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BACKGROUND: Juvenile Dermatomyositis (JDM) is the most common chronic idiopathic inflammatory myopathy in children. The diagnosis is clinical. Baseline laboratory and complementary studies trace the phenotype of these patients. The objective of this study was to describe epidemiological, clinical and laboratory characteristics at diagnosis of JDM patients included in the Spanish JDM registry, as well as to identify prognostic factors on these patients. METHODS: We retrospectively reviewed clinical features, laboratory tests, and complementary studies at diagnosis of JDM patients included on the Spanish JDM registry. These data were analyzed to assess whether there was a relationship with the development of complications and time to disease inactivity. RESULTS: One hundred and sixteen patients from 17 Spanish paediatric rheumatology centres were included, 76 girls (65%). Median age at diagnosis was 7.3 years (Interquartile range (IQR) 4.5-10.2). All patients had pathognomonic skin lesions at the beginning of the disease. Muscle weakness was present in 86.2%. Median Childhood Muscle Assessment Scale was 34 (IQR 22-47). Twelve patients (34%) had dysphagia and 3,5% dysphonia. Anti-p155 was the most frequently detected myositis specific antibody, followed by anti-MDA5. Twenty-nine patients developed calcinosis and 4 presented with macrophage activation syndrome. 70% reached inactivity in a median time of 8.9 months (IQR 4.5-34.8). 41% relapsed after a median time of 14.4 months (IQR 8.6-22.8) of inactivity. Shorter time to treatment was associated with better prognosis (Hazard ratio (HR) = 0.95 per month of evolution, p = 0.02). Heliotrope rash at diagnosis correlates with higher risk of development complications. CONCLUSIONS: We describe heliotrope rash as a risk factor for developing complications in our cohort of JDM patients, an easy-to-evaluate clinical sign that could help us to identify the group of patients we should monitor closely for this complication.
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Dermatomiosite , Sistema de Registros , Humanos , Dermatomiosite/epidemiologia , Dermatomiosite/diagnóstico , Feminino , Criança , Masculino , Espanha/epidemiologia , Prognóstico , Estudos Retrospectivos , Pré-Escolar , Autoanticorpos/sangue , Debilidade Muscular/etiologia , Debilidade Muscular/epidemiologia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/epidemiologiaRESUMO
Background: Juvenile idiopathic arthritis (JIA) is the most frequent chronic rheumatic disease in children. If inflammation is not adequately treated, joint damage, long-term disability, and active disease during adulthood can occur. Identifying and implementing early and adequate therapy are critical for improving clinical outcomes. The burden of JIA on affected children, their families, and the healthcare system in Spain has not been adequately assessed. The greatest contribution to direct costs is medication, but other expenses contribute to the consumption of resources, negatively impacting healthcare cost and the economic conditions of affected families. Objective: To assess the direct healthcare, indirect resource utilization, and associated cost of moderate-to-severe JIA in children in routine clinical practice in Spain. Methods: Children were enrolled in this 24-month observational, multicentric, cross-sectional, retrospective study (N = 107) if they had been treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), had participated in a previous study (ITACA), and continued to be followed up at pediatric rheumatology units at 3 tertiary Spanish hospitals. Direct costs included medication, specialist and primary care visits, hospitalizations, emergency visits or consultations, surgeries, physiotherapy, and tests. Indirect costs included hospital travel expenses and loss of caregiver working hours. Unitary costs were obtained from official sources (, 2020). Results: Overall, children had inactive disease/low disease activity according to JADAS-71 score and very low functional disability as measured by Childhood Health Assessment Questionnaire score. Up to 94.4% of children received treatment, mainly with bDMARDs as monotherapy (84.5%). Among anti-TNFα treatments, adalimumab (47.4%) and etanercept (40.2%) were used in similar proportions. Annual mean (SD) total JIA cost was 7516.40 (5627.30). Average cost of pharmacological treatment was 3021.80 (3956.20), mainly due to biologic therapy 2789.00 (3399.80). Direct annual cost (excluding treatments) was 3654.60 (3899.00). Indirect JIA cost per family was 747.20 (1452.80). Conclusion: JIA causes significant costs to the Spanish healthcare system and affected families. Public costs are partly due to the high cost of biologic treatments, which nevertheless remain an effective long-term treatment, maintaining inactive disease/low disease activity state; a very low functional disability score; and a good quality of life.
