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Osteomielitis , Calidad de Vida , Humanos , Niño , Femenino , Masculino , Adolescente , Dolor/fisiopatología , Sueño/fisiología , Enfermedad Crónica , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: Canakinumab, a human monoclonal antibody targeted at interleukin-1 beta, has demonstrated safety and efficacy in preventing familial Mediterranean fever (FMF) attacks among individuals with colchicine-resistant (crFMF). The manufacturer orders prescribe monthly subcutaneous injections. However, a subset of our patients is treated with an "canakinumab on demand " (COD) strategy, with wider intervals between drug administrations. Therefore, we aimed to compare disease activity and drug safety between COD and "canakinumab fixed frequency" (CFF) policies. METHODS: This retrospective study collected data from three Israeli paediatric rheumatology centres, of children with crFMF who were treated with canakinumab. Epidemiological and clinical parameters, cumulative drug dosages, and adverse events were compared between children treated by both policies. RESULTS: Twenty-five (49 %) children were treated according to COD policy and 26 according to CFF policy. Demographic parameters and most of the disease features did not differ significantly between the groups. Both groups showed significant reduction in attacks after canakinumab introduction. The median number (interquartile range) of attacks per month did not differ significantly between the COD and CFF groups (0.33 (0.08, 0.58) and 0.13 (0, 0.5), respectively, p = 0.485 (even though, per definition, COD patients presumably had an attack before receiving the second canakinumab dose). The mean monthly dose was lower for the COD than the CFF group (1.13 ± 1.13 vs. 3.16 ± 1.46 mg/kg, p < 0.001). Adverse events were similar between the groups. CONCLUSION: For individuals with crFMF, COD compared to CFF policy can achieve similar efficacy and safety, with a lower accumulated canakinumab dose, rendering it less immunosuppressive and less expensive.
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Anticuerpos Monoclonales Humanizados , Colchicina , Resistencia a Medicamentos , Fiebre Mediterránea Familiar , Humanos , Fiebre Mediterránea Familiar/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Niño , Masculino , Femenino , Estudios Retrospectivos , Colchicina/uso terapéutico , Colchicina/administración & dosificación , Colchicina/efectos adversos , Adolescente , Interleucina-1beta/antagonistas & inhibidores , Interleucina-1beta/inmunología , Resultado del Tratamiento , Preescolar , Israel , Esquema de MedicaciónRESUMEN
BACKGROUND: Pediatric immune thrombocytopenia (ITP) may precede systemic autoimmune disorders. In adolescent patients with ITP, routine screening for systemic lupus erythematosus (SLE) may be performed by testing for antinuclear antibody (ANA) titer. Hydroxychloroquine (HCQ) is a safe and effective immunomodulatory drug in patients with SLE but rarely used in ITP. We analyzed the platelet count response and safety of HCQ in treating pediatric patients with SLE-related ITP. METHODS: A retrospective study including pediatric patients with ITP and definite or incomplete SLE, who were treated with HCQ during 2010-2021. SLE was defined by ANA titer ≥ 1:160 as measured by immunofluorescence and ≥10 points according to the 2019 EULAR/ACR 2019 classification criteria, while patients with incomplete SLE achieved a score < 10. Complete response (CR) of the platelet count was defined as platelet count > 100 × 109/L; partial response (PR) as platelet count 30-100 × 109/L and exceeding ≥ twice baseline counts. RESULTS: Of the 17 patients included (median age 15.5 years; IQR 3.6), 15 (88.2%) were female, 13 had definite SLE, and four had incomplete SLE. HCQ was initiated at a median of 17 months after ITP diagnosis with a median platelet count of 38 × 109/L (IQR 28). At 8 weeks, 8 (47.1%) patients responded, including 6 (35.3%) achieving CR. After one year, the overall response was 82.4%, with the remaining patients having stable platelet counts requiring no additional ITP therapy. The response was maintained at a median follow-up of 42 months. No adverse effects to HCQ were noted. CONCLUSION: Pediatric patients with SLE-related ITP may benefit from treatment with HCQ.
