A pediatric case of food-dependent exercise-induced anaphylaxis due to rice bran.

Food-dependent exercise-induced anaphylaxis (FDEIA) caused by fruits and vegetables is increasing in recent years, but rice-induced FDEIA is rarely reported. The mechanism of FDEIA is unclear, although percutaneous sensitization occurs in some cases. A 14-year-old adolescent came our hospital who had 6 episodes of unknown FDEIA occurring from age 13. He affected atopic dermatitis in infancy, and he had been polishing rice daily to help with housework, and also had occasionally begun to observe urticaria while bathing after eating rice from 5 years old. Antigen-specific immunoglobulin E antibody titers (ImmunoCAP) were 1.35 UAmL for rice, 23.6 UAmL for orchard grass. Oral food challenge and exercise provocation test with polished rice were negative. An oral food challenge with rice bran was also negative, but exercise provocation test induced severe anaphylaxis. IgE immunoblotting with rice bran detected patient-specific bands, as 25-, 35-, 50-, and 60 kDa, and the 25- and 60-kDa bands were heat-resistant. In a suppression test using rice bran, these bands disappeared or diminished. In an inhibition test against orchard grass pollen with rice bran, inhibition was not observed. Conversely, an inhibition test against rice bran with orchard grass pollen, inhibition was observed in a concentration-dependent manner. This is extremely rare case of FDEIA in children, caused by rice bran. Furthermore, it might be induced by percutaneous sensitization. In FDEIA, it is necessary to scrutinize the possibility that rice bran may be the cause even in children.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy.

Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T4) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts.

[Establishment of "Anaphylaxis Scoring Aichi (ASCA)," a new symptom scoring system to be used in an oral food challenge (OFC)].

BACKGROUND: An original symptom score sheet named "Anaphylaxis Scoring Aichi (ASCA)" was created to quantitatively determine the severity of allergic symptoms provoked in an oral food challenge. METHODS: ASCA lists and sorts subjective and objective symptoms into five organs (respiratory, skin-mucosal, gastrointestinal, psycho-neurological and cardiovascular). The organ scores were given (0 to 60 points) in accordance with the severity of each symptom. The total score was defined as the sum of the highest 5 organ scores (maximum 240 points) observed throughout the course of an OFC. This study evaluated the ASCA score in 253 cases of a positive food challenge (age 1-16 years, mean 5.3±3.2 years) conducted from April to August 2011 in our institute. The results were compared to the modified anaphylaxis grading presented in the Japanese Pediatric Guideline for Oral Food Challenge Test in Food Allergy 2009. At the same time, we evaluated the indications of symptomatic treatment using ASCA score. RESULTS: The total score closely correlated with the anaphylaxis grading, but there was a wide range of overlap between grade 2 and grade 3. All cases with a total score≥60 points were equivalent to grade 4 or 5, and that were consisted of three or more organ symptoms. These severe cases contained respiratory or skin/mucosal symptoms, and despite the early induction of initial therapy, the symptoms became worse. CONCLUSION: ASCA is therefore considered to be a useful tool for use in an oral food challenge test.

Amino acids exhibit anti-inflammatory effects in human monocytic leukemia cell line, THP-1 cells.

OBJECTIVE: The elemental diet is one of the effective therapies for inflammatory bowel disease. However, the mechanism remains unclear, and there have never been reports about the inhibitory effects of amino acids in human monocytes/macrophages. We investigated the inhibitory effects of amino acids on cytokine production or expression of adhesion molecules that are involved in inflammatory diseases, in human monocytes/macrophages. METHODS: We examined the inhibitory effects of cysteine, histidine or glycine on the induction of nuclear factor-κB (NF-κB) activation, expression of intracellular adhesion molecule-1 (ICAM-1, CD54) and production of interleukin-8 (IL-8) in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood mononuclear cells (PBMCs) stimulated with tumor necrosis factor-α (TNF-α). RESULTS: Cysteine, histidine and glycine significantly reduced the activation of NF-κB in THP-1 cells stimulated with TNF-α. In addition, cysteine and histidine significantly inhibited the expression of ICAM-1 and production of IL-8 in THP-1 cells and PBMCs. CONCLUSIONS: Our results suggest that cysteine and histidine exhibit anti-inflammatory effects in THP-1 cells, and may be responsible for the efficacy of treatment in inflammatory bowel diseases.

Leukotriene D4 enhances tumor necrosis factor-α-induced vascular endothelial growth factor production in human monocytes/macrophages.