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BACKGROUND: Increasing evidence links genetic defects affecting actin-regulatory proteins to diseases with severe autoimmunity and autoinflammation, yet the underlying molecular mechanisms are poorly understood. Dedicator of cytokinesis 11 (DOCK11) activates the small Rho guanosine triphosphatase (GTPase) cell division cycle 42 (CDC42), a central regulator of actin cytoskeleton dynamics. The role of DOCK11 in human immune-cell function and disease remains unknown. METHODS: We conducted genetic, immunologic, and molecular assays in four patients from four unrelated families who presented with infections, early-onset severe immune dysregulation, normocytic anemia of variable severity associated with anisopoikilocytosis, and developmental delay. Functional assays were performed in patient-derived cells, as well as in mouse and zebrafish models. RESULTS: We identified rare, X-linked germline mutations in DOCK11 in the patients, leading to a loss of protein expression in two patients and impaired CDC42 activation in all four patients. Patient-derived T cells did not form filopodia and showed abnormal migration. In addition, the patient-derived T cells, as well as the T cells from Dock11-knockout mice, showed overt activation and production of proinflammatory cytokines that were associated with an increased degree of nuclear translocation of nuclear factor of activated T cell 1 (NFATc1). Anemia and aberrant erythrocyte morphologic features were recapitulated in a newly generated dock11-knockout zebrafish model, and anemia was amenable to rescue on ectopic expression of constitutively active CDC42. CONCLUSIONS: Germline hemizygous loss-of-function mutations affecting the actin regulator DOCK11 were shown to cause a previously unknown inborn error of hematopoiesis and immunity characterized by severe immune dysregulation and systemic inflammation, recurrent infections, and anemia. (Funded by the European Research Council and others.).
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Actinas , Anemia , Fatores de Troca do Nucleotídeo Guanina , Inflamação , Animais , Humanos , Camundongos , Actinas/genética , Actinas/metabolismo , Anemia/etiologia , Anemia/genética , Modelos Animais de Doenças , Fatores de Troca do Nucleotídeo Guanina/deficiência , Fatores de Troca do Nucleotídeo Guanina/genética , Hematopoese , Inflamação/etiologia , Inflamação/genética , Peixe-Zebra/genética , Peixe-Zebra/metabolismoRESUMO
The authors describe a 5-year-old girl who developed a Noonan syndrome-like disorder as a result of the CBL c.1194C>G/p.His398Gln variant, including headache, papilledema, intracranial hypertension, hyperproteinorrhachia, leucorrhachia, and brain inflammation and vasculitis with CD3 positive lymphocyte infiltration. The patient responded partially to corticosteroids, acetazolamide, and ventriculoperitoneal valve placement. The serum cytokine profile revealed persistently elevated levels of IL-1 RA, IL-2R alpha, IL-6, IL-18, MCP-1, and MCP-3. Cyclophosphamide was used as a bridge to allogeneic hematopoietic stem cell transplantation in this case.
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Síndrome de Noonan , Vasculite do Sistema Nervoso Central , Biópsia , Encéfalo/diagnóstico por imagem , Pré-Escolar , Ciclofosfamida , Feminino , Humanos , Síndrome de Noonan/complicações , Síndrome de Noonan/genéticaRESUMO
Autoinflammatory diseases constitute a family of disorders defined by aberrant stimulation of inflammatory pathways without involving antigen-directed autoimmunity. They may be divided into monogenic and polygenic types. Monogenic autoinflammatory syndromes are those with identified genetic mutations, such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency or hyperimmunoglobulin D syndrome, cryopyrin-associated periodic fever syndromes (CAPS), pyogenic arthritis pyoderma gangrenosum and acne (PAPA) syndrome, interleukin-10 and interleukin-10 receptor deficiencies, adenosine deaminase 2 deficiency and pediatric sarcoidosis. Those without an identified genetic mutation are known as polygenic and include systemic-onset juvenile idiopathic arthritis, idiopathic recurrent acute pericarditis, Behçet syndrome, chronic recurrent multifocal osteomyelitis and inflammatory bowel disease among others. Autoinflammatory disorders are defined by repeating episodes or persistent fever, rash, serositis, lymphadenopathy, arthritis and increased acute phase reactants, and thus may mimic infections clinically. Most monogenic autoinflammatory syndromes present in childhood. However, because of their infrequency, diverse and nonspecific presentation, and the relatively new genetic recognition, diagnosis is usually delayed. In this article, which is Part 1 of a two-part series, the authors update monogenic autoinflammatory diseases in children with special emphasis on imaging features that may help establish the correct diagnosis.
