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1.
BMC Med Genet ; 20(1): 53, 2019 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-30922245

RESUMEN

BACKGROUND: Progressive pseudorheumatoid dysplasia (PPRD) is a rare autosomal-recessive, non-inflammatory arthropathy, shown to be caused by mutations in the WNT1-inducible signaling pathway protein 3 (WISP3) gene. Although several hundred cases were reported worldwide, the diagnosis remains challenging. Subsequently, the syndrome is often unrecognized and misdiagnosed (for instance, as Juvenile Idiopathic Arthritis), leading to unnecessary procedures and treatments. The objective of the current study was to identify the molecular basis in a family with PPRD and describe their phenotype and course of illness. PATIENTS AND METHODS: We present here a multiply affected consanguineous family of Iraqi-Jewish descent with PPRD. The proband, a 6.5 years old girl, presented with bilateral symmetric bony enlargements of the 1st interphalangeal joints of the hands, without signs of synovitis. Molecular analysis of the family was pursued using Whole Exome Sequencing (WES) and homozygosity mapping. RESULTS: WES analysis brought to the identification of a novel homozygous missense mutation (c.257G > T, p.C86F) in the WISP3 gene. Following this diagnosis, an additional 53 years old affected family member was found to harbor the mutation. Two other individuals in the family were reported to have had similar involvement however both had died of unrelated causes. CONCLUSION: The reported family underscores the importance of recognition of this unique skeletal dysplasia by clinicians, and especially by pediatric rheumatologists and orthopedic surgeons.


Asunto(s)
Proteínas CCN de Señalización Intercelular/genética , Secuenciación del Exoma/métodos , Artropatías/congénito , Mutación Missense , Niño , Consanguinidad , Diagnóstico Precoz , Femenino , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Irak/etnología , Judíos/genética , Artropatías/diagnóstico , Artropatías/etnología , Artropatías/genética , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Literatura de Revisión como Asunto
2.
N Engl J Med ; 370(10): 921-31, 2014 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-24552285

RESUMEN

BACKGROUND: Polyarteritis nodosa is a systemic necrotizing vasculitis with a pathogenesis that is poorly understood. We identified six families with multiple cases of systemic and cutaneous polyarteritis nodosa, consistent with autosomal recessive inheritance. In most cases, onset of the disease occurred during childhood. METHODS: We carried out exome sequencing in persons from multiply affected families of Georgian Jewish or German ancestry. We performed targeted sequencing in additional family members and in unrelated affected persons, 3 of Georgian Jewish ancestry and 14 of Turkish ancestry. Mutations were assessed by testing their effect on enzymatic activity in serum specimens from patients, analysis of protein structure, expression in mammalian cells, and biophysical analysis of purified protein. RESULTS: In all the families, vasculitis was caused by recessive mutations in CECR1, the gene encoding adenosine deaminase 2 (ADA2). All the Georgian Jewish patients were homozygous for a mutation encoding a Gly47Arg substitution, the German patients were compound heterozygous for Arg169Gln and Pro251Leu mutations, and one Turkish patient was compound heterozygous for Gly47Val and Trp264Ser mutations. In the endogamous Georgian Jewish population, the Gly47Arg carrier frequency was 0.102, which is consistent with the high prevalence of disease. The other mutations either were found in only one family member or patient or were extremely rare. ADA2 activity was significantly reduced in serum specimens from patients. Expression in human embryonic kidney 293T cells revealed low amounts of mutant secreted protein. CONCLUSIONS: Recessive loss-of-function mutations of ADA2, a growth factor that is the major extracellular adenosine deaminase, can cause polyarteritis nodosa vasculopathy with highly varied clinical expression. (Funded by the Shaare Zedek Medical Center and others.).


Asunto(s)
Adenosina Desaminasa/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Mutación , Poliarteritis Nudosa/genética , Adenosina Desaminasa/química , Adenosina Desaminasa/metabolismo , Adolescente , Edad de Inicio , Niño , Preescolar , Exoma , Femenino , Genes Recesivos , Georgia (República) , Humanos , Lactante , Péptidos y Proteínas de Señalización Intercelular/química , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Judíos/genética , Masculino , Persona de Mediana Edad , Linaje , Poliarteritis Nudosa/patología , Turquía
3.
Clin Exp Rheumatol ; 35 Suppl 103(1): 209-212, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28079513

