Haematological and other manifestations in the presence of antiphospholipid antibodies in a multicentric paediatric cohort.

OBJECTIVES: To identify the variables associated with the development of haematological manifestations in the presence of antiphospholipid antibodies (aPLs) in a paediatric cohort. METHODS: We conducted a multicentric retrospective cohort study of children under the age of 18 years. RESULTS: One hundred and thirty-four children were included; 12.2% had at least one thrombotic event (TE) and 67% at least one non-criterion manifestation. Of them, 90% did not develop any TE. Haematological manifestations were the most frequent (42%), followed by neurological (19.8%), cutaneous (17.6%), cardiac (16.8%) and renal (1.5%) manifestations. In those children with haematological disorders, the aPLs positivity rate was: 67.3% LA, 65.6% aß2GPI, 60% aCL, 45.5% single, 23.6% double and 30.9% triple. A univariate analysis showed that children with IgM aCL+, IgM aß2GPI+, triple positivity and with a SLE diagnosis had a significantly higher frequency of haematological manifestations (p<0.05). Finally, a stepwise regression analysis identified IgG aß2GPI positivity [OR 2.91, 95% CI (1.26-6.74), p=0.013], SLE [OR 2.67, 95% CI (1.13-6.3), p=0.026] and LA positivity [OR 2.53, 95% CI (1.08-5.94), p=0.033] as independent risk factors for the development of haematological manifestations. CONCLUSIONS: Non-criteria manifestations and among them haematological disorders, are the most frequent events in the presence of aPLs and/or LA in our paediatric cohort. Children with SLE, LA and/or IgG aß2GPI positivity showed a higher risk of haematological manifestations.

Importancia de la determinación de actividad enzimática en el diagnóstico del déficit de adenosina desaminasa 2 (DADA2) / Importance of the determination of enzymatic activity in the diagnosis of deficiency of adenosine deaminase 2 (DADA2)

Objetivo: Describir la utilidad de la determinación de la actividad enzimática de adenosina desaminasa 2 (ADA2) en los pacientes con sospecha de déficit de ADA2 (DADA2).MétodoEstudio retrospectivo multicéntrico con análisis de los datos clínicos, bioquímicos y genéticos de los pacientes a los que se ha determinado la actividad enzimática de ADA2 mediante método espectrofotométrico.ResultadoEn tres de los 20 pacientes se confirmó el diagnóstico de DADA2 mediante la combinación de actividad enzimática reducida y variantes patogénicas bialélicas en el gen CECR1. En dos pacientes portadores de variantes de significado incierto en CECR1, el estudio de actividad enzimática permitió descartar la enfermedad.ConclusionesLa actividad enzimática reducida de ADA2 confirma el diagnóstico de DADA2, de especial importancia en los portadores de variantes de significado incierto en CECR1. (AU)

Objective: To describe the usefulness of determining the enzymatic activity of adenosine deaminase 2 (ADA2) in patients with suspected ADA2 deficiency (DADA2).MethodRetrospective multicenter study. Review with analysis of the clinical, biochemical and genetic data of the patients in whom the enzymatic activity of ADA2 has been determined by spectrophotometric method.ResultIn 3 of the 20 patients, the diagnosis of DADA2 was confirmed by the combination of reduced enzyme activity and biallelic pathogenic variants in the CECR1 gene. In 2 patients with variants of uncertain significance in CECR1, the study of enzymatic activity allowed to rule out the disease.ConclusionsThe reduced enzymatic detection of ADA2 confirms the diagnosis of DADA2, particularly important in carriers of variants of uncertain significance in CECR1. (AU)

Importance of the determination of enzymatic activity in the diagnosis of deficiency of adenosine deaminase 2 (DADA2). / Importancia de la determinación de actividad enzimática en el diagnóstico del déficit de adenosina desaminasa 2 (DADA2).

OBJECTIVE: To describe the usefulness of determining the enzymatic activity of adenosine deaminase 2 (ADA2) in patients with suspected ADA2 deficiency (DADA2). METHOD: Retrospective multicenter study. Review with analysis of the clinical, biochemical and genetic data of the patients in whom the enzymatic activity of ADA2 has been determined by spectrophotometric method. RESULT: In 3 of the 20 patients, the diagnosis of DADA2 was confirmed by the combination of reduced enzyme activity and biallelic pathogenic variants in the CECR1 gene. In 2 patients with variants of uncertain significance in CECR1, the study of enzymatic activity allowed to rule out the disease. CONCLUSIONS: The reduced enzymatic detection of ADA2 confirms the diagnosis of DADA2, particularly important in carriers of variants of uncertain significance in CECR1.

