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Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease, linked to mutations in the MEFV gene. The p.E148Q variant, found on exon 2, has an uncertain role in FMF, with debates on whether it is a benign polymorphism or a pathogenic mutation. This study aimed to assess the clinical characteristics and severity of FMF in patients homozygous for the p.E148Q variant and to evaluate the impact of the p.V726A variant in these patients. This retrospective cohort study analyzed data from electronic medical records at Carmel Medical Center, Israel. Patients who underwent genetic testing for FMF from November 2004 to December 2019 and had p.E148Q/p.E148Q or p.E148Q/p.E148Q + p.V726A variants were included. Disease severity was assessed using the Tel Hashomer Key to Severity Score. Statistical analyses compared clinical characteristics and severity between genotype groups. The study included 61 FMF patients, with 24 (39%) having p.E148Q/p.E148Q and 37 (61%) having p.E148Q/p.E148Q + p.V726A variants. The majority (72%) were Druze. Most patients (65.5%) exhibited mild disease, while 31.1% had moderate disease, with no cases of severe disease. Colchicine treatment significantly reduced CRP levels in all patients. CONCLUSION: These findings suggest that the p.E148Q variant, whether alone or with p.V726A, generally results in mild to moderate FMF severity, supporting its pathogenic role in particular ethnicity. These results contribute to understanding the clinical significance of the p.E148Q variant and considering the patient's need for Colchicine treatment. WHAT IS KNOWN: ⢠The role of the p.E148Q variant in FMF is debated, with questions about whether it is a benign polymorphism or a pathogenic mutation. ⢠The prevalence of MEFV variants can vary significantly among different ethnic groups. WHAT IS NEW: ⢠The p.E148Q variant has clinical significance in particular ethnicities, as supported by a significant reduction in CRP levels following colchicine treatment. ⢠The p.E148Q variant, whether alone or with p.V726A, generally results in mild to moderate FMF severity.
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OBJECTIVE: To investigate phenotypic and molecular characteristics of a consanguineous family with autosomal-recessive, polyarticular, juvenile isiopathic arthriris (JIA) with extra-articular manifestations, including renal amyloidosis and Crohn's disease, associated with a novel homozygous truncating variant in LACC1. METHODS: Whole exome sequencing (WES) or targeted Sanger verification were performed in 15 participants. LACC1 expression and cytokine array were analysed in patient-derived and CRISPR/Cas9-generated LACC1-knockout macrophages (MÏ). RESULTS: A homozygous truncating variant (p.Glu348Ter) in LACC1 was identified in three affected and one asymptomatic family member, and predicted harmful by causing premature stop of the LACC1 protein sequences, and by absence from ethnically-matched controls and public variation databases. Expression studies in patient-derived macrophages (MÏ) showed no endogenous p.Glu348Ter-LACC1 RNA transcription or protein expression, compatible with nonsense-mediated mRNA decay. WES analysis in the asymptomatic homozygous subject for p. Glu348Ter-LACC1 detected an exclusive heterozygous variant (p.Arg928Gln) in complement component C5. Further complement activity analysis suggested a protective role for the p.Arg928Gln-C5 variant as a phenotypic modifier of LACC1-associated disease. Finally, cytokine profile analysis indicated increased levels of pro-inflammatory cytokines in LACC1-disrupted as compared with wild-type MÏ. CONCLUSIONS: Our findings reinforce the role of LACC1 disruption in autosomal-recessive JIA, extend the clinical spectrum and intra-familial heterogeneity of the disease-associated phenotype, indicate a modulatory effect of complement factor C5 on phenotypic severity, and suggest an inhibitory role for wild-type LACC1 on pro-inflammatory pathways.