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Lupus Eritematoso Sistémico , Púrpura Trombocitopénica Idiopática , Trombocitopenia , Adolescente , Humanos , Femenino , Niño , Masculino , Hidroxicloroquina/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Estudios Retrospectivos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Trombocitopenia/tratamiento farmacológicoRESUMEN
OBJECTIVES: Familial Mediterranean Fever (FMF) patients are required to adhere to a life-long treatment with colchicine, primarily for preventing amyloidosis. As some patients may be asymptomatic for long periods of time, it remains unclear whether it is possible to discontinue colchicine treatment in a selective group of patients. We aimed to identify predictive characteristics for a successful cessation of colchicine therapy. METHODS: Out of 646 FMF pediatric patients followed in our referral FMF clinic, colchicine treatment was discontinued in 51 patients. In this study we compared the genetic, demographic, and clinical characteristics between patients for whom a successful cessation of therapy was made (Group 1; n = 21) and patients for whom cessation of therapy was deemed a failure (Group 2; n = 30) and consequently had to resume colchicine therapy. RESULTS: Patients for whom a successful cessation of therapy was achieved had no biallelic pathogenic MEFV mutations, were less likely to have "severe attacks" (two or more FMF characteristic symptoms) (24% vs 80%; P = 0.000067) and did not require higher than 1 mg/day of colchicine, prior to the drug cessation. Remission duration under colchicine treatment was significantly higher in group 1 compared with group 2 (4.36 years ±2.12 vs 2.53 years ±2; P = 0.0036). CONCLUSION: This study supports the concept of colchicine free remission in a minority of FMF patients (3%). Holding treatment, under close monitoring, may be reasonable when selecting the appropriate patients.
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Amiloidosis , Colchicina , Fiebre Mediterránea Familiar , Niño , Humanos , Amiloidosis/tratamiento farmacológico , Amiloidosis/genética , Colchicina/uso terapéutico , Fiebre Mediterránea Familiar/tratamiento farmacológico , Fiebre Mediterránea Familiar/genética , Fiebre Mediterránea Familiar/diagnóstico , Pirina/genéticaRESUMEN
INTRODUCTION: Familial Mediterranean Fever (FMF) is the most common monogentic autoinflammatory disease. FMF results from mutations in MEFV, which lead to a pro-inflammatory state and increased production of Interleukin 1 beta subunit (IL-1b) by myeloid cells. Despite the overall positive results obtained with anti-IL-1 agents in FMF patients, little is known about the long-term growth impact of these drugs in the pediatric population. OBJECTIVES: To assess the long-term body weight and height trajectories in children with FMF treated with anti-IL-1 agents. METHODS: We conducted a retrospective analysis of 646 pediatric FMF patients followed in our center, of whom 22 were treated with either anakinra (36.3%) and/or canakinumab (90.9%). Patients were assessed for demographic, clinical and genetic characteristics and were followed for a mean of 3.05 ± 1.75 years. Data of height and weight percentiles were recorded before and after treatment. RESULTS: The most common indication for IL-1 blockers treatment was colchicine resistance (66.6%). Ninety percent of those patients had a moderate or severe disease according to the Pras score and had higher proportion of M694V homozygosity compared with patients who did not require anti IL-1 agents (95.2% vs. 30.5%, p < 0.001). Overall, anakinra and canakinumab resulted in a complete response in 80% of patients and exhibited low rates of adverse effects. We found a significant increase in height and body weight percentiles following treatment (19.6 ± 16% vs. 30.8 ± 23%, p = 0.007, and 29.5 ± 30% vs. 39.1 ± 36%, p = 0.043, respectively). CONCLUSION: Treatment with anti-IL-1 agents in children with FMF is effective and safe and may potentiate long-term growth.
