The HyperPed-COVID international registry: Impact of age of onset, disease presentation and geographical distribution on the final outcome of MIS-C.

OBJECTIVES: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome. STUDY DESIGN: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1-4, 5-11, 12-16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified. RESULTS: Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes. CONCLUSIONS: The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities.

Monitoring of Adverse Events and Safety in Autoinflammatory Diseases: Real-Life Data from the Eurofever Registry.

OBJECTIVES: The study is aimed to evaluate the impact of safety events in the Eurofever registry for Autoinflammatory diseases. METHODS: This was a retrospective and longitudinal observational multicentre study. Data were retrieved from the international registry Eurofever, starting patients' enrolment since 2009. All moderate, severe, or very severe AEs reported by treating physician in Eurofever were analyzed regardless of a possible suspected causal relationship to any therapies and according to the latest release of the Medical Dictionary for Regulatory Activities. RESULTS: Complete information on safety were available in 2464 patients enrolled in the registry. In 1499 of them retrospective data encompassing the period from disease onset to enrolment were available, whereas 965 consecutive patients entered in the longitudinal part of the study. A total of 479 AEs have been reported in 275 patients. Eighty-two AEs were reported as serious and 99 were drug-related according to the physicians. Infections or infestations (94; 19.6%), gastrointestinal disorders (66; 13.8%), nervous system disorders (41; 8.6%) and systemic disorders or administration site reactions (35; 7.3%) were the most frequent reported events. The highest absolute number of drug-related AEs were related to biologic DMARDs (40/99 reports, 40,4%) and colchicine (31/99 reports, 31.3%). CONCLUSIONS: Present study shows the importance of a longitudinal and homogeneous registration of the AEs in rare conditions, with a particular focus on the safety profile of the treatments used in these conditions.

Thrombotic manifestations in pediatric Behcet syndrome: A multicenter comparative study from the EUROFEVER registry.

INTRODUCTION: Vascular events account for a considerable burden of morbidity and mortality in Behçet syndrome (BS). Thrombosis occurs in 1.8-21 % pediatric BS patients, even if the real prevalence is still largely unknown. OBJECTIVES: To report clinical features and outcomes of pediatric BS patients with thrombosis and to compare the demographic and clinical characteristics of BS patients with and without thrombosis. METHODS: Retrospective data collection of BS patients with thrombosis (T+) included in the EUROFEVER registry. BS patients without thrombosis (T-), belonging to the same rheumatology units, were matched in a 2:1 ratio. RESULTS: 37 T+ were compared to 74 T- patients. At onset, ICBD criteria fulfillment was higher in the T- group (p = 0.015). Caucasian patients were more often T-, Turkish patients were more frequent in T+ group (p = 0.002). At onset, pustulosis was most frequently observed in the T- (p < 0.001) as well as gastrointestinal symptoms (p < 0.001) and ocular involvement (p = 0.022). Neurological symptoms were more often described in T+ (p = 0.034). As for T+, thrombosis was reported at BS presentation in 8/37 (21.6 %). For the T + e patients who developed thrombosis later, oral aphthosis (p = 0.003), genital aphthosis (p = 0.014) were more frequently observed at BS onset, while pustulosis (p = 0.005) and fever (p = 0.043) coexisted with thrombosis. Thrombosis was mainly venous (26/37,70.3 %), involving the cerebral sinuses (21/37, 56.8 %). After thrombosis, 35/37 (94.6 %) T+ patients received an immunomodulatory treatment compared with 16/29 (55.2 %) pre-thrombosis. A recurrence was reported in 6/31(19.4 %). CONCLUSION: Thrombosis was reported at BS presentation in one fifth of cases. Pustolosis and fever were more frequently concomitant to thrombosis. Sinus veins were the most frequent site.

Real-World Health Care Outcomes and Costs Among Patients With Juvenile Idiopathic Arthritis in Spain.