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Artritis Juvenil/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación con Pérdida de Función/genética , Adolescente , Adulto , Artritis Juvenil/patología , Proteína 9 Asociada a CRISPR , Sistemas CRISPR-Cas , Citocinas/sangre , Femenino , Citometría de Flujo , Edición Génica , Humanos , Immunoblotting , Masculino , Linaje , Secuenciación del Exoma , Adulto JovenRESUMEN
Introduction: Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) is the most common periodic fever syndrome in the pediatric population, yet its pathogenesis is unknown. PFAPA was believed to be sporadic but family clustering has been widely observed. Objective: To identify demographic and clinical differences between patients with PFAPA and a positive family history (FH+) as compared to those with no family history (FH-). Methods: In a database comprising demographic and clinical data of 273 pediatric PFAPA patients treated at two tertiary centers in Israel, 31 (14.3%) had FH+. Data from patients with FH+ were compared to data from those with FH-. Furthermore, family members (FMs) of those with FH+ were contacted via telephone for more demographic and clinical details. Results: The FH+ group as compared to the FH- group had more myalgia (56 vs. 19%, respectively, p = 0.001), headaches (32 vs. 2%, respectively, p = 0.016), and a higher carrier frequency of M694V mutation (54% vs. 25%, respectively, p = 0.05). Colchicine was seen to be a more beneficial treatment for the FH+ group as compared to the FH- group; however, with no statistical significance (p = 0.096). FMs displayed almost identical characteristics to patients in the FH+ group except for greater arthralgia during flares (64 vs. 23%, respectively, p = 0.008), and compared to the FH- group they had more oral aphthae (68 vs. 43%, respectively, p = 0.002), myalgia/arthralgia (64 vs. 19%/16%, respectively, p < 0.0001), and higher rates of FH of Familial Mediterranean fever (FMF) (45 vs.15%, respectively, p = 0.003). Conclusions: Our findings suggest that patients with a FH+ likely experience a different subset of disease with higher frequency of family history of FMF, arthralgia, myalgia, and might have a better response to colchicine compared to FH-. Colchicine prophylaxis for PFAPA should be considered in FH+.
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OBJECTIVES: To evaluate the ethnic distribution of Israeli patients with the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA). STUDY DESIGN: The medical records of patients with PFAPA attending 2 pediatric tertiary medical centers in Israel from March 2014 to March 2019 were retrospectively reviewed. Patients with concomitant familial Mediterranean fever were excluded. Ethnicity was categorized as Mediterranean, non-Mediterranean, and multiethnic. Findings were compared with patients with asthma under treatment at the same medical centers during the same period. RESULTS: The cohort included 303 patients with PFAPA and 475 with asthma. Among the patients with PFAPA, 178 (58.7%) were of Mediterranean descent (Sephardic Jews or Israeli Arabs), 96 (33.0%) were multiethnic, and 17 (5.8%) were of non-Mediterranean descent (all Ashkenazi Jews). Patients with PFAPA had a significantly higher likelihood of being of Mediterranean descent than the patients with asthma (58.7% vs 35.8%; P < .0001). The Mediterranean PFAPA subgroup had a significantly earlier disease onset than the non-Mediterranean subgroup (2.75 ± 1.7 vs 3.78 ± 1.9 years, P < .04) and were younger at disease diagnosis (4.77 ± 2.3 vs 6.27 ± 2.9 years, P < .04). CONCLUSIONS: PFAPA was significantly more common in patients of Mediterranean than non-Mediterranean descent. Further studies are needed to determine the genetic background of these findings.