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Diagnóstico por Imagem/métodos , Doenças Hereditárias Autoinflamatórias/diagnóstico por imagem , Doenças Hereditárias Autoinflamatórias/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , SíndromeRESUMO
Autoinflammatory diseases are a family of disorders characterized by aberrant stimulation of inflammatory pathways without involvement of antigen-directed autoimmunity. They can be further divided in monogenic and polygenic types. Those without an identified genetic mutation are known as polygenic and include systemic-onset juvenile idiopathic arthritis, idiopathic recurrent acute pericarditis, Behçet syndrome, chronic recurrent multifocal osteomyelitis and inflammatory bowel disease among others. Autoinflammatory diseases are characterized by recurrent flares or persistent systemic inflammation and fever, as well as lymphadenopathy and cutaneous, abdominal, thoracic and articular symptoms. Although these syndromes can mimic infections clinically, the inflammatory lesions in autoinflammatory disorders are aseptic. However, because of their infrequency, varied and nonspecific presentation, and the new genetic identification, diagnosis is usually delayed. In this article, which is Part 2 of a two-part series, the authors review the main polygenic autoinflammatory diseases that can be seen in childhood, with special emphasis wherever applicable on imaging features that may help establish the correct diagnosis. However, the major role of imaging is to delineate organ involvement and disease extent.
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Diagnóstico por Imagem/métodos , Doenças Hereditárias Autoinflamatórias/diagnóstico por imagem , Doenças Hereditárias Autoinflamatórias/genética , Herança Multifatorial/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , SíndromeRESUMO
Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease with both autoimmune and autoinflammatory components. Recently, familial cases of systemic-onset JIA have been attributed to mutations in LACC1/FAMIN. We describe three affected siblings from a Moroccan consanguineous family with an early-onset chronic, symmetric and erosive arthritis previously diagnosed as rheumatoid factor (RF)-negative polyarticular JIA. Autozygosity mapping identified four homozygous regions shared by all patients, located in chromosomes 3, 6 (n:2) and 13, containing over 330 genes. Subsequent whole exome sequencing identified two potential candidate variants within these regions (in FARS2 and LACC1/FAMIN). Genotyping of a cohort of healthy Moroccan individuals (n: 352) and bioinformatics analyses finally supported the frameshift c.128_129delGT mutation in the LACC1/FAMIN gene, leading to a truncated protein (p.Cys43Tyrfs*6), as the most probable causative gene defect. Additional targeted sequencing studies performed in patients with systemic-onset JIA (n:23) and RF-negative polyarticular JIA (n: 44) revealed no pathogenic LACC1/FAMIN mutations. Our findings support the homozygous genotype in the LACC1/FAMIN gene as the defect underlying the family here described with a recessively inherited severe inflammatory joint disease. Our evidences provide further support to the involvement of LACC1/FAMIN deficiency in different types of JIA in addition to the initially described systemic-onset JIA.
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Alelos , Artrite Juvenil/etiologia , Artrite Juvenil/patologia , Estudos de Associação Genética , Predisposição Genética para Doença , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação com Perda de Função , Substituição de Aminoácidos , Artrite Juvenil/metabolismo , Consanguinidade , Análise Mutacional de DNA , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Linhagem , IrmãosRESUMO
Objective: To report 2 patients with anti-myelin oligodendrocyte glycoprotein (MOG)-associated encephalitis who were initially misdiagnosed with small vessel primary CNS vasculitis. Methods: Review of symptoms, MRI and neuropathologic features, and response to treatment. MOG antibodies were determined in serum and CSF using a cell-based assay. Results: Symptoms included fever, headache, and progressive mental status changes and focal neurologic deficits. CSF studies revealed lymphocytic pleocytosis, and both patients had abnormal brain MRIs. Brain biopsy samples showed prominent lymphocytic infiltration of the wall of small vessels; these findings initially suggested small vessel CNS vasculitis, and both patients were treated accordingly. Although 1 patient had a relapsing-remitting course not responsive to cyclophosphamide, the other one (also treated with cyclophosphamide) did not relapse. Retrospective assessment of serum and CSF demonstrated MOG antibodies in both cases, and review of biopsy specimens showed absence of fibrinoid necrosis (a pathologic requirement for small vessel CNS vasculitis). Conclusions: Anti-MOG-associated encephalitis can be mistaken for small vessel CNS vasculitis. This is important because the diagnosis of anti-MOG-associated encephalitis does not require brain biopsy and can be established with a serologic test.