Background: Juvenile idiopathic arthritis (JIA) is the most frequent chronic rheumatic disease in children. If inflammation is not adequately treated, joint damage, long-term disability, and active disease during adulthood can occur. Identifying and implementing early and adequate therapy are critical for improving clinical outcomes. The burden of JIA on affected children, their families, and the healthcare system in Spain has not been adequately assessed. The greatest contribution to direct costs is medication, but other expenses contribute to the consumption of resources, negatively impacting healthcare cost and the economic conditions of affected families. Objective: To assess the direct healthcare, indirect resource utilization, and associated cost of moderate-to-severe JIA in children in routine clinical practice in Spain. Methods: Children were enrolled in this 24-month observational, multicentric, cross-sectional, retrospective study (N = 107) if they had been treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), had participated in a previous study (ITACA), and continued to be followed up at pediatric rheumatology units at 3 tertiary Spanish hospitals. Direct costs included medication, specialist and primary care visits, hospitalizations, emergency visits or consultations, surgeries, physiotherapy, and tests. Indirect costs included hospital travel expenses and loss of caregiver working hours. Unitary costs were obtained from official sources (€, 2020). Results: Overall, children had inactive disease/low disease activity according to JADAS-71 score and very low functional disability as measured by Childhood Health Assessment Questionnaire score. Up to 94.4% of children received treatment, mainly with bDMARDs as monotherapy (84.5%). Among anti-TNFα treatments, adalimumab (47.4%) and etanercept (40.2%) were used in similar proportions. Annual mean (SD) total JIA cost was €7516.40 (€5627.30). Average cost of pharmacological treatment was €3021.80 (€3956.20), mainly due to biologic therapy €2789.00 (€3399.80). Direct annual cost (excluding treatments) was €3654.60 (€3899.00). Indirect JIA cost per family was €747.20 (€1452.80). Conclusion: JIA causes significant costs to the Spanish healthcare system and affected families. Public costs are partly due to the high cost of biologic treatments, which nevertheless remain an effective long-term treatment, maintaining inactive disease/low disease activity state; a very low functional disability score; and a good quality of life.

TNFRSF1A-pR92Q variant identifies a subset of patients more similar to systemic undifferentiated recurrent fever than TNF receptor-associated periodic syndrome.

OBJECTIVES: To describe the clinical phenotype and response to treatment of autoinflammatory disease (AID) patients with the TNFRSF1A-pR92Q variant compared to patients with tumour necrosis factor receptor-associated periodic syndrome (TRAPS) due to pathogenic mutations in the same gene and patients diagnosed with other recurrent fever syndromes including periodic fever with aphthous stomatitis, pharyngitis, and adenitis (PFAPA) and syndrome of undefined recurrent fever (SURF). METHODS: Clinical data from pR92Q variant associated AID, classical TRAPS, PFAPA and SURF patients were obtained from the Eurofever registry, an international, multicentre registry enabling retrospective collection of data on AID patients. RESULTS: In this study, 361 patients were enrolled, including 77 pR92Q variant, 72 classical TRAPS, 152 PFAPA and 60 SURF patients. pR92Q carriers had an older age of disease onset than classical TRAPS and PFAPA patients. Compared to pR92Q variant patients, classical TRAPS patients had more relatives affected and were more likely to have migratory rash and AA-amyloidosis. Despite several differences in disease characteristics and symptoms between pR92Q variant and PFAPA patients, part of the pR92Q variant patients experienced PFAPA-like symptoms. pR92Q variant and SURF patients showed a comparable clinical phenotype. No major differences were observed in response to treatment between the four patient groups. Steroids were most often prescribed and effective in the majority of patients. CONCLUSIONS: Patients with AID carrying the TNFRSF1A-pR92Q variant behave more like SURF patients and differ from patients diagnosed with classical TRAPS and PFAPA in clinical phenotype. Hence, they should no longer be diagnosed as having TRAPS and management should differ accordingly.