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Fiebre/etnología , Linfadenitis/etnología , Faringitis/etnología , Estomatitis Aftosa/etnología , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Israel/epidemiología , Masculino , Estudios Retrospectivos , SíndromeRESUMEN
OBJECTIVES: To describe a cohort of pediatric patients diagnosed with periodic fever aphthous stomatitis, pharyngitis and adenitis (PFAPA) and familial Mediterranean fever (FMF) and compare them with children diagnosed solely with PFAPA (sPFAPA). STUDY DESIGN: Clinical, laboratory, and genetic data of all pediatric patients diagnosed with sPFAPA or PFAPA/FMF were retrospectively collected from 2 primary Israeli medical referral centers and compared. RESULTS: Of 270 patients with PFAPA, more than one-half were of Mediterranean ancestry. Among patients with PFAPA, 51 (18.9%) also were diagnosed with FMF (PFAPA/FMF). Genetic data on the 9 most common MEFV variants were available for 45 children (88%) in the PFAPA/FMF group. Two variants were found in 15 children (33.3 %), 1 variant was found 27 patients (60%), and 3 patients (6.6%) had no variants. Abdominal pain, myalgia, and arthralgia each were more commonly reported in the PFAPA/FMF group compared with the sPFAPA group (90% vs 49% [P < .0001]; 46% vs 23% [P = .02]; and 30% vs 17% [P = .049], respectively). Colchicine was more commonly prescribed for the PFAPA/FMF group compared with the sPFAPA group (82% vs 29%; P < .0001), but alleviation of PFAPA symptoms with colchicine was similar between groups (75% vs 63%; P = .23). CONCLUSION: We show a strong association between 2 common autoinflammatory syndromes, PFAPA and FMF, in patients from Mediterranean ancestry. Clinicians should be aware that presentation of 1 disease may clinically evolve into another. The association between PFAPA and FMF poses the question similar pathogenesis and genetic influence of the MEFV gene on PFAPA.
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Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Niño , Preescolar , Colchicina/administración & dosificación , Femenino , Enfermedades Autoinflamatorias Hereditarias/tratamiento farmacológico , Enfermedades Autoinflamatorias Hereditarias/genética , Humanos , Israel , Masculino , Mutación , Pirina/genética , Estudios Retrospectivos , Moduladores de Tubulina/administración & dosificaciónRESUMEN
BACKGROUND: Diagnosis of Periodic Fever, Aphthous stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) syndrome is currently based on the modified Marshall's criteria, but no validated evidence based classification criteria for PFAPA has been established so far. METHODS: A multistep process, based on the Delphi and Nominal Group Technique was conducted. After 2 rounds of e-mail Delphi survey involving 21 experts in autoinflammation we obtained a list of variables that were discussed in an International Consensus Conference. Variables reaching the 80% of consensus between participants were included in the new classification criteria. In the second phase the new classification criteria and the modified Marshall's criteria were applied on a cohort of 80 pediatric PFAPA patients to compare their performance. RESULTS: The Delphi Survey was sent to 22 participants, 21 accepted to participate. Thirty variables were obtained from the survey and have been discussed at the Consensus Conference. Through the Nominal Group Technique we obtained a new set of classification criteria. These criteria were more restrictive in respect to the modified Marshall's criteria when applied on our cohort of patients. CONCLUSION: Our work led us to identify a new set of classification criteria for PFAPA syndrome, but they resulted to be too restrictive to be applied in daily clinical practice for the diagnosis of PFAPA.
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Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Consenso , Técnica Delphi , Diagnóstico Diferencial , Fiebre/complicaciones , Enfermedades Autoinflamatorias Hereditarias/clasificación , Humanos , Linfadenitis/complicaciones , Faringitis/complicaciones , Estomatitis Aftosa/complicaciones , SíndromeRESUMEN
AIM: This study assessed the validity of using established Japanese risk scoring methods to predict intravenous immunoglobulin (IVIG) resistance to Kawasaki disease in Israeli children. METHODS: We reviewed the medical records of 282 patients (70% male) with Kawasaki disease from six Israeli medical centres between 2004 and 2013. Their mean age was 2.5 years. The risk scores were calculated using the Kobayashi, Sano and Egami scoring methods and analysed to determine whether a higher risk score predicted IVIG resistance in this population. Factors that predicted a lack of response to the initial IVIG dose were identified. RESULTS: We found that 18% did not respond to the first IVIG dose. The three scoring methods were unable to reliably predict IVIG resistance, with sensitivities of 23%-32% and specificities of 67%-87%. Calculating a predictive score that was specific for this population was also unsuccessful. The factors that predicted a lacked of response to the first IVIG dose included low albumin, elevated total bilirubin and ethnicity. CONCLUSION: The established risk scoring methods created for Japanese populations with Kawasaki disease were not suitable for predicting IVIG resistance in Caucasian Israeli children, and we were unable to create a specific scoring method that was able to do this.
