration since diagnosis had an estimated MDI score increase of 0.16 units for the seronegative group (reference). Compared with the seronegative group as reference, patients with dermatomyositis-specific autoantibodies developed less damage per year of follow-up since diagnosis (average 0.08 less score, P = 0.04), whereas patients with anti-PM/Scl autoantibodies developed more damage per year of follow-up since diagnosis (average 0.28 higher score, P = 0.03) independent of sex and age at diagnosis. The seronegative subgroup and the immune-mediated necrotizing myopathy autoantibody subgroup had the strongest correlation between severity of muscle damage and HAQ-DI scores at five years of follow-up, rho=0.84, P < 0.001 and rho=0.72, P < 0.001, respectively. CONCLUSION: Our study is the first to describe patterns and trajectories of change in damage over time in relation to autoantibody defined subgroups in a large international multicenter cohort of patients with IIM. Patients with anti-PM/Scl scored a greater extent of damage, whereas patients with dermatomyositis-specific antibodies had less damage than seronegative patients. Severity in muscle damage had moderate to strong correlation with functional disability among the IMNM and seronegative subgroups with lower correlations for the other subgroups. These findings suggest that autoantibodies may be useful predictors of long-term damage.
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Autoanticuerpos , Miositis , Sistema de Registros , Humanos , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Masculino , Femenino , Miositis/inmunología , Miositis/sangre , Persona de Mediana Edad , Estudios Longitudinales , Adulto , Índice de Severidad de la Enfermedad , Anciano , Progresión de la Enfermedad , Dermatomiositis/inmunología , Dermatomiositis/sangreAsunto(s)
Biomarcadores , Quimiocina CXCL16 , Dermatomiositis , Progresión de la Enfermedad , Enfermedades Pulmonares Intersticiales , Humanos , Enfermedades Pulmonares Intersticiales/complicaciones , Dermatomiositis/complicaciones , Dermatomiositis/sangre , Biomarcadores/sangre , Pronóstico , Quimiocina CXCL16/sangre , Femenino , MasculinoAsunto(s)
Biomarcadores , Quimiocina CXCL16 , Dermatomiositis , Progresión de la Enfermedad , Enfermedades Pulmonares Intersticiales , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/complicaciones , Humanos , Dermatomiositis/sangre , Dermatomiositis/complicaciones , Dermatomiositis/inmunología , Biomarcadores/sangre , Pronóstico , Quimiocina CXCL16/sangreRESUMEN
Purpose: Amyopathic dermatomyositis (ADM) is a rare, idiopathic, connective tissue disease and melanoma differentiation-associated protein 5 (MDA5) antibody-positive ADM is more treatment-resistant, especially in patients with interstitial lung disease (ILD). The purpose of this article is to report a case of anti-MDA5-positive ADM successfully treated with JAK inhibitor Upadacitinib.Materials and methods: A 35-year-old Chinese woman presented with recurrent itchy erythema on her face and scalp for 4 years. Upon examination, there were heliotrope erythema and eyelid edema, reddish rash on neck and scalp. Biopsy of the lesions was consistent with DM and a line blot assay confirmed the presence of anti-MDA5 antibodies. This patient was treated with oral Upadacitinib at a dosage of 30 mg daily.Results: After 6 weeks of treatment, she achieved complete clinical remission with no reported side effects or instances of relapse. The antibody titer of anti-MDA5 was also decreased.Conclusions: Upadacitinib may be a potential drug candidate in patients with treatment-resistant ADM, especially in cases with refractory cutaneous conditions.
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Dermatomiositis , Compuestos Heterocíclicos con 3 Anillos , Helicasa Inducida por Interferón IFIH1 , Humanos , Femenino , Dermatomiositis/tratamiento farmacológico , Dermatomiositis/inmunología , Dermatomiositis/complicaciones , Dermatomiositis/patología , Helicasa Inducida por Interferón IFIH1/inmunología , Adulto , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Resultado del Tratamiento , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/administración & dosificaciónRESUMEN
BACKGROUND: Juvenile dermatomyositis (JDM) is a systemic vasculopathy associated with metabolic derangements and possible increased risk for premature atherosclerosis. Oxidation of low-density lipoprotein (LDL) in the endothelium is an early step in atherosclerotic plaque formation. It is not known if oxidized LDL is altered in children with untreated JDM. The deposition of oxidized LDL in the vasculature of muscle biopsies (MBx) from patients with untreated JDM and pediatric controls was assessed. FINDINGS: Frozen tissue sections of MRI-directed MBx from 20 female children with untreated JDM and 5 female controls were stained with DAPI and fluorescently labeled antibodies against von Willebrand factor (vWF) and LDL oxidized by copper (oxLDL). Blood vessels were identified by positive vWF staining, and total fluorescence of oxLDL within the vessel walls was measured. Children with untreated JDM had increased deposition of oxLDL in the walls of muscle vasculature compared to healthy children (difference in means ± SEM = 19.86 ± 8.195, p = 0.03). Within the JDM cohort, there was a trend towards increased oxLDL deposition with longer duration of untreated disease (r = 0.43, p = 0.06). There was no significant correlation found between oxLDL deposition and markers of acute JDM disease activity including disease activity scores or muscle enzymes. CONCLUSIONS: This study found increased deposition of oxLDL within blood vessels of children with untreated JDM supporting the concern that these children are at increased risk for premature atherosclerosis from chronic exposure to vascular oxLDL. This study highlights the importance of early diagnosis and treatment initiation to ameliorate cardiovascular damage.