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Diagnóstico Diferencial , Encefalite/diagnóstico , Encefalite/patologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Vasculite do Sistema Nervoso Central/patologia , Adulto , Encéfalo , Pré-Escolar , Encefalite/complicações , Encefalite/tratamento farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Glicoproteína Associada a Mielina , Estudos Retrospectivos , Vasculite do Sistema Nervoso Central/diagnósticoRESUMO
INTRODUCTION: Mevalonate Kinase Deficiency (MKD) is a rare monogenic autoinflammatory disorder (AID) with autosomal recessive inheritance caused by mutations in the MVK gene. It includes hyperimmunoglobulinemia D syndrome (HIDS) and mevalonic aciduria (a severe form). Patients have recurrent inflammatory attacks with high fever, gastrointestinal symptoms, lymphadenopathy, splenomegaly, arthralgia, rash, pharyngitis, aphtosis and constitutional complaints. Heightened understanding of molecular mechanisms in monogenic autoinflammatory disorders has provided tools for targeted treatment. HIDS is an extrinsic inflammasomopathy and is responsive to anti-IL-1 therapies, such as the recombinant IL-1-receptor antagonist anakinra, the monoclonal antibody against IL-1b canakinumab (CAN), and the recombinant IL-1R fusion protein rilonacept. Areas covered: CAN is a human monoclonal anti-IL-1ß antibody that binds with high affinity and neutralizes the activity of IL-1 ß. Both observational registries and some case reports have seemed promising in the efficacy of CAN in the HIDS treatment. Two clinical trials have corroborated CAN as an effective and safe drug. Expert commentary: CAN is effective and safe for the treatment of HIDS patients. Some data suggest these patients may need higher dosage or shorter dosing interval than other AIDs, to achieve and maintain complete clinical and laboratory response. Reported adverse events were mild, most often non-complicated infections.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Deficiência de Mevalonato Quinase/tratamento farmacológico , HumanosRESUMO
Systemic connective tissue disorders are characterized by the presence of autoantibodies and multiorgan system involvement. Juvenile systemic lupus erythematosus with or without associated antiphospholipid syndrome; juvenile dermatomyositis; sclerodermiform syndromes, including systemic and localized sclerodermas and eosinophilic fasciitis; mixed connective tissue disease; and Sjögren syndrome are the disorders that affect children most frequently. Diagnosis is difficult, because the clinical presentation of patients is diverse, from mild to severe disease. In addition, all organs may be affected. However, a variety of imaging techniques are now available to investigate rheumatic disease in children. These imaging modalities offer the potential for earlier diagnosis and improved assessment of therapeutic response. This article reviews the main connective tissue disorders that affect children, highlighting their key imaging features on images acquired with different diagnostic imaging modalities and correlating these features with clinical and pathologic findings, when available. ©RSNA, 2019.
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Doenças do Tecido Conjuntivo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Adolescente , Encéfalo/diagnóstico por imagem , Criança , Dermatomiosite , Feminino , Humanos , Pulmão/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Doença Mista do Tecido Conjuntivo/diagnóstico por imagem , Esclerodermia Localizada/diagnóstico por imagem , Síndrome de Sjogren/diagnóstico por imagemRESUMO
The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Castilian Spanish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability and construct validity (convergent and discriminant validity). A total of 526 JIA patients (8.6% systemic, 49.4% oligoarticular, 18.2% RF negative polyarthritis, 23.8% other categories) and 78 healthy children, were enrolled in six centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Castilian Spanish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practise and clinical research.