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Aneurisma Coronario/etiología , Inmunoglobulinas Intravenosas/uso terapéutico , Síndrome Mucocutáneo Linfonodular/etnología , Preescolar , Femenino , Humanos , Masculino , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/terapia , Estudios Retrospectivos , Medición de Riesgo , Insuficiencia del Tratamiento , Población Blanca/estadística & datos numéricosRESUMEN
BACKGROUND: Palindromic rheumatism is an idiopathic, periodic arthritis characterized by multiple, transient, recurring episodes. Palindromic rheumatism is well-characterized in adults, but has never been reported in pediatric populations. The aim of this study was to characterize the clinical features and outcomes of a series of pediatric patients with palindromic rheumatism. METHODS: We defined clinical criteria for palindromic rheumatism and reviewed all clinical visits in three Pediatric Rheumatology centers in Israel from 2006through 2015, to identify patients with the disease. We collected retrospective clinical and laboratory data on patients who fulfilled the criteria, and reviewed their medical records in order to determine the proportion of patients who had developed juvenile idiopathic arthritis. RESULTS: Overall, 10 patients were identified. Their mean age at diagnosis was 8.3 ± 4.5 years and the average follow-up was 3.8 ± 2.7 years. The mean duration of attacks was 12.2 ± 8.4 days. The most frequently involved joints were knees. Patients tested positive for rheumatoid factor in 20% of cases. One patient developed polyarticular juvenile idiopathic arthritis after three years of follow-up, six patients (60%) continued to have attacks at their last follow-up and only three children (30%) achieved long-term remission. CONCLUSIONS: Progression to juvenile idiopathic arthritis is rare amongst children with palindromic rheumatism and most patients continued to have attacks at their last follow-up. Longer follow-up periods are required to predict the long-term outcomes of pediatric patients with palindromic rheumatism.
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Artritis Juvenil/epidemiología , Artritis Reumatoide/diagnóstico , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Juvenil/etiología , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Niño , Preescolar , Colchicina/uso terapéutico , Estudios Transversales , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Humanos , Israel , Masculino , Estudios RetrospectivosRESUMEN
INTRODUCTION: Juvenile Idiopathic Arthritis (JIA) includes a group of systemic inflammatory disorders of unknown etiology for which no curative treatment currently exists. The traditional treatment for these disorders which includes the use of NSAIDs and disease modifying anti-rheumatic drugs (DMRADs) is only effective in a subset of patients. Recent advances in understanding the pathophysiology of the inflammatory response, have led to the development of a new class of medications, termed biologic agents which are capable of selectively inhibiting the principal mediators of inflammation. The introduction of biologic drugs has opened a new era in the treatment of rheumatic disorders in children. In this review we describe the characteristics of the currently available biologic agents in Israel, and the updated information regarding indications, efficacy and the safety of these drugs in pediatric patients. Disclosure: Consultant and participating in clinical trials for Novartis com.
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Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Terapia Biológica , Antiinflamatorios no Esteroideos , Niño , Humanos , IsraelRESUMEN
INTRODUCTION: Atherosclerosis is emerging as one of the most important causes of morbidity and mortality among patients with different rheumatologic disease. Endothelial dysfunction may be an early sign of atherosclerosis. OBJECTIVES: To evaluate the occurrence of endothelial dysfunction in children with autoimmune diseases, including juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE) and dermatomyositis, using a novel noninvasive technique. METHODS: The study group consisted of 24 children with autoimmune diseases, and was compared to a control group of 17 healthy, age- and BMI-matched controls. Endothelial function was assessed by a noninvasive technology that captures a beat-to-beat plethysmographic recording of the finger arterial pulse-wave amplitude with pneumatic probes, utilizing a Peripheral Arterial Tonometry (PAT) device. RESULTS: In the study group, 7 out of the 24 (29%) patients had evidence of impaired endothelial function, compared to 1 out of 17 (6%) children in the control group (p <0.05). Thirty-three per cent of our patients with SLE and 23% of patients with JIA had impaired endothelial function. There were no differences between the two groups of patients with and without endothelial dysfunction as to age, body mass index, fasting glucose level, triglycerides, cholesterol, and dose and duration of steroid treatment. The patients with normal endothelial function had higher systolic blood pressure compared with the group with impaired endothelial function (112.82 ± 7.65 vs13.88 ± 104.85 respectively, p=0.04). CONCLUSIONS: Children with autoimmune diseases may have a high tendency to develop endothelial dysfunction. Larger studies are needed to confirm our findings and to explore the influence of endothelial dysfunction on the development of atherosclerosis in young children.