RESUMEN

OBJECTIVES: To compare the efficacy and safety of intravenous immunoglobulin (IVIG) plus high-dose aspirin (HDA) vs. IVIG plus low-dose aspirin (LDA) for the treatment of Kawasaki disease, with an emphasis on coronary artery outcomes. METHODS: This study was a retrospective, medical record review of paediatric patients with Kawasaki disease comparing 6 centres that routinely used HAD for initial treatment and 2 that used LDA in 2004-2013. Treatment response and adverse events were compared. The primary outcome measure was the occurrence of coronary aneurysm at the subacute or convalescent stage. RESULTS: The cohort included 358 patients, of whom 315 were initially treated with adjunctive HDA and 43 with LDA. There were no demographic differences between the groups. Coronary aneurysms occurred in 10% (20/196) of the HDA group and 4% (1/24) of the LDA group (p=0.34). Equivalence tests indicate it is unlikely that the risk of coronary aneurysm in LDA exceeds HDA by more than 3.5%. There were no significant between-group differences in the need for glucocorticoid pulse therapy or disease recurrence. Coronary ectasia rate and hospitalisation time were significantly greater in the HDA group. Adverse events were similar in the two groups. CONCLUSIONS: We found no significant clinical benefit in using IVIG+HDA in Kawasaki disease compared to IVIG+LDA. The use of adjunctive HDA in this setting should be reconsidered.


Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Aspirina/administración & dosificación , Aneurisma Coronario/prevención & control , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos/administración & dosificación , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Niño , Preescolar , Aneurisma Coronario/diagnóstico , Aneurisma Coronario/inmunología , Quimioterapia Combinada , Femenino , Humanos , Inmunoglobulinas Intravenosas/efectos adversos , Factores Inmunológicos/efectos adversos , Lactante , Israel , Masculino , Registros Médicos , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/inmunología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
4.
Curr Opin Rheumatol ; 28(5): 523-9, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27286236

RESUMEN

PURPOSE OF REVIEW: Familial Mediterranean fever (FMF) is the oldest and most common of the hereditary autoinflammatory diseases (AIDs). A large body of information has been accumulated over recent years on the pathophysiology, diagnosis and treatment of these diseases. The purpose of this review is to bring an up-to-date summary of the clinic manifestations, diagnostic criteria and treatment of FMF. RECENT FINDINGS: An overview of the pathophysiologic basis of FMF as part of the AID is discussed. Over the last year, attempts to establish new criteria for childhood FMF, new guidelines for treatment and follow-up of disease and novel treatment for FMF were made. A comparison of the different disease severity scores for research purposes suggests that a new score is needed. New evidence for antiinterleukin-1 blockade as a new treatment modality is described. SUMMARY: New diagnostic criteria, disease severity score, treatment and follow-up guidelines have been proposed, and need validation in the next several years.


Asunto(s)
Antirreumáticos/uso terapéutico , Fiebre Mediterránea Familiar/tratamiento farmacológico , Moduladores de Tubulina/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Colchicina/uso terapéutico , Fiebre Mediterránea Familiar/complicaciones , Fiebre Mediterránea Familiar/genética , Fiebre Mediterránea Familiar/fisiopatología , Fiebre/etiología , Fiebre/fisiopatología , Enfermedades Autoinflamatorias Hereditarias , Humanos , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Peritonitis/etiología , Peritonitis/fisiopatología , Pleuresia/etiología , Pleuresia/fisiopatología , Pirina/genética , Proteínas Recombinantes de Fusión/uso terapéutico , Sinovitis/etiología , Sinovitis/fisiopatología
5.
Clin Exp Rheumatol ; 33(1): 122-6, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25571969

RESUMEN

OBJECTIVES: The aim of this study was to determine the seasonality of month of birth (MOB) in children with juvenile idiopathic arthritis (JIA) as compared to the general population. METHODS: Cosinor analysis was used to analyse MOB rhythmicity in 558 children with JIA from a simple rheumatology clinic compared with the MOB pattern of the general population in Israel (n=1.040558). Statistical differences between groups were also analysed by non-parametrical tests. RESULTS: Patients with JIA showed different patterns from that of the general population. A rhythmic pattern of 12 months was found in the MOB patterns of JIA patients. This rhythm with a peak between November to March and a nadir in summer was a mirror image of the rhythmic pattern observed for MOB of the healthy population. Males showed a pattern with combined rhythm of 8 and 6 months with peaks in winter, while females' MOB pattern showed no rhythmicity. Testing different JIA subtypes, only the patients with the enthesitis-related arthritis (ERA) subtype showed rhythmicity in MOB. Rhythmicity patterns were different for males and females, and differed according to several disease characteristics. CONCLUSIONS: The observed pattern of MOB in JIA patients is distinctive and different from that in the healthy population supporting the hypothesis that autoimmune process may begin in utero or in the perinatal period due to seasonal environmental pathogenic agents.