Non-criteria manifestations in the presence of antiphospholipid antibodies in a paediatric cohort.

OBJECTIVE: To identify the variables associated with the development of non-criteria manifestations in the presence of antiphospholipid antibodies (aPLs) in a paediatric cohort. METHODS: Multicentric historical cohort study of children under the age of 18 years to determine thrombotic events (TEs) and non-criteria manifestations in the presence of aPL. RESULTS: Eighty-two children were included; 8.5% had at least one TE and 69.5% at least one non-criteria manifestation. Of them, 96.5% did not associate TEs. Haematological manifestations were the most frequent (43.65%), followed by cutaneous (22%), neurological (15.9%) and cardiac (4.9%) events. The most frequent aPLs were: 77.8% LA; 42.7% aCL and 41.5% aß2GP. The positivity rate was: 64.6% simple, 18.3% double and 17.1% triple. ANA positivity was 68.1%. A bivariate analysis revealed that children with IgM aCL+, IgM aß2GP+, ANA+, an SLE diagnosis or the absence of TEs had a significantly higher percentage of non-criteria manifestations (P <0.05). The logistic regression showed family history of autoimmune diseases [odds ratio (OR) 4.26, 95% CI: 0.8, 22.2, P =0.086] and the absence of TEs (OR 17.18, 95% CI: 1.2, 244.6, P =0.03) as independent risk factors of developing non-criteria manifestations. An SLE diagnosis, aPL profile and ANA+ were not identified. CONCLUSION: Non-criteria manifestations were more frequent than TEs. A positive family history of autoimmune diseases and the absence of TEs were associated with a higher risk of developing non-criteria manifestations. Therefore, their inclusion as APS classification criteria should be considered in order to get an improved prognosis in the paediatric population.

Infecciones previas o coincidentes con la sospecha de enfermedad de Kawasaki ¿debemos cambiar nuestra actitud? / Previous or coincident infections with suspected Kawasaki disease. Should we change our approach?

Introducción: La enfermedad de Kawasaki (EK) es una vasculitis multisistémica asociada a lesiones en las arterias coronarias. Las infecciones podrían ser un desencadenante de la inflamación. Nuestro objetivo fue describir la presencia de infecciones en los niños con EK y analizar las características clínicas y la presencia de alteraciones coronarias en estos casos. Pacientes y métodos: Análisis retrospectivo de los pacientes incluidos en la red KAWA-RACE entre 2011 y 2016. Se estudió tanto a los pacientes que tuvieron una identificación microbiológica confirmada (IMC) en el periodo agudo como a los que presentaron antecedente de infección previa reciente (IPR) las 4 semanas anteriores. Resultados: Se incluyó a un total de 621 niños, de los cuales 101 (16,3%) tuvieron una IMC y 107 (17,2%) una IPR. Encontramos una significativa menor afectación ecocardiográfica en el grupo de IPR respecto a los niños sin infección previa (23 vs. 35%; p 0,01), con menor proporción no significativa de las alteraciones coronarias globales (16 vs. 25%; p 0,054). Sin embargo, no se detectaron diferencias en la proporción de aneurismas en ninguno de los 2 grupos (IMC o IPR) respecto al resto de los pacientes sin infecciones asociadas. Conclusiones: En nuestro estudio no encontramos diferencias en la incidencia de aneurismas coronarios en niños con y sin IMC o IPR, por lo que ante la sospecha de EK debe iniciarse siempre tratamiento, aunque se tenga infección confirmada microbiológicamente

Introduction: Kawasaki disease (KD) is a multisystem vasculitis associated with coronary artery abnormalities. Infections could be a trigger of the inflammation. The main aim of this study was to describe the presence of infections in children with KD, and to analyse the clinical characteristics and the presence of coronary abnormalities in these cases. Patients and methods: A retrospective study was performed within the Kawasaki Diseases Network (KAWA-RACE (2011-2016). An analysis was performed that included patients with positive microbiological findings (PMF) during the acute phase, as well as those with a previous recent infection (PRI) during the 4 weeks preceding KD diagnosis. Results: The study included total of 621 children with KD, with PMF being found in 101 (16.3%) patients, and a PRI in 107 (17.2%). Significantly less echocardiographic abnormalities were found in the in the group with a PRI, when compared to those without a PRI (23 vs. 35%, P = .01) and also a lower proportion of overall coronary artery lesions (16 vs. 25%, P = .054). No significant differences were found in the proportion of aneurysms in either of these groups (PRI or PMF) when compared to those without infection. Conclusions: In the present study, no differences were found in the incidence of coronary aneurysms in either of the groups, with or without PRI or PMF. Therefore, if KD is suspected, appropriate treatment should be started despite having a confirmed infection

