Formulation of Adult Food-Protein-Induced Enterocolitis Syndrome Diagnostic Scoring System Differentiating from Immediate-type Food Allergy.

BACKGROUND: Adult food protein-induced enterocolitis syndrome (FPIES) has recently been recognized, and there are no international diagnostic criteria for this disease. Differentiating adult FPIES from immediate-type food allergy reactions and providing specific treatment for each in an emergency is important, but methods have not been developed. OBJECTIVE: To develop a diagnostic scoring system for adult FPIES by comparing it with an immediate-type food allergy (IgE-FA). METHODS: This retrospective cohort study of food-avoidant adults based on the diagnostic criteria for adult FPIES reported by Gonzalez et al. was conducted by telephone interviews. We compared the clinical profiles of the patients with FPIES and IgE-FA. Adult FPIES-associated factors were extracted using multivariate analysis, and a diagnostic scoring system was developed based on odds ratios (OR). RESULTS: Forty-eight (16.7%) of 288 adults with food allergies were diagnosed with FPIES; of these, 240 (83.3%) had IgE-FA. Seafood was the most common cause of FPIES in adults (68.8%). Multivariate analysis identified age of onset > 26, >10 episodes, a longer latency period, cold sweat, abdominal distention, and vomiting as adult FPIES-associated factors. An adult FPIES diagnostic scoring system was developed using ORs with a high area under the curve (AUC = .978), 100% sensitivity and 87.0% specificity. CONCLUSION: Clinical profiles and an adult FPIES diagnostic scoring system were developed for the first time. This scoring system can be useful in differentiating adult FPIES and IgE-FA while treating a food-related acute reactions.

A detailed intake-status profiling of seafoods in adult food-protein-induced enterocolitis syndrome patients.

BACKGROUND: Adults with food-protein-induced enterocolitis syndrome (FPIES) often develop severe abdominal symptoms after eating seafood. However, no investigation of a food elimination strategy for adult FPIES patients has been performed to date. METHODS: We conducted a retrospective cohort study of seafood-avoidant adults by telephone interview, based on the diagnostic criteria for adult FPIES reported by González et al. We compared the clinical profiles, abdominal symptoms, and causative seafoods between FPIES and immediate-type food allergy (IgE-mediated FA) patients. We also profiled the detailed intake-status of seafoods in adult FPIES patients. RESULTS: Twenty-two (18.8 %) of 117 adults with seafood-allergy were diagnosed with FPIES. Compared with the IgE-mediated FA patients, FPIES patients had an older age of onset, more pre-existing gastrointestinal and atopic diseases, more episodes, longer latency and duration of symptoms, more nausea, abdominal distention, and severe abdominal pain, and more frequent vomiting and diarrhea. In particular, abdominal distention-reflecting intestinal edema and luminal fluid retention-may be the most distinctive characteristic symptom in adult FPIES (p < 0.001). Bivalves, especially oysters, were the most common cause of FPIES. Strikingly, intake-status profiling revealed that many FPIES patients can safely ingest an average of 92.6 % of seafood species other than the causative species. CONCLUSIONS: There are many differentiators between FPIES and IgE-mediated FA, which may reflect differences in the underlying immunological mechanisms. Although seafood FPIES is unlikely to induce tolerance, many patients can ingest a wide variety of seafood species after a long period from onset.

A nationwide survey of non-IgE-mediated gastrointestinal food allergies in neonates and infants.

BACKGROUND: Non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) seem to be increasing rapidly worldwide. However, nationwide studies have been limited to food-protein-induced enterocolitis (FPIES) and food-protein-induced allergic proctocolitis (FPIAP), with little attention to other non-IgE-GIFA subgroups. The aim of this study was to elucidate the clinical features of all patients with non-IgE-GIFAs, not just certain subgroups. METHODS: We conducted a nationwide cross-sectional survey of non-IgE-GIFAs in Japan from April 2015 through March 2016. A questionnaire was sent to hospitals and clinics throughout Japan. The questionnaire asked about the number of physician-diagnosed non-IgE-GIFA patients, the status of fulfillment of the diagnostic criteria, tentative classification into 4 clusters based on the initial symptoms, the day of onset after birth, complications, and the suspected offending food(s). RESULTS: The response rate to that questionnaire was 67.6% from hospitals and 47.4% from clinics. Analyses were conducted about "diagnosis-probable" patient cohort (n = 402) and the "diagnosis-confirmed" patients (n = 80). In half of the reported non-IgE-GIFA patients, onset occurred in the neonatal period. The patients were evenly distributed among 4 non-IgE-GIFA clusters. In Cluster 1, with symptoms of vomiting and bloody stool, the onset showed a median of 7 days after birth, which was the earliest among the clusters. Cow's milk was the most common causative food. CONCLUSIONS: In half of the patients, the onset of non-IgE-GIFAs was in the neonatal period. This highlights the importance of studying the pathogenesis in the fetal and neonatal periods.