BACKGROUND: Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic mitogens specific for vascular endothelial cells. It also induces vascular hyperpermeability and protein leakage into the extracellular space. Leukotriene D(4) (LTD(4)), one of the cysteinyl leukotrienes (CysLTs), is known to be one of the key molecules of allergic inflammation. The interaction between LTD(4) and VEGF production in human monocytes/macrophages is not well characterized. METHODS: We examined VEGF production by THP-1 cells, a human monocytic leukemia cell line, and human peripheral blood CD14+monocytes/macrophages stimulated with LTD(4) and/or tumor necrosis factor-α (TNF-α). We also determined the inhibitory effects of pranlukast, a CysLT(1) receptor antagonist, on VEGF production by LTD(4) stimulation. RESULTS: LTD(4) significantly induced VEGF production and enhanced TNF-α-induced VEGF release in THP-1 cells and human peripheral blood CD14+monocytes/macrophages. VEGF mRNA expression was also induced by stimulation of THP-1 cells with LTD(4) and TNF-α. In addition, 10(-7)-10(-10)M pranlukast completely inhibited VEGF production enhanced by LTD(4). The 50% inhibitory concentration (IC50) for VEGF production in THP-1 cells was 10(-10)-10(-11)M. CONCLUSIONS: LTD(4) induced VEGF production and enhanced VEGF release induced by TNF-α via CysLT(1) receptors in human monocytes/macrophages. These effects were completely inhibited by pranlukast.

Characteristics of atopic children with pandemic H1N1 influenza viral infection: pandemic H1N1 influenza reveals 'occult' asthma of childhood.

The number of human cases of pandemic H1N1 influenza viral infection has increased in Japan since April 2009, as it has worldwide. This virus is widespread in the Yamaguchi prefecture in western Japan, where most infected children exhibited respiratory symptoms. Bronchial asthma is thought to be one of the risk factors that exacerbate respiratory symptoms of pandemic H1N1-infected patients, but the pathogenesis remains unclear. We retrospectively investigated the records of 33 children with pandemic H1N1 influenza viral infection who were admitted to our hospital between October and December 2009 and analyzed their clinical features. The percentage of children with asthma attack, with or without abnormal findings on chest radiographs (pneumonia, atelectasis, etc.), caused by pandemic H1N1 influenza infection was significantly higher than that of children with asthma attack and 2008-2009 seasonal influenza infection. Of the 33 children in our study, 22 (66.7%) experienced an asthma attack. Among these children, 20 (90.9%) did not receive long-term management for bronchial asthma, whereas 7 (31.8%) were not diagnosed with bronchial asthma and had experienced their first asthma attack. However, the severity of the attack did not correlate with the severity of the pulmonary complications of pandemic H1N1 influenza viral infection. The pandemic H1N1 influenza virus greatly increases the risk of lower respiratory tract complications such as asthma attack, pneumonia, and atelectasis, when compared to the seasonal influenza virus. Furthermore, our results suggest that pandemic H1N1 influenza viral infection can easily induce a severe asthma attack, pneumonia, and atelectasis in atopic children without any history of either an asthma attack or asthma treatment.

Human thymic stromal lymphopoietin enhances expression of CD80 in human CD14+ monocytes/macrophages.

OBJECTIVE: Human thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine, promotes inflammatory T helper type 2 cell (Th2) differentiation of naive CD4(+) T cells. TSLP is highly produced in keratinocytes of patients with atopic dermatitis and bronchial epithelia of patients with asthma and was thought to be a master switch for allergic inflammation. We sought to examine the effect of TSLP in human monocytes/macrophages. METHODS: The effect of TSLP on the expression of cell surface antigens (CD11c, CD16, CD54, CD80, CD86, and HLA-DR) in peripheral blood CD14(+) monocytes/macrophages was examined. RESULTS: TSLP enhanced the expression of CD80 in peripheral blood CD14(+) monocytes/macrophages but not that of other cell surface antigens. It was associated with an increased percentage of CD14(dim/-), CD80(+), CD11c(+), and HLA-DR(+) cells, which was consistent with the increased differentiation of myeloid dendritic cells. CONCLUSIONS: TSLP induces CD80 expression in human peripheral blood CD14(+) monocytes/macrophages; this indicates monocyte/macrophage activation. This may be associated with their differentiation into myeloid dendritic cells.

Prostaglandin E2 suppresses beta1-integrin expression via E-prostanoid receptor in human monocytes/macrophages.

Beta1-integrins mediate cell attachment to different extracellular matrix proteins, intracellular proteins, and intercellular adhesions. Recently, it has been reported that prostaglandin E2 (PGE2) has anti-inflammatory properties such as inhibition of the expression of adhesion molecules or production of chemokines. However, the effect of PGE2 on the expression of beta1-integrin remains unknown. In this study, we investigated the effects of PGE2 on the expression of beta1-integrin in the human monocytic cell line THP-1 and in CD14+ monocytes/macrophages in human peripheral blood. For this, we examined the role of four subtypes of PGE2 receptors and E-prostanoid (EP) receptors on PGE2-mediated inhibition. We found that PGE2 significantly inhibited the expression of beta1-integrin, mainly through EP4 receptors in THP-1 cells and CD14+ monocytes/macrophages in human peripheral blood. We suggest that PGE2 has anti-inflammatory effects, leading to the inhibited expression of beta1-integrin in human monocytes/macrophages, and that the EP4 receptor may play an important role in PGE2-mediated inhibition.