Caracterización del microbioma nasofaríngeo en pacientes con enfermedad de Kawasaki / Characterization of the nasopharyngeal microbiome in patients with Kawasaki disease

Introducción: La etiología de la enfermedad de Kawasaki (EK) sigue siendo desconocida. Varios estudios han relacionado el microbioma humano con algunas enfermedades. Sin embargo, los estudios sobre el microbioma respiratorio en EK son limitados. Este estudio intenta profundizar en las causas y procesos que predisponen al desarrollo de la EK. Métodos: Estudio de casos y controles en el que se compara el microbioma respiratorio de pacientes con EK con el de niños sanos. La región V3-V4 del gen bacteriano del ARNr 16S y 16 virus respiratorios se analizaron mediante reacción en cadena de la polimerasa en tiempo real. Se utilizó la base de datos RDP (Ribosomal Database Project) versión 11.5 (asignación taxonómica). Resultados: Se incluyeron 11casos y 11 controles emparejados por edad, sexo y estacionalidad. Uno de los casos fue descartado por mala calidad de la muestra. El estudio final se realizó a 10 casos y 10 controles. En el grupo de casos se encontraron Haemophilus, Moraxella, Streptococcus y Corynebacterium (27,62%, 19,71%, 25,28% y 11,86%, respectivamente). En el grupo control, Haemophilus, Streptococcus, Moraxella y Dolosigranulum (38,59%, 23,71%, 16,08 y 8,93%, respectivamente). Corynebacterium mostró una mayor abundancia en pacientes con EK (11,86% vs. 1,55%; p = 0,004). Conclusiones: Hasta donde sabemos, este es el primer estudio que ha encontrado diferencias en la composición del microbioma respiratorio entre pacientes con EK y controles sanos. Corynebacterium spp. presentó una mayor abundancia en el grupo de EK. Este estudio muestra diferencias en el microbioma entre pacientes y controles, lo que sugiere un papel facilitador del microbioma en el desarrollo de la EK. (AU)

Introduction: The aetiology of Kawasaki disease (KD) remains unknown. Several studies have linked the human microbiome with some diseases. However, there are limited studies on the role of the respiratory microbiome in KD. The aim of our study was to make a more thorough analysis of the causes and processes that increase the susceptibility to KD. Methods: Case-control study comparing the respiratory microbiome of KD patients with that of healthy children. The V3–V4 region of the 16S rRNA bacterial gene and 16 respiratory viruses were analysed by real-time polimerase-chain reaction. We used the Ribosomal Database Project (RDP) version 11.5 (taxonomic assignment). Results: The initial sample included 11 cases and 11 controls matched for age, sex and seasonality. One of the cases was excluded to poor sample quality. The final analysis included 10 cases and 10 controls. In the case group, the analysis detected Haemophilus, Moraxella, Streptococcus and Corynebacterium species (27.62%, 19.71%, 25.28%, 11.86%, respectively). In the control group, it found Haemophilus, Streptococcus, Moraxella, and Dolosigranulum species (38.59%, 23.71%, 16.08, 8.93%, respectively). We found a higher relative abundance of Corynebacterium in patients with KD (11.86% vs. 1.55%; P=.004). Conclusions: To our knowledge, this is the first study that has found differences in the composition of the respiratory microbiome between patients with KD and healthy controls. The relative abundance of Corynebacterium spp. was greater in the KD group. This study shows differences in the microbiome between cases and controls, which suggests that the microbiome may play a role in facilitating the development of KD. (AU)

Characterization of the nasopharyngeal microbiome in patients with Kawasaki disease.

INTRODUCTION: The aetiology of Kawasaki disease (KD) remains unknown. Several studies have linked the human microbiome with some diseases. However, there are limited studies on the role of the respiratory microbiome in KD. The aim of our study was to make a more thorough analysis of the causes and processes that increase the susceptibility to KD. METHODS: Case-control study comparing the respiratory microbiome of KD patients with that of healthy children. The V3-V4 region of the 16S rRNA bacterial gene and 16 respiratory viruses were analysed by real-time polimerase-chain reaction. We used the Ribosomal Database Project (RDP) version 11.5 (taxonomic assignment). RESULTS: The initial sample included 11 cases and 11 controls matched for age, sex and seasonality. One of the cases was excluded to poor sample quality. The final analysis included 10 cases and 10 controls. In the case group, the analysis detected Haemophilus, Moraxella, Streptococcus and Corynebacterium species (27.62%, 19.71%, 25.28%, 11.86%, respectively). In the control group, it found Haemophilus, Streptococcus, Moraxella, and Dolosigranulum species (38.59%, 23.71%, 16.08, 8.93%, respectively). We found a higher relative abundance of Corynebacterium in patients with KD (11.86% vs. 1.55%; P = 0.004). CONCLUSIONS: To our knowledge, this is the first study that has found differences in the composition of the respiratory microbiome between patients with KD and healthy controls. The relative abundance of Corynebacterium spp. was greater in the KD group. This study shows differences in the microbiome between cases and controls, which suggests that the microbiome may play a role in facilitating the development of KD.

