RESUMEN
OBJECTIVE: To test the hypothesis that first re-treatment with infliximab, compared with intravenous immunoglobulin (IVIG), might improve outcomes in IVIG-resistant Kawasaki disease. STUDY DESIGN: In a two-center retrospective review from January 2000 to March 2008, we compared duration of fever and coronary artery dimensions in patients with IVIG-resistance whose first re-treatment was with IVIG compared with infliximab given for fever ≥38.0°C beyond 36 hours after first IVIG completion. RESULTS: Patients in the IVIG group (n = 86, 2 g/kg) and infliximab group (n = 20, 5 mg/kg) were similar in demographics, days of fever at diagnosis, and baseline coronary artery dimensions. Patients had similar coronary dimensions 6 weeks after diagnosis, both in univariate and multivariate analysis. The infliximab group had fewer days of fever (median 8 days versus10 days, P = .028), and in a multivariate analysis, the infliximab group had 1.2 fewer days of fever (P = .033). Patients who received infliximab had shorter lengths of hospitalization (median 5.5 days versus 6 days, P = .040). Treatment groups did not differ significantly in adverse events (0% versus 2.3%, P = 1.0). CONCLUSIONS: In our retrospective study, patients with IVIG-resistant Kawasaki disease whose first re-treatment was with infliximab, compared with IVIG, had faster resolution of fever and fewer days of hospitalization. Coronary artery outcomes and adverse events were similar; the power of the study was limited.
Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Anticuerpos Monoclonales/efectos adversos , Preescolar , Vasos Coronarios/patología , Dilatación Patológica , Femenino , Hepatomegalia/inducido químicamente , Humanos , Lactante , Infliximab , Tiempo de Internación , Masculino , Retratamiento , Estudios RetrospectivosRESUMEN
Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) patients comprise at least 20% of treated patients and are at high risk for coronary artery abnormalities. If identified early in the course of the disease, such patients may benefit from additional anti-inflammatory therapy. The aim of this study was to compare the transcript abundance between IVIG resistant and -responsive KD patients, to identify biomarkers that might differentiate between these two groups and to generate new targets for therapies in IVIG resistant KD patients. We compared the transcript abundance profiles of whole-blood RNA on Agilent arrays from acute and convalescent KD subjects and age-similar, healthy controls. KD subjects were stratified as IVIG resistant or -responsive based on response to initial IVIG therapy. Transcript abundance was higher for IL-1 pathway genes (IL-1 receptor, interleukin receptor associated kinase, p38 mitogen-activated protein kinase), and MMP-8. These findings point to candidate biomarkers that may predict IVIG resistance in acute KD patients. The results also underscore the importance of the IL-1 pathway as a mediator of inflammation in KD and suggest that IL-1 or its receptor may be reasonable targets for therapy, particularly for IVIG resistant patients.
Asunto(s)
Resistencia a Medicamentos/genética , Perfilación de la Expresión Génica , Inmunoglobulinas Intravenosas/uso terapéutico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/genética , ARN Mensajero/análisis , Transcripción Genética/genética , Antígenos CD/genética , Biomarcadores/sangre , Moléculas de Adhesión Celular/genética , Niño , Preescolar , Complemento C1q/genética , Femenino , Proteínas Ligadas a GPI/genética , Expresión Génica/genética , Humanos , Lactante , Interleucina-1/metabolismo , Quinasas Asociadas a Receptores de Interleucina-1/genética , Masculino , Metaloproteinasa 8 de la Matriz/sangre , Metaloproteinasa 8 de la Matriz/genética , Síndrome Mucocutáneo Linfonodular/sangre , FN-kappa B/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , Receptores Tipo II de Interleucina-1/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas S100/genética , Transducción de Señal/genética , Regulación hacia Arriba/genéticaRESUMEN
BACKGROUND: Acute Kawasaki disease (KD) is difficult to distinguish from other illnesses that involve acute rash or fever, in part because the etiologic agent(s) and pathophysiology remain poorly characterized. As a result, diagnosis and critical therapies may be delayed. METHODS: We used DNA microarrays to identify possible diagnostic features of KD. We compared gene expression patterns in the blood of 23 children with acute KD and 18 age-matched febrile children with 3 illnesses that resemble KD. RESULTS: Genes associated with platelet and neutrophil activation were expressed at higher levels in patients with KD than in patients with acute adenovirus infections or systemic adverse drug reactions, but levels in patients with KD were not higher than those in patients with scarlet fever. Genes associated with B cell activation were also expressed at higher levels in patients with KD than in control subjects. A striking absence of interferon-stimulated gene expression in patients with KD was confirmed in an independent cohort of patients with KD. Using a set of 38 gene transcripts, we successfully predicted the diagnosis for 21 of 23 patients with KD and 7 of 8 patients with adenovirus infection. CONCLUSIONS: These findings provide insight into the molecular features that distinguish KD from other febrile illnesses and support the feasibility of developing novel diagnostic reagents for KD based on the host response.
Asunto(s)
Infecciones por Adenovirus Humanos/diagnóstico , Perfilación de la Expresión Génica , Síndrome Mucocutáneo Linfonodular/diagnóstico , Infecciones por Adenovirus Humanos/virología , Linfocitos B/fisiología , Estudios de Casos y Controles , Adhesión Celular , Niño , Regulación de la Expresión Génica , Humanos , Inmunidad Innata , Interferones/metabolismo , ARN ViralRESUMEN
OBJECTIVE: We sought to define the characteristics that distinguish Kawasaki disease shock syndrome from hemodynamically normal Kawasaki disease. METHODS: We collected data prospectively for all patients with Kawasaki disease who were treated at a single institution during a 4-year period. We defined Kawasaki disease shock syndrome on the basis of systolic hypotension for age, a sustained decrease in systolic blood pressure from baseline of > or =20%, or clinical signs of poor perfusion. We compared clinical and laboratory features, coronary artery measurements, and responses to therapy and analyzed indices of ventricular systolic and diastolic function during acute and convalescent Kawasaki disease. RESULTS: Of 187 consecutive patients with Kawasaki disease, 13 (7%) met the definition for Kawasaki disease shock syndrome. All received fluid resuscitation, and 7 (54%) required vasoactive infusions. Compared with patients without shock, patients with Kawasaki disease shock syndrome were more often female and had larger proportions of bands, higher C-reactive protein concentrations, and lower hemoglobin concentrations and platelet counts. Evidence of consumptive coagulopathy was common in the Kawasaki disease shock syndrome group. Patients with Kawasaki disease shock syndrome more often had impaired left ventricular systolic function (ejection fraction of <54%: 4 of 13 patients [31%] vs 2 of 86 patients [4%]), mitral regurgitation (5 of 13 patients [39%] vs 2 of 83 patients [2%]), coronary artery abnormalities (8 of 13 patients [62%] vs 20 of 86 patients [23%]), and intravenous immunoglobulin resistance (6 of 13 patients [46%] vs 32 of 174 patients [18%]). Impairment of ventricular relaxation and compliance persisted among patients with Kawasaki disease shock syndrome after the resolution of other hemodynamic disturbances. CONCLUSIONS: Kawasaki disease shock syndrome is associated with more-severe laboratory markers of inflammation and greater risk of coronary artery abnormalities, mitral regurgitation, and prolonged myocardial dysfunction. These patients may be resistant to immunoglobulin therapy and require additional antiinflammatory treatment.