Comparison of adult food protein-induced enterocolitis syndrome to crustaceans and immediate-type food allergy.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is increasingly found in adults. FPIES requires different treatment from immediate-type food allergy (FA) in emergency medicine. However, no comparison of the clinical presentations of these diseases has been reported. OBJECTIVE: To compare the clinical presentations and causative crustaceans of adult FPIES and FA using a standardized questionnaire and to thereby lay the groundwork for establishing an algorithm that distinguishes those diseases. METHODS: We conducted a retrospective cohort study of crustacean-avoidant adults by telephone interview based on the previously reported diagnostic criteria for adult FPIES to compare the clinical features and crustacean intake status between FPIES and FA. RESULTS: Of 73 adult patients with crustacean allergy, 8 (11%) were diagnosed with having FPIES and 53 (73%) FA. Compared with the patients with FA, those with FPIES had a longer latency period (P < .01), more episodes (P = .02), longer duration of symptoms (P = .04), more frequent abdominal distention (P = .02), and severe colic pain (P = .02). Half of the patients with FPIES experienced fear of death during an episode. Panulirus japonicus (Japanese spiny lobster) and Homarus weber (lobster) were significantly common FPIES-causing foods. A statistically significant 62.5% of patients with FPIES were able to ingest some type of crustacean. CONCLUSION: FPIES and FA can be clearly differentiated by the abdominal symptoms, latency period, and duration of episodes. Furthermore, some patients with FPIES do not necessarily need to avoid all crustaceans. Our findings lay the groundwork for establishing an algorithm that distinguishes FPIES from FA in adults.

Tolerability and safety of a new elimination diet for pediatric eosinophilic gastritis and duodenitis.

BACKGROUND: Non-esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs) are chronic inflammatory disorders with massive infiltration of eosinophils into the gastrointestinal tract. Food elimination diets are potentially effective treatments. But the existing dietary therapies have various weak points. We developed a new regimen to compensate for the shortcomings of the elemental diet and 6-food elimination diet. The new regimen consists of an amino-acid-based formula, potatoes, vegetables, fruits and restricted seasonings. We named it the "Rainbow Elimination Diet (ED)." The aims of this study were to evaluate the tolerability and safety of this diet. METHODS: A retrospective medical record examination was conducted at the National Center for Child Health and Development covering the period from January 2010 through December 2018. The medical records of patients (age 2-17 y) with histologically diagnosed non-EoE EGIDs were reviewed. The tolerability, nutritional intake, symptoms, and blood test findings were evaluated. RESULTS: Nineteen patients were offered several kinds of food-elimination diets. Seven patients (eosinophilic gastritis: 5; gastroenteritis: 1; duodenitis: 1) were treated with Rainbow ED. Six patients were compliant with this diet. The median duration of the diet induction phase was 15 days (range 14-30). All 5 patients who had had symptoms just before the induction phase became symptom-free. The body weight decreased in 5 patients (median -0.6 kg), probably because the serum protein increased, resulting in reduced edema. All 5 patients with hypoproteinemia had elevated serum albumin (median 2.9-3.5 g/dL). The ingested nutritional elements were calculated, and most of them were sufficient, except for fat and selenium. CONCLUSIONS: The Rainbow ED was well-tolerated and safe for pediatric non-EoE EGIDs.

Comparison of Nonesophageal Eosinophilic Gastrointestinal Disorders with Eosinophilic Esophagitis: A Nationwide Survey.

BACKGROUND: Eosinophilic esophagitis (EoE) has increased rapidly and has been well characterized. However, no nationwide survey has been conducted regarding non-esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs), and they remain poorly understood. OBJECTIVE: To compare the clinical features and natural histories of non-EoE EGIDs and EoE by using the same questionnaire, for all ages. METHODS: We conducted a nationwide hospital-based survey of patients who visited hospitals from January 2013 through December 2017. We randomly selected 10,000 hospitals that perform endoscopy. We analyzed the demographics, symptoms, gastrointestinal histology, treatments, and natural histories of EoE and non-EoE EGIDs. RESULTS: A total of 2906 hospitals responded to the questionnaire. We identified 1542 patients and obtained detailed data for 786 patients, consisting of 39% EoE and 61% non-EoE EGIDs. The clinical characteristics were analyzed for patients who met the "definite" criteria that excluded comorbidities. Non-EoE EGIDs showed no gender difference, whereas EoE was male-predominant. Tissue eosinophilia was often seen in the small intestine (62%) and stomach (49%). The frequency of hypoproteinemia was high (27%) in childhood. Children also had more serious symptoms and complications than adults: restriction of daily life activity (P = .009), failure to grow/weight loss (P = .008), and surgery (P = .01). For both diseases, the most common natural history was the continuous type: 66% (95% confidence interval [CI]: 58-74) in EoE and 64% (95% CI: 55-72) in non-EoE EGIDs. CONCLUSIONS: The percentage of persistent patients with non-EoE EGIDs was almost the same as those with EoE. Complications were more frequent in children than in adults.

[Chronic recurrent multifocal osteomyelitis with interstitial myositis].

Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory, non-infectious disorder of skeletal system mainly seen in children. We report a case of CRMO presenting with fever and leg pain. The patient was an 11-year-old boy complaining of a fever, swelling and pain on his right foot, and pain on both legs. Although serum levels of CK and aldolase were not increased, MRI imaging suggested polymyositis. Muscle biopsy showed interstitial infiltration of inflammatory cells without any evidences of dermatomyositis or polymyositis. One month later, he complained of a swelling, pain and redness of his left clavicle as recurrently experienced during the recent 6 months, and MRI investigation indicated the diagnosis of osteomyelitis. Bone biopsy was performed and showed chronic inflammatory changes with negative bacterial culture. Multiple bone lesions and muscle uptake of FDG in his legs were revealed by whole body FDG-PET/CT, and he was diagnosed as having CRMO with interstitial myositis. The combinatorial administration of non-steroidal anti-inflammatory drugs and bisphosphonate successfully improved his clinical symptoms and laboratory abnormalities. To our knowledge, there is no report of a patient of CRMO associated with interstitial myositis.