Differences in Thymus and Activation-Regulated Chemokine and Squamous Cell Carcinoma Antigen 2 Levels in Food Protein-Induced Enterocolitis Syndrome and Atopic Dermatitis.

INTRODUCTION: We previously reported that thymus and activation-regulated chemokine (TARC) levels measured after vomiting are useful predictors of a food protein-induced enterocolitis syndrome (FPIES) diagnosis. However, interpreting TARC levels in patients with eczema is difficult, as the levels are similarly elevated in patients with eczema caused by atopic dermatitis (AD). Therefore, we aimed to investigate whether it is possible to predict whether FPIES or AD is responsible for elevated TARC levels by simultaneously measuring TARC and squamous cell carcinoma antigen 2 (SCCA2), another T-helper type 2 biomarker. METHODS: Twenty-one episodes in 11 patients with FPIES (FPIES group) and 42 age-matched patients with AD (AD group) were included in this study. Serum TARC and SCCA2 levels were measured, and those values and relative ratios were compared between groups. RESULTS: The median age was 1.1 years in the FPIES group and 1.6 years in the AD group (p = 0.492). The median (interquartile range [IQR]) serum TARC concentration was significantly higher in the FPIES group than in the AD group (2,486 [1,815-4,097] pg/mL and 1,451 [1,201-1,751] pg/mL, respectively; p = 0.002). The median (IQR) SCCA2 concentration was significantly higher in the AD group than in the FPIES group (1.9 [1.3-2.9] pg/mL and 0.8 [0.6-1.5] pg/mL, respectively; p < 0.001). After matching, the analysis using stratified TARC values revealed no significant difference in TARC values between the FPIES and AD groups; however, the TARC/SCCA2 ratio was significantly higher in the FPIES group. CONCLUSION: Assessing the relative TARC/SCCA2 ratio may help predict whether elevated TARC levels measured after vomiting are caused by FPIES or AD.

Potential of Thymus and Activation-Regulated Chemokine (TARC) as a Prognostic Biomarker of Food Protein-Induced Enterocolitis Syndrome (FPIES) Caused by Egg Yolk.

BACKGROUND: Several recent studies have reported egg yolk-associated food protein-induced enterocolitis syndrome (FPIES) in Japan. We previously reported the usefulness of post-emetic thymus and activation-regulated chemokine (TARC) levels for the diagnosis and evaluation of symptom severity in FPIES caused by solid foods including egg yolk. However, there are no studies on the usefulness of TARC as a prognostic biomarker. OBJECTIVE: The aim of the study was to evaluate the post-emetic TARC levels, clinical symptoms, and post-index event results of the egg yolk oral food challenge test (OFC), and retrospectively investigate predictive factors of the subsequent OFC result. METHOD: This retrospective study included 12 patients with egg yolk FPIES. The following long-term management protocol for egg yolk FPIES was mandatory for study inclusion: Patients visited the emergency department, met the diagnostic criteria of FPIES, and underwent an egg yolk OFC 6-12 months after complete elimination of egg yolk. If the result of the OFC was positive, the patient underwent the OFC every year until it was negative. We analyzed a total of 20 episodes (12 department visits and eight positive OFCs). The blood test data, including post-emetic TARC level and symptom severity, were compared between the next-OFC-positive group and the next-OFC-negative group. In addition, tolerance development over follow-up was analyzed. RESULTS: The median (range) ages of the next-OFC-positive and negative groups were 11 (6-33) and 10 (7-21) months, respectively. The median (range) serum TARC (pg/mL) level was 5,208 (2,009-8,147) in the next-OFC-positive group, which was significantly higher (p = 0.004) than that in the next-OFC-negative group, which was 1,803 (905-3,754). There were no significant differences in other hematological results. The next-OFC-positive group had greater severity compared to the next-OFC-negative group (p = 0.026). The remission rate was approximately 30% at 24 months and 80% at 36 months. CONCLUSION: Post-emetic TARC levels may predict the short-term prognosis of egg yolk FPIES after approximately 1 year and could be useful for the management of egg yolk FPIES.

Evaluation of the Diagnostic Accuracy of Thymus and Activation-Regulated Chemokine to Discriminate Food Protein-Induced Enterocolitis Syndrome from Infectious Gastroenteritis.