[Previous or coincident infections with suspected Kawasaki disease. Should we change our approach?] / Infecciones previas o coincidentes con la sospecha de enfermedad de Kawasaki ¿debemos cambiar nuestra actitud?

INTRODUCTION: Kawasaki disease (KD) is a multisystem vasculitis associated with coronary artery abnormalities. Infections could be a trigger of the inflammation. The main aim of this study was to describe the presence of infections in children with KD, and to analyse the clinical characteristics and the presence of coronary abnormalities in these cases. PATIENTS AND METHODS: A retrospective study was performed within the Kawasaki Diseases Network (KAWA-RACE (2011-2016). An analysis was performed that included patients with positive microbiological findings (PMF) during the acute phase, as well as those with a previous recent infection (PRI) during the 4 weeks preceding KD diagnosis. RESULTS: The study included total of 621 children with KD, with PMF being found in 101 (16.3%) patients, and a PRI in 107 (17.2%). Significantly less echocardiographic abnormalities were found in the in the group with a PRI, when compared to those without a PRI (23 vs. 35%, P=.01) and also a lower proportion of overall coronary artery lesions (16 vs. 25%, P=.054). No significant differences were found in the proportion of aneurysms in either of these groups (PRI or PMF) when compared to those without infection. CONCLUSIONS: In the present study, no differences were found in the incidence of coronary aneurysms in either of the groups, with or without PRI or PMF. Therefore, if KD is suspected, appropriate treatment should be started despite having a confirmed infection.

Previous or coincident infections with suspected Kawasaki disease. Should we change our approach?

INTRODUCTION: Kawasaki disease (KD) is a multisystem vasculitis associated with coronary artery abnormalities. Infections could be a trigger of the inflammation. The main aim of this study was to describe the presence of infections in children with KD, and to analyse the clinical characteristics and the presence of coronary abnormalities in these cases. PATIENTS AND METHODS: A retrospective study was performed within the Kawasaki Disease network (KAWA-RACE (2011-2016). An analysis was performed that included patients with positive microbiological findings (PMF) during the acute phase, as well as those with a previous recent infection (PRI) during the 4 weeks preceding KD diagnosis. RESULTS: The study included a total of 621 children with KD, with PMF being found in 101 (16.3%) patients, and a PRI in 107 (17.2%). Significantly less echocardiographic abnormalities were found in the group with a PRI, when compared to those without a PRI (23 vs. 35%, P = .01) and also a lower proportion of overall coronary artery lesions (16 vs. 25%, P = .054). No significant differences were found in the proportion of aneurysms in either of these groups (PRI or PMF) when compared to those without infection. CONCLUSIONS: In the present study, no differences were found in the incidence of coronary aneurysms in either of the groups, with or without PRI or PMF. Therefore, if KD is suspected, appropriate treatment should be started despite having a confirmed infection.

INTRODUCCIÓN: La enfermedad de Kawasaki (EK) es una vasculitis multisistémica asociada a lesiones en las arterias coronarias. Las infecciones podrían ser un desencadenante de la inflamación. Nuestro objetivo fue describir la presencia de infecciones en los niños con EK y analizar las características clínicas y la presencia de alteraciones coronarias en estos casos. PACIENTES Y MÉTODOS: Análisis retrospectivo de los pacientes incluidos en la red KAWA-RACE entre 2011 y 2016. Se estudió tanto a los pacientes que tuvieron una identificación microbiológica confirmada (IMC) en el periodo agudo como a los que presentaron antecedente de infección previa reciente (IPR) las 4 semanas anteriores. RESULTADOS: Se incluyó a un total de 621 niños, de los cuales 101 (16,3%) tuvieron una IMC y 107 (17,2%) una IPR. Encontramos una significativa menor afectación ecocardiográfica en el grupo de IPR respecto a los niños sin infección previa (23 vs. 35%; p 0,01), con menor proporción no significativa de las alteraciones coronarias globales (16 vs. 25%; p 0,054). Sin embargo, no se detectaron diferencias en la proporción de aneurismas en ninguno de los 2 grupos (IMC o IPR) respecto al resto de los pacientes sin infecciones asociadas. CONCLUSIONES: En nuestro estudio no encontramos diferencias en la incidencia de aneurismas coronarios en niños con y sin IMC o IPR, por lo que ante la sospecha de EK debe iniciarse siempre tratamiento, aunque se tenga infección confirmada microbiológicamente.