Asunto(s)
Artritis Juvenil/epidemiología , Parto , Estaciones del Año , Artritis Juvenil/diagnóstico , Artritis Juvenil/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Israel/epidemiología , Masculino , Factores de Riesgo , Distribución por Sexo , Factores Sexuales , Factores de Tiempo
6.
Clin Exp Rheumatol ; 33(6 Suppl 94): S163-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26486489

RESUMEN

OBJECTIVES: Central nervous system (CNS) involvement, one of the most severe manifestations of Behçet's disease (BD), is uncommon in children. Because it is rare, the clinical features of this disease in children are not well characterised. Here we describe a teenager with BD which was disclosed following an episode of cerebral sinus vein thrombosis (CSVT) and review the available literature on children with CSVT associated with BD. METHODS: A 12-year-old boy who presented with CSVT is described and the relevant literature, based on a Medline search from 1966 to January 2015 is reviewed. RESULTS: Twenty-three well-documented reports of children with CSVT and BD are described. This manifestation affected mainly males (61%) with a mean age of 12 years (range 4-18). BD was first diagnosed simultaneously or following CSVT in the majority of cases (75%). Multiple sinuses were involved in 30% of the cases. Thrombosis of additional large vessel was identified in 5 of the 23 children. The most common presenting symptom and signs were headache (91%), lasting more than 3 days in most cases (75%), followed by papilledema (43%), seizures (17%), and personality changes (9%). A mixed pattern of CNS involvement including both parenchymal involvement and CSVT, was demonstrated in only two patients (9%). Management of CSVT differed between reports. CONCLUSIONS: CSVT in children is a rarely reported manifestation of BD and has a characteristic clinical picture of a teenage boy presenting with prolonged headache, with no previous diagnosis of BD. A therapeutic approach has not been established yet.


Asunto(s)
Síndrome de Behçet/complicaciones , Trombosis de los Senos Intracraneales/etiología , Factores de Edad , Anticoagulantes/uso terapéutico , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamiento farmacológico , Niño , Humanos , Inmunosupresores/uso terapéutico , Masculino , Valor Predictivo de las Pruebas , Factores de Riesgo , Trombosis de los Senos Intracraneales/diagnóstico , Trombosis de los Senos Intracraneales/tratamiento farmacológico , Resultado del Tratamiento
7.
J Immunol ; 188(9): 4349-59, 2012 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-22450805

RESUMEN

The pathogenesis of juvenile idiopathic arthritis (JIA) is thought to involve multiple components of the cellular immune system, including subsets of γδ T cells. In this study, we conducted experiments to define the functional roles of one of the major synovial fluid (SF) T cell subsets, Vγ9(+)Vδ2(+) (Vγ9(+)) T cells, in JIA. We found that as opposed to CD4(+) T cells, equally high percentages (∼35%) of Vγ9(+) T cells in SF and peripheral blood (PB) produced TNF-α and IFN-γ. Furthermore, stimulation with isopentenyl pyrophosphate (IPP), a metabolite in the mevalonate pathway, which is a specific potent Ag for Vγ9Jγ1.2(+) T cells, similarly amplified cytokine secretion by SF and PB Vγ9(+) T cells. Significantly, the SF subset expressed higher levels of CD69 in situ, suggesting their recent activation. Furthermore, 24-h coculturing with SF-derived fibroblasts enhanced CD69 on the SF > PB Vγ9(+) T cells, a phenomenon strongly augmented by zoledronate, a farnesyl pyrophosphate synthase inhibitor that increases endogenous intracellular IPP. Importantly, although Vγ9(+) T cell proliferation in response to IPP was significantly lower in SF than PBMC cultures, it could be enhanced by depleting SF CD4(+)CD25(+)FOXP3(+) cells (regulatory T cells). Furthermore, coculture with the Vγ9(+) T cells in medium containing zoledronate or IPP strongly increased SF-derived fibroblasts' apoptosis. The findings that IPP-responsive proinflammatory synovial Vγ9(+) T cells for which proliferation is partly controlled by regulatory T cells can recognize and become activated by SF fibroblasts and then induce their apoptosis suggest their crucial role in the pathogenesis and control of synovial inflammation.