Risk scores for Kawasaki disease, a management tool developed by the KAWA-RACE cohort.

INTRODUCTION/OBJECTIVES: Asian scores developed to predict unresponsiveness to intravenous immunoglobulin (IVIG) or development of coronary artery aneurysms (CAA) in patients with Kawasaki disease (KD) are not appropriate in Western populations. The purpose of this study is to develop 2 scores, to predict unresponsiveness to IVIG and development of CAA, appropriate for Spanish population. METHOD: Data of 625 Spanish children with KD collected retrospectively (2011-2016) were used to identify variables to develop the 2 scores of interest: unresponsiveness to IVIG and development of CAA. A statistical model selected best variables to create the scores, and scores were validated with data from 98 patients collected prospectively. RESULTS: From 625 patients of the retrospective cohort, final analysis was performed in 439 subjects: 37 developed CAA, and 212 were unresponsive to IVIG. For the score to predict CAA, a cutoff ≥ 8 was considered for high risk, considering a score system with a different weight for each of the eight variables. External validation showed a sensitivity of 22% and a specificity of 75%. The score to predict unresponsiveness to IVIG established a cutoff ≥ 8 for high risk, considering a score system with a different weight for each of the nine variables. External validation showed a sensitivity of 78% and a specificity of 50%. CONCLUSIONS: Two risk scores for KD were developed from Spanish population, to predict development of CAA and unresponsiveness to IVIG; validation in other cohorts could help to implement these tools in the management of KD in other Western populations.

Giant coronary aneurysm in a 6-week-old infant, an unusual finding?

Kawasaki disease (KD) is a self-limited vasculitis with significant morbidity and even mortality if not treated early. The diagnosis and timely treatment in children younger than 3 months is challenging as most of them have an incomplete or atypical presentation. Coronary artery abnormalities are frequent in this type of patients. We present a 6-week-old female infant with KD who developed a giant coronary aneurysm. An early diagnosis and promptly treatment, as well as the echocardiographic and multimodality follow-up allowed us to improve our clinical approach and management.

Kawasaki disease in children younger than 6 months of age: characteristics of a Spanish cohort.

A retrospective study that compared children younger than 6 months versus older children of a Spanish cohort of patients diagnosed with Kawasaki disease between 2011 and 2016 (Kawa-Race study). From the 598 patients recruited, 42 patients were younger than 6 months (7%) and presented more frequently with an incomplete diagnosis of Kawasaki disease (52.4 vs 27.9%, p = 0.001). Cardiac abnormalities detected by echocardiography were more common in younger patients (52.4 vs 30%, p = 0.002). These younger patients presented with a higher proportion of coronary aneurysms as well (19 vs 8.6%, p < 0.001). Shock at diagnosis (9.5 vs 1.9%, p = 0.016) and admission to intensive care units (17.7 vs 4.1%, p = 0.003) were more frequent in patients younger than 6 months. There were no statistically significant differences in relation to infections, non-response to IVIG, or mid- or long-term outcomes.Conclusion: Data of the Spanish cohort are consistent with other American and Asian studies, although Spanish children younger than 6 months had a lower rate of non-response to IVIG and better clinical outcomes. A high index of suspicion should be considered for this population due to a higher risk of coronary abnormalities, presentation of shock, and admission to the intensive care unit. What is Known: •Children below 6 months of age with Kawasaki disease (KD) have different features compared to older. •Younger patients usually have an incomplete form of KD and coronary artery abnormalities. What is New: •Younger than 6 months with KD presented with shock and required admission to PICU more frequently compared to older. •Infections play a similar role in KD despite the age of the patients.

Similarities and differences between the immunopathogenesis of COVID-19-related pediatric multisystem inflammatory syndrome and Kawasaki disease.