Tuberculosis in pediatric patients treated with anti-TNFα drugs: a cohort study.

BACKGROUND: Adult patients receiving anti-TNFα drugs are at increased risk of tuberculosis (TB), but studies in pediatric populations are limited, and the best strategy for latent tuberculosis infection (LTBI) screening in this population remains controversial. We describe the prevalence of LTBI prior to anti-TNFα therapy and the long-term follow-up after biological treatment initiation in a cohort of children and adolescents. METHODS: Cohort observational study in children and adolescents receiving anti-TNFα agents in a tertiary-care pediatric hospital. LTBI was ruled out prior to the implementation of anti-TNFα drugs by tuberculin skin test (TST), and, from March 2012 on, QuantiFERON Gold-In Tube test (QTF-G). During anti-TNFα treatment, patients were evaluated every 6 months for TB with history and physical examination. TST/QTF-G were not repeated unless signs or symptoms consistent with TB arose or there was proven TB contact. RESULTS: The final cohort consisted of 221 patients (56.1% female; 261 treatments), of whom 51.7%/30.0%/17.3% were treated with etanercept/adalimumab/infliximab, respectively, for a variety of rheumatic diseases (75.6%), inflammatory bowel disease (20.8%), and inflammatory eye diseases (3.6%). The median (IQR) age at diagnosis of the primary condition was 6.8 years (2.7-11.0) and the duration of the disease before implementing the anti-TNFα agent was 1.8 years (0.6-4.2). LTBI was diagnosed in 3 adolescent girls (prevalence rate: 1.4%; 95% CI: 0.4-4.2) affected with juvenile idiopathic arthritis: TST tested positive in only 1, while QTF-G was positive in all cases (including 2 patients already on etanercept). They all received antiTB chemoprophylaxis and were later (re)treated with etanercept for 24-29 months, without incidences. No incident cases of TB disease were observed during the follow-up period under anti-TNFα treatment of 641 patients-year, with a median (IQR) time per patient of 2.3 years (1.4-4.3). CONCLUSIONS: In our study, the prevalence of LTBI (1.4%) was similar to that reported in population screening studies in Spain; no incident cases of TB disease were observed. In low-burden TB settings, initial screening for TB in children prior to anti-TNFα treatment should include both TST and an IGRA test, but systematic repetition of LTBI immunodiagnostic tests seems unnecessary in the absence of symptoms or known TB contact.

Artritis idiopàtica juvenil. Revisió i nous conceptes / Artritis idiopática juvenil. Revisión y nuevos conceptos / Juvenile idiopathic arthritis. Review and new concepts

L'artritis idiopàtica juvenil és la malaltia reumàtica més freqüent en la infància. Representa un grup heterogeni que inclou diferents formes de presentació d'artritis de causa desconeguda en pacients menors de 16 anys. L'etiopatogènia no és gaire coneguda, però es postula que té lloc com a conseqüència d'un estímul desconegut sobre un individu genèticament predisposat. L'aparició de nous tractaments els darrers anys ha significat un gran avenç en el tracta-ment, ja que s'han aconseguit grans millores en el pronòs-tic i la qualitat de vida. És necessari que tots els pediatres coneguin les característiques més importants de la malaltia i dels tractaments utilitzats, per tal que puguin participar de manera coordinada amb l'equip de reumatologia pe-diàtrica en l'atenció d'aquests pacients

La artritis idiopática juvenil es la enfermedad reumática más frecuente en la infancia. Representa un grupo heterogéneo que incluye diferentes formas de presentación de artritis de causa desconocida en pacientes menores de 16 años. La etiopatogenia no es muy conocida, pero se postula se desarrolla consecuencia de un estímulo desconocido sobre un individuo genéticamente predispuesto. La aparición de nuevos tratamientos en los últimos años ha significado un gran avance en el tratamiento, ya que se han logrado grandes mejoras en el pronóstico y la calidad de vida. Es necesario que todos los pediatras conozcan las características más importantes de la enfermedad y los tratamientos utilizados, para que puedan participar de manera coordinada con el equipo de reumatología pediátrica en la atención de estos pacientes (AU)

