Search

BACKGROUND Kawasaki disease (KD) is an acute febrile illness with systemic vasculitides, mostly affecting infants and young children. The etiology of KD is still unclear; however, altered gut microbiota have been recently implicated as a contributing factor for the development of vasculitis. METHODS We conducted an age- and gender-matched case-control study on 50 patients and 200 control subjects to search for potential factors leading to intestinal dysbiosis associated with KD. Data were analyzed using conditional multivariable logistic regression. RESULTS Previous antibiotic administration was associated with the patients who developed KD (odds ratio [OR] 11.7, 95% confidence interval [CI] 4.7-29.1, P < 0.0001), but not other variables, including breastfeeding and group nursery. In subgroup analyses, cesarean birth was indicated as an associated factor in addition to previous antibiotic administration in infants under 12 months of age (OR: 8.0, 95% CI: 1.8-34.4, P = 0.005), but not in older children. CONCLUSIONS The association between previous antibiotic administration and the onset of KD was demonstrated. Antibiotics may contribute to the development of KD by affecting the intestinal microbiota in infants and young children.

Background: Plexiform fibromyxoma (PF) is a rare gastric mesenchymal tumor, with approximately 80 cases reported to date. Gastrointestinal stromal tumor, the most common primary mesenchymal tumor of the stomach, shows different biological and clinical characteristics between adult and pediatric patients. Objectives: This systematic literature review was conducted to elucidate the pathological and clinical features of pediatric PF compared to adult PF. Methods: MEDLINE (1948 to March 2018) and EMBASE (1947 to March 2018) were searched, and all English articles that reported clinical data on PF patients were identified. Two authors independently reviewed the articles and extracted data to assess immunohistochemistry, sex, chief complaint, tumor size, tumor-related mortality, and tumor recurrence and metastasis. Results: A total of 41 reports with 80 PF patients (of whom 70 were adult PF and 10 were pediatric PF patients) confirmed by histological and immunohistochemical findings were included. Of a total of 80 tumors, 62 (78%) were located in the gastric antrum, 42 (65%) presented with ulceration, and 48 (74%) were resected by partial gastrectomy. Median tumor size of the resected specimen was larger in pediatric PF than in adult PF cases (5.3 cm vs 4.0 cm, P = .036). However, there was no difference between pediatric and adult PFs in immunohistochemical expression, sex predominance, chief complaint, tumor-related mortality, and tumor recurrence and metastasis during the follow-up periods. Conclusion: Other than increased tumor growth in pediatric PFs, PF is a single disease entity with similar pathological features and benign clinical behavior regardless of onset age.

Background We previously reported that biofilms and innate immunity contribute to the pathogenesis of Kawasaki disease. Therefore, we aimed to assess the efficacy of clarithromycin, an antibiofilm agent, in patients with Kawasaki disease. Methods and Results We conducted an open‐label, multicenter, randomized, phase 2 trial at 8 hospitals in Japan. Eligible patients included children aged between 4 months and 5 years who were enrolled between days 4 and 8 of illness. Participants were randomly allocated to receive either intravenous immunoglobulin (IVIG) or IVIG plus clarithromycin. The primary end point was the duration of fever after the initiation of IVIG treatment. Eighty‐one eligible patients were randomized. The duration of the fever did not differ between the 2 groups (mean±SD, 34.3±32.4 and 31.1±31.1 hours in the IVIG plus clarithromycin group and the IVIG group, respectively [ P =0.66]). The relapse rate of patients in the IVIG plus clarithromycin group was significantly lower than that in the IVIG group (12.5% versus 30.8%, P =0.046). No serious adverse events occurred during the study period. In a post hoc analysis, the patients in the IVIG plus clarithromycin group required significantly shorter mean lengths of hospital stays than those in the IVIG group (8.9 days versus 10.3 days, P =0.049). Conclusions Although IVIG plus clarithromycin therapy failed to shorten the duration of fever, it reduced the relapse rate and shortened the duration of hospitalization in patients with Kawasaki disease. Clinical Trial Registration URL: http://www.umin.ac.jp/ctr/index.htm . Unique identifier: UMIN000015437.

Aim: Immune globulin is the most effective treatment of Kawasaki Disease, however, 15-20% of patients with Kawasaki disease (KD) is resistant to 2g/kg of IVIG (refractory case), and those patients are high risk for complication of coronary artery abnormalities, to detect these refractory KD before treatment of acute phase is very important to determine their treatment, but the methods to predict the refractory case is not yet established. We analyze the relation of IVIG-resistant Kawasaki disease and serum levels of procalcitonin (PCT) or serum amyloid A (SAA). Method: 192 patients with KD were involved in this study, and 48 were IVIG-resistant cases. Refractory case was defined as patients who needed additional treatment with IVIG and/or steroid after the first treatment with total 2g/kg of IVIG. Serum levels of PCT and SAA were measured before treatment, and the relationship to clinical course was analyzed. Result: Median level of PCT of patients with IVIG-resistant KD was 2.24 ng/ml and those with non- IVIG-resistant KD was 0.47 ng/ml, and median levels of PCT of patients with IVIG-resistant KD was significantly higher than those with non- IVIG-resistant KD (p Conclusion: As PCT levels of patients with IVIG-resistant Kawasaki disease were significantly higher than those with non- IVIG-resistant KD, PCT could be one of the predictor of IVIG-resistant KD.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by fever, cytopenias, hepatosplenomegaly, and coagulopathy with the background of hypercytokinemia. Early diagnosis and etoposide therapy are not established for affected newborns. An afebrile infant suffered from apnea 4 days after birth, showing leukocytosis, thrombocytopenia, coagulopathy, and cerebrospinal fluid pleocytosis. Serum levels of ferritin and sIL-2R were high. Bone marrow studies revealed activated/hemophagocytosing macrophages. Coxsackievirus B1 (CB1) was isolated from the throat and stool. Serum anti-CB1 antibody titers were elevated in the patient (4 → 16; 6 → 43 days after birth) and mother (128; 10 days after delivery). Normal expressions of perforin and CD107a precluded inherited HLH. The vertically transmitted CB1-HLH was successfully treated without administration of corticosteroid, cyclosporine, or etoposide. Serum cytokine levels showed dominant expression of monokines (IL-1β/6/8, and TNF-α) but not IFN-γ, which is the central player of inherited HLH. The cytokine profile might represent a unique pathophysiology of enterovirus-driven neonatal HLH.