Asunto(s)
Artritis Juvenil/inmunología , Comunicación Celular/inmunología , Fibroblastos/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Líquido Sinovial/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos T/inmunología , Artritis Juvenil/patología , Conservadores de la Densidad Ósea/farmacología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Niño , Preescolar , Técnicas de Cocultivo , Difosfonatos/inmunología , Difosfonatos/farmacología , Femenino , Fibroblastos/patología , Geraniltranstransferasa/antagonistas & inhibidores , Geraniltranstransferasa/inmunología , Hemiterpenos/inmunología , Humanos , Imidazoles/inmunología , Imidazoles/farmacología , Interferón gamma/inmunología , Lectinas Tipo C/inmunología , Masculino , Compuestos Organofosforados/inmunología , Linfocitos T Reguladores/patología , Factor de Necrosis Tumoral alfa/inmunología , Ácido Zoledrónico
9.
Clin Exp Rheumatol ; 31(3): 463-8, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23414913

RESUMEN

OBJECTIVES: Children often present during winter with painful, red-purple swollen fingers and/or toes, usually misdiagnosed as Raynaud's phenomenon. Pernio, or chronic chilblains, is a localised inflammatory lesion of the skin resulting from an abnormal response to cold. The aim of this study was to better characterise the clinical presentation of chronic chilblains in children. METHODS: This is a single-centre retrospective study of patients referred to our paediatric rheumatology clinic with cold, purple, and painful hands. Patients were identified from the paediatric rheumatology clinic database, at the Safra Children Hospital, Israel. Data of the clinical presentation, physical findings, laboratory investigations and the course of the disease were extracted from the patients' charts and analysed. RESULTS: A total of 33 patients (27 females, sex ratio 4.5:1) were identified. Patients age at presentation was 13.5±2.1, and disease duration was 2.0±1.0 winters. Patients presented with prolonged capillary refill time (100%) and abnormal modified Allen test (75.6%). Fingers swelling was the most common finding (81.8%), followed by proximal interphalangeal joint (PIPs) swelling (63.6%), skin ulceration (54.5%), and dry, irritated skin (45.5%). Nailfold capillary microscopy was normal in all patients. The only abnormal laboratory test was the test for anti-nuclear factor (ANA) in 25%. CONCLUSIONS: We report a large series of children with a unique symptomatology consisting in chronic chilblains.


Asunto(s)
Anticuerpos Antinucleares/inmunología , Eritema Pernio/diagnóstico , Enfermedad de Raynaud/diagnóstico , Adolescente , Artritis/diagnóstico , Artritis/etiología , Eritema Pernio/complicaciones , Eritema Pernio/inmunología , Niño , Enfermedad Crónica , Estudios de Cohortes , Diagnóstico Diferencial , Progresión de la Enfermedad , Edema/diagnóstico , Edema/etiología , Femenino , Articulaciones de los Dedos/patología , Humanos , Masculino , Examen Físico , Estudios Retrospectivos , Úlcera Cutánea/diagnóstico , Úlcera Cutánea/etiología
10.
J Pediatr ; 161(6): 1142-6, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22738946

RESUMEN

OBJECTIVE: To identify any adverse effects of colchicine in a pediatric patients with familial Mediterranean fever (FMF). STUDY DESIGN: Clinical presentation, Mediterranean fever gene genotype, disease duration, colchicine dose, laboratory tests, and reported adverse effects in children with FMF were analyzed. RESULTS: Of the 153 patients with FMF, 22 (14.4%) developed diarrhea during a follow-up of 4 years; the colchicine dose was reduced to control this symptom in only 4 patients. In 18 (11.8%) patients, a mild transitory increase of transaminases (45-158 IU/L) was found during a follow-up of 1 year. Blood cell counts and kidney function tests were normal in all patients. No correlation was found between the adverse effects and patient's age, disease onset, treatment duration, or any of the clinical characteristics of the disease. CONCLUSION: Colchicine is a safe drug in the treatment of children with FMF, even in infancy. The only significant adverse effects are diarrhea (in a small number of patients), which can be controlled by a decrease in the colchicine dose and transitory elevation of transaminases.