BACKGROUND: Post-emetic elevation in thymus and activation-regulated chemokine (TARC) levels has been reported in patients with food protein-induced enterocolitis syndrome (FPIES); however, no studies have investigated differences in TARC levels between FPIES and other diseases. OBJECTIVES: We evaluated the clinical usefulness of TARC measurement in differentiating between FPIES and infectious gastroenteritis. METHODS: This study included 8 patients with solid-food FPIES (FPIES group; hen's egg [n = 6], rice [n = 1], and short-neck clam [n = 1]; a total of 11 episodes necessitating emergency department visit or positive result of oral food challenge test) and 17 patients with infectious gastroenteritis (control group), and all patients had no eczema. Post-emetic serum TARC levels and modified TARC levels (serum TARC value - normal mean for each age) were compared between the 2 groups. RESULTS: The median (range) ages for the FPIES and control groups were 0.7 (0.5-6.2) and 1.8 (0.1-4.4) years, respectively (p > 0.05). In the FPIES and control groups, median (range) TARC levels were 2,911 (1,062-7,816) and 600 (277-2,034) pg/mL, and median (range) modified TARC levels were 2,204 (355-7,109) and 129 (0-1,314), respectively. The TARC and modified TARC levels were significantly higher in the FPIES group than in the control group (p < 0.001 for both). CONCLUSION: In the absence of eczema, post-emetic serum TARC levels might be a potential diagnostic biomarker for distinguishing FPIES from infectious gastroenteritis.

[EVALUATION OF THE RELATIONSHIP BETWEEN THE SEVERITY OF SOLID FOOD PROTEIN-INDUCED ENTEROCOLITIS SYNDROME AND POST-EMETIC SERUM THYMUS AND ACTIVATION-REGULATED CHEMOKINE LEVELS].

BACKGROUND: We reported that post-emetic serum thymus and activation-regulated chemokine (TARC) levels may be a potential biomarker to diagnose solid food protein-induced enterocolitis syndrome (FPIES). However, there are no reports on the relationship between FPIES severity and serum TARC levels. METHODS: The subjects were 13 cases of FPIES (hen's egg=10, Wheat=1, rice=1, short-neck clam=1) for a total of 22 events (7 emergency outpatient visits, 9 positive and 6 negative results of oral food challenge test). Serum TARC levels at 6 and 24 h after antigen ingestion were compared between the symptomatic and asymptomatic events and the mild-moderate and severe events. We also evaluated the correlation between vomiting duration and serum TARC levels. RESULTS: The median serum TARC (pg/ml) in the asymptomatic, mild-moderate, and severe events were 546, 1093, and 3127 at 6 h after ingestion, and 910, 2053, and 6496 at 24 h after ingestion, respectively. The serum TARC level was significantly higher in the symptomatic events than the asymptomatic events, and it was significantly higher in the severe events than the mild-moderate events (p < 0.01). There was a moderate correlation between serum TARC levels and vomiting duration. CONCLUSION: Post-emetic serum TARC correlates with the severity of FPIES. It is expected that this information will lead to an objective evaluation of the severity of FPIES.

Comparison of methemoglobin levels in food protein-induced enterocolitis syndrome and other gastrointestinal diseases in neonates.

INTRODUCTION AND OBJECTIVES: Methemoglobinemia has been reported to be associated with severe food protein-induced enterocolitis syndrome (FPIES). However, no reports have evaluated methemoglobin (MHb) levels in FPIES without symptomatic methemoglobinemia or the usefulness of MHb measurement for the diagnostic prediction of FPIES. To evaluate the MHb levels of patients with neonatal-onset FPIES and determine whether MHb levels are higher in FPIES than in other gastrointestinal diseases. PATIENTS AND METHODS: Eleven neonates with severe acute FPIES (FPIES group) and 139 neonates with other gastrointestinal diseases (non-FPIES group) were included in this study. Patient characteristics, symptoms, and venous blood test values (MHb, pH, HCO3-, and C-reactive protein) were evaluated. RESULTS: The median age at onset was 16 days vs. 1 day; males comprised 64% vs. 46%, the median gestational age was 38 weeks vs. 38 weeks, the median birth weight was 2710g vs. 2880g, and the median hospitalization duration was 31 days vs. 6 days for the FPIES vs. non-FPIES groups, respectively. MHb (%) was higher in the FPIES group than in the non-FPIES group [median (range), 1.1 (0.6-10.9) and 0.6 (0.3-1.2), respectively, p<0.001]. There were no differences in terms of pH, HCO3-, and C-reactive protein (p>0.05). In the receiver operating characteristic analysis for FPIES diagnosis based on MHb (%), the area under the curve was 0.885, specificity was 97.1%, and sensitivity was 72.7% at a MHb cutoff of 1.0. CONCLUSION: High MHb levels may help diagnose severe acute FPIES in neonates, but careful evaluation is needed.