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Aterosclerosis/etiología , Células Endoteliales/fisiología , Endotelio Vascular/fisiopatología , Enfermedades Reumáticas/complicaciones , Arterias , Aterosclerosis/prevención & control , Índice de Masa Corporal , Enfermedades Cardiovasculares , Estudios de Casos y Controles , Niño , Humanos , Lupus Eritematoso SistémicoRESUMEN
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.
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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 TratamientoRESUMEN
BACKGROUND: Although Henoch-Schonlein purpura (HSP) is the most common form of systemic vasculitis in children, the long term effect of HSP on endothelial function is still not clear. The aim of our study was to evaluate the long term effect of HSP on endothelial function in children and adolescents. METHODS: This research was an observational prospective study. The study group comprised of 19 children diagnosed with HSP. The minimum interval between the diagnosis with HSP and endothelial testing was 5 months. Endothelial function evaluation was assessed by a noninvasive technology named peripheral arterial tonometry, using an EndoPAT™ device. This method measures blood flow in the limb, in response to arterial occlusion, and calculates a Reactive Hyperemic Index (RHI) as an index of endothelial function. RHI values of the study group were compared to those of a known control group. RESULTS: Nineteen children and adolescents with HSP underwent endothelial function studies. Endothelial function was compared to that of a known control group comprising of 23 healthy children and adolescents. The two groups had similar characteristics, including age, male to female ratio, height, weight and BMI. Mean RHI was 1.81 in the study group, and 1.87 in the control group (p = 0.18). Linear regression of the study group, showed a positive correlation between the time interval from HSP diagnosis to participation in the study, and between the RHI value (r = 0.542, p = 0.016). RHI levels were significantly higher in patients who had endothelial function measured more than 6 years since the diagnosis of HSP compared with those patients with less than 6 years follow up (1.98 + 0.74 vs. 1.38 ± 0.43 P = 0.037). CONCLUSIONS: These results suggest that HSP causes short term endothelial dysfunction that improves with time.
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Endotelio Vascular/fisiopatología , Vasculitis por IgA/fisiopatología , Dolor Abdominal/etiología , Adolescente , Artritis Juvenil/complicaciones , Estudios de Casos y Controles , Niño , Femenino , Hematuria/complicaciones , Humanos , Hiperemia/diagnóstico , Hiperemia/fisiopatología , Vasculitis por IgA/diagnóstico , Vasculitis por IgA/terapia , Tiempo de Internación , Masculino , Estudios Prospectivos , Tiempo de Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Canakinumab is a human anti-interleukin-1ß (IL-1ß) monoclonal antibody neutralizing IL-1ß-mediated pathways. We sought to characterize the molecular response to canakinumab and evaluate potential markers of response using samples from two pivotal trials in systemic juvenile idiopathic arthritis (SJIA). METHODS: Gene expression was measured in patients with febrile SJIA and in matched healthy controls by Affymetrix DNA microarrays. Transcriptional response was assessed by gene expression changes from baseline to day 3 using adapted JIA American College of Rheumatology (aACR) response criteria (50 aACR JIA). Changes in pro-inflammatory cytokines IL-6 and IL-18 were assessed up to day 197. RESULTS: Microarray analysis identified 984 probe sets differentially expressed (≥2-fold difference; P < 0.05) in patients versus controls. Over 50% of patients with ≥50 aACR JIA were recognizable by baseline expression values. Analysis of gene expression profiles from patients achieving ≥50 aACR JIA response at day 15 identified 102 probe sets differentially expressed upon treatment (≥2-fold difference; P < 0.05) on day 3 versus baseline, including IL-1ß, IL-1 receptors (IL1-R1 and IL1-R2), IL-1 receptor accessory protein (IL1-RAP), and IL-6. The strongest clinical response was observed in patients with higher baseline expression of dysregulated genes and a strong transcriptional response on day 3. IL-6 declined by day 3 (≥8-fold decline; P < 0.0001) and remained suppressed. IL-18 declined on day 57 (≥1.5-fold decline, P ≤ 0.002). CONCLUSIONS: Treatment with canakinumab in SJIA patients resulted in downregulation of innate immune response genes and reductions in IL-6 and clinical symptoms. Additional research is needed to investigate potential differences in the disease mechanisms in patients with heterogeneous gene transcription profiles. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00886769 (trial 1). Registered on 22 April 2009; NCT00889863 (trial 2). Registered on 21 April 2009.