Asunto(s)
Colchicina/efectos adversos , Fiebre Mediterránea Familiar/tratamiento farmacológico , Moduladores de Tubulina/efectos adversos , Adolescente , Factores de Edad , Niño , Preescolar , Colchicina/uso terapéutico , Proteínas del Citoesqueleto/genética , Análisis Mutacional de ADN , Diarrea/inducido químicamente , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Fiebre Mediterránea Familiar/diagnóstico , Fiebre Mediterránea Familiar/genética , Femenino , Estudios de Seguimiento , Marcadores Genéticos , Humanos , Lactante , Masculino , Estudios Prospectivos , Pirina , Sistema de Registros , Factores de Tiempo , Resultado del Tratamiento , Moduladores de Tubulina/uso terapéutico
11.
J Clin Immunol ; 31(6): 1021-8, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21901393

RESUMEN

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is an autoimmune disease where T cells are key players. It can be classified into two main clinical diseases: polyarticular and pauciarticular, based on the number of joints involved. Oligoarthritis, which is considered a pauciarticular subtype since it involves up to four joints upon presentation, is further divided into persistent or extended forms based on disease progression. METHODOLOGY/PRINCIPAL FINDINGS: Here we assessed the T-cell compartment in synovial fluid obtained from 33 JIA patients with active disease and correlated the analyzed parameters with the patients' clinical characteristics. The T-cell compartment was determined by the representation of T-cell receptor (TCR) repertoires and the amount of TCR excision circles (TRECs). RESULTS: Patients with polyarticular disease have more a clonal pattern of their TCR repertoire. These findings were consistent in all tested TCR-Vγ consensus primers. Similarly, patients with polyarticular disease had lower TREC levels than patients with pauciarticular disease. A predictive value of TRECs may be suggested, as lower TREC levels were observed in patients in whom disease modifying anti rheumatic drugs were initiated subsequently during the follow-up. CONCLUSION: In pediatric JIA patients, we showed an alteration in the T cells from synovial fluid, which correlated with disease phenotype, assumedly secondary to enhanced proliferation, clonal TCR restriction, and reduced T-cell production, possibly reflecting a different disease or a different course of disease progression.


Asunto(s)
Artritis Juvenil/inmunología , Líquido Sinovial/inmunología , Linfocitos T/inmunología , Adolescente , Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/genética , Niño , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Genes Codificadores de los Receptores de Linfocitos T , Humanos , Masculino , Valor Predictivo de las Pruebas
12.
J Pediatr ; 159(5): 832-837.e1-2, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21621220

RESUMEN

OBJECTIVE: To assess linear growth in patients with persistent oligoarticular juvenile idiopathic arthritis (JIA) treated by intra-articular corticosteroid injections (IACSI). STUDY DESIGN: Data were obtained from a retrospective review of the charts of 95 patients with persistent oligoarticular JIA (69 females). The mean age at first visit was 4.9 ± 3.4 years, with follow-up of 6 ± 3.7 years. The height SDS for chronologic age (z-score) was correlated with the clinical course of the disease and compared among patients treated by IACSI alone (group I) or by a combination of disease-modifying antirheumatic drugs (DMARDs) (group II). RESULTS: Growth retardation was found in 35.8% of patients (Δ z-score <-0.3), including 11.6% with severe growth retardation (Δ z-score <-1.0). Growth retardation was found in a smaller proportion of patients in group I (any growth retardation, 30.6%; severe growth retardation, 6.5%) than in patients in group II (any growth retardation, 44.4%; severe growth retardation, 21.2%; P < .05). Elevated erythrocyte sedimentation rate values (≥ 40 mm/1sth) indicated a significantly higher risk for growth retardation. All other clinical variables had no association with growth retardation. CONCLUSION: A significant proportion of patients with persistent oligoarticular JIA have growth retardation and a minority have severe growth retardation. Only elevated erythrocyte sedimentation rate values were proven to be a good predictor of risk for growth retardation.


Asunto(s)
Artritis Juvenil/complicaciones , Trastornos del Crecimiento/etiología , Adolescente , Edad de Inicio , Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Sedimentación Sanguínea , Estatura , Niño , Preescolar , Femenino , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Humanos , Lactante , Inyecciones Intraarticulares , Masculino , Estudios Retrospectivos , Triamcinolona Acetonida/uso terapéutico
13.
J Pediatr ; 156(6): 985-989, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20227729