Comparison of Acute Phase Thymus and Activation-Regulated Chemokine (TARC) Levels in Food Protein-Induced Enterocolitis Syndrome and IgE-Dependent Food Allergy.

Introduction: Patients with food protein-induced enterocolitis syndrome (FPIES) have elevated thymus and activation-regulated chemokine (TARC) levels in the acute phase. However, to the best of our knowledge, no study has evaluated TARC levels in the acute phase of immunoglobulin E-dependent food allergy (IgE-FA). If TARC elevation is a specific response to FPIES among FAs, TARC measurement may help distinguish between FPIES and IgE-FA. Thus, we investigated acute phase TARC levels in patients with FPIES and IgE-FA. Methods: Thirty-one episodes in 16 patients with FPIES and 20 episodes (13 were anaphylaxis) in 20 patients with IgE-FA were included. Patients with eczema were excluded. Serum TARC levels within 6 h of allergic reaction onset and age-adjusted TARC ratios (TARC levels divided by age-specific normal TARC values) were compared between the groups. Results: The median age was 1.1 and 3.6 years in the FPIES and IgE-FA groups, respectively (P < 0.001). The median (range) serum TARC (pg/mL) levels were significantly higher in the FPIES group than in the IgE-FA group [1,283 (410-3,821) versus 377 (109-1,539); P < 0.001]. The median (range) age-adjusted TARC ratios were also significantly higher in the FPIES group [2.56 (0.57-7.86) versus 1.08 (0.15-2.17); P < 0.001]. The area under the curve (AUC) for TARC to distinguish FPIES from IgE-FA was 0.926, and the AUC for the age-adjusted TARC ratio was 0.850. The odds ratio for FPIES diagnosis per 1,000 pg/mL increase in TARC was 31.6 (P = 0.002), and the odds ratio adjusted by age was 17.1 (P = 0.016). Conclusion: Acute phase TARC levels were higher in patients with FPIES than in patients with IgE-FA. The increase in acute phase TARC levels was considered to be a specific response to FPIES among FAs. Measurement of TARC levels in the acute phase may help differentiate FPIES from IgE-FA.

Comparison of methemoglobin levels in food protein-induced enterocolitis syndrome and other gastrointestinal diseases in neonates

INTRODUCTION AND OBJECTIVES: Methemoglobinemia has been reported to be associated with severe food protein-induced enterocolitis syndrome (FPIES). However, no reports have evaluated methemoglobin (MHb) levels in FPIES without symptomatic methemoglobinemia or the usefulness of MHb measurement for the diagnostic prediction of FPIES. To evaluate the MHb levels of patients with neonatal-onset FPIES and determine whether MHb levels are higher in FPIES than in other gastrointestinal diseases. PATIENTS AND METHODS: Eleven neonates with severe acute FPIES (FPIES group) and 139 neonates with other gastrointestinal diseases (non-FPIES group) were included in this study. Patient characteristics, symptoms, and venous blood test values (MHb, pH, HCO3-, and C-reactive protein) were evaluated. RESULTS: The median age at onset was 16 days vs. 1 day; males comprised 64% vs. 46%, the median gestational age was 38 weeks vs. 38 weeks, the median birth weight was 2710g vs. 2880g, and the median hospitalization duration was 31 days vs. 6 days for the FPIES vs. non-FPIES groups, respectively. MHb (%) was higher in the FPIES group than in the non-FPIES group [median (range), 1.1 (0.6-10.9) and 0.6 (0.3-1.2), respectively, p < 0.001]. There were no differences in terms of pH, HCO3-, and C-reactive protein (p > 0.05). In the receiver operating characteristic analysis for FPIES diagnosis based on MHb (%), the area under the curve was 0.885, specificity was 97.1%, and sensitivity was 72.7% at a MHb cutoff of 1.0. CONCLUSION: High MHb levels may help diagnose severe acute FPIES in neonates, but careful evaluation is needed

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