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Five years have passed since the Japanese Pediatric Guideline for Food Allergy (JPGFA) was first revised in 2011 from its original version. As many scientific papers related to food allergy have been published during the last 5 years, the second major revision of the JPGFA was carried out in 2016. In this guideline, food allergies are generally classified into four clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type of food allergy (urticaria, anaphylaxis, etc.), and (4) special forms of immediate-type of food allergy such as food-dependent exercise-induced anaphylaxis and oral allergy syndrome (OAS). Much of this guideline covers the immediate-type of food allergy that is seen during childhood to adolescence. Infantile atopic dermatitis associated with food allergy type is especially important as the onset of most food allergies occurs during infancy. We have discussed the neonatal and infantile gastrointestinal allergy and special forms of immediate type food allergy types separately. Diagnostic procedures are highlighted, such as probability curves and component-resolved diagnosis, including the recent advancement utilizing antigen-specific IgE. The oral food challenge using a stepwise approach is recommended to avoid complete elimination of causative foods. Although oral immunotherapy (OIT) has not been approved as a routine treatment by nationwide insurance, we included a chapter for OIT, focusing on efficacy and problems. Prevention of food allergy is currently the focus of interest, and many changes were made based on recent evidence. Finally, the contraindication between adrenaline and antipsychotic drugs in Japan was discussed among related medical societies, and we reached an agreement that the use of adrenaline can be allowed based on the physician's discretion. In conclusion, this guideline encourages physicians to follow the principle to let patients consume causative foods in any way and as early as possible.

A food allergy is defined as "a phenomenon in which adverse reactions are caused through antigen-specific immunological mechanisms after exposure to given food."

Anaphylaxis is one of the severest forms of allergic diseases. Some kinds of mushroom are known as causative allergens in food anaphylaxis. Matsutake mushroom (Tricholoma matsutake)is a typical edible mushroom available in autumn in Japan. We encountered an 8-year-old Japanese girl who developed anaphylaxis after ingesting matsutake mushrooms.

Reactivation of human herpesvirus (HHV) infection, especially HHV-6, has been observed in patients with drug-induced hypersensitivity syndrome (DIHS). In toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), the relevance of HHV infection to the symptoms is unclear.

Eosinophilic myocarditis is characterized by an acute inflammatory infiltration of eosinophils in the myocardium. Diagnosis is confirmed by a heart muscle biopsy. Immunopathological studies suggest that several toxic proteins, such as eosinophilic cationic protein (ECP) derived from the degranulation of eosinophils, may play an important role in the patho- genesis of this cardiac disorder. Serum levels of ECP, which are related to the inflammatory activity of the disease are used to monitor and determine the effects of treatment in adult patients. Herein, we present the case of a 12-year-old, previously healthy, junior high school girl with eosinophilic myocarditis. The diagnosis was confirmed by a myocardial biopsy and the patient was treated successfully with prednisolone. On admission, her peripheral blood eosinophil count (3342 /μL) and serum ECP level (124 μg/L) were extremely high, but both decreased significantly during corticosteroid therapy. In the present case, corticosteroid treatment was successful and early diagnosis by endomyocardial biopsy is recommended. Furthermore, serum ECP is useful to monitor the efficacy of treatment in pediatric patients.

Background:Food-dependent, exercise-induced anaphylaxis (FEIAn) is classified among the physical allergies. The pathophysiology of FEIAn remains unknown, as does the frequency of FEIAn in the general population. Objective:We sought to study the epidemiology of FEIAn, especially its frequency in junior-high-school students in Yokohama, Japan. Methods:A questionnaire asking about the occurrence of FEIAn in school students was sent to all 145 public junior-high-school nurses in Yokohama. Results:One hundred thirty-two junior-high-school nurses responded to the questionnaire, and 13 (11 boys and 2 girls) cases of FEIAn among 76,229 junior-high-school students were reported. In addition, 24 (12 boys and 12 girls) subjects with exercise-induced anaphylaxis (EIAn) were detected. From this survey, the frequency of FEIAn was 0.017% in this population, and its frequency was significantly higher in boys than in girls (P< .05). The frequency of EIAn was 0.031%, and there was no difference according to sex. Only one third of junior-high-school nurses had any knowledge of FEIAn. We also performed provocation tests in 5 of the 13 cases with FEIAn after obtaining informed consent from the students and their parents and were able to confirm the diagnosis. Conclusion:This study showed that FEIAn and EIAn are relatively rare diseases among junior-high-school students in Yokohama. To avoid serious outcomes, we believe it is important that not only physicians but also school nurses and teachers of physical education be aware of these diseases. (J Allergy Clin Immunol 2001;108:1035-9.)

Background:Food-dependent exercised-induced anaphylaxis (FEIAn) is classified among the physical allergies. Many different food allergens have been reported, but the pathophysiology of FEIAn remains unknown. Furthermore, provocation tests with a suspected food do not always succeed in patients with FEIAn. Objective:We sought to clarify and investigate causative foods and mechanisms of FEIAn in a 14-year-old boy. In addition, we tested in vivo and in vitro effects of cromolyn sodium in the same patient. Methods:We used open challenge tests for the provocation of FEIAn and measured changes in plasma histamine levels and FEV1. In addition, we investigated the mechanism of FEIAn in this case with in vitro histamine release testing. Results:The patient was diagnosed as having FEIAn by provocation testing with a simultaneous intake of wheat and umeboshi, but not when each food was eaten singly, followed by exercise. In addition, his plasma histamine level increased transiently and forced expiratory volume 1, expressed as a percentage change from baseline, decreased significantly. A synergistic effect on in vitro histamine release testing with 2 kinds of the causative foods was shown. Administration of cromolyn sodium proved to be effective on both the in vitro and in vivo tests. Conclusion:This is the first report of FEIAn provoked by the test with a simultaneous intake of 2 kinds of food. This case might in part explain negative challenge test results in patients with FEIAn. (J Allergy Clin Immunol 2001;107:1100-5.)