RESUMEN

OBJECTIVE: To characterize the clinical and genetic features of familial Mediterranean fever (FMF). STUDY DESIGN: Clinical presentation and MEditerranean FeVer mutation type of all patients with FMF, who first manifested the disease at < or =2 years of age were analyzed and compared with patients who first presented with FMF between 2 and 16 years. RESULTS: Of 814 patients with FMF, in 254 patients (31.2%) the first FMF attack was at < or =2 years of age, with a mean age at onset of 1.1 +/- 0.8 years. They were compared with 242 patients who presented with their first manifestation of FMF at 2 to 16 years. The clinical manifestations of FMF were comparable in the 2 patient groups, but the delay of diagnosis was longer in patients with early presentation (3.2 +/- 3.2 years vs.1.9 +/- 2.7 years in the group with onset at 2-16 years, P < .001). A subgroup of patients (60/254), who were diagnosed at < or =2 years had the highest rate of attacks of fever alone as their sole manifestation (40.0% vs 8.4%, P < .05), and less peritonitis (45% vs 86.1%, P < .05) and pleuritis (3.4% vs 32.9%, P < .05). Most of these patients were homozygous for the M694V mutation and were of North African (Sephardic Jewish) extraction. CONCLUSION: In early life, FMF often begins with an atypical presentation, characterized by attacks of fever alone, and its diagnosis and initiation of treatment is therefore significantly delayed.


Asunto(s)
Fiebre Mediterránea Familiar/diagnóstico , Adolescente , Edad de Inicio , Niño , Preescolar , Proteínas del Citoesqueleto/genética , Análisis Mutacional de ADN , Fiebre Mediterránea Familiar/epidemiología , Fiebre Mediterránea Familiar/genética , Femenino , Humanos , Lactante , Masculino , Mutación , Fenotipo , Pirina
14.
Pediatr Neurol ; 40(4): 321-3, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19302950

RESUMEN

Parry-Romberg is a rare syndrome of unknown origin, characterized by hemiatrophy of the face including subcutaneous tissue, skeletal muscle, and bones, along with various ocular and central nervous system abnormalities. Some investigators consider that injury to the sympathetic fibers of the trigeminal nerve is a cause for evolution of this syndrome. Various central nervous system symptoms have been reported in correlation with the syndrome, including epilepsy and hemiparesis. These symptoms were related to ipsilateral (or, less frequently, contralateral) facial lesions, and in a few case reports were consistent with Rasmussen's encephalitis-like lesions. Many clinical features overlap between facial linear scleroderma and en coup de sabre syndrome, which is characterized by localized inflammation leading to atrophy of the skin and subcutaneous tissues mainly on one side of the face; such overlap can lead to confusion in diagnosis. Furthermore, central nervous system involvement has been reported in en coup de sabre syndrome, leading to further misdiagnosis. The distinction between these two disorders is much disputed. Detailed here is the case of a child who had been diagnosed with en coup de sabre syndrome presenting with severe status migrainosus. Subsequent pathologic clinical, and neuroimaging findings led to a diagnosis of Parry-Romberg syndrome. This diagnosis is set in the context of the similarities, contradictions, and growing confusion between the two syndromes.


Asunto(s)
Hemiatrofia Facial/diagnóstico , Trastornos Migrañosos/etiología , Adolescente , Alopecia/etiología , Encéfalo/patología , Diagnóstico Diferencial , Hemiatrofia Facial/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos Migrañosos/patología , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/patología , Piel/patología , Tomografía Computarizada por Rayos X
15.
Rheumatol Int ; 29(5): 575-7, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18850100

RESUMEN

Behçet disease (BD) is an inflammatory disorder of unknown origin. We present here an unusual case of juvenile Behçet with hemoptysis due to large pulmonary artery aneurysms (PAA), large intra-cardiac thrombus and prolonged fever, which posed several therapeutic challenges. In this case, a 14-year-old boy was admitted with a 3-month history of fever, painful oral ulcers, skin rash and intermittent hemoptysis. A high resolution helical computed tomography angiogram demonstrated thrombi in the right ventricle, two large aneurysms located in the right lung and two smaller ones in the left. The patient was successfully treated with colchicine, prednisone, cyclophosphamide and enoxaparine. A discussion about PAA and intracardiac thrombi and their role in BD is provided in this case.


