Differences in Characteristics Between Patients Who Met or Partly Met the Diagnostic Criteria for Food Protein-Induced Enterocolitis Syndrome (FPIES).

BACKGROUND: Some patients with food protein-induced enterocolitis (FPIES)-like allergy do not completely fulfill the diagnostic criteria of the international consensus guideline for FPIES. However, it is unclear whether such FPIES-like patients represent a completely different population from FPIES. OBJECTIVE: This study aimed to clarify differences in characteristics between patients with FPIES who fully met diagnostic criteria and those who partly met them. METHODS: This was a cross-sectional study using data at the time of registration in multicenter, prospective studies of patients with FPIES in Japan. Children who had delayed emesis within 1 to 4 hours and/or diarrhea within 5 to 10 hours after ingestion of food were recruited between March 2020 and February 2022. We examined their compatibility with the diagnostic criteria of the international consensus guideline and their detailed clinical characteristics, including trigger foods, the serving size that elicited symptoms, and antigen-specific IgE antibody titers. RESULTS: Of the 225 patients with FPIES, 140 fully met the diagnostic criteria whereas 79 patients did not fully meet them but demonstrated reproducible symptoms. The frequencies of pallor, lethargy, and diarrhea were significantly higher in those who met the criteria fully, whereas the age at onset, trigger foods, comorbidity, and perinatal information were comparable. Analysis of patients with FPIES to hen's egg revealed significantly higher levels of egg white- and egg yolk-specific IgE in patients who partly met criteria, whereas the serving size eliciting symptoms was comparable. CONCLUSIONS: Patients who partly met the diagnostic criteria may have a milder phenotype of FPIES, but this needs to be validated in further studies using biomarkers reflecting the pathophysiology.

Heterogeneity of food protein-induced enterocolitis syndrome (FPIES).

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with gastrointestinal symptoms such as vomiting and diarrhea. The development of international consensus guidelines for the diagnosis and management of FPIES in 2017 enabled us to compare patients worldwide, regardless of geographic variation in disease features. As a result, it has become clear that there is heterogeneity among patients with FPIES or that there are cases that partly fit the diagnostic criteria for FPIES but have different characteristics. This review highlights the heterogeneity in FPIES characteristics in terms of trigger foods, the age of onset, differences in geographic regions, and symptoms; it further proposes four disease entities, including acute FPIES in children, acute FPIES in adults, chronic FPIES, and early-onset neonatal FPIES, depending on the age of onset and presumed pathophysiology. The major symptoms at onset and trigger foods differ in acute FPIES in children, acute FPIES in adults, and chronic FPIES, whereas the disease entities may share a similar pathophysiology. Early-onset neonatal FPIES may have a different pathophysiology than acute or chronic FPIES, and may not necessarily fulfil the full diagnostic criteria for acute or chronic FPIES described in the international consensus guidelines. Due to the similarity in symptoms, early-onset neonatal FPIES may sometimes be misdiagnosed as necrotizing enterocolitis. We aim to increase awareness of FPIES among medical staff in pediatrics, neonatology, and internal medicine and promote research, to gain a better understanding of the heterogeneity and pathophysiology of FPIES.

Seizure caused by Hypocalcemia as a Rare Manifestation in an Infant with Eosinophilic Gastroenteritis.

Eosinophilic gastroenteritis (EGE) can occur throughout the gastrointestinal tract, from the stomach to the colon. Typical known symptoms are abdominal pain, nausea, vomiting, and diarrhea. In addition, lesions in the intestinal mucosa may cause weight loss, protein-losing enteropathy (PLE), and other problems. A 6-month-old girl with no previous medical history was brought to our hospital after an afebrile 1-min clonic seizure. Blood tests showed low concentrations of serum calcium and albumin. After the correction of hypocalcemia with gluconic acid, there was no recurrence of seizure. Technetium-99m scintigraphy showed slight leakage of protein from the intestinal tract, which led us to conclude that the hypocalcemia and hypoalbuminemia were caused by PLE. Gastrointestinal endoscopy and biopsy performed to detect the cause of PLE revealed the presence of EGE. After starting administration of an amino acid-based formula, gastrointestinal symptoms of diarrhea or vomiting did not reappear. The serum albumin concentration normalized, and her weight gain improved. We report the first case of EGE in an infant who was diagnosed based on seizure. This case shows that infants with EGE may present with seizure resulting from hypocalcemia caused by PLE.

Food Protein-induced Enterocolitis Syndrome.

