Clinical and laboratory observation

Nationwide survey of Kawasaki disease and acute rheumatic fever*

Coronary artery dilation (CAD) had rarely been described as a cardiac complication of febrile disease other than Kawasaki disease (KD). There are rare cases complicated by CAD reported in patients with Mycoplasma pneumoniae (MP) infection.

A 6-year-old boy with severe Mycoplasma pneumoniae pneumonia (MPP) was transferred to our hospital due to significant respiratory distress on the 11th day from disease onset. Nadroparin, levofloxacin, and methylprednisolone followed by oral prednisone were aggressively prescribed. His clinical condition gradually achieved remission, and the drugs were withdrawn on the 27th day. Regrettably, the recurrent fever attacked him again in the absence of infection-toxic manifestations. Necrotizing pneumonia (NP) was found on chest CT. And echocardiography revealed right CAD (diameter, 3.40mm; z-score, 3.8), however, his clinical and laboratory findings did not meet the diagnostic criteria of KD. CAD was proposed to result from MP infection, and aspirin was prescribed. Encouragingly, the CAD regressed one week later (diameter, 2.50mm; z-score, 1.4). Additionally, the child defervesced seven days after the initiation of prednisone and Nadroparin treatment. The patient was ultimately discharged home on the 50th day. During follow-up, the child was uneventful with normal echocardiography and fully resolved chest CT lung lesions.

CAD can develop in patients with severe MP infection. Pediatricians should be alert to the possibility of CAD in patients with severe MP infection and recognize that CAD might also develop in febrile disease rather than KD.

Environmental factors have been suspected to have effects on the development of Kawasaki disease. However, the associations have been conflicting. The aim of this study was to investigate the effects of air pollution, weather conditions, and epidemic infections on the risks for Kawasaki disease in Japan. The concentrations of air pollutants (nitric oxide, nitrogen dioxide, and sulfur dioxide); ambient weather conditions (temperature, atmospheric pressure, relative air humidity, precipitation, sunshine duration, and wind velocity); and the epidemic conditions of 14 infectious diseases in hospitalized patients with Kawasaki disease were monitored from 2011 to 2018 in Beppu, Japan. The overdispersed generalized additive model was used to evaluate the effects, and a combination model with a distributed lag nonlinear model was used to estimate the cumulative effects. The incidence of Kawasaki disease had positive associations with preceding hot temperature and increased concentrations of nitric oxide and sulfur dioxide and a negative association with epidemic herpangina. The cumulative relative risk of Kawasaki disease at 5 lagged days of increased temperature was 1.76 (95% confidence interval: 1.01–3.07). This city-level observational study suggested that the incidence of Kawasaki disease was associated with air pollution and increased temperature and may be indirectly influenced by epidemic herpangina.

Kawasaki disease (KD) is an inflammatory condition in children, which has unknown etiology with an insufficiently described genetic mechanism. There is no accurate molecular diagnostic test for KD, but some genetic factors have been proposed in previous studies. In this study, we investigated the underlying molecular alterations based on both in silico and wet lab analysis to candidate transcriptional biosignature and biomarker. metaQC, metaDE, and metapath packages have been used in the bioinformatic analysis for the assessment of quality control, investigation of differentially expressed genes, and enrichment of detected genes, respectively. In the next step, miRNA array was analyzed by biobase, GEOquery, and limma packages. All bioinformatic studies were conducted with the R software platform. Finally, Real-Time PCR was performed on patient samples for the evaluation of the bioinformatic results. The results of bioinformatic analysis led to the introduction of 28 genes with the highest difference in gene expression, and 14 miRNAs with the highest difference in expression after microRNA array analysis. Real-time PCR results validated candidate genes and miRNAs as KD transcriptional biosignatures and biomarkers, respectively. Our studies have shown MyD88, KREMEN1, TLR5, ALPK1, IRAK4, PFKFB3, HK3, CREB, CR1, SLC2A14, and FPR1 as the most important genes involved in KD. Also, hsa-miR-575, hsa-miR-483-5p, hsa-miR-4271, hsa-miR-4327 as the most likely miRNAs to interfere with KD. The altered expression levels of the aforementioned genes and miRNAs can be studied further for therapeutic targets.

Intravenous administration of immunoglobulins has been routinely used for more than 60 years in clinical practice, developed initially as replacement therapy in immunodeficiency disorders. Today, the use of intravenous immunoglobulins (IVIGs) is embedded in the modern algorithms for the management of a few diseases, while in most cases, their application is off-label and thus different from their registered therapeutic indications according to the summary of product characteristics. In this review, we present the state-of-the-art use of IVIGs in various autoimmune conditions and immune-mediated disorders associated with reproductive failure, as approved therapy, based on indications or off-label. IVIGs are often an alternative to other treatments, and the administration of IVIGs continues to expand as data accumulate. Additionally, new insights into the pathophysiology of immune-mediated disorders have been gained. Therefore, the need for immunomodulation has increased, where IVIG therapy represents an option for stimulating, inhibiting and regulating various immune processes.