Asunto(s)
Aneurisma/diagnóstico , Síndrome de Behçet/diagnóstico , Cardiopatías/diagnóstico , Arteria Pulmonar/diagnóstico por imagen , Trombosis/diagnóstico , Adolescente , Aneurisma/diagnóstico por imagen , Aneurisma/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Síndrome de Behçet/diagnóstico por imagen , Síndrome de Behçet/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Estudios de Seguimiento , Cardiopatías/diagnóstico por imagen , Cardiopatías/tratamiento farmacológico , Hemoptisis/diagnóstico por imagen , Hemoptisis/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Masculino , Trombosis/diagnóstico por imagen , Trombosis/tratamiento farmacológico , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Rayos X
16.
Pediatr Rheumatol Online J ; 17(1): 52, 2019 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-31362757

RESUMEN

BACKGROUND: Systemic lupus erythematosus (SLE) comprise a diverse range of clinical manifestations. To date, more than 30 single gene causes of lupus/lupus like syndromes in humans have been identified. In the clinical setting, identifying the underlying molecular diagnosis is challenging due to phenotypic and genetic heterogeneity. METHODS: We employed whole exome sequencing (WES) in patients presenting with childhood-onset lupus with severe and/or atypical presentations to identify cases that are explained by a single-gene (monogenic) cause. RESULTS: From January 2015 to June 2018 15 new cases of childhood-onset SLE were diagnosed in Edmond and Lily Safra Children's Hospital. By WES we identified causative mutations in four subjects in five different genes: C1QC, SLC7A7, MAN2B1, PTEN and STAT1. No molecular diagnoses were established on clinical grounds prior to genetic testing. CONCLUSIONS: We identified a significant fraction of monogenic SLE etiologies using WES and confirm the genetic locus heterogeneity in childhood-onset lupus. These results highlight the importance of establishing a genetic diagnosis for children with severe or atypical lupus by providing accurate and early etiology-based diagnoses and improving subsequent clinical management.


Asunto(s)
Secuenciación del Exoma/métodos , Lupus Eritematoso Sistémico/genética , Mutación/genética , Adolescente , Sistema de Transporte de Aminoácidos y+L/genética , Niño , Preescolar , Complemento C1q/genética , Femenino , Mutación con Ganancia de Función/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Fosfohidrolasa PTEN/genética , Factor de Transcripción STAT1/genética , alfa-Manosidasa/genética
17.
J Pediatr ; 153(5): 696-9, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18657830

RESUMEN

OBJECTIVE: To perform a retrospective study comparing clinical and laboratory aspects of patients with acute rheumatic fever (ARF) and patients with post-streptococcal reactive arthritis (PSRA), to discern whether these are 2 separate entities or varying clinical manifestations of the same disease. STUDY DESIGN: We located the records of 68 patients with ARF and 159 patients with PSRA, whose diseases were diagnosed with standardized criteria and treated by 8 pediatric rheumatologists in 7 medical centers, using the Israeli internet-based pediatric rheumatology registry. The medical records of these patients were reviewed for demographic, clinical, and laboratory variables, and the data were compared and analyzed with univariate, multivariate, and discriminatory analysis. RESULTS: Four variables were found to differ significantly between ARF and PSRA and serve also as predictors: sedimentation rate, C-reactive protein, duration of joint symptoms after starting anti-inflammatory treatment, and relapse of joint symptoms after cessation of treatment. A discriminative equation was derived that enabled us to correctly classify >80% of the patients. CONCLUSION: On the basis of simple clinical and laboratory variables, we were able to differentiate ARF from PSRA and correctly classify >80% of the patients. It appears that ARF and PSRA are distinct entities.


Asunto(s)
Artritis Reactiva/diagnóstico , Fiebre Reumática/diagnóstico , Infecciones Estreptocócicas/diagnóstico , Streptococcus pyogenes/metabolismo , Enfermedad Aguda , Antiinflamatorios/farmacología , Proteína C-Reactiva/metabolismo , Diagnóstico Diferencial , Humanos , Israel , Análisis Multivariante , Pediatría/métodos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Reumatología/métodos , Infecciones Estreptocócicas/complicaciones
18.
Isr Med Assoc J ; 10(5): 358-60, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18605359