Food protein-induced enterocolitis syndrome (FPIES) is a type of non-IgE-mediated gastrointestinal food allergy. FPIES is characterized by repetitive vomiting without classic IgE-mediated allergic skin or respiratory symptoms 1-4 h after causative food ingestion. The condition may be classified as acute or chronic, typical or atypical, and liquid or solid according to the course of symptoms, presence of IgE antibodies, and causative food, respectively. Since the development of international consensus guidelines in 2017, epidemiological studies have been conducted in many countries. FPIES is a relatively rare disease, with a prevalence of 0.015%-0.7%. However, the number of patients has been increasing in recent years. Most patients develop the disease in infancy. The natural history of FPIES is generally favorable, with most FPIES cases resolving before school age. FPIES is diagnosed using symptoms such as vomiting or diarrhea, or via an oral food challenge (OFC). Currently, no validated biomarker is available for diagnosis, and the mechanisms related to gastrointestinal manifestations and immune system involved in the development of FPIES have not yet been elucidated. Treatment with intravenous fluids and ondansetron is recommended in the acute phase. Long-term management consists of complete causative food elimination and periodic OFC to confirm tolerance. Given that many diagnoses are delayed because of a lack of awareness of the condition, FPIES must be widely recognized by healthcare providers. In the future, it is expected that FPIES pathogenesis will be further clarified, and more objective diagnostic criteria will be developed.

[USE OF MULTIPLE DOSES OF ADRENALINE FOR FOOD-INDUCED ANAPHYLAXIS].

BACKGROUND: The aim of this study was to determine the rate, characteristics, and risk factors in patients who required multiple doses of adrenaline for treatment of anaphylaxis. METHODS: We retrospectively reviewed the positive oral food challenges (OFCs) with anaphylaxis in pediatric patients at Saitama City Hospital between January 2013 and November 2014, analyzing age, sex, comorbid allergic disease, specific IgE level, food, symptoms, and treatment. RESULT: There were 42 positive challenges with anaphylaxis, and the median age of the patients was 4 years old. Eighteen patients were treated with adrenaline, 5 of whom (11.9% of anaphylaxis cases) were administered multiple doses of adrenaline. Among the 5 patients, 3 were treated with infusion. We compared patients who were not administered adrenaline or were administered a single dose of adrenaline with those who were administered multiple doses of adrenaline. No significant differences were found among the groups in relation to age, sex, comorbid allergic disease, and the aim of OFCs. The number of patients who received multiple doses of adrenaline treatment was more in the milk OFCs than the other foods OFCs. Cardiovascular and neurological symptoms were more severe in patients who received multiple doses of adrenaline. CONCLUSION: Information that multiple doses of adrenaline may be required at the time of anaphylaxis should be widely disseminated.

[A CASE OF A CHILD DIAGNOSED AS HYPERSENSITIVITY REACTIONS TO NONSTEROIDAL ANTI-INFLAMMATORY DRUGS AFTER ONSET OF ORAL MITE ANAPHYLAXIS].

Oral mite anaphylaxis (OMA) caused by mite-containing food that was initially reported in 1993 has become commonly known after accumulating the case reports. Although it has been pointed out as being related to aspirin intolerance overseas, there are only a few cases reported in Japan so far, particularly no case for children. We report a child case which is seemingly related to OMA and aspirin intolerance. The case is for a boy at the age of 10. After eating Takoyaki with the ingredient of mite-containing flour, he was diagnosed as OMA due to the occurrence of anaphylaxis with respiratory discomfort, abdominal pain, and vomiting. One month later, he was suspected of aspirin intolerance, since he presented with symptoms such as swelling of the eyelid and coughing after taking loxoprofen which he never have taken, and intradermal test with loxoprofen was negative. Because the mechanism with a connection between mite allergy and aspirin intolerance still remains unknown, it would be necessary to accumulate more cases and clarify the pathology in future.

Listeria monocytogenes Meningitis Complicating Rotavirus Gastroenteritis in an Immunocompetent Child.

Listeria monocytogenes only occasionally causes bacterial meningitis in immunocompetent children. We report a case of L. monocytogenes meningitis associated with rotavirus gastroenteritis. The patient was a previously healthy 20-month-old girl who was admitted because of sustained fever and lethargy after suffering from gastroenteritis for 6 days. The patient's peripheral white blood cell count was 18,600/µL and the C-reactive protein level was 2.44 mg/dL. A stool sample tested positive for rotavirus antigen. A cerebrospinal fluid (CSF) sample showed pleocytosis. Cultures of the CSF and stool samples revealed the presence of L. monocytogenes. The patient was successfully treated with ampicillin and gentamicin. We speculate that translocation of enteric flora across the intestinal epithelium that had been damaged by rotavirus gastroenteritis might have caused bacteremia that disseminated into the CSF. Both listeriosis and secondary systemic infection after rotavirus gastroenteritis are rare but not unknown. Initiation of appropriate treatment as soon as possible is important for all types of bacterial meningitis. This rare but serious complication should be taken into consideration even if the patient does not have any medical history of immune-related problems.