Multisystem inflammatory syndrome associated with the SARS-CoV-2 pandemic has recently been described in children (MIS-C), partially overlapping with Kawasaki disease (KD). We hypothesized that (a) MIS-C and prepandemic KD cytokine profiles may be unique and justify the clinical differences observed, and (b) SARS-CoV-2-specific immune complexes (ICs) may explain the immunopathology of MIS-C. Seventy-four children were included: 14 with MIS-C, 9 patients positive for SARS-CoV-2 by PCR without MIS-C (COVID), 14 with prepandemic KD, and 37 healthy controls (HCs). Thirty-four circulating cytokines were quantified in pretreatment serum or plasma samples and the presence of circulating SARS-CoV-2 ICs was evaluated in MIS-C patients. Compared with HCs, the MIS-C and KD groups showed most cytokines to be significantly elevated, with IFN-γ-induced response markers (including IFN-γ, IL-18, and IP-10) and inflammatory monocyte activation markers (including MCP-1, IL-1α, and IL-1RA) being the main triggers of inflammation. In linear discriminant analysis, MIS-C and KD profiles overlapped; however, a subgroup of MIS-C patients (MIS-Cplus) differentiated from the remaining MIS-C patients in IFN-γ, IL-18, GM-CSF, RANTES, IP-10, IL-1α, and SDF-1 and incipient signs of macrophage activation syndrome. Circulating SARS-CoV-2 ICs were not detected in MIS-C patients. Our findings suggest a major role for IFN-γ in the pathogenesis of MIS-C, which may be relevant for therapeutic management.

Tromboembolisme pulmonar com a presentació d'una síndrome antifosfolípid / Trombolismo pulmonar como presentación de un síndrome antifosfolípido / Pulmonary thomboembolism as a presenting sign of antiphospholipid syndrome

INTRODUCCIÓ: Els fenòmens tromboembòlics són poc freqüents en l'edat pediàtrica. La majoria de casos són secundaris a un factor de risc identificable. Quan són espontanis, recurrents, de localització inusual o de gravetat desproporcionada, requereixen estudi de trombofília. CAS CLÍNIC: Pacient de 14 anys, home, amb antecedent de trombosi venosa profunda I anticoagulant lúpic positiu, que consulta a urgències per episodi de pèrdua de consciència autolimitada. Presenta afectació de l'estat general, pal·lidesa I taquipnea. Saturació d'oxigen 87%, hipotensió (85/45 mmHg), taquicàrdia (155 ppm) I reompliment capil·lar allargat. En l'analítica sanguínia destaca dímer-D 7.224 ng/mL I troponina T 243 ng/L. Electrocardiograma amb descens difús del segment ST I ones T precordials negatives I radiografia de tòrax normal. Davant d'un quadre compatible amb tromboembolisme pulmonar (TEP) en pacient amb factors de risc de trombosi es completa l'estudi amb angio-TC, que mostra TEP massiu. Ingressa a unitat de cures intensives pediàtriques per tractament fibrinolític I posteriorment anticoagulació. En l'estudi de trombofilia es comprova persistència de l'anticoagulant lúpic positiu, que al costat de trombosi de repetició comporta el diagnòstic de síndrome antifosfolípid (SAF). COMENTARIS: La SAF és un estat d'hipercoagulabilitat d'origen autoimmunitari caracteritzat per la presència de trombosis, complicacions obstètriques I títols elevats d'anticossos antifosfolípids. La importància del seu diagnòstic precoç és la instauració de tractament anticoagulant indefinit per prevenir nous episodis trombòtics i, per tant, millorar el pronòstic