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Colchicina , Fiebre Mediterránea Familiar , Niño , Humanos , Colchicina/uso terapéutico , Fiebre Mediterránea Familiar/tratamiento farmacológico , Fiebre Mediterránea Familiar/genética , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Estudios Retrospectivos , Peso Corporal , PirinaRESUMEN
OBJECTIVE: Characterization of the stages that patients with juvenile idiopathic arthritis (JIA) pass until they are diagnosed, and analysis of the different causes that lead to a delay in JIA diagnosis in Israel. METHODS: This is a retrospective cohort study conducted in 8 pediatric rheumatology centers in Israel. All patients diagnosed with JIA between October 2017 and October 2019 were included in the study. Demographic, clinical, and data regarding the referring physicians were collected from hospital and community medical charts. RESULTS: Of 207 patients included in the study, 201 cases were analyzed, 71.1% of the population were female. Patients, on average, were evaluated during the diagnostic process by 3.1 different physicians. In most cases, they initially met with a pediatrician in the community setting (61.2%), and later, most commonly referred to a rheumatologist by the community pediatrician (27.9%). The median time until diagnosis was 56.0 days (range: 1.0-2451.0 days). Patients diagnosed with polyarticular and spondyloarthritis/enthesitis-related arthritis (SpA/ERA) JIA subtypes had the longest period until diagnosis (median: 115.5 and 112.0 days, respectively). Younger age correlated with a quicker diagnosis, and females were diagnosed earlier compared to males. Fever at presentation significantly shortened the time to diagnosis (P < 0.01), whereas involvement of the small joints/sacroiliac joints significantly lengthened the time (P < 0.05). CONCLUSION: This is the first nationwide multicenter study that analyzes obstacles in the diagnosis of JIA in Israel. Raising awareness about JIA, especially for patients with SpA/ERA, is crucial in order to avoid delays in diagnosis and treatment.
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Artritis Juvenil , Masculino , Humanos , Niño , Femenino , Artritis Juvenil/tratamiento farmacológico , Estudios Retrospectivos , Israel , Reumatólogos , Diagnóstico PrecozRESUMEN
BACKGROUND: Psoriasis and psoriatic arthritis can present simultaneously or separately in children and may pose a diagnostic challenge. OBJECTIVE: To compare the dermatological manifestations in pediatric psoriatic patients with and without arthritis. METHODS: A retrospective case-control study of psoriatic patients ≤ 18 years old at Sheba Medical Center was conducted between 2011 and 2021. Patients with psoriatic arthritis versus psoriasis-only were compared according to body surface area (BSA) involvement, cutaneous distribution, severity of skin disease, response to treatment and related side effects. RESULTS: The study cohort included 29 psoriatic arthritis and 64 psoriasis-only patients matched by age and sex. The psoriasis-only group had a significantly higher mean BSA (19.7%, SD ± 18.7) than the psoriatic arthritis group (6.1%, SD ± 11.4), (p = 0.029). The skin distribution differed with the psoriasis group showing more involvement of the extremities, scalp, trunk, and genitals. Both groups primarily experienced partial responses to methotrexate, whereas the psoriasis group mainly saw complete responses to biologics. Adverse events were rare, with a higher incidence in the psoriasis group. CONCLUSION: This retrospective study highlights the differences in cutaneous disease characteristics, severity, and treatment response in pediatric patients with psoriasis and psoriatic arthritis, providing valuable insights for diagnosis and disease course in the pediatric population.
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INTRODUCTION: Since the development of COVID-19 vaccines, more than 4.8 billion people have been immunized worldwide. Soon after vaccinations were initiated, reports on cases of myocarditis following the second vaccine dose emerged. This study aimed to report our experience with adolescent and young adults who developed post-COVID-19 vaccine myocarditis and to compare these patients to a cohort of patients who acquired pediatric inflammatory multisystem syndrome (PIMS/PIMS-TS) post-COVID-19 infection. METHODS: We collected reported cases of patients who developed myocarditis following COVID-19 vaccination (Pfizer mRNA BNT162b2) from all pediatric rheumatology centers in Israel and compared them to a cohort of patients with PIMS. RESULTS: Nine patients with post-vaccination myocarditis were identified and compared to 78 patients diagnosed with PIMS. All patients with post-vaccination myocarditis were males who developed symptoms following their second dose of the vaccine. Patients with post-vaccination myocarditis had a shorter duration of stay in the hospital (mean 4.4 ± 1.9 vs. 8.7 ± 4.7 days) and less myocardial dysfunction (11.1% vs. 61.5%), and all had excellent outcomes as compared to the chronic changes among 9.2% of the patients with PIMS. CONCLUSION: The clinical course of vaccine-associated myocarditis appears favorable, with resolution of the symptoms in all the patients in our cohort.