Randomized controlled trial of oral immunotherapy for egg allergy in Japanese patients.

BACKGROUND: Egg allergy is one of the most common food allergies in young children. While oral immunotherapy (OIT) is not routinely recommended in current guidelines, it has been considered as a potential alternative treatment strategy. Studies on OIT for food allergy have been explored, but no controlled trials have been reported in Japan. METHODS: The first oral food challenge (OFC) was performed before treatment to ensure diagnosis and evaluate the threshold dose for egg using the double-blind, placebo-controlled food challenge. Participants were randomly assigned by computerized algorithm to receive OIT using egg (OIT group) or no egg (egg elimination [EE] group). A second OFC was performed in both groups approximately 6 months after therapy. Blood samples were collected and egg white-specific immunoglobulin (Ig)E and IgG4 were measured before and after the treatment period. RESULTS: Eight of the 14 patients (57%) in the OIT group had no allergic reaction to 4 g dry egg powder whereas none of the 16 patients in the EE group did. All 14 patients in the OIT group had increased threshold for egg powder in the second OFC compared with baseline. There was no significant change in egg white-specific IgE level during therapy. After therapy, egg white-specific IgG4 increased significantly in the OIT group, but not in the EE group. CONCLUSION: OIT is effective in increasing the threshold for allergens and inducing desensitization in Japanese egg allergy patients, similarly to North American and European patients.

INCIDENCE OF APNEA ATTACK AS ALLERGIC REACTION AFTER ORAL FOOD CHALLENGE IN PATIENT WITH IgE-MEDIATED WHEAT ALLERGY.

Anaphylaxis is a severe allergic reaction that is rapid in onset and might cause death. Although wheezes, dyspnea or loss of consciousness are known to occur with severe allergic reactions with IgE-mediated food allergy, reports of apnea attack associated with IgE-mediated food allergy are rare. In this case, 9-year-old boy with IgE-mediated wheat allergy experienced apnea attack with strong desaturation after an immediate allergic reaction including erythema, abdominal pain, vomiting, and anaphylactic shock. The patient had asphyxia and cyanosis confirmed by medical staff when his oxygen saturation decreased to the 60% level, and he had occasional asphyxia over 10 seconds with no thoracic motion after a desaturation episode. Central apnea attack might be occurred in patient with IgE-mediated food allergy. However, the exact mechanism responsible remains unknown and further research is needed.

Age-related prevalence of allergic diseases in Tokyo schoolchildren.

BACKGROUND: The International Study of Asthma and Allergies in Childhood (ISAAC) has reported the prevalence of asthma and allergic diseases in many countries. METHODS: We used the ISAAC core written questionnaire to examine the prevalence of asthma and allergic diseases in 6- to 14-year old schoolchildren in Tokyo. In 2005, we conducted a cross-sectional survey of all schoolchildren in all public schools located in the Setagaya area of Tokyo. RESULTS: Data were collected from 27,196 children in 95 schools. Prevalence ranged from 10.5% to 18.2% for asthma symptoms and from 10.9% to 19.6% for atopic dermatitis, with both conditions tending to decrease with age. As has been previously reported for all age groups, significantly higher rates of current asthma are observed in boys than in girls. The prevalence of allergic rhinoconjunctivitis exhibited a different pattern from that of asthma and atopic dermatitis, peaking at the age of 10 (34.8%). Prevalence of allergic rhinoconjunctivitis was 1.5 to 2-fold higher than the previous ISAAC studies that were performed in Tochigi and Fukuoka. In all age groups, symptoms of allergic conjunctivitis were more frequent from February to May, which coincides with the Japanese cedar pollen season, and were less frequent between June to September. CONCLUSIONS: The prevalence of asthma and atopic dermatitis was higher in younger schoolchildren. Tokyo schoolchildren appear to have extremely high prevalence rates of seasonal allergic rhinoconjunctivitis.

[Factors influencing parental medication adherence in pediatric asthma].