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Anticuerpos Monoclonales/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Interleucina-18/biosíntesis , Interleucina-6/biosíntesis , Transcriptoma/efectos de los fármacos , Adolescente , Anticuerpos Monoclonales Humanizados , Niño , Preescolar , Regulación hacia Abajo , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunoensayo , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Adulto JovenRESUMEN
BACKGROUND: Acute bronchiolitis is the most frequent lower respiratory tract infection in infants. Only small subsets of patients develop severe disease resulting in hospitalization despite having no identifiable risk factors. There is still a debate as to the role of capnometry in assessing ventilation in children with acute respiratory distress, and bronchiolitis in particular. METHODS: This was a prospective, single blind cohort study in which children younger than two years presenting to the emergency department (ED) with bronchiolitis were included. Our primary outcome was the correlation between the end tidal CO2 (EtCO2) and the clinical decision of hospital admission and discharge. Our secondary outcome measure was the correlation of EtCO2 upon arrival to the ED and clinical measures of bronchiolitis severity. Finally, by using multivariate models, we looked for other parameters that could contribute to the prediction of illness severity. RESULTS: One hundred and fourteen children with bronchiolitis were evaluated. Their median EtCO2 upon arrival to the ED was 34 mmHg (range 24-65 mmHg). EtCO2 values upon admission or discharge were not statistically different among patients who were hospitalized and among those who were discharged from the ED. Among admitted patients, we found no correlation between capnometry readings at admission and number of oxygen desaturation days, nor with the length of hospitalization. Wang clinical respiratory severity score was found, by using multivariate models, to predict nasogastric tube need, oxygen desaturation days, and length of hospitalization. CONCLUSION: Capnometry readings upon arrival to the ED did not predict hospital admission or hospital discharge eligibility. Among hospitalized patients, EtCO2 did not correlate with the evaluated disease severity measures. Wang score was found to be the most consistent predictor of significant outcomes.
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Bronquiolitis/diagnóstico , Capnografía/métodos , Estudios de Cohortes , Femenino , Hospitalización , Humanos , Lactante , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Síndrome de Dificultad Respiratoria/diagnóstico , Índice de Severidad de la Enfermedad , Método Simple CiegoRESUMEN
OBJECTIVE: To evaluate the efficacy of colchicine in reducing the frequency of attacks in patients with PFAPA. STUDY DESIGN: We conducted a 6-month open label, randomized, controlled study among patients with PFAPA who attend the Pediatric Rheumatology Clinic at the Rambam Medical Center in Israel. A total of 18 patients aged4 -11 years (males:females ratio = 11:7) were randomized into a control group (I, 10 children) and a study group (II, 8 children). Group I was followed for 6 months without any intervention, and group II was initially followed for 3 months and was thereafter treated with colchicine for 3 additional months, according to standard regimen. During the 6-month period of the study the patients and their physician recorded all the episodes of PFAPA in a constructed log. DNA analyses for the 5 common FMF mutations in Israel were performed in 17 out of the 18 patients. RESULTS: The number of episodes during the first 3 months was similar in both groups (group I 3.2 ± 1.5, group II 4.9 ± 2.3; p ≤ 0.12). Group II had significantly less PFAPA attacks in the second period while on colchicine therapy (4.9 ± 2.3 vs. 1.6 ± 1.2; p ≤ 0.01), in opposition to group I, where no difference in the number of attacks was noted between the first and second period of follow-up (3.2 ± 1.5 vs. 2.7 ± 1.5; p = 0.33). Of the 17 patients tested, 8 were carriers for FMF mutations (2 in group I and 6 in group II). CONCLUSION: Colchicine prophylaxis seems to be effective in reducing the number of attacks in PFAPA.