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Dermatomiositis , Lipoproteínas LDL , Humanos , Femenino , Lipoproteínas LDL/metabolismo , Dermatomiositis/metabolismo , Dermatomiositis/patología , Niño , Adolescente , Músculo Esquelético/metabolismo , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/patología , Preescolar , Estudios de Casos y Controles , Imagen por Resonancia Magnética/métodos , BiopsiaRESUMEN
Since the introduction of mRNA vaccines against SARS-CoV-2, the induction of autoimmunity by mRNA vaccination has been discussed. Several cases of dermatomyositis (DM) associated with mRNA vaccination against SARS-CoV-2 infection have been reported. The question is whether there is a common pathomechanism for the induction of DM by this mRNA vaccination. The aim of this review is to analyse the sample of previously published case reports of DM following COVID-19 mRNA vaccination for common indicators of a possible immune pathomechanism.In this review, we summarised case reports of DM following mRNA vaccination against COVID-19. We considered this case report landscape as a cumulative sample (n = 32) and identified common clinical and molecular parameters in the intersection of case reports and statistically analysed the effect of these parameters on the development of DM.MDA-5 antibodies seem to play a role in the autoantibody signature after mRNA vaccination. MDA-5-positive DM is statistically more strongly associated with mRNA vaccination and interstitial lung disease/rapidly progressive interstitial lung disease (ILD/RP-ILD) than MDA-5-negative DM. MDA-5-positive DM seems not to be associated with an increased risk of malignancy, whereas MDA-5-negative DM is more strongly associated with malignancy.Our findings emphasize the potential role of innate antiviral signalling pathways in connecting DM to mRNA vaccination. MDA-5 autoantibodies appear to be predictive of a severe DM progression following mRNA vaccination. There seems to be an association between MDA-5 autoantibodies and paraneoplastic DM post-vaccination. Further studies are required to uncover the underlying mechanisms of autoimmunity triggered by mRNA vaccination.
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Autoanticuerpos , COVID-19 , Dermatomiositis , Helicasa Inducida por Interferón IFIH1 , Humanos , Dermatomiositis/inmunología , Helicasa Inducida por Interferón IFIH1/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Estudios Retrospectivos , Persona de Mediana Edad , Masculino , SARS-CoV-2/inmunología , Femenino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , Vacunas de ARNm/inmunología , Anciano , AdultoRESUMEN
Anti-melanoma differentiation-associated protein 5 (MDA5) antibody positive clinically amyopathic dermatomyositis (CADM) is a subtype of inflammatory myopathy associated with a distinct clinical phenotype, characterized by rapidly progressing interstitial lung disease and limited muscle involvement. Although cases with onset of anti-MDA5 antibody positive CADM during pregnancy or the postpartum period are rare, they present unique challenges due to a potential pregnancy complications and the possible severity of the disease course. We present a case of anti-MDA5 antibody positive CADM that developed during the postpartum period following childbirth without any pregnancy complication. Additionally, we conducted a comprehensive review of case reports and series of similar cases to elucidate the clinical characteristics and outcomes. Our analysis revealed considerable variability in disease presentation, ranging from severe cases requiring multi-targeted therapy to well-controlled cases with less demanding treatments. The scarcity of evidence in this population underscores the importance of accumulating evidence from case series to inform treatment strategies. More precise prediction tools are needed to effectively manage this rare subset of patients.