INTRODUCCIÓN: Los fenómenos tromboembólicos son poco frecuentes en la edad pediátrica. En la mayoría de casos son secundarios a un factor de riesgo identificable. Cuando son espontáneos, recurrentes, de localización inusual o de gravedad desproporcionada, requieren estudio de trombofilia. CASO CLÍNICO: Paciente de 14 años, varón, con antecedente de trombosis venosa profunda y anticoagulante lúpico positivo, que acude a urgencias tras episodio de pérdida de conciencia autolimitada. Presenta afectación del estado general, palidez y taquipnea. Saturación de oxígeno 87%, hipotensión (85/45 mmHg), taquicardia (155 lpm) y relleno capilar prolongado. En la analítica sanguínea destaca dímero-D 7.224 ng/mL y troponina T 243 ng/L. Electrocardiograma con descenso difuso del segmento ST y ondas T precordiales negativas y radiografía de tórax normal. Ante el cuadro compatible con tromboembolismo pulmonar (TEP) en paciente con factores de riesgo de trombosis, se completa el estudio con angio-TC, que muestra TEP masivo. Ingresa en unidad de cuidados intensivos pediátricos para tratamiento fibrinolítico y posteriormente anticoagulación. En el estudio de trombofilia se comprueba la persistencia del anticoagulante lúpico positivo, que junto a trombosis de repetición supone el diagnóstico de síndrome antifos-folípido (SAF). COMENTARIOS: El SAF es un estado de hipercoagulabilidad de origen autoinmune caracterizado por la presencia de trombosis, complicaciones obstétricas y títulos elevados de anticuerpos antifosfolípido. La importancia de su diagnóstico precoz es la instauración de tratamiento anticoagulante indefinido y así prevenir nuevos episodios trombóticos y, por tanto, mejorar el pronóstico

INTRODUCTION: Thromboembolic phenomena are rare in the pediatric age. In most cases they are secondary to an identifiable risk factor. When they are spontaneous, recurrent, in unusual location or of disproportionate severity, they require a work-up for thrombophilia. CASE REPORT: A 14-year-old boy with history of deep vein thrombosis and positive lupus anticoagulant was admitted in the emergency department after an episode of self-limited loss of consciousness. He presented altered general appearance, pallor and tachypnea. Oxygen saturation was 87%, and had hypotension (85/45 mmHg), tachycardia (155 ppm) and prolonged capillary refill. Laboratory evaluation was remarkable for D-Dimer 7224 ng/mL and Troponin T 243 ng/L. Electrocardiogram showed diffuse decline of the ST segment and negative precordial T waves, and chest radiography was normal. Due to the clinical findings compatible with pulmonary thromboembolism (PE) in a patient with risk factors for thrombosis, a CT-angiography was performed and showed massive PE. The patient was admitted to the pediatric intensive care unit for fibrinolytic treatment and subsequently anticoagulation. In the thrombophilia study, persistence of the positive lupus anticoagulant was confirmed, which, together with repeated thrombosis, suggested the diagnosis of antiphospholipid syndrome (APS). COMMENTS: APS is a state of hypercoagulability of autoimmune origin characterized by the presence of thrombosis, obstetric complications and high titers of antiphospholipid antibodies. The importance of early diagnosis is the establishment of indefinite anticoagulant treatment to prevent new thrombotic episodes and therefore improve prognosis

Prevalence and Clinical Characteristics of SARS-CoV-2 Confirmed and Negative Kawasaki Disease Patients During the Pandemic in Spain.

Introduction: COVID-19 has a less severe course in children. In April 2020, some children presented with signs of multisystem inflammation with clinical signs overlapping with Kawasaki disease (KD), most of them requiring admission to the pediatric intensive care unit (PICU). This study aimed to describe the prevalence and clinical characteristics of KD SARS-CoV-2 confirmed and negative patients during the pandemic in Spain. Material and Methods: Medical data of KD patients from January 1, 2018 until May 30, 2020 was collected from the KAWA-RACE study group. We compared the KD cases diagnosed during the COVID-19 period (March 1-May 30, 2020) that were either SARS-CoV-2 confirmed (CoV+) or negative (CoV-) to those from the same period during 2018 and 2019 (PreCoV). Results: One hundred and twenty-four cases were collected. There was a significant increase in cases and PICU admissions in 2020 (P-trend = 0.001 and 0.0004, respectively). CoV+ patients were significantly older (7.5 vs. 2.5 yr) and mainly non-Caucasian (64 vs. 29%), had incomplete KD presentation (73 vs. 32%), lower leucocyte (9.5 vs. 15.5 × 109) and platelet count (174 vs. 423 × 109/L), higher inflammatory markers (C-Reactive Protein 18.5vs. 10.9 mg/dl) and terminal segment of the natriuretic atrial peptide (4,766 vs. 505 pg/ml), less aneurysm development (3.8 vs. 11.1%), and more myocardial dysfunction (30.8 vs. 1.6%) than PreCoV patients. Respiratory symptoms were not increased during the COVID-19 period. Conclusion: The KD CoV+ patients mostly meet pediatric inflammatory multisystem syndrome temporally associated with COVID-19/multisystem inflammatory syndrome in children criteria. Whether this is a novel entity or the same disease on different ends of the spectrum is yet to be clarified.

