Clinical features of Kawasaki disease complicated by macrophage activation syndrome: an analysis of 27 cases / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical manifestations and laboratory examination results of children with Kawasaki disease complicated by macrophage activation syndrome (KD-MAS), and to provide a basis for identifying early warning indicators for the early diagnosis and treatment of KD-MAS.@*METHODS@#A retrospective study was performed on 27 children with KD-MAS (KD-MAS group) and 110 children with KD (KD group) who were admitted to Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2014 to January 2022. Clinical and laboratory data were compared between the two groups. The receiver operating characteristic (ROC) curve was used to investigate the value of laboratory markers with statistical significance in the diagnosis of KD-MAS.@*RESULTS@#Compared with the KD group, the KD-MAS group had significantly higher incidence rates of hepatomegaly, splenomegaly, incomplete KD, no response to intravenous immunoglobulin, coronary artery damage, multiple organ damage, and KD recurrence, as well as a significantly longer length of hospital stay (P<0.05). Compared with the KD group, the KD-MAS group had significantly lower levels of white blood cell count, absolute neutrophil count, hemoglobin, platelet count (PLT), erythrocyte sedimentation rate, serum albumin, serum sodium, prealbumin, and fibrinogen (FIB), a significantly lower incidence rate of non-exudative conjunctiva, and significantly higher levels of C-reactive protein, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase (LDH), and serum ferritin (SF) (P<0.05). The ROC curve analysis showed that SF, PLT, FIB, and LDH had high value in the diagnosis of KD-MAS, with areas under the curve (AUC) of 0.989, 0.966, 0.932, and 0.897, respectively (P<0.001), and optimal cut-off values of 349.95 μg/L, 159×109/L, 3.85 g/L, and 403.50 U/L, respectively. The combination of SF, PLT, FIB, and LDH had a larger AUC than PLT, FIB, and LDH alone in the diagnosis of KD-MAS (P<0.05), but there was no significant difference in the AUC between the combination of SF, PLT, FIB, and LDH and SF alone (P>0.05).@*CONCLUSIONS@#KD-MAS should be considered when children with KD have hepatosplenomegaly, no response to intravenous immunoglobulin, coronary artery damage, and KD recurrence during treatment. SF, PLT, FIB, and LDH are of high value in the diagnosis of KD-MAS, especially SF is of great significance in the diagnosis of KD-MAS.

Precordial pain, leukocytosis and bicytopenia in a teenager with systemic juvenile idiopathic arthritis under immunosuppressive therapy / Dor precordial, leucocitose e bicitopenia em adolescente com artrite idiopática juvenil sistêmica em terapia imunossupressora

ABSTRACT Objective: To highlight the importance of the new classification criteria for the macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis in order to reduce morbidity and mortality outcome related to this disease. Case description: A 12-year-old female patient with diagnosis of systemic juvenile idiopathic arthritis under immunosuppression therapy for two years developed cough, acute precordial chest pain, tachypnea, tachycardia and hypoxemia for two days. Chest tomography showed bilateral laminar pleural effusion with bibasilar consolidation. The electrocardiogram was consistent with acute pericarditis and the echocardiogram showed no abnormalities. Laboratory exams revealed anemia, leukocytosis and increased erythrocyte sedimentation rate, as well as C-reactive protein rate and serum biomarkers indicative of myocardial injury. Systemic infection and/or active systemic juvenile idiopathic arthritis were considered. She was treated with antibiotics and glucocorticoids. However, 10 days later she developed active systemic disease (fever, evanescent rash and myopericarditis with signs of heart failure) associated with macrophage activation syndrome, according to the 2016 Classification Criteria for Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis. She was treated for five days with pulse therapy, using glucocorticoids, immunoglobulin and cyclosporine A, with improvement of all clinical signs and laboratory tests. Comments: Myopericarditis with signs of heart failure associated with MAS is a rare clinical presentation of systemic juvenile idiopathic arthritis. Macrophage activation syndrome occurs mainly during periods of active systemic juvenile idiopathic arthritis and may be triggered by infection. Knowledge about this syndrome is crucial to reduce morbidity and mortality.

RESUMO Objetivo: Destacar a importância do conhecimento sobre os novos critérios de classificação para síndrome de ativação macrofágica (SAM) na artrite idiopática juvenil sistêmica para reduzir a morbidade e mortalidade desse desfecho. Descrição do caso: Adolescente do sexo feminino de 12 anos de idade, em terapia imunossupressora por diagnóstico de artrite idiopática juvenil sistêmica há 2 anos, com quadro de tosse, dor precordial aguda, taquipneia, taquicardia e hipoxemia há 2 dias. A tomografia de tórax evidenciou efusão pleural laminar bilateral com consolidação bibasal. O eletrocardiograma foi compatível com pericardite aguda, e o ecocardiograma foi normal. Os exames laboratoriais revelaram anemia, leucocitose e aumento da velocidade de hemossedimentação, proteína C-reativa e marcadores séricos de lesão miocárdica. Infecção sistêmica e/ou doença sistêmica em atividade foram consideradas. A paciente foi tratada com antibióticos e glicocorticoide. Entretanto, dez dias depois, evoluiu com doença sistêmica em atividade (febre, exantema e miopericardite com insuficiência cardíaca) associada à SAM, de acordo com o 2016 Classification Criteria for Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis, e necessitou de cinco dias de pulsoterapia com glicocorticoide, imunoglobulina e ciclosporina A, com melhora de todos os parâmetros clínicos e laboratoriais. Comentários: A miopericardite com sinais de insuficiência cardíaca associada à SAM é uma apresentação clínica rara da artrite idiopática juvenil sistêmica, que ocorre principalmente em períodos de atividade sistêmica da doença e pode ser deflagrada por infecções. O conhecimento sobre essa síndrome é fundamental para reduzir morbidade e mortalidade desse grave desfecho.

