Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.
Mycoplasma pneumoniae pneumonia (MP) is responsible for 10-40% of cases of pediatric community-acquired pneumonia. Occasionally, progression to severe pneumonia occurs despite appropriate antibiotic therapy. We retrospectively evaluated the effect of prednisolone in 15 children with MP whose clinical and radiographic course worsened despite broad-spectrum antibiotics, including appropriate macrolides. The mean ( +/- SD) age was 6.1 +/- 1.9 years, and 10 were boys. All children had received macrolides at presentation, but they had persistent fever and progressively worsening radiographic findings. In addition to broad-spectrum antimicrobial therapy, we added prednisolone (1 mg/kg for 3-7 days, then tapered over 7 days) on day 6 (+/-1.5 days) of admission. Fourteen children became afebrile within 24 hr, and their clinical status and radiographic findings improved over several days. The white blood cell count at presentation was 7,500 +/- 2,000/mm3, with a proportion demonstrating lymphopenia (lymphocyte differential, 19.7 +/- 5.7%). In conclusion, corticosteroid treatment appeared to be temporally associated with clinical and radiographic improvement, and may be helpful for reducing morbidity in children with macrolide-nonresponsive severe MP. Further studies may be warranted.
The incidence of KD in South Korea increased to 194.7 per 100,000 children younger than 5 years in 2014; meanwhile, the coronary aneurysm rate decreased to 1.7%.
Acute respiratory distress syndrome (ARDS) is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved in the immunopathogenesis of ARDS. There may be etiologic substances that have an affinity for respiratory cells and induce lung cell injury in cases of ARDS. These substances originate not only from pathogens, but also from injured host cells. At the molecular level, these substances have various sizes and biochemical characteristics, classifying them as protein substances and non-protein substances. Immune cells and immune proteins may recognize and act on these substances, including pathogenic proteins and peptides, depending upon the size and biochemical properties of the substances (this theory is known as the protein-homeostasis-system hypothesis). The severity or chronicity of ARDS depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, or the repertoire of specific immune cells that control the substances. Therefore, treatment with early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) as soon as possible may reduce aberrant immune responses in the potential stage of ARDS.
Kawasaki disease (KD) is a self-limited systemic inflammatory illness, and coronary artery lesions (CALs) are a major complication determining the prognosis of the disease. Epidemiologic studies in Asian children suggest that the etiologic agent(s) of KD may be associated with environmental changes. Laboratory findings are useful for the diagnosis of incomplete KD, and they can guide the next-step in treatment of initial intravenous immunoglobulin non-responders. CALs seem to develop in the early stages of the disease before a peak in inflammation. Therefore early treatment, before the peak in inflammation, is mandatory to reduce the risk of CAL progression and severity of CALs. The immunopathogenesis of KD is more likely that of acute rheumatic fever than scarlet fever. A hypothetical pathogenesis of KD is proposed under the premise of a "protein homeostasis system"; where innate and adaptive immune cells control pathogenic proteins that are toxic to host cells at a molecular level. After an infection of unknown KD pathogen(s), the pathogenic proteins produced from an unknown focus, spread and bind to endothelial cells of coronary arteries as main target cells. To control the action of pathogenic proteins and/or substances from the injured cells, immune cells are activated. Initially, non-specific T cells and non-specific antibodies are involved in this reaction, while hyperactivated immune cells produce various cytokines, leading to a cytokine imbalance associated with further endothelial cell injury. After the emergence of specific T cells and specific antibodies against the pathogenic proteins, tissue injury ceases and a repair reaction begins with the immune cells.
Mycoplasma pneumoniae (MP), the smallest self-replicating biological system, is a common cause of upper and lower respiratory tract infections, leading to a wide range of pulmonary and extra-pulmonary manifestations. MP pneumonia has been reported in 10 to 40% of cases of community-acquired pneumonia and shows an even higher proportion during epidemics. MP infection is endemic in larger communities of the world with cyclic epidemics every 3 to 7 years. In Korea, 3 to 4-year cycles have been observed from the mid-1980s to present. Although a variety of serologic assays and polymerase chain reaction (PCR) techniques are available for the diagnosis of MP infections, early diagnosis of MP pneumonia is limited by the lack of immunoglobulin (Ig) M antibodies and variable PCR results in the early stages of the infection. Thus, short-term paired IgM serologic tests may be mandatory for an early and definitive diagnosis. MP infection is usually a mild and self-limiting disease without specific treatment, and if needed, macrolides are generally used as a first-choice drug for children. Recently, macrolide-resistant MP strains have been reported worldwide. However, there are few reports of apparent treatment failure, such as progression of pneumonia to acute respiratory distress syndrome despite macrolide treatment. The immunopathogenesis of MP pneumonia is believed to be a hyperimmune reaction of the host to the insults from MP infection, including cytokine overproduction and immune cell activation (T cells). In this context, immunomodulatory treatment (corticosteroids or/and intravenous Ig), in addition to antibiotic treatment, might be considered for patients with severe infection.
BackgroundM. pneumoniae pneumonia (MP) has been reported in 10-40% of community-acquired pneumonia cases. We aimed to evaluate the difference of clinical features in children with MP, according to their age and chest radiographic patterns.MethodsThe diagnosis of MP was made by examinations at both admission and discharge and by two serologic tests: the indirect microparticle agglutinin assay (≥1:40) and the cold agglutinins titer (≥1:32). A total of 191 children with MP were grouped by age: ≤2 years of age (29 patients), 3-5 years of age (81 patients), and ≥6 years of age (81 patients). They were also grouped by pneumonia pattern: bronchopneumonia group (96 patients) and segmental/lobar pneumonia group (95 patients).ResultsEighty-six patients (45%) were seroconverters, and the others showed increased antibody titers during hospitalization. Among the three age groups, the oldest children showed the longest duration of fever, highest C-reactive protein (CRP) values, and the most severe pneumonia pattern. The patients with segmental/lobar pneumonia were older and had longer fever duration and lower white blood cell (WBC) and lymphocyte counts, compared with those with bronchopneumonia. The patient group with the most severe pulmonary lesions had the most prolonged fever, highest CRP, highest rate of seroconverters, and lowest lymphocyte counts. Thrombocytosis was observed in 8% of patients at admission, but in 33% of patients at discharge.ConclusionsIn MP, older children had more prolonged fever and more severe pulmonary lesions. The severity of pulmonary lesions was associated with the absence of diagnostic IgM antibodies at presentation and lymphocyte count. Short-term paired IgM serologic test may be mandatory for early and definitive diagnosis of MP.
Mycoplasma pneumoniae is one of the most common agents of community-acquired pneumonia in children and young adults. Although M. pneumoniae is a small bacterium that can reproduce in an artificial culture medium and is known to be sensitive to certain antibiotics in vitro as well as in vivo, the immunopathogenesis of M. pneumoniae in the human host is not fully understood. The epidemiologic characteristics, including periodic epidemics, and some clinical characteristics of M. pneumoniae are similar to those observed in systemic viral infections. Many experimental and clinical studies have suggested that the pathogenesis of lung injuries in M. pneumoniae infection is associated with a cell-mediated immune reaction, including high responsiveness to corticosteroid therapy. This paper presents an overview of M. pneumoniae infections, with emphasis on epidemiology, pathogenesis and treatment.
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