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Artrite Juvenil/diagnóstico , Avaliação da Deficiência , Medidas de Resultados Relatados pelo Paciente , Reumatologia/métodos , Adolescente , Idade de Início , Artrite Juvenil/fisiopatologia , Artrite Juvenil/psicologia , Artrite Juvenil/terapia , Estudos de Casos e Controles , Criança , Pré-Escolar , Características Culturais , Feminino , Nível de Saúde , Humanos , Masculino , Pais/psicologia , Pacientes/psicologia , Valor Preditivo dos Testes , Prognóstico , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , TraduçãoRESUMO
Introducción: La enfermedad de Kawasaki (EK) es una vasculitis aguda autolimitada relativamente frecuente en la infancia. La etiología de la EK es aún desconocida, aunque los datos clínicos y de laboratorio y las características epidemiológicas sugieren un origen infeccioso. Las diferencias en la incidencia entre los países se han relacionado con factores genéticos, étnicos y otros factores socioculturales y ambientales. Presentamos un estudio poblacional sobre la incidencia de la EK en Cataluña (España), centrándose en las diferencias entre los pacientes en zonas rurales y no rurales de la región. Métodos: Estudio observacional poblacional incluyendo todas las unidades pediátricas en los hospitales catalanes, entre 2004 y 2014. Recogida prospectiva de nuevos casos de EK durante 12 meses (marzo de 2013-marzo de 2014) para determinar la incidencia de la EK. El resto de los datos se recuperaron de forma retrospectiva. Se analizaron los datos de 399 pacientes durante el período de estudio de 10 años. Resultados: Entre el total de pacientes con EK, 353 (88,5%) vivían en zonas no rurales y 46 (11,5%) en zonas rurales. Se encontró una diferencia significativa (p < 0,001) entre el porcentaje de la población rural observada en los pacientes con EK (11,5%), y el esperado 5% para la población catalana. Conclusión: Este es el primer estudio poblacional que muestra diferencias significativas entre las tasas de incidencia de EK entre las zonas rurales y no rurales (AU)
Introduction: Kawasaki disease (KD) is an acute self-limited systemic vasculitis relatively common in childhood. The etiology of KD is still unknown, although clinical, laboratory and epidemiological features suggest an infectious origin or trigger. Differences on incidence between countries have been related to specific genetic factors, ethnicity, country of birth and some other sociocultural and environmental factors. We present a population-based study on incidence of KD in Catalonia (Spain), focusing on differences between patients in rural and non-rural areas of the region. Methods: Observational population-based study including all Pediatric Units in Catalan hospitals, between 2004 and 2014. A 12-month (March 2013-March 2014) prospective collection of new cases of KD was carried out to determine the incidence of KD. The rest of the data was retrieved retrospectively. Results: Data from 399 patients over the 10-year study period was analyzed. Among the total KD patients, 353 (88.5%) lived in non-rural areas and 46 (11.5%) in rural areas. It was found that there is a significant difference (P < .001) between the percentage of rural population observed in patients with KD (11.5%), and the expected 5% of the Catalan population. Conclusion: This is the first population-based study showing significant differences on KD incidence rates between rural and non-rural areas (AU)
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Humanos , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Vasculite Sistêmica/epidemiologia , Aneurisma Coronário/epidemiologia , População Rural/estatística & dados numéricos , Estudos Prospectivos , Doenças Autoimunes/epidemiologiaRESUMO
OBJECTIVE: To evaluate the efficacy and safety of canakinumab treatment in active hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). METHODS: This was a 3-part open-label study with an initial 6-month treatment period in which patients with HIDS (n = 9) received canakinumab subcutaneously at a dose of 300 mg (or 4 mg/kg for those weighing ≤40 kg) every 6 weeks (period 1 [P1]), followed by a 6-month withdrawal period (period 2 [P2]), and then a 24-month extension treatment period with canakinumab at the same dose (period 3 [P3]). The primary end point was reduction in the frequency of attacks during treatment periods as compared to the historical period (HP; defined as the period in which patients did not receive drugs other than nonsteroidal antiinflammatory drugs and/or steroids). RESULTS: All 9 patients completed P1 and P2, whereas only 8 patients completed P3. All patients achieved a complete response during P1, and only 2 required dose adjustments. The number of attacks per patient decreased from a median of 5 (range 3-12) during the HP to a median of 0 (range 0-2) during P1. During P2, 7 of 9 patients experienced a disease flare within a median of 110 days (range 62-196) after the last canakinumab dose. Laboratory findings were normalized by day 15 of treatment and remained at normal levels throughout the study. Analysis of blood transcriptome profiles, assessed during P1, showed up-regulated levels of interferon and myeloid-related inflammatory responses in untreated patients compared to healthy controls, and these rapidly decreased following canakinumab injection, reaching levels comparable to those of healthy controls. At least 1 adverse event (AE) was detected in all 9 patients. Most of the AEs were mild in intensity, with infections being the most frequent AE. Serious AEs were reported in 4 patients. CONCLUSION: The results of this study demonstrate the efficacy and safety of canakinumab treatment to control active HIDS and to suppress inflammation-related transcriptional responses.