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Autoanticuerpos , Dermatomiositis , Helicasa Inducida por Interferón IFIH1 , Humanos , Dermatomiositis/inmunología , Dermatomiositis/tratamiento farmacológico , Dermatomiositis/complicaciones , Dermatomiositis/diagnóstico , Femenino , Helicasa Inducida por Interferón IFIH1/inmunología , Embarazo , Autoanticuerpos/sangre , Adulto , Periodo PospartoRESUMEN
INTRODUCTION: Adult dermatomyositis (DM) and juvenile dermatomyositis (JDM) are rare autoimmune diseases with characteristic skin rashes, weakness, and other systemic features. Upregulated interferon signaling has been consistently described in both adult and juvenile DM which makes janus kinase inhibitors (jakinibs) an attractive therapeutic agent that has a targeted mechanism of action. AREAS COVERED: Herein is a review of the growing literature of jakinib use in adult and juvenile DM, including reports on specific disease features and safety of jakinibs in this population and a comparison between adult and juvenile DM. We performed a literature review using PubMed including all English-language publications before 1 February 2024 and abstracts from key recent rheumatology conferences. EXPERT OPINION: Jakinibs are an exciting and promising treatment in both adult and juvenile DM. Current Phase 2 and 3 randomized placebo-controlled trials of jakinibs in both adult and JDM will provide significant insights into the efficacy of this class of medication as a potentially more mechanistically targeted treatment of both skin and muscle disease. In fact, these results will likely inform the treatment paradigm of dermatomyositis in that it may even be considered as first or second line. The next five years in the therapeutic landscape of both juvenile and adult DM is an exciting time for both patients and medical providers.
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Dermatomiositis , Inhibidores de las Cinasas Janus , Humanos , Dermatomiositis/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/farmacología , Inhibidores de las Cinasas Janus/efectos adversos , Niño , Adulto , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de EdadRESUMEN
OBJECTIVE: To evaluate the influence of environmental factors and prematurity relating to juvenile dermatomyositis (JDM), its course and refractoriness to treatment. METHODS: A case-control study with 35 patients followed up at a tertiary hospital and 124 healthy controls, all residents of São Paulo. Patients were classified according to monocyclic, polycyclic or chronic disease courses and refractoriness to treatment. The daily concentrations of pollutants (inhalable particulate matter-PM10, sulfur dioxide-SO2, nitrogen dioxide-NO2, ozone-O3 and carbon monoxide-CO) were provided by the Environmental Company of São Paulo. Data from the population were obtained through a questionnaire. RESULTS: Fifteen patients had monocyclic courses, and 19 polycyclic/chronic courses. Eighteen patients were refractory to treatment. Maternal occupational exposure to inhalable agents (OR = 17.88; IC 95% 2.15-148.16, p = 0.01) and exposure to O3 in the fifth year of life (third tertile > 86.28µg/m3; OR = 6.53, IC95% 1.60-26.77, p = 0.01) were risk factors for JDM in the multivariate logistic regression model. The presence of a factory/quarry at a distance farther than 200 meters from daycare/school (OR = 0.22; IC 95% 0.06-0.77; p = 0.02) was a protective factor in the same analysis. Prematurity, exposure to air pollutants/cigarette smoke/sources of inhalable pollutants in the mother's places of residence and work during the gestational period were not associated with JDM. Prematurity, maternal exposure to occupational pollutants during pregnancy as well as patient's exposure to ground-level pollutants up to the fifth year of life were not associated with disease course and treatment refractoriness. CONCLUSION: Risk factors for JDM were maternal occupational exposure and exposure to O3 in the fifth year of life.
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Dermatomiositis , Exposición Profesional , Material Particulado , Humanos , Dermatomiositis/etiología , Femenino , Estudios de Casos y Controles , Masculino , Factores de Riesgo , Material Particulado/análisis , Material Particulado/efectos adversos , Niño , Brasil/epidemiología , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Embarazo , Ozono/análisis , Ozono/efectos adversos , Exposición Materna/efectos adversos , Monóxido de Carbono/análisis , Dióxido de Nitrógeno/análisis , Dióxido de Nitrógeno/efectos adversos , Dióxido de Azufre/análisis , Dióxido de Azufre/efectos adversos , Preescolar , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Modelos Logísticos , Nacimiento PrematuroRESUMEN
BACKGROUND: This study investigates the association between inflammatory myopathies (IM), and their correlation with cancer. There are several potential causes behind the association of cancer and inflammatory myopathies. The positivity of specific antibodies for myositis plays a significant role. Our objective is to describe cancer and inflammatory myopathies in Colombia, focusing on demographics, clinical characteristics, and laboratory data. METHODS: We retrospectively analyzed 112 IM patients diagnosed at Fundación Valle del Lili in Cali, Colombia, the cases met the EULAR/ACR criteria. Data included demographics, clinical signs, laboratory findings, and malignancy. Malignancy associations were explored using logistic regression. The survival analysis was assessed using Kaplan-Meier curves and the Log-Rank test. RESULTS: Dermatomyositis was the most common subtype (45.5%), with a female predominance (66.1%). Cancer diagnosis occurred in 11.6% of cases, predominantly thyroid cancer. The median time from myopathy onset to cancer diagnosis was 11 months, with 75% of cases within the first year. Bivariate analysis indicated associations between cancer and age, Gottron's papules, digital ulcers, and heliotrope rash. However, multivariate analysis identified age as the only significant malignancy risk factor. Survival analysis showed better rates in younger patients. CONCLUSION: This study provides into the link between IM and cancer in the Colombian population. Thyroid cancer predominated, with a slightly higher proportion of female cancer diagnoses. Age emerged as a significant risk factor for malignancy. Understanding this association is crucial for early detection and improving patient outcomes related to IM-associated malignancies.