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A bulk of studies showed an association between stressful events and juvenile idiopathic arthritis (JIA) but failed to identify specific psychological tendencies that contribute to the patients' vulnerability to stress. The purpose of this paper is to identify psychological tendencies specific to JIA that would unravel characteristic sources of stress. The study is based on the cognitive orientation model of health, which enables us to identify these kinds of tendencies in terms of four belief types (beliefs about self, general beliefs, beliefs about norms, and goals) that refer to specific themes. This is a case-control-cohort study that included a sample of 36 patients (mean age = 12.44 years, SD = 2.97, 21 females) and 41 matched controls (mean age = 13.15 years, SD = 2.01, 22 females). The JIA cognitive-orientation questionnaire was administered, and relevant medical parameters were recorded. The belief types differentiated between the two groups, and the patients were characterized using six themes. Examples of the themes are being over-sensitive, striving for success, and not fulfilling duties well. The themes differentiated between the participants' groups with an accuracy of 89.1%. The likelihood of the patients being characterized by the themes is 3.24-9.35 times more than the controls. The psychological tendencies of JIA were discussed as generators of stress (e.g., being over-sensitive) and cognitive conflicts (e.g., the contradiction between striving for success versus not fulfilling duties well). Also, the suggested reflections of these tendencies in the health workers' and patients' relationships, such as egalitarian interaction, and non-formal communication style, were described.
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Artritis Juvenil , Niño , Femenino , Humanos , Adolescente , Artritis Juvenil/psicología , Estudios de Cohortes , Encuestas y Cuestionarios , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Limping and/or refusal to walk is a common complaint in the setting of the pediatric department, with a widely diverse differential diagnosis. An unusual etiology, is that of a hereditary neuropathy. Hereditary neuropathy with liability to pressure palsies (HNPP) is a recurrent, episodic demyelinating neuropathy, most commonly caused by a 17p11.2 chromosomal deletion encompassing the PMP22 gene. METHODS: We pursued chromosomal microarray analysis (CMA) in multiple affected individuals of a single extended family, manifesting a range of phenotypic features consistent with HNPP. RESULTS: A 4.5 years-old boy presented for in-patient evaluation due to refusal to walk. Initial investigations including spine MRI and bone scan failed to yield a conclusive diagnosis. Following family history, which implied an autosomal dominant mode of inheritance, CMA was pursued and confirmed a 17p11.2 deletion in the proband consistent with HNPP. Importantly, following this diagnosis, four additional affected family members were demonstrated to harbor the deletion. Their variable phenotypic features, ranging from a prenatal diagnosis of a 6 months-old sibling, to recurrent paresthesias manifesting in the fourth decade of life, are discussed. CONCLUSIONS: Our experience with the family reported herein demonstrates how a thorough anamnesis can lead to a rare genetic etiology with a favorable prognosis and prevent unnecessary investigations, and underscores HNPP as an uncommon diagnostic possibility in the limping child.
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Artrogriposis , Neuropatía Hereditaria Motora y Sensorial , Artrogriposis/diagnóstico , Artrogriposis/genética , Variación Biológica Poblacional , Niño , Preescolar , Neuropatía Hereditaria Motora y Sensorial/diagnóstico , Neuropatía Hereditaria Motora y Sensorial/genética , Humanos , Lactante , Masculino , Proteínas de la Mielina/genéticaRESUMEN
We compare cases of familial Mediterranean fever-related protracted febrile myalgia and poststreptococcal myalgia, both rare disorders presenting with fever, myalgia, and inflammatory biomarkers. Although clinical symptoms may be undistinguishable, steroids are usually required in protracted febrile myalgia syndrome and poststreptococcal myalgia most often respond to nonsteroidal anti-inflammatory drugs. Awareness of poststreptococcal myalgia and preceding history may prevent unnecessary tests or overtreatment.