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Anticorpos Monoclonais/uso terapêutico , Deficiência de Mevalonato Quinase/tratamento farmacológico , Adolescente , Adulto , Anticorpos Monoclonais Humanizados , Criança , Feminino , Expressão Gênica , Humanos , Interferons/genética , Interferons/imunologia , Masculino , Deficiência de Mevalonato Quinase/genética , Deficiência de Mevalonato Quinase/imunologia , Projetos Piloto , Indução de Remissão , Espanha , Resultado do Tratamento , Regulação para Cima , Adulto JovemRESUMO
BACKGROUND: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal-dominant autoinflammatory disease caused by mutations in the TNFRSF1A gene. R92Q, a low-penetrance variant, is usually associated with a milder TRAPS phenotype than structural or pathogenic mutations. No studies differentiating R92Q-related disease in patients with pediatric and adult onset have been performed to date. OBJECTIVE: To analyze clinical features and disease outcomes in patients diagnosed with TRAPS associated with R92Q variant and to investigate differences between patients with pediatric and adult disease onset. METHODS: A retrospective review of patients with R92Q-related disease from four reference centers for autoinflammatory diseases was performed. Clinical and laboratory features, family history of autoinflammatory diseases, treatments received, and outcomes during follow-up were recorded and separately analyzed in pediatric and adult patients. Our results were included in the analysis with other reported pediatric and adult R92Q-related disease series. RESULTS: Our series encompassed 18 patients (9 females and 9 males) with R92Q variant. In 61% of patients, disease onset occurred during infancy and in 39%, during adulthood, with a median diagnostic delay of 5 years and a follow-up of 5.4 years. A positive family history of autoinflammatory disease was detected in 28% of patients. All patients presented with febrile recurrent episodes. Other common symptoms included arthralgia/arthritis (61%), myalgia (39%), asthenia/fatigue (44%), abdominal pain (39%), headache (33%), odynophagia (33%), skin rash (28%), and chest pain (22%). During attacks, 80% of patients increased acute phase reactants levels. No patient had developed amyloidosis during the study period. At the end of follow-up, 28% of patients were asymptomatic and treatment free, 50% were receiving non-steroidal anti-inflammatory drugs or glucocorticoids on demand, and 22% were being treated with biologic agents. When differences between pediatric and adult patients were globally analyzed, adults tended to have longer attacks duration and presented more frequently with chest pain and headache, while abdominal pain, vomiting, cervical adenitis, and pharyngitis predominated in pediatric patients. No differences in outcomes and treatment requirements were observed in both age groups. CONCLUSION: This study has contributed to characterize R92Q-related disease by identifying trends in disease phenotypes depending on the age at disease onset.
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The term juvenile idiopathic arthritis (JIA) encompasses a group of arthritides of unknown cause that begin before 16 years of age and last for at least 6 weeks. Temporomandibular joint (TMJ) involvement has been described in up to 87% of children with JIA and has been associated with all JIA subtypes. TMJ involvement is difficult to detect clinically. In one study, 71% of JIA patients with active TMJ synovitis were asymptomatic and 63% had normal physical examination results. Moreover, the main growth center of the mandible is located in the condyle, separated from the joint space by only a thin layer of fibrocartilage. This makes mandibular growth vulnerable to arthritic changes, eventually resulting in facial asymmetry and retrognathia. Therefore, early detection and treatment of TMJ arthritis are paramount to preserving motility and preventing deformity. As clinical symptoms and physical examination results are not good markers of TMJ involvement, imaging plays a key role in diagnosis and treatment monitoring. Magnetic resonance imaging is the technique of choice for the study of TMJ arthritis. It has the advantages of displaying both soft tissue and bone, is the most sensitive technique for detecting acute synovitis, and is the only one able to demonstrate bone marrow edema. In addition, it allows the assessment of changes to the joint over time and evaluation of the effectiveness of therapeutic interventions. ©RSNA, 2017.