Epidemiological and clinical features of Kawasaki disease in Spain over 5 years and risk factors for aneurysm development. (2011-2016): KAWA-RACE study group.

BACKGROUND: Kawasaki disease (KD) is an acute self-limited systemic vasculitis of unknown etiology affecting mainly children less than 5 years of age. Risk factors for cardiac involvement and resistance to treatment are insufficiently studied in non-Japanese children. OBJECTIVE: This study aimed to investigate the epidemiology, clinical features and risk factors for resistance to treatment and coronary artery lesions (CAL) in KD in Spain. METHODS: Retrospective study (May 2011-June 2016) of all patients less than 16 years of age diagnosed with KD included in KAWA-RACE network (84 Spanish hospitals). RESULTS: A total of 625 cases were analyzed, 63% were males, 79% under 5 year-olds and 16.8% younger than 12 months. On echocardiographic examination CAL were the most frequent findings (23%) being ectasia the most common (12%). Coronary aneurysms were diagnosed in 9.6%, reaching 20% in infants under 12 months (p<0.001). A total of 97% of the patients received intravenous immunoglobulin (IVIG) with a median number of days from fever onset to IVIG administration of 7.2. A second dose was given to 15.7% and steroids to 14.5% patients. Only 1.4% patients received infliximab. No deaths were reported. A multivariate analysis identified anemia, hypoalbuminemia, hyponatremia, higher creatinine and procalcitonin as independent risk factors for treatment failure and length under 103 cm, hemoglobin < 10.2 mg/dL, platelets > 900,000 cells/mm3, maximum temperature < 39.5°C, total duration of fever > 10 days and fever before treatment ≥ 8 days as independent risk factors for developing coronary aneurysms. CONCLUSIONS: In our population, children under 12 months develop coronary aneurysms more frequently and children with KD with anemia and leukocytosis have high risk of cardiac involvement. Adding steroids early should be considered in those patients, especially if the treatment is not started before 8 days of fever. A score applicable to non-Japanese children able to predict the risk of aneurysm development and IVIG resistance is necessary.

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

Consenso nacional sobre diagnóstico, tratamiento y seguimiento cardiológico de la enfermedad de Kawasaki / National consensus on the cardiological treatment and follow-up of Kawasaki disease

No disponible

Canakinumab for the treatment of hyperimmunoglobulin D syndrome.

INTRODUCTION: Mevalonate Kinase Deficiency (MKD) is a rare monogenic autoinflammatory disorder (AID) with autosomal recessive inheritance caused by mutations in the MVK gene. It includes hyperimmunoglobulinemia D syndrome (HIDS) and mevalonic aciduria (a severe form). Patients have recurrent inflammatory attacks with high fever, gastrointestinal symptoms, lymphadenopathy, splenomegaly, arthralgia, rash, pharyngitis, aphtosis and constitutional complaints. Heightened understanding of molecular mechanisms in monogenic autoinflammatory disorders has provided tools for targeted treatment. HIDS is an extrinsic inflammasomopathy and is responsive to anti-IL-1 therapies, such as the recombinant IL-1-receptor antagonist anakinra, the monoclonal antibody against IL-1b canakinumab (CAN), and the recombinant IL-1R fusion protein rilonacept. Areas covered: CAN is a human monoclonal anti-IL-1ß antibody that binds with high affinity and neutralizes the activity of IL-1 ß. Both observational registries and some case reports have seemed promising in the efficacy of CAN in the HIDS treatment. Two clinical trials have corroborated CAN as an effective and safe drug. Expert commentary: CAN is effective and safe for the treatment of HIDS patients. Some data suggest these patients may need higher dosage or shorter dosing interval than other AIDs, to achieve and maintain complete clinical and laboratory response. Reported adverse events were mild, most often non-complicated infections.