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Fiebre Mediterránea Familiar , Mialgia , Antiinflamatorios no Esteroideos/uso terapéutico , Fiebre Mediterránea Familiar/complicaciones , Fiebre Mediterránea Familiar/diagnóstico , Fiebre Mediterránea Familiar/tratamiento farmacológico , Fiebre/diagnóstico , Fiebre/tratamiento farmacológico , Fiebre/etiología , Humanos , Mialgia/diagnóstico , Mialgia/etiología , SobretratamientoRESUMEN
OBJECTIVE: Juvenile psoriatic arthritis (JPsA) is a severe inflammatory arthritis, which is associated with psoriasis in most cases. While there are few validated screening tools for diagnosis of arthritis for adult patients with psoriasis, those screening tools were never evaluated in children. The aims of this study were to evaluate two screening tools among pediatric patients with psoriasis. METHODS: Thirty-nine patients with the diagnosis of psoriasis completed two screening questionnaires: The Psoriasis Epidemiology Screening Tool (PEST) questionnaire and the new Early Arthritis for Psoriatic Patients (EARP) questionnaire. All patients were evaluated by a rheumatologist for the diagnosis of JPsA, and the accuracy of the two questionnaires was compared. RESULTS: The 4/39 (10.1%) patients diagnosed with JPsA had a PEST questionnaire score of ≥ 3, compared to a median PEST score of the patients without the diagnosis of JPsA of 0 (0-2). Thus, both the sensitivity and specificity of the PEST in diagnosing JPsA were 100%. For the EARP questionnaire, 8/39 patients had a screening questionnaire score of ≥ 3, suggestive of JPsA, four were true positive, and four false positive. Thus, the sensitivity and specificity of EARP in diagnosing JPsA were 100% and 89%, respectively. CONCLUSION: Both the PEST and EARP questionnaires were easy to use and had high sensitivity for the diagnosis of JPsA in the pediatric population with psoriasis. The PEST questionnaire had a higher specificity than the EARP. KEY POINTS: ⢠EARP and PEST are good screening tools for diagnosis of arthritis in pediatric population with psoriasis.
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Artritis Psoriásica , Psoriasis , Adulto , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/epidemiología , Niño , Humanos , Tamizaje Masivo , Proyectos Piloto , Psoriasis/complicaciones , Psoriasis/diagnóstico , Psoriasis/epidemiología , Sensibilidad y Especificidad , Encuestas y CuestionariosRESUMEN
Osteosclerotic metaphyseal dysplasia is a rare disorder which features osteosclerosis involving long bones, vertebrae, ribs, clavicles and the iliac crests. Additional features which have variably been reported include developmental delay, short stature, hypotonia and seizures. The disease is caused by pathogenic variants in the LRRK1 gene, and inherited in an autosomal recessive manner. We report three siblings (ages 14 years, 11.5 years and 0.9 years), born to consanguineous parents of Arab-Muslim descent, harboring a homozygous pathogenic variant in the LRRK1 gene (Chr15:101068759 AGGGGCT>A, c.5965_5970del TGGGGC, p.Trp1989Gly1990del). The patients displayed variable degrees of skeletal dysplasia, with the oldest sibling most severely affected, and the youngest infant with minor skeletal involvement. Two of the siblings exhibited normal neurological development, while the youngest sibling exhibited global developmental delay. None of the siblings had seizures; however, two of them exhibited nystagmus. Optic nerve involvement has not previously been reported to be part of the clinical spectrum of this disease. The degree of optic nerve involvement did not correlate with the degree of skeletal involvement. This indicates both intra-familial variable expressivity along with a broadening of the spectrum of LRRK1-associated disease. These findings warrant reconsideration of therapeutic strategies, including the possibility of hematopoietic stem cell transplantation (HSCT) as is performed in cases of malignant and intermediate forms of osteopetrosis.
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Discapacidades del Desarrollo/genética , Atrofia Óptica/genética , Osteopetrosis/genética , Proteínas Serina-Treonina Quinasas/genética , Adolescente , Niño , Femenino , Humanos , Lactante , Masculino , Mutación , Fenotipo , HermanosRESUMEN
Background: Genetic conditions contribute a significant portion of disease etiologies in children admitted to general pediatric wards worldwide. While exome sequencing (ES) has improved clinical diagnosis and management over a variety of pediatric subspecialties, it is not yet routinely used by general pediatric hospitalists. We aim to investigate the impact of exome sequencing in sequencing-naive children suspected of having monogenic disorders while receiving inpatient care. Methods: We prospectively employed exome sequencing in children admitted to the general pediatric inpatient service at a large tertiary medical center in Israel. Genetic analysis was triggered by general and/or subspecialist pediatricians who were part of the primary inpatient team. We determined the diagnostic yield among children who were referred for exome sequencing and observed the effects of genetic diagnosis on medical care. Results: A total of fifty probands were evaluated and exome sequenced during the study period. The most common phenotypes included were neurodevelopmental (56%), gastrointestinal (34%), and congenital cardiac anomalies (24%). A molecular diagnosis was reached in 38% of patients. Among seven patients (37%), the molecular genetic diagnosis influenced subsequent clinical management already during admission or shortly following discharge. Conclusion: We identified a significant fraction of genetic etiologies among undiagnosed children admitted to the general pediatric ward. Our results support that early application of exome sequencing may be maximized by pediatric hospitalists' high index of suspicion for an underlying genetic etiology, prompting an in-house genetic evaluation. This framework should include a multidisciplinary co-management approach of the primary care team working alongside with subspecialties, geneticists and bioinformaticians.