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Artrite Juvenil/diagnóstico por imagem , Artrite Juvenil/patologia , Imageamento por Ressonância Magnética , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/patologia , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/patologia , Diagnóstico Diferencial , HumanosRESUMO
INTRODUCTION: Kawasaki disease (KD) is an acute self-limited systemic vasculitis relatively common in childhood. The etiology of KD is still unknown, although clinical, laboratory and epidemiological features suggest an infectious origin or trigger. Differences on incidence between countries have been related to specific genetic factors, ethnicity, country of birth and some other sociocultural and environmental factors. We present a population-based study on incidence of KD in Catalonia (Spain), focusing on differences between patients in rural and non-rural areas of the region. METHODS: Observational population-based study including all Pediatric Units in Catalan hospitals, between 2004 and 2014. A 12-month (March 2013-March 2014) prospective collection of new cases of KD was carried out to determine the incidence of KD. The rest of the data was retrieved retrospectively. RESULTS: Data from 399 patients over the 10-year study period was analyzed. Among the total KD patients, 353 (88.5%) lived in non-rural areas and 46 (11.5%) in rural areas. It was found that there is a significant difference (P<.001) between the percentage of rural population observed in patients with KD (11.5%), and the expected 5% of the Catalan population. CONCLUSION: This is the first population-based study showing significant differences on KD incidence rates between rural and non-rural areas.
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Síndrome de Linfonodos Mucocutâneos/epidemiologia , Pré-Escolar , Feminino , Humanos , Masculino , Prevalência , Saúde da População Rural , Espanha/epidemiologiaRESUMO
Alongside well-known nuclear factor κB (NFκB) and its associated cytokine networks, nuclear factor of activated T cells 5 (NFAT5), the master regulator of cellular osmoprotective programs, comes forward as an inflammatory regulator. To gain insight into its yet unexplored role in muscle disease, we studied the expression of NFAT5 target proteins involved in osmolyte accumulation: aldose reductase (AR), taurine transporter (TauT), and sodium myo-inositol co-transporter (SMIT). We analyzed idiopathic inflammatory myopathy and Duchenne muscular dystrophy muscle biopsies and myotubes in culture, using immunohistochemistry, immunofluorescence, and western blotting. We report that the level of constitutive AR was upregulated in patients, most strongly so in Duchenne muscular dystrophy. TauT and SMIT expression levels were induced in patients' muscle fibers, mostly representing regenerating and atrophic fibers. In dermatomyositis, strong staining for AR, TauT, and SMIT in atrophic perifascicular fibers was accompanied by staining for other molecular NFAT5 targets, including chaperones, chemokines, and inducible nitric oxide synthase. In these fibers, NFAT5 and NFκB p65 staining coincided, linking both transcription factors with this important pathogenic hallmark. In sporadic inclusion body myositis, SMIT localized to inclusions inside muscle fibers. In addition, SMIT was expressed by a substantial subset of muscle-infiltrating macrophages and T cells in patient biopsies. Our results indicate that osmolyte pathways may contribute to normal muscle functioning, and that activation of AR, TauT, and SMIT in muscle inflammation possibly contributes to the tissue's failing program of damage control.