RESUMEN

BACKGROUND: The new syndrome, known as PFAPA, of periodic fever characterized by abrupt onset of fever, malaise, aphthous stomatitis, tonsillitis, pharyngitis and cervical adenopathy has been described only in pediatric patients. It usually begins before the age of 5 years and in most cases resolves spontaneously before age 10. OBJECTIVES: To describe a series of adults with PFAPA syndrome. METHODS: This 6 year retrospective descriptive study includes all newly diagnosed incident adult cases aged 18 years and over referred to our center with symptomatology suggestive of PFAPA syndrome. Patients' medical records were reviewed for past history of the disease, demographic characteristics, symptoms and signs, course of the disease, laboratory findings, and outcome following corticosteroid therapy. The comparison group included our pediatric cohort children (N=320, age 0-18 years) followed for the last 14 years (1994-2008). RESULTS: Fifteen adult patients were diagnosed with PFAPA syndrome. Episodes of fever occurred at 4.6 +/- 1.3 week intervals, beginning at the age of 20.9 +/- 7.5. All patients had monthly attacks at the peak of the disease, with attacks recurring at 4-8 week intervals over the years. Between episodes the patients were apparently healthy, without any accompanying diseases. Attacks were aborted by a single 60 mg dose of oral prednisone in all patients. CONCLUSIONS: This study reports the presence of PFAPA syndrome in adult patients. Although the disease is rare, an increased awareness by both patients and family physicians of this clinical syndrome has resulted in more frequent diagnosis in adult patients.


Asunto(s)
Fiebre/complicaciones , Linfadenitis/complicaciones , Faringitis/complicaciones , Estomatitis Aftosa/complicaciones , Adolescente , Adulto , Antiinflamatorios/uso terapéutico , Sedimentación Sanguínea , Niño , Femenino , Fiebre/diagnóstico , Fiebre/tratamiento farmacológico , Humanos , Leucocitosis/complicaciones , Linfadenitis/diagnóstico , Linfadenitis/tratamiento farmacológico , Masculino , Periodicidad , Faringitis/diagnóstico , Faringitis/tratamiento farmacológico , Prednisona/uso terapéutico , Estudios Retrospectivos , Estomatitis Aftosa/diagnóstico , Estomatitis Aftosa/tratamiento farmacológico , Síndrome
19.
Semin Arthritis Rheum ; 37(3): 182-8, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17512038

RESUMEN

OBJECTIVES: In a significant proportion of patients with familial Mediterranean fever (FMF), serum amyloid A (SAA) remains elevated during attack-free periods, thereby increasing the risk of developing amyloidosis. The aim of the study was to determine various correlates of elevated SAA and evaluate the role of SAA measurement in the diagnosis and management of FMF. METHODS: We reviewed the medical files of all 204 patients from our FMF center in whom SAA measurements were performed. SAA levels and the resulting diagnostic and therapeutic decisions were analyzed in relation to the reasons of SAA testing and to several clinical and genetic parameters. RESULTS: SAA measurements were made for diagnostic purposes in 29% of the patients. In the remainder, SAA measurements were used for adjustment of colchicine dose. Elevated SAA levels are found in a third of FMF patients during an attack-free period. The highest rate of elevated SAA levels was found in patients with proteinuria (60% of this patient group), followed by noncompliant (40%) and genetically positive asymptomatic patients (38%). Elevated SAA levels during remission were associated with family history of FMF, M694V homozygosity, and elevated C-reactive protein (CRP) (P<0.05 for each). Patients homozygous for the M694V mutation had the highest level of SAA. SAA measurement led to a change in colchicine dose in 30% of the patients, predominantly in noncompliant patients and patients with proteinuria or with atypical manifestations. CONCLUSIONS: Measurement of SAA level may help in the diagnosis of FMF and in adjustment of the colchicine dose.


Asunto(s)
Colchicina/administración & dosificación , Fiebre Mediterránea Familiar/diagnóstico , Fiebre Mediterránea Familiar/tratamiento farmacológico , Proteína Amiloide A Sérica/genética , Proteína Amiloide A Sérica/metabolismo , Moduladores de Tubulina/administración & dosificación , Adolescente , Adulto , Biomarcadores/sangre , Monitoreo de Drogas , Fiebre Mediterránea Familiar/sangre , Fiebre Mediterránea Familiar/genética , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Masculino , Cooperación del Paciente , Mutación Puntual
20.
Rheum Dis Clin North Am ; 33(3): 585-623, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17936178

RESUMEN

Human autoinflammatory diseases (except for PFAPA) are a heterogeneous group of genetically determined diseases characterized by seemingly unprovoked inflammation in the absence of autoimmune or infective causes (Table 2). The last decade has witnessed tremendous advances in the understanding of these disorders. These advances have allowed therapeutic interventions resulting in improvement in the short-term and long-term morbidity of all of these diseases. Future research into the molecular mechanisms underlying these inflammatory diseases should lead to a better understanding of inflammatory diseases in general and, it is hoped, to better and more targeted therapies.

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