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.

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.

Stratified therapy for Kawasaki disease using a new scoring system to predict the response to a lower dose of intravenous immunoglobulin therapy.

BACKGROUND: Several studies have reported treatment options for patients with Kawasaki disease refractory to standard immunoglobulin therapy; however, no studies have reported low-dose immunoglobulin therapy for patients with a low risk of Kawasaki disease. METHODS: A total of 277 patients with Kawasaki disease were included in this study. We used Kobayashi score and our Less high-risk score to divide the patients into three groups. Patients in the high-risk group (Kobayashi score ≥ 5 points) received 2 g/kg intravenous immunoglobulin and prednisolone. Patients in the moderate-risk group (Kobayashi score < 5 points and Less high-risk score ≥ 2 points) received 2 g/kg intravenous immunoglobulin treatment. Patients in the low-risk group (Kobayashi score < 5 points and Less high-risk score < 2 points) received 1 g/kg intravenous immunoglobulin treatment. The response rate and the incidence of coronary artery lesions at 4 weeks after treatment were evaluated in each group. RESULTS: The treatment response rates in the high-risk (n = 110), moderate-risk (n = 80), and low-risk (n = 87) groups were 74.5, 72.5, and 77.0%, respectively. Coronary artery lesions occurred in 7.3, 3.8, and 2.3% of patients in the high-, moderate-, and low-risk groups, respectively. There were no significant differences between the groups regarding treatment response or coronary artery lesion rate. CONCLUSION: The therapeutic response rate and the therapeutic effect of low-dose intravenous immunoglobulin in the low-risk group identified with our new scoring were satisfactory. Stratified therapies for patients with Kawasaki disease based on the scoring system may be useful.

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.

Vigabatrin Therapy for Infantile Spasms in a Case of Cardiofaciocutaneous Syndrome with Cardiac Hypertrophy Developing during Adrenocorticotropic Hormone Treatment.

In a patient with cardiofaciocutaneous syndrome complicated by intractable infantile spasms (West syndrome), cardiac hypertrophy developed during adrenocorticotropic hormone treatment. Various types of antiepileptic drugs, intravenous immunoglobulin, thyrotropin releasing hormone, and a ketogenic diet were ineffective in this case. However, vigabatrin both decreased clinical seizures and improved electroencephalogram findings. Although vigabatrin has not been approved for use in Japan, the results in the present case suggest that this drug should be considered as an alternative therapy for cases of infantile spasms associated with syndromes involving cardiomyopathy or its potential risk factors, such as cardiofaciocutaneous syndrome.

Volume measurement of the left ventricle in children using real-time three-dimensional echocardiography: comparison with ventriculography.

OBJECTIVES: Recently, a real-time three-dimensional echocardiography (RT3DE) volume scanning technique was developed and used clinically. For precise ventricular volumetry, independent of mathematical assumptions, imaging techniques such as three-dimensional echocardiography are required in children with heart disease. This study evaluated whether RT3DE is suitable for left ventricular volumetry in children, and whether left ventricular volumes measured by RT3DE correlate sufficiently well with those measured by left ventriculography (LVG). METHODS: Twenty-five children with heart disease, 17 boys and 8 girls aged from 8 months to 18 years (mean age 5.9 +/- 5.3 years), underwent cardiac catheterization at our institution. RT3DE was performed within 30 min after LVG using the Philips SONOS 7500 ultrasound system with an electronic sector probe consisting of a X 4 matrix phased array transducer (center frequency of 2-4 MHz). Ultrasound images of the ventricle were calculated offline using TomTec 4D Cardio-View RT 1.2 software. Left ventricular volumes by LVG were calculated using Siemens Hicor T.O.P. Finally, the left ventricular volumes by RT3DE and LVG were compared. RESULTS: Left ventricular volumes measured by RT3DE correlated and agreed well with those measured by LVG(r = 0.996, Y = 0.566 + 0.964 X, mean difference -0.29 +/- 1.90ml; left ventricular end-systolic volume, r = 0.979, Y=-0.187 + 0.897 X, mean difference -6.76 +/- 10.58ml; left ventricular end-diastolic volume). CONCLUSIONS: RT3DE is suitable for left ventricular volumetry in children. There was a good correlation between RT3DE and LVG, but the volume of left ventricular end-diastolic volume estimated by RT3DE was smaller than that by LVG.