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BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA). METHODS: This double-blind, withdrawal phase 3 trial enrolled patients with polyarticular course JIA (extended oligoarthritis, rheumatoid factor-positive or rheumatoid factor-negative polyarthritis, or systemic JIA without active systemic features) aged 2 years to younger than 18 years, and was done at 64 centres of the Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Collaborative Study Group networks in 14 countries. Patients with psoriatic arthritis or enthesitis-related arthritis were enrolled for exploratory endpoints. During part 1 of the study, patients received oral open-label tofacitinib (weight-based doses; 5 mg twice daily or lower) for 18 weeks. Patients achieving at least JIA/American College of Rheumatology 30 response were randomly assigned (1:1) using an Interactive Response Technology system to continue tofacitinib or switch to placebo in part 2 of the study for 26 weeks. The primary endpoint was JIA flare rate by week 44 in part 2 in patients with polyarticular course JIA; the intention-to-treat principle was applied. Safety was evaluated throughout part 1 and part 2 of the study in all patients who received one dose or more of study medication. This trial is registered with ClinicalTrials.gov, NCT02592434. FINDINGS: Between June 10, 2016, and May 16, 2019, of 225 patients enrolled, 184 (82%) patients had polyarticular course JIA, 20 (9%) had psoriatic arthritis, and 21 (9%) had enthesitis-related arthritis. 147 (65%) of 225 patients received concomitant methotrexate. In part 2, 142 patients with polyarticular course JIA were assigned to tofacitinib (n=72) or placebo (n=70). Flare rate by week 44 was significantly lower with tofacitinib (21 [29%] of 72 patients) than with placebo (37 [53%] of 70 patients; hazard ratio 0·46, 95% CI 0·27-0·79; p=0·0031). In part 2 of the study, adverse events occurred in 68 (77%) of 88 patients receiving tofacitinib and 63 (74%) of 85 in the placebo group. Serious adverse events occurred in one (1%) and two (2%), respectively. In the entire tofacitinib exposure period, 107 (48%) of 225 patients had infections or infestations. There were no deaths during this study. INTERPRETATION: The results of this pivotal trial show that tofacitinib is an effective treatment in patients with polyarticular course JIA. New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections. FUNDING: Pfizer.
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Artritis Juvenil/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Piperidinas/uso terapéutico , Pirimidinas/uso terapéutico , Administración Oral , Adolescente , Niño , Preescolar , Humanos , Resultado del TratamientoAsunto(s)
Biopsia/métodos , Encéfalo , Cuidados Críticos/métodos , Ciclofosfamida , Paro Cardíaco , Esteroides , Vasculitis del Sistema Nervioso Central , Adolescente , Antiinflamatorios/administración & dosificación , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Angiografía Cerebral/métodos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Diagnóstico Diferencial , Resultado Fatal , Humanos , Inmunosupresores/administración & dosificación , Angiografía por Resonancia Magnética/métodos , Masculino , Paraplejía/diagnóstico , Paraplejía/etiología , Médula Espinal/diagnóstico por imagen , Esteroides/administración & dosificación , Esteroides/efectos adversos , Retención Urinaria/diagnóstico , Retención Urinaria/etiología , Vasculitis del Sistema Nervioso Central/diagnóstico , Vasculitis del Sistema Nervioso Central/fisiopatología , Vasculitis del Sistema Nervioso Central/terapiaRESUMEN
OBJECTIVES: FMF results from mutations in the Mediterranean fever (MEFV) gene. The p. E148Q protein alternation is one of the most frequent in the MEFV gene, yet the exact E148Q genotype-phenotype correlation remains unclear. The aim of this study was to examine clinical significance of heterozygous E148Q variant in a paediatric FMF cohort. METHODS: We compared the clinical manifestations and disease severity score of four genetic subgroups: (group 1) patients harbouring a single heterozygous p. E148Q variant (n = 6); (group 2) patients harbouring a single p. M694V heterozygous variant (n = 88); (group 3) patients harbouring compound heterozygous p. M694V and p. E148Q variants (n = 36); and (group 4) homozygotes for p. M694V variant (n = 160). RESULTS: Of 646 FMF children from our centre, only 1% (six patients) of our genetically characterized FMF cohort had a single E148Q variant, most presenting with recurrent fevers and abdominal pain. None of the participants was found to harbour homozygous E148Q. Overall, M694V/E148Q compound heterozygosity did not exhibit a more severe phenotype compared with patients with a single M694V variant. The former group were less likely to have abdominal pain and exertional leg pain (P < 0.004 and P < 0.001, respectively) and more likely to have chest pain (P < 0.01). Both subgroups showed milder clinical phenotype compared with patients with M694V homozygosity. CONCLUSION: Our findings demonstrate that a single heterozygous E148Q variant is unlikely to cause FMF in children and that E148Q/M694V is clinically indistinguishable from a single M694V variant. Thus, E148Q heterozygosity does not result in clinically meaningful phenotype in children.
