Efficacy of infliximab in the treatment of Kawasaki disease: A systematic review and meta-analysis.
Lu Zhongxing,Wang Fen,Lv Haitao
Experimental and therapeutic medicine
The present study aimed to review the relevant studies in order to determine the efficacy of infliximab (IFX) in the treatment of Kawasaki disease (KD). The relevant studies were retrieved using the PubMed, Cochrane and Embase databases. Key sources in the literature were reviewed; all articles published by July 2019 were considered for inclusion. For each study, odds ratios, mean difference and 95% confidence interval (95% CI) were assessed to evaluate study outcomes. A total of 16 studies involving 429 patients were relevant to the questions of interest of the current meta-analysis. Compared with intravenous immunoglobulin (IVIG), IFX or IFX plus IVIG significantly reduced the incidence of adverse events, including the number of patients with fever, changes in lip and oral cavity and/or cervical lymphadenopathy. The white blood cell (WBC), neutrophil and C-reactive protein (CRP) levels were also reduced in the IFX or IFX plus IVIG group compared with those in the IVIG or polyethylene glycol-treated human immunoglobulin (VGIH) groups. The platelet counts, alanine aminotransferase (ALT) levels and Z-scores were increased in the IFX or IFX plus IVIG groups compared with those in the IVIG or VGIH groups. In the single-arm studies, the incidence of coronary artery aneurysm was 0.150 (95% CI: 0.024, 0.277), the non-response rate was 0.097 (95% CI: 0.056, 0.138), and the incidence of adverse events was 0.156 (95% CI: 0.122, 0.190). IFX not only effectively reduced the incidence of fever, conjunctival injection, changes in lip and oral cavity and cervical lymphadenopathy polymorphous exanthema, but also the WBC, neutrophil, ALT and CRP levels. The platelet levels were increased in patients after the IFX therapy compared with patients in the IVIG or VGIH groups. IFX or IFX plus IVIG exhibited improved clinical efficacy in the treatment of KD compared with that of IVIG or VGIH. However, as a limited number of studies was included in the current study, the findings should be verified further.
Distinguishing between typical Kawasaki disease and multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2.
Yeo Wee Song,Ng Qin Xiang
In recent months, there are increasing reports of a Kawasaki disease-like syndrome in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed 'Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS)' in the UK. Debate is ongoing regarding the nature of these pro-inflammatory syndromes. We herein propose that the platelet count may, at least in part, be able to help us differentiate between the two aforementioned syndromes. In a recent report, compared to a historical 'classical' Kawasaki disease (KD) cohort, patients with PIMS-TS had significantly lower platelet counts (188 vs 383 g/L, p < 0.0001). A possible explanation for this is their difference in underlying immunopathogenesis. In KD, the fundamental pathogenesis is thought to be immune complex-mediated, hence, the use of intravenous immunoglobulin (IVIg) which competes with the immunoglobulin Fc receptors (FcRs) on inflammatory cells, preventing the activation of these cells and thereby ameliorating the inflammatory response. If left untreated, these immune complexes activates the inflammatory cells (including monocytes and neutrophils), which also results in recruitment of platelets, resulting in the thrombocytosis we commonly see in KD. These immune complexes may also bind to platelets directly via FcRs on platelet membranes. In contrast, in viral-associated hyperinflammatory syndromes (e.g. PIMS-TS or MIS-C), there are mediators being secreted in the process of eradication of the virus (mainly to stimulate CD8+ cells to kill viral infected cells), which would inadvertently suppress bone marrow function and activate platelets, culminating in thrombocytopenia.
A Presumed Etiology of Kawasaki Disease Based on Epidemiological Comparison With Infectious or Immune-Mediated Diseases.
Rhim Jung-Woo,Kang Hyun Mi,Han Ji-Whan,Lee Kyung-Yil
Frontiers in pediatrics
Kawasaki disease (KD) may be associated with infection of unknown pathogen(s). For predicting of the etiology of KD, we evaluated epidemiological characteristics in KD, common infectious diseases and immune-mediated diseases in childhood. We respectively, reviewed the data of patients with KD, influenza, aseptic meningitis, exanthem subitum (ES), (MP) pneumonia, acute pyelonephritis (APN), Henoch-Schönlein purpura (HSP), acute poststreptococcal glomerulonephritis (APSGN), and childhood asthma. We compared and interpreted epidemiological data across the groups. In age distribution, KD, APN, and ES showed a similar pattern in that majority of patients were infants or young children, and other diseases showed a relatively even age-distribution which had a peak age, mainly 5-6 years, with bell-shape patterns. In annual-case pattern, there were epidemic years in aseptic meningitis and MP pneumonia, and the fluctuated annual cases were seen in other diseases. The trends of decreasing cases were seen in APSGN, HSP, and childhood asthma in recent years. In seasonal frequency, influenza or aseptic meningitis occurred in mainly winter or summer season, respectively. HSP and APSGN cases had less in summer, and KD, APN, and ES showed relatively even occurrence throughout a year without significant seasonal variations. Our results suggest that KD agents may be associated with normal flora that are influenced by environmental changes, since pathogens of APN and ES could be regarded as normal flora that originate from the host itself or ubiquitously existing human reservoirs.
Clinical characteristics of Kawasaki disease complicated with Mycoplasma pneumoniae pneumonia: A retrospective study.
Lan Yinle,Li Shuxian,Yang Dehua,Zhou Junfen,Wang Yingshuo,Wang Jianhua,Xu Yingchun,Chen Zhimin
This study aimed to investigate the inner linkage and mechanism of Mycoplasma pneumoniae (MP) infection and Kawasaki disease (KD), as well as the risk factors of outcome in this cohort of patients.A retrospective study was performed in 210 patients diagnosed with KD complicated with community acquired pneumonia (CAP) in Children's Hospital, Zhejiang University School of Medicine from January 2014 to December 2017. They were divided into two groups based on MP infection: MP infection group (n = 97) and non-MP infection group (n = 113). We compared the variables of these two groups based on medical records.The MP infection group had higher ESR than the non-MP infection group. During hospitalization, the non-MP infection group had higher levels of WBC during hospital, LDH, PCT, and lower HB when compared to the MP infection group. No differences were found in the hs-CRP level, N%, PLT, ALT, CKMB, and cytokine levels (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) between MP and non-MP infection group. Likewise, no difference was found in fever duration or hospital stays between them. Totally 19 patients in the infection group had CAA with a rate of 19.59%; and 27 (23.89%) patients had CAA in the non-MP infection group. Unfortunately, no difference was found in CAA rate between the two groups.MP infection may occur simultaneously in children with Kawasaki disease. KD patients with MP infection tended to occur in older population. MP infection may not increase the risk of CAA, which still needs further large-scaled studies to confirm. Clinicians should be alert to KD patients with high level of ESR. MP should be screened and early treatment with macrolides should be given timely.