Syndrome d'activation macrophagique secondaire chez l'enfant. Rapport de 5 cas sénégalais

Le Syndrome d'Activation Macrophagique (SAM) est défini comme la traduction clinico-biologique d'une prolifération et d'une activation non-spécifique des macrophages du système réticulo-histiocytaire avec phagocytose des éléments figurés du sang. Nous rapportons 5 cas de SAM secondaires chez des enfants hospitalisés dans le service de pédiatrie de l'hôpital Aristide le Dantec entre août 2015 et avril 2016. Il s'agissait de 3 filles et 2 garçons âgés de 7 ans à 14 ans. Cliniquement, la fièvre, l'altération de l'état général et la splénomégalie étaient constantes. Quatre patients ont présenté des adénopathies et chez 2 patients une hépatomégalie a été retrouvée. Au niveau de l'hémogramme, l'anémie était constante, la thrombopénie et la leuco-neutropénie étaient retrouvées chez 3 patients et le frottis sanguin révélait 36% de blastes chez un patient. L'hémophagocytose médullaire était retrouvée chez tous les patients, l'hyper ferritinémie était constante et chez trois patients une hypertriglycéridémie avec un taux élevé de lactate déshydrogénase (LDH) ont été notés. Le diagnostic était surtout guidé par le médullogramme et basé sur les critères de l'hemophagocytic histiocytosis et les étiologies étaient infectieuses et néoplasiques. Chez trois patients, le SAM était d'origine infectieuse et les germes retrouvés étaient le Streptococcus, l'Escherichia coli et le Mycobacterium tuberculosis alors que les deux autres cas étaient d'origines néoplasiques secondaires à une leucémie aiguë myéloïde et à un lymphome hodgkinien. Le traitement était basé sur l'antibiothérapie (cas 1 et 2), les antituberculeux (cas 3) et la chimiothérapie (cas 4 et 5). L'évolution était favorable chez tous nos patients

Síndrome de ativação macrofágica em paciente com artrite idiopática juvenil sistêmica / Macrophage activation syndrome in a patient with systemic juvenile idiopathic arthritis

A síndrome de ativação macrofágica (SAM) é uma doença rara e potencialmente fatal, normalmente associada às doenças reumáticas crônicas, em especial a artrite idiopática juvenil. É incluída no grupo das formas secundárias de síndrome hemofagocítica, cujas outras causas podem ser as doenças linfoproliferativas e infecções. As manifestações clínicas e laboratoriais mais importantes são a febre não remitente, esplenomegalia, hemorragias, disfunção hepática, citopenias, hipoalbuminemia, hipertrigliceridemia e hiperferritinemia. O tratamento deve ser iniciado rapidamente, e a maioria dos casos responde bem aos corticosteroides e à ciclosporina (CSA). O vírus Epstein-Barr (EBV) é descrito como possível gatilho para muitos casos de SAM, especialmente naqueles em tratamento com bloqueadores do fator de necrose tumoral (TNF). Nos casos refratários ao tratamento convencional, etoposide (VP16) deve ser administrado, em associação com corticosteroides e CSA. Nosso objetivo foi descrever um caso raro de síndrome hematofagocítica provavelmente secundária à infecção pelo vírus Epstein-Barr (EBV), em paciente com artrite idiopática juvenil sistêmica, confirmada pelas manifestações clínicas e laboratoriais típicas, mielograma e sorologia positiva contra o EBV, que atingiu remissão completa após inclusão no protocolo de tratamento HLH-04.

Machrophage activation syndrome (MAS) is a rare and potentially fatal disease, commonly associated with chronic rheumatic diseases, mainly juvenile idiopathic arthritis. It is included in the group of secondary forms of haemophagocytic syndrome, and other causes are lymphoproliferative diseases and infections. Its most important clinical and laboratorial manifestations are non-remitting fever, splenomegaly, bleeding, impairment of liver function, cytopenias, hypoalbuminemia, hypertriglyceridemia, hypofibrinogenemia and hyperferritinemia. The treatment needs to be started quickly, and the majority of cases have a good response with corticosteroids and cyclosporine. The Epstein–Barr virus is described as a possible trigger for many cases of MAS, especially in these patients in treatment with tumor necrosis factor (TNF) blockers. In these refractory cases, etoposide (VP16) should be administered, associated with corticosteroids and cyclosporine. Our objective is to describe a rare case of MAS probably due to EBV infection in a subject with systemiconset juvenile idiopathic arthritis, which achieved complete remission of the disease after therapy guided by 2004-HLH protocol.

Pleuritic chest pain; where should we search for?

Pleuritic pain is not an unusual problem in children. Other concomitant symptoms should be considered for diagnostic approach in a child with pleuritic chest pain. In this report we discuss chest pain in a 6-year-old child with regard to other signs and symptoms. Finally, we found a rare life-threatening complication of juvenile systemic lupus erythematosus [JSLE] in our patient