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Colchicina/uso terapéutico , Fiebre/tratamiento farmacológico , Linfadenitis/tratamiento farmacológico , Faringitis/tratamiento farmacológico , Estomatitis Aftosa/tratamiento farmacológico , Moduladores de Tubulina/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Masculino , Síndrome , Resultado del TratamientoRESUMEN
OBJECTIVE: The objective of this study is to examine if the B-type natriuretic peptide (BNP) can be used in diagnosing heart failure (HF) in children with congenital heart disease (CHD) who present to the emergency department (ED) with acute bronchiolitis. METHODS: A prospective cohort single-group study of children with CHD and respiratory syncytial virus bronchiolitis was conducted in a pediatric ED. The reference standard for the presence of HF was the clinical and echocardiographic assessment of a pediatric cardiologist blinded to the BNP test results. RESULTS: Eighteen cases were diagnosed, 7 (39%) had acute HF and 11 (61%) did not have acute HF. Patients with HF had a higher level of BNP compared with patients who did not have HF (783 pg/mL [interquartile range, 70-1345] vs 59 pg/mL [interquartile range, 23-90]; P<.013). A BNP level of 95 pg/mL was the optimal cutoff point, having a sensitivity of 0.71 (95% confidence interval, 0.29-0.96) and a specificity of 0.91 (95% confidence interval, 0.58-0.99). CONCLUSION: The results of this small study suggest that the BNP test can be useful to ascertain the presence of HF in children with CHD who present to the ED with respiratory syncytial virus bronchiolitis.
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Bronquiolitis Viral/complicaciones , Cardiopatías Congénitas/complicaciones , Insuficiencia Cardíaca/diagnóstico , Péptido Natriurético Encefálico/sangre , Infecciones por Virus Sincitial Respiratorio/complicaciones , Biomarcadores/sangre , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/etiología , Humanos , Lactante , Masculino , Estudios Prospectivos , Virus Sincitial Respiratorio Humano , Sensibilidad y EspecificidadAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Colchicina/uso terapéutico , Resistencia a Medicamentos , Fiebre Mediterránea Familiar/tratamiento farmacológico , Interleucina-1beta/inmunología , Adolescente , Anticuerpos Monoclonales Humanizados , Sedimentación Sanguínea , Proteína C-Reactiva/metabolismo , Niño , Relación Dosis-Respuesta a Droga , Fiebre Mediterránea Familiar/metabolismo , Femenino , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Proyectos Piloto , Factores de Tiempo , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
Respiratory disease is a common reason for hospitalization and mortality in persons with severe intellectual and developmental disability. Capnography is the measurement and numerical display of end-tidal carbon dioxide (EtCO2). This was a prospective, case controlled, cross sectional study to assess differences of baseline EtCO2 values between neurologically impaired patients and healthy individuals. 86 neurologically impaired patients were evaluated in the study group. Their mean age ± SD was 25.65 ± 10.48 years with 41% males. 53 healthy children and young adults were evaluated in the control group. Their mean age ± SD was 21.95 ± 10.38 years with 54.7% males. Patients with severe neurological impairment had higher baseline EtCO2 values than healthy individuals. Kyphoscoliosis and the use of antipsychotic drugs were the major factors to increase EtCO2 levels. Knowing the patient's baseline EtCO2 value, as well as baseline oximetry, could guide treatment decisions, when assessing the patient's oxygenation and ventilation during acute respiratory illness, and can potentially prevent unnecessary laboratory and imaging investigations as well as over treatment. Future research can shed light on the utility of capnometry and clinical implications of higher baseline EtCO2 values among neurologically impaired patients.
