Two Distinct Cases of Adult-onset Kawasaki Disease.

Kawasaki disease (KD) is a systemic vasculitis syndrome that mostly affects children under 4 years old. Among the reported KD cases, only 1% were over 10 years old. We herein report 2 cases of adult-onset KD (AKD) in 19- and 17-year-old boys diagnosed with a persistent fever and cervical lymphadenitis. Both patients showed cardiac complications, such as coronary artery dilation and myocarditis. Repeated intravenous immunoglobulin therapy was effective in the 19-year-old, while plasma exchange therapy was needed for the 17-year-old, with no sequelae noted at discharge. KD should be considered as a differential diagnosis for persistent fever in adults.

Augmented ILT3/LILRB4 Expression of Peripheral Blood Antibody Secreting Cells in the Acute Phase of Kawasaki Disease.

BACKGROUND: Kawasaki disease (KD) is an acute, systemic vasculitis syndrome that occurs in children. The clinical symptoms and epidemiologic features of KD strongly suggest that KD is triggered by unidentified infectious agents in genetically predisposed patients. In addition, a number of studies have described the role of B cells in the development of KD. To obtain a mechanistic insight into the humoral immune response of B-lineage cells in KD patients, we examined peripheral blood antibody secreting cells (ASCs) and inhibitory immunoreceptors, immunoglobulin-like transcript (ILT)/leukocyte immunoglobulin-like receptor (LILR), on each B cell subpopulation. METHODS: Eighteen Japanese KD patients and thirteen healthy control subjects were recruited for this study. Their peripheral blood mononuclear cells were examined by flow cytometry for the number of CD19 B cells, the size of each B cell subset and the expression of the inhibitory isoforms of ILT/LILR on the B cell subset. RESULTS: The frequency of CD19CD27 ASCs was significantly increased in the acute phase of KD and reduced after high-dose intravenous immunoglobulin (IVIG) treatment. Interestingly, while ILT2/LILRB1 expression was ubiquitously observed on every B cell/ASCs subset and the level was not significantly different after IVIG, ILT3/LILRB4 (B4) was uniquely expressed on only ASCs, and its expression was significantly decreased after IVIG. CONCLUSIONS: In the acute phase of KD, the frequency of ASCs is high with augmented B4 expression, whereas it is lower with decreased B4 expression after IVIG. Further studies of B4 expression on ASCs in autoimmune and infectious diseases will be needed to confirm the significance of our findings.

Onset of Hemophagocytic Lymphohistiocytosis during Piperacillin-Tazobactam Therapy in Three Children with Acute Focal Bacterial Nephritis.

Hemophagoytic lymphohistiocytosis (HLH) is a rare life-threatening disorder caused by overactivation of the immune system, associated with infections, autoimmune disorders, and malignancies. The pathological hallmark of HLH is phagocytosis of blood cells and platelets by activated macrophages and histiocytes. In this report, we describe the onset of HLH in three children, aged 2, 5 and 7 years old, during the treatment of acute focal bacterial nephritis (AFBN) with an antibiotic, piperacillin-tazobactam (PIPC-TAZ). AFBN is acute localized bacterial infection of the kidney without abscess formation. PIPC-TAZ was chosen for the treatment of AFBN, because it not only has indications for complicated urinary tract infections, but also covers most of the causative bacteria of urinary tract infections, including ß-lactamase-producing Escherichia coli. The clinical courses of the three patients were similar, and they were treated with PIPC-TAZ and amikacin (AMK) for AFBN. Fever went down 2 to 5 days later, and AMK was discontinued by day 6. However, fever recurred on 13 to 15 days after introduction of PIPC-TAZ therapy, even though all of the patients had no signs of recurrence of AFBN. The clinical features and laboratory tests of two patients fulfilled the criteria of HLH, whereas the other patient had initiated therapy before fulfilling the criteria. Cessation of PIPC-TAZ combined with corticosteroid therapy improved clinical symptoms. HLH of our patients was probably induced by PIPC-TAZ, as judged by the timing of the onset of HLH and the positivity of the drug-lymphocyte stimulation test. In conclusion, prolonged antibiotic therapy with PIPC-TAZ could be a cause of HLH.

Concurrent Community Transmission of Enterovirus D68 With Human Rhinoviruses and Respiratory Syncytial Virus Among Children in Sendai, Japan.

BACKGROUND: In the autumn of 2015, we experienced a surge in the number of pediatric cases of wheeze in our hospital, which was suspected to be caused by enterovirus (EV)-D68 transmission in the community. Thus, we implemented an ad hoc retrospective surveillance for EV-D68. METHODS: Patients <15 years of age with acute respiratory infection were eligible for inclusion in this study. All enrolled patients underwent virus detection test. Additionally, neutralization tests (NTs) were performed using the stored serum samples of the enrolled patients to compare the antigenicity of the virus isolated in this study with that isolated in 2010 and evaluate the anti-EV-D68 antibody prevalence. RESULTS: Respiratory syncytial virus (RSV) was the most commonly detected virus (35%), followed by EV-D68 (19%) and non-EV-D68 enteroviruses/human rhinoviruses (14%). Patients with EV-D68 infection had higher median age than those with RSV infection (P < 0.05). Moreover, patients with EV-D68 infection showed a higher expiratory wheeze prevalence than those with non-EV-D68 enterovirus/rhinovirus and RSV infections. The antigenicity of the isolate from the current study was similar to the virus that circulated in 2010. At the early study phase, children in our community did not have high NT titers, but the median log NT titer increased from 1.5 to 5 over time (P < 0.05). CONCLUSION: This study showed the concurrent circulation of EV-D68 with non-EV-D68 enteroviruses/rhinoviruses and RSV in infants and children in our community and captured the early stage of EV-D68 transmission.

A Term Infant of Neonatal Toxic Shock Syndrome-Like Exanthematous Disease Complicated with Hemophagocytic Syndrome.

Neonatal toxic shock syndrome-like exanthematous disease (NTED) is a newly recognized neonatal infectious disease, caused by the superantigen toxic shock syndrome toxin-1 (TSST-1). TSST-1 is mainly produced by methicillin-resistant Staphylococcus aureus, and the immune responses to TSST-1 are known to cause toxic shock syndrome, a life-threatening infectious disease. The clinical symptoms of NTED are skin rash, fever, and thrombocytopenia, but severe thrombocytopenia is rare in term infants with NTED. Although the cause of NTED is the same as that of toxic shock syndrome, the clinical symptoms of NTED are milder than toxic shock syndrome. The mild phenotype of NTED has been explained by selectively elevated serum levels of anti-inflammatory cytokine interleukin (IL)-10, which suppress immune responses to TSST-1. In the present study, we report a term female infant of NTED complicated with hemophagocytic syndrome (HPS). HPS is characterized by systemic inflammation and hemophagocytosis, caused by uncontrolled activation of T cells and macrophages. The serum IL-10 level of the patient at 4 days of age was relatively low (67 pg/mL) for NTED but still higher than normal controls (< 2.0 pg/mL). The patient also showed severe thrombocytopenia. We speculate that the serum IL-10 level of the patient was enough to supress immune responses to TSST-1, thereby resulting in NTED, but not enough to suppress the onset of HPS. This is the first reported case of NTED complicated with HPS. If a physician encounters an NTED patient with severe cytopenia, microscopic examination of peripheral blood smear should be carried out to exclude HPS.