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Fiebre Mediterránea Familiar/genética , Pirina/genética , Sustitución de Aminoácidos , Niño , Preescolar , Femenino , Heterocigoto , Humanos , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVES: The European League Against Rheumatism and American College of Rheumatology 2019 (EULAR/ACR-19) criteria for the diagnosis of SLE were recently published, with the stated goal of maintaining the level of sensitivity and raising the level of specificity for classification of SLE in adults. The aim of this study is to examine their application to juvenile SLE (jSLE) patients. METHODS: In this multicentre study the charts of jSLE patients from three tertiary medical centres were reviewed and compared with patients with non-jSLE diagnosis. Paediatric rheumatologists, blinded to the original diagnosis, reviewed and diagnosed all cases. Paediatric patients' clinical and laboratory data were retrospectively extracted and then examined with regard to how they met the new and old criteria. RESULTS: Included were 225 patients (112 jSLE, 113 non-SLE). When applied to juvenile SLE classification, the sensitivity of the new EULAR/ACR-19 criteria was 0.96 (95% CI: 0.9, 0.99) and the specificity was 0.89 (95% CI: 0.82, 0.94). These were comparable to the SLICC criteria. The sensitivity of the EULAR/ACR-19 criteria improves over time and was 0.83 12 months following disease onset, reaching 0.96 after longer than 24 months. CONCLUSION: Among a cohort of jSLE patients, sensitivity of the new EULAR/ACR-19 criteria was found to be high and specificity may have improved slightly compared with the SLICC-12 criteria. We support the use of the new classification criteria for paediatric patients in future jSLE studies, but it should be noted that its specificity is lower than for adults.
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Lupus Eritematoso Sistémico/diagnóstico , Adolescente , Niño , Femenino , Humanos , Masculino , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Observations among Israeli pediatric rheumatologists reveal that pediatric Juvenile Spondyloarthritis (JSpA) may present differently compared to patients from the United States (US). This study is aimed to compare the demographic and clinical variables of Israeli and US JSpA patients upon presentation. METHODS: We performed a retrospective, cross-sectional, multicenter comparison of JSpA patients among 3 large Israeli pediatric rheumatology centers and a large US pediatric rheumatology center. Patients with diagnosis of Juvenile Ankylosing Spondylitis (JAS) and/or Enthesitis-related Arthritis (ERA) were included. The demographic, clinical and radiologic features were compared. RESULTS: Overall 87 patients were included (39 Israeli, 48 US patients). Upon presentation, inflammatory back pain, sacroiliac joint tenderness and abnormal modified Schober test, were significantly more prevalent among Israeli patients (59% vs. 35.4, 48.7% vs. 16.7, and 41.2% vs. 21.5%, respectively, all p < 0.05), whereas peripheral arthritis and enthesitis were significantly more prevalent among US patients (43.6% vs. 91.7 and 7.7% vs. 39.6% in Israeli patients vs. US patients, p < 0.05). In addition, 96.7% of the Israeli patients versus 29.7% of the US patients demonstrated sacroiliitis on MRI (p < 0.001, N = 67). Less than one-third of the Israeli patients (32%) were HLA-B27 positive vs. 66.7% of US patients (p = 0.007). CONCLUSION: Israeli children with JSpA presented almost exclusively with axial disease compared to US patients who were more likely to present with peripheral symptoms. HLA B27 prevalence was significantly lower in the Israeli cohort compared to the US cohort. Further studies are needed to unravel the genetic and possibly environmental factors associated with these findings.