Asunto(s)
Antipsicóticos/uso terapéutico , Capnografía , Dióxido de Carbono/metabolismo , Discapacidades del Desarrollo , Discapacidad Intelectual , Cifosis , Intercambio Gaseoso Pulmonar , Escoliosis , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Oximetría , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVES: The aims of this study were to describe the clinical features of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) and identify distinct phenotypes in a large cohort of patients from different countries. METHODS: We established a web-based multicentre cohort through an international collaboration within the periodic fevers working party of the Pediatric Rheumatology European Society (PReS). The inclusion criterion was a diagnosis of PFAPA given by an experienced paediatric rheumatologist participating in an international working group on periodic fever syndromes. RESULTS: Of the 301 patients included from the 15 centres, 271 had pharyngitis, 236 cervical adenitis, 171 oral aphthosis and 132 with all three clinical features. A total of 228 patients presented with additional symptoms (131 gastrointestinal symptoms, 86 arthralgias and/or myalgias, 36 skin rashes, 8 neurological symptoms). Thirty-one patients had disease onset after 5 years and they reported more additional symptoms. A positive family history for recurrent fever or recurrent tonsillitis was found in 81 patients (26.9%). Genetic testing for monogenic periodic fever syndromes was performed on 111 patients, who reported fewer occurrences of oral aphthosis or additional symptoms. Twenty-four patients reported symptoms (oral aphthosis and malaise) outside the flares. The CRP was >50 mg/l in the majority (131/190) of the patients tested during the fever. CONCLUSION: We describe the largest cohort of PFAPA patients presented so far. We confirm that PFAPA may present with varied clinical manifestations and we show the limitations of the commonly used diagnostic criteria. Based on detailed analysis of this cohort, a consensus definition of PFAPA with better-defined criteria should be proposed.
Asunto(s)
Fiebre Mediterránea Familiar/diagnóstico , Linfadenitis/diagnóstico , Faringitis/diagnóstico , Estomatitis Aftosa/diagnóstico , Adolescente , Adulto , Edad de Inicio , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Niño , Preescolar , Estudios de Cohortes , Europa (Continente)/epidemiología , Fiebre Mediterránea Familiar/epidemiología , Femenino , Humanos , Lactante , Cooperación Internacional , Linfadenitis/epidemiología , Masculino , Cuello , Faringitis/epidemiología , Fenotipo , Recurrencia , Estomatitis Aftosa/epidemiología , Síndrome , Adulto JovenRESUMEN
OBJECTIVE: The myeloid-related proteins 8 and 14 (MRP-8/MRP-14) and neutrophil-derived S100A12 are biomarkers of inflammation. They can be used to determine the relapse risk in patients with juvenile idiopathic arthritis (JIA) after stopping antiinflammatory treatment. In this study, we tested the performance of different enzyme-linked immunosorbent assays (ELISAs) in order to validate systems available for routine use. METHODS: MRP-8/MRP-14 and S100A12 serum concentrations of 188 JIA patients in remission were analyzed. Commercially available test systems were compared to experimental ELISAs established in house. The ability of the assays to identify JIA patients at risk for relapse was analyzed. RESULTS: For MRP-8/MRP-14, the PhiCal Calprotectin and Buhlmann MRP8/14 Calprotectin ELISAs revealed hazard ratios of 2.3 and 2.1, respectively. For S100A12, the CircuLex S100A12/EN-RAGE ELISA revealed a hazard ratio of 3.1. The commercial assays allowed a JIA relapse prediction that was at least comparable to the experimental ELISAs. CONCLUSION: For the prediction of JIA relapse after stopping medication, the biomarkers MRP-8/MRP-14 and S100A12 can be determined by using assays that are available for routine use. The tested commercial MRP-8/MRP-14 and S100A12 ELISAs showed a performance comparable to well-established experimental ELISA protocols when assay-specific cutoffs for the indication of relapse prediction are thoroughly applied.