Assuntos
Distrofia Muscular de Duchenne/etiologia , Distrofia Muscular de Duchenne/metabolismo , Miosite/etiologia , Miosite/metabolismo , Osmorregulação , Adulto , Idoso , Idoso de 80 Anos ou mais , Aldeído Redutase/metabolismo , Linhagem Celular , Criança , Pré-Escolar , Dermatomiosite/metabolismo , Feminino , Proteínas de Choque Térmico/metabolismo , Humanos , Masculino , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/imunologia , Miosite/imunologia , Polimiosite/metabolismo , Simportadores/metabolismo , Fator de Transcrição RelA/metabolismo , Fatores de Transcrição/metabolismo , Adulto JovemRESUMO
Kawasaki disease is an acute self-limited systemic vasculitis common in childhood. Intravenous immunoglobulin (IVIG) is an effective treatment, and it reduces the incidence of cardiac complications. Egami score has been validated to identify IVIG non-responder patients in Japanese population, and it has shown high sensitivity and specificity to identify these non-responder patients. Although its effectiveness in Japan, Egami score has shown to be ineffective in non-Japanese populations. The aim of this study was to apply the Egami score in a Western Mediterranean population in Catalonia (Spain). Observational population-based study that includes patients from all Pediatric Units in 33 Catalan hospitals, both public and private management, between January 2004 and March 2014. Sensitivity and specificity for the Egami score was calculated, and a logistic regression analysis of predictors of overall response to IVIG was also developed. Predicting IVIG resistance with a cutoff for Egami score ≥3 obtained 26 % sensitivity and 82 % specificity. Negative predictive value was 85 % and positive predictive value 22 %. This low sensitivity implies that three out of four non-responders will not be identified by the Egami score. Besides, logistic regression models did not found significance for the use of the Egami score to predict IVIG resistance in Catalan population although having an area under the ROC curve of 0.618 (IC 95 % 0.538-0.698, p < 0.001). Although regression models found an area under the ROC curve >0.5 to predict IVIG resistance, the low sensitivity excludes the Egami score as a useful tool to predict IVIG resistance in Catalan population.
Assuntos
Técnicas de Apoio para a Decisão , Resistência a Medicamentos , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Adolescente , Área Sob a Curva , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Feminino , Humanos , Modelos Logísticos , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/imunologia , Razão de Chances , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Resultado do TratamentoRESUMO
OBJECTIVES: To assess the incidence, epidemiology and clinical features of Kawasaki disease (KD) in Catalonia (northeast region of Spain). METHODS: This was an observational population-based study including all Paediatric Units in Catalonia, under both public and private management. Retrospective data retrieval was performed for 10 years (2004-2013). A 12-month (March 2013 to March 2014) prospective collection of new cases of KD was carried out to determine the incidence of KD. RESULTS: Data from 399 patients over the 10-year study period was analysed, revealing that 233 (58.4%) had complete KD, 159 (39.8) incomplete KD and 7 (1.7%) were considered atypical KD. Mean annual incidence was 3.5/105 children <14 years old (yo) and 8/105 children <5 yo (mean age 37±33 months, range 1.3-191.3). KD was more frequent in boys (59.6%, p<0.001) and in rural areas (p<0.001). Patients with IVIG non-responsiveness, need of a 2(nd) IVIG dose, delay of treatment >10(th) day of illness, ages <1 yo and >8 yo and the presence of sterile piuria, aseptic meningitis, abdominal pain and uveitis at diagnosis were found to have higher risk of coronary aneurisms (CAA) (p<0.05). CONCLUSIONS: This is the first population-based study on the epidemiology of KD in the western Mediterranean area. Incidence, clinical features and treatment plans in our cohort are similar to those described in other European studies.
Assuntos
Síndrome de Linfonodos Mucocutâneos/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
La dermatomiositis juvenil, la miopatia inflamatòria més freqüent en pediatria, és una vasculopatia sistèmica que afecta habitualment la pell i el teixit musculoesquelètic, però que també pot afectar el tracte gastrointestinal i altres òrgans. El diagnòstic es basa en els criteris de Bohan i Peter i l'objectiu del tractament inclou el control dels símp-tomes i la prevenció de les complicacions. Un tractament escalonat precoç disminueix l'activitat de la malaltia i mi-llora el pronòstic a llarg termini
La dermatomiositis juvenil, la miopatía inflamatoria más frecuente en pediatría, es una vasculopatía sistémica que afecta habitualmente la piel y el tejido musculoesquelético, pero que también puede afectar el tracto gastrointestinal y otros órganos. El diagnóstico se basa en los criterios de Bohan y Peter y el objetivo del tratamiento incluye el control de los síntomas y la prevención de las complicaciones. Un tratamiento escalonado precoz disminuye la actividad de la enfermedad y mejora el pronóstico a largo plazo (AU)
Juvenile dermatomyositis, the most common inflammatory myopathy in children, is a systemic vasculopathy that usually affects skin and musculoskeletal tissue, but can also affect the gastrointestinal tract and other organs. Diagnosis is based on the criteria of Bohan and Peter and the treatment goal includes controlling symptoms and preventing complications. Staggered early treatment reduces disease activity and improves long-term prognosis (AU)