PURPOSE: To identify the factors influencing parental medication control behaviors (inhaling corticosteroids and medication-taking) in pediatric asthma management. METHODS: A specially-designed questionnaire survey was conducted on 942 parents with asthmatic children in hospitals and elementary schools. RESULTS: Factor analysis on inhalation behaviors resulted in five factors: understanding of benefit, mastering on inhalation skills and medication management, family support, anxiety of side effects, and explanation from a doctor (cumulative contribution ratio=51.3%). Factor analysis on medication-taking behavior resulted in five factors: understanding of medication effectiveness and benefit, family support, anxiety of side effects, skills on giving medicines, and family routine (cumulative contribution ratio=50.6%). CONCLUSION: The results indicate the importance of recognizing factors influencing parental medication control behaviors in developing education strategies to maintain and reinforce their asthma management behaviors.

[Prospective observational study of clinical course after stopping inhaled corticosteroids in child asthma].

BACKGROUND: Prospective study was carried out to observe the clinical course and find out the clinical index to predict the outcome after stopping of inhaled corticosteroids (ICS). SUBJECTS: One hundred twelve asthmatic children (aged 12.9+/-9.6 years old) who were totally controlled with 100 microg/day of inhaled corticosteroids and have not experienced asthma symptom over 3 months, were enrolled. METHODS: Patients with over PC20 0.5 mg/mL of methacholine challenge test (MCT) were recommended to stop ICS therapy. Clinical course, lung function and bronchial hyperreactivity were followed at 7, 16 and 24 months after stopping of ICS. RESULTS: Eighty-one percent of 63 patients followed up to 24 months run on as symptom less than one time per month without remarkable change of lung function. PC20 in group of no asthma symptom during 24 months (group A) decreased weakly. That of other groups decreased remarkably. Days using ICS and plasma IgE antibody at stopping of ICS were different in clinical course at 24 months after stopping ICS. CONCLUSION: Over 80% of totally controlled asthmatic children with MCT PC20 over 0.5 mg/mL could stop ICS therapy and run on without relapse.

Exercise-induced asthma is associated with impaired quality of life among children with asthma in Japan.

BACKGROUND: Asthma is the most common chronic diseases in school-aged children in Japan. It is important to consider health-related quality of life (QoL) among children with chronic diseases when treatment decisions are made. METHODS: A school-based survey was conducted in randomly selected public schools in Tokyo by using a KINDL questionnaire for evaluating QoL and the international study of asthma and allergy on childhood (ISAAC) questionnaire, which is designed for comparing the asthma prevalence in various countries, from May to June in 2005. We recruited approximately 10% of the total children 6-7-years-old and 13-14-years-old living in Tokyo for sampling. RESULTS: Response rate of this questionnaire was 86% (22,645 children) in the 6-7-year-old group and 64% (12,879 children) in the 13-14-year-old group. Comparing asthmatics with non-asthmatics in the same age, QoL of children with asthma was significantly impaired. The severity of QoL of children with asthma was significantly impaired. QoL of children with exercise-induced asthma (EIA) were more significantly impaired than ones without EIA and showed lower scores in the categories of physical functioning, emotional and school activities than those without EIA. Of note, QoL was more impaired in the EIA-positive group among severe asthmatics, suggesting that QoL of children with even severe asthma could be improved when EIA is appropriately controlled. CONCLUSIONS: Existence of EIA among asthmatic children most strongly impairs their QoL. We should be more cautious about the management of EIA.

[Clinical features of severe infant atopic dermatitis with hypoproteinemia].

OBJECTIVE: In recent years, there have been sporadic reports of severe atopic dermatitis (AD) with hypoproteinemia and growth impairment. The present study was conduced in order to ascertain the characteristics of patients with severe infant AD with hypoproteinemia at the initial visit and their treatment courses. SUBJECTS: Of AD patients younger than 1 year of age who visited the department over a 27-month period from March 2002, subjects were those with severe AD accompanied by hypoproteinemia. The clinical characteristics of these patients at the initial visit and the changes in symptoms and laboratory findings were statistically analyzed. RESULTS: Of the total of 119 AD patients younger than 1 year of age visited to the department during the above-mentioned period, 15 patients had severe AD with hypoproteinemia. The height and body weight of approximately half of the patients were less than 3rd percentile, and 10% and more of the patients had severe hyponatremia or hyperpotassemia. The platelet count for 60% of the patients exceeded 800 x 10(3)/microl. After visiting the department, therapy involving the use of skin care products and topical steroids and the removal of exacerbation factors quickly improved dermal symptoms and laboratory findings. CONCLUSION: Severe AD is a disease that should be cautiously treated because of the risk of hypoproteinemia, growth impairment, electrolyte abnormalities, and thrombocytosis; however, it should be noted that appropriate treatments can improve this condition.