Increased interleukin-1ß and basic fibroblast growth factor levels in the cerebrospinal fluid during human herpesvirus-6B (HHV-6B) encephalitis.

Human herpesvirus 6B (HHV-6B) causes exanthema subitum in infants and is known to be mildly pathogenic. However, HHV-6B infection can induce febrile seizures in a high percentage of patients, and in rare cases, result in encephalitis. We detected higher levels of interleukin (IL)-1ß and basic fibroblast growth factor (bFGF) in the cerebrospinal fluid (CFS) of patients with HHV-6B encephalitis when compared to those in patients with non-HHV-6B-induced febrile seizures. In vitro, IL-1ß and bFGF enhanced HHV-6B gene expression in infected U373 astrocytes during the initial and maintenance phases of infection, respectively. These findings indicated that IL-1ß and bFGF contribute to HHV-6B growth and the onset of encephalitis.

Familial cases with MYH9 disorders caused by MYH9 S96L mutation.

We report familial cases with MYH9 disorders: a 1-year-old Japanese boy who presented only with macrothrombocytopenia, and his 33-year-old father who had been diagnosed with refractory chronic idiopathic thrombocytopenic purpura, and suffered from hearing loss and chronic renal failure. Peripheral blood smears revealed giant platelets but no Döhle body-like cytoplasmic inclusion bodies in neutrophils. Heterozygous MYH9 S96L mutations were found in the patient and his father, resulting in the diagnosis of a familial case with MYH9 disorders. The possibility of MYH9 disorders including Epstein syndrome should be assessed in cases of thrombocytopenia through the careful examination of hematological features.

Hepcidin in Kawasaki disease: upregulation by acute inflammation in patients having resistance to intravenous immunoglobulin therapy.

Hepcidin is an iron metabolism inhibitor that increases with chronic inflammation. However, it is unclear whether hepcidin indicates acute inflammatory response in Kawasaki disease (KD), which is an acute systemic vasculitis. In this study, we examined the serum hepcidin levels before and after intravenous immunoglobulin (IVIG) therapy in responders and non-responders to IVIG. This was a pilot prospective observational study at a university hospital. All KD patients were initially administered 2 g/kg of IVIG as the first IVIG therapy (IVIG1) on day 4 to day 7 after onset. Non-responders to IVIG1 were additionally treated with the second IVIG therapy (IVIG2) using 1 g/kg of IVIG. All KD patients were also treated with aspirin. We measured serum hepcidin levels before IVIG1, after IVIG1, and during the recovery period. Among the 31 KD patients, 21 patients and 5 patients improved after IVIG1 (responders-1) and IVIG2 (responders-2), respectively, but 5 patients did not improve after IVIG2 (non-responders). Serum hepcidin levels before IVIG1 were significantly higher in responders-2 (159.0 ng/mL) and non-responders (240.0 ng/mL), compared to responders-1 (103.0 ng/mL). Serum hepcidin levels after IVIG1 were significantly higher in non-responders (163.0 ng/mL), compared to responders-1 (43.4 ng/mL) and responders-2 (54.6 ng/mL). Serum hepcidin levels of non-responders to IVIG were higher before IVIG and remained high after IVIG. Erythrocyte-related indexes, including hemoglobin, reticulocytes, iron, and ferritin before IVIG1, were not significantly different among the three groups. Serum hepcidin might be excessively upregulated by acute inflammation in KD patients having resistance to IVIG. Key Points • Hepcidin, an iron metabolism inhibitor in chronic inflammation, increases during the acute phase of Kawasaki disease. • Hepcidin levels before IVIG of non-responders were higher than those of responders in Kawasaki disease. • Hepcidin might be excessively upregulated by acute inflammation in KD patients having resistance to IVIG.

Clinical features and prognoses of 23 patients with chronic granulomatous disease followed for 21 years by a single hospital in Japan.

In this paper, we examined the details of severe infections, treatment efficacies, and the prognoses of 23 Japanese patients with chronic granulomatous disease (CGD). We described the mean ages at diagnosis and follow-up, which were 2.8 years (range, 0.7-10 years) and 14.9 years (range, 0.2-28.4 years), respectively. There were three deaths, two from Aspergillus pneumonia and one from liver abscess. Eighteen of the 23 patients (78%) had a complete loss of gp91phox, and three had p22-phox and one had p67phox deficiencies. Aspergillus species were found in 45% of 174 severe infections. The mean height and weight of the 20 surviving patients were -0.8 +/- 1.3SD and -1.9 +/- 1.9SD below the means for age, respectively. Short stature and underweight (below the 10th percentile of the means) for age were seen in 22% and 17% of the patients, respectively. This growth retardation reflects the severity of the disease. At 20 years of age, there was 87% survival. Ongoing prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) or antifungal drugs was given in 16 and 11 patients, respectively. Interferon-gamma (IFN-gamma) was given once a week to 14 patients. Four patients underwent hematopoietic stem cell transplantation (HSCT) and are currently well. There were infections observed in three of 21 identified related carriers of X-linked CGD. A carrier with a liver abscess had 5% normal neutrophils during the acute phase of infection, which returned to 40% normal neutrophils after recovery. The high survival rate in this hospital results from regular follow-up and prophylaxis with TMP-SMX and anti-fungal drugs beginning at the time of diagnosis, along with treatment with weekly IFN-gamma.

Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren.

BACKGROUND: To our knowledge, no rigorously designed clinical trials have evaluated the relation between vitamin D and physician-diagnosed seasonal influenza. OBJECTIVE: We investigated the effect of vitamin D supplements on the incidence of seasonal influenza A in schoolchildren. DESIGN: From December 2008 through March 2009, we conducted a randomized, double-blind, placebo-controlled trial comparing vitamin D(3) supplements (1200 IU/d) with placebo in schoolchildren. The primary outcome was the incidence of influenza A, diagnosed with influenza antigen testing with a nasopharyngeal swab specimen. RESULTS: Influenza A occurred in 18 of 167 (10.8%) children in the vitamin D(3) group compared with 31 of 167 (18.6%) children in the placebo group [relative risk (RR), 0.58; 95% CI: 0.34, 0.99; P = 0.04]. The reduction in influenza A was more prominent in children who had not been taking other vitamin D supplements (RR: 0.36; 95% CI: 0.17, 0.79; P = 0.006) and who started nursery school after age 3 y (RR: 0.36; 95% CI: 0.17, 0.78; P = 0.005). In children with a previous diagnosis of asthma, asthma attacks as a secondary outcome occurred in 2 children receiving vitamin D(3) compared with 12 children receiving placebo (RR: 0.17; 95% CI: 0.04, 0.73; P = 0.006). CONCLUSION: This study suggests that vitamin D(3) supplementation during the winter may reduce the incidence of influenza A, especially in specific subgroups of schoolchildren. This trial was registered at https://center.umin.ac.jp as UMIN000001373.