Abstract: Methotrexate (MTX) therapy is now a main-stream drug for the treatment of patients with rheumatoid arthritis (RA). Similarly, the therapy is being established in the treatment of juvenile rheumatoid arthritis (JRA). However, little is known about the therapy for JRA in Japan. Therefore, to establish MTX therapy for JRA we investigated the current state of therapy in Japan. In September 1996 a questionnaire about MTX therapy was sent to the main facilities in Japan where members of the Japan Pediatric Rheumatology Association have been treating patients with JRA. From seven main facilities, a total of 56 JRA patients treated with MTX were reported. From this survey, it was revealed that MTX was used frequently for the treatment of patients with JRA in combination with other drugs such as non-steroidal anti-inflammatory drugs and prednisolone. MTX therapy was determined effective in 80% of cases; moreover, this therapy was tolerable in most cases. However, there were a few mild adverse effects including hepatotoxicity. Thus, MTX therapy was applied broadly to JRA patients in Japan. The therapy was determined to be more effective than prior medications when combined with other drugs to treat JRA.

The central features of Kawasaki disease are immune activation and cytokine-mediated generalized vasculitis. To identify the predisposing factors, we examined the antibody response to BCG antigens, since reactivation of a previous BCG inoculation site is an early, specific manifestation of this disease. BCG antigens were separated on SDS-PAGE, transferred to membrane, and incubated with acute- and convalescent-phase sera of 21 patients with Kawasaki disease. Sera were also examined for the presence of antibodies to mycobacterial 65-kDa heat-shock protein (HSP65), and to its human homolog P1 antigen using synthetic peptides of nonhomologous region. To demonstrate the HSP65-sensitized T cells, in vitro proliferation assay was performed. All convalescent, but not acute phase, sera showed a strong antibody reactivity against 65-kDa protein. The reactivity was directed to recombinant HSP65. Non-crossreactive sequences between rHSP65 and human HSP65 cognate were synthesized. The sera recognized these peptides of rHSP65 and autologous P1 antigen. Peripheral lymphocytes proliferated following the addition of rHSP65 (stimulation indices, 2.16-7.82; mean, 4.54). These findings suggest that HSP65 may be the most potent factor predisposing to Kawasaki disease, and that an autoreactivity to the epitope of the human HSP65 homolog may be related to the susceptibility to the disease. Copyright 1993, 1999 Academic Press

ABSTRACTThis study investigated the applicability of molecular epidemiological techniques to the identification of the causal agent of an outbreak of diarrhea caused by ingestion of food contaminated with enterotoxigenic Escherichia coli(ETEC). The outbreak occurred at four elementary schools in July 1996 and affected more than 800 people. Illness was most strongly associated with eating tuna paste (relative risk, 1.79; 95% confidence interval = 1.16 to 2.79; P= 0.0001). To evaluate the epidemiological characteristics of the pathogen, the DNAs from numerous isolated ETEC strains were subjected to randomly amplified polymorphic DNA analysis, pulsed-field gel electrophoresis of nuclease S1-treated plasmid DNA, and analysis of genomic DNA restriction fragment length polymorphisms. All ETEC isolates were of the O25:NM (nonmotile) serotype, which carries a heat-stable enterotoxin Ib gene. Genotypic analysis demonstrated that the strains isolated from the patients at all four schools were identical. The isolates of ETEC O25:NM obtained from the tuna paste that had been served for lunch at these schools were genetically indistinguishable from those isolated from the patients. Results suggest that this outbreak was food borne. The molecular biology-based epidemiological techniques used in this study were useful in characterizing the causal agent in this food-borne epidemic.

Hapten specific T cell proliferation was induced in several strains of mice. When lymph node T cells from 4‐hydroxy‐3‐nitrophenyl acetyl‐keyhole lympet hemocyanin (NP‐KLH)‐primed mice were stimulated in vitrowith NP‐polymer glutamic acid‐lysine‐phenyl alanine (NP‐GLφ) or NP‐ovalbumin (NP‐OVA), they displayed a good level of proliferative responses. It was observed that NP‐GLφcould induce NP‐hapten specific proliferation even with NP‐KLH lymphocytes from GLφnon‐responder strains.

A 13-year-old girl with nephrotic syndrome (NS) developed acute leucoencephalopathy during combination therapy with cyclosporin A (CyA) and prednisolone (PSL). The patient had a generalized motor seizure followed by coma at 19 days after CyA administration. Magnetic resonance scanning performed on the 1st hospital day revealed white matter lesions in the subcortices of the parietal and occipital lobes, brain stem and cerebellum. These lesions had completely resolved on the 10th hospital day. This episode might be caused by CyA because the clinical course and laboratory data revealed neither inflammation nor other causative factors. To our knowledge, this is the first report of acute leucoencephalopathy during combination therapy with CyA and PSL in a patient with NS.

Norovirus is a common cause of gastroenteritis. We describe the case of a 23-month-old girl with encephalopathy possibly associated with norovirus infection. The viral genome was detected in stool, serum and cerebrospinal fluid (CSF) by reverse transcription polymerase chain reaction. This is the first report of encephalopathy potentially caused by norovirus as indicated by the presence of the virus genome in CSF.