Juvenile idiopathic arthritis is the most common rheumatic disease in childhood. It represents a diverse group that includes different forms of presentation of arthritis of unknown cause in patients under 16 years. The pathogenesis is not very well known, but it is postulated that it develops as a result of unknown stimuli on a genetically predisposed individual. The emergence of new treatments in recent years has meant a breakthrough in treatment, since they have made great improvements in the prognosis and quality of life. It is necessary that all pediatricians know the most important characteristics of the disease, so they can participate in a coordinated manner with the paediatric rheumatology team, in the care of these patients (AU)

Dermatomiositis de comienzo precoz: a propósito de un caso / Early-onset juvenile dermatomyositis

Introducción. La dermatomiositis es una vasculopatía sistémica, de origen autoinmune, que afecta sobre todo a músculo y piel. Su incidencia es de 0,2/100.000. El síntoma más frecuente es la debilidad de la musculatura proximal y la aparición del exantema típico de esta enfermedad. El diagnóstico se basa en el cumplimiento de los criterios de Bohan y Peter (1975). El tratamiento de primera línea son los corticoides. El pronóstico en las formas agudas y tratadas suele ser favorable en el 80% de los casos, con remisión de la sintomatología a los 2 años. Puede haber recidivas. Caso clínico. Presentamos un paciente varón de 2 años y medio de edad con pérdida de fuerza muscular progresiva y dolor en el área Dermatomiositis juvenil d’inici precoç Alicia Mainou-Pintó 1, Carlos Mainou-Cid 1, Fernando Plaza-Martín 1, Joan Ros-Viladons 2, Jordi Antón-López 2 1 Unitat de Pediatria. EAP Sarrià/Vallvidrera/Les Planes. Barcelona. 2 Unitat de Reumatologia Pediàtrica. Servei de Pediatria. Hospital Sant Joan de Déu. Universitat de Barcelona. Esplugues de Llobregat (Barcelona) proximal de las extremidades inferiores, de 3 semanas de evolución. En los últimos 15 días le aparece una erupción en cara y manos. Como pruebas complementarias destacan: analítica sanguínea con elevación de ALT, AST, LDH, CPK y aldolasa, electromiograma mostrando un patrón miopático, resonancia nuclear magnética de cintura escapular con edema muscular, y biopsia muscular normal. Tras el tratamiento con prednisona, cloroquina, omeprazol y suplementos de calcio y vitamina D su evolución es favorable, y recupera paulatinamente todas las habilidades musculares perdidas. Comentarios. Se presenta un caso clínico que, aunque es típico en cuanto a la forma de presentación y la sintomatología, no lo es tanto por la edad de su comienzo. La dermatomiositis suele ser una enfermedad de diagnóstico hospitalario, aunque, conociendo bien las peculiaridades de su sintomatología, su sospecha y confirmación puede llegar del pediatra de atención primaria, como en el caso publicado(AU)

Introduction. Dermatomyositis is a systemic vasculopathy of autoimmune origin that affects especially muscle and skin. Its incidence is 0.2/100,000. The most frequent symptom is a progressive proximal muscle weakness and a typical skin rash. The diagnosis is based on the Bohan and Peter criteria (1975). The first line of treatment is with steroids. The prognosis of the acute and treated forms is favourable in 80% of patients with remission in 2 years, although there is risk of recurrence. Clinical observation. A 2.5 year-old boy presented with a 3-week history of progressive loss of muscle strength and pain in the proximal the lower limbs. Two weeks prior to presentation, a rash developed on his hands and face. Diagnostic work-up showed elevated ALT, AST, LDH, CPK and aldolase, abnormal electromyography with myopathic pattern, magnetic resonance of scapular area with muscle edema, and normal muscle biopsy. He was treated with prednisone, chloroquine, omeprazole, calcium supplements and vitamin D, with good evolution and progressive recovery of muscular strength. Commentary. Although this case presented with typical symptoms, of dermatomyositis, the young age of the patient is unusual. Dermatomyositis is usually diagnosed in the hospital setting; however, as highlighted by this case, awareness of the disease and its clinical presentation may facilitate its diagnosis and treatment by the primary care pediatrician(AU)