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Miositis , Neoplasias , Humanos , Femenino , Estudios Retrospectivos , Colombia/epidemiología , Masculino , Persona de Mediana Edad , Miositis/epidemiología , Neoplasias/epidemiología , Adulto , Anciano , Adulto Joven , Dermatomiositis/epidemiología , Factores de Riesgo , Anciano de 80 o más AñosRESUMEN
BACKGROUND: This study aims to investigate the involvement of acid sphingomyelinase (ASM) in the pathology of dermatomyositis (DM), making it a potential therapeutic target for DM. METHODS: Patients with DM and healthy controls (HCs) were included to assess the serum level and activity of ASM, and to explore the associations between ASM and clinical indicators. Subsequently, a myositis mouse model was established using ASM gene knockout and wild-type mice to study the significant role of ASM in the pathology and to assess the treatment effect of amitriptyline, an ASM inhibitor. Additionally, we investigated the potential treatment mechanism by targeting ASM both in vivo and in vitro. RESULTS: A total of 58 DM patients along with 30 HCs were included. The ASM levels were found to be significantly higher in DM patients compared to HCs, with median (quartile) values of 2.63 (1.80-4.94) ng/mL and 1.64 (1.47-1.96) ng/mL respectively. The activity of ASM in the serum of DM patients was significantly higher than that in HCs. Furthermore, the serum levels of ASM showed correlations with disease activity and muscle enzyme levels. Knockout of ASM or treatment with amitriptyline improved the severity of the disease, rebalanced the CD4 T cell subsets Th17 and Treg, and reduced the production of their secreted cytokines. Subsequent investigations revealed that targeting ASM could regulate the expression of relevant transcription factors and key regulatory proteins. CONCLUSION: ASM is involved in the pathology of DM by regulating the differentiation of naive CD4 + T cells and can be a potential treatment target.
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Amitriptilina , Diferenciación Celular , Dermatomiositis , Ratones Noqueados , Esfingomielina Fosfodiesterasa , Linfocitos T Reguladores , Células Th17 , Dermatomiositis/tratamiento farmacológico , Dermatomiositis/inmunología , Dermatomiositis/genética , Humanos , Animales , Diferenciación Celular/efectos de los fármacos , Masculino , Femenino , Persona de Mediana Edad , Células Th17/efectos de los fármacos , Células Th17/inmunología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Amitriptilina/farmacología , Amitriptilina/uso terapéutico , Adulto , Ratones , Esfingomielina Fosfodiesterasa/genética , Esfingomielina Fosfodiesterasa/metabolismo , Ratones Endogámicos C57BLAsunto(s)
Dermatomiositis , Helicasa Inducida por Interferón IFIH1 , Linfohistiocitosis Hemofagocítica , Humanos , Dermatomiositis/complicaciones , Linfohistiocitosis Hemofagocítica/complicaciones , Helicasa Inducida por Interferón IFIH1/inmunología , Masculino , Femenino , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Persona de Mediana EdadRESUMEN
Dermatomyositis (DM) is a multi-organ idiopathic inflammatory myopathy that presents with proximal symmetric muscle weakness accompanied by characteristic cutaneous findings. Most individuals present with skin manifestations prior to muscle involvement and its course can involve the blood vessels, joints, esophagus, and lungs and can be paraneoplastic, making a malignancy assessment imperative. Although its etiology is unknown, type I interferon appears to be a component in evoking the characteristic inflammatory response and patients with DM often have an increase in type I inducible genes. Suspected triggers for DM are environmental factors, drugs, viral infections, and vaccines. The association of DM with vaccination poses a new conundrum within the medical community as people continue to get vaccinated and boosted with SARS-CoV2 vaccines, though it is worth noting that the most common challenges arose as type I hypersensitivity reactions and new onset autoimmune disorders are rare. Presented here is a 53-year-old man who was diagnosed with DM after receiving the second dose of the Pfizer vaccine. His case highlights the importance of the potential onset of autoimmune diseases following the COVID-19 vaccine, a phenomenon that clinicians should be aware of as the discourse concerning the pandemic continues.