The immune mechanism and potential biomarkers of non-IgE-mediated food allergy / 中华实用儿科临床杂志

The immune mechanism of non-IgE-mediated food allergy is quite complex.Due to the lack of specific laboratory indicators and limited diagnosis and treatment methods, non-IgE-mediated food allergy is usually misdiagnosed.Therefore, it is urgent to clarify the pathogenesis of the disease and search for specific biomarkers and novel therapeutic targets.This review aims to summarize current research results on the immune mechanism of non-IgE-mediated food allergy from two aspects, including the specific immunity and innate immunity, and to explore the potential diagnostic markers.The results may provide novel ideas for effective therapeutic strategies of non-IgE-mediated food allergy.

Features of intestinal flora in children with food protein-induced proctocolitis based on high-throughput sequencing / 中国当代儿科杂志

OBJECTIVES@#To study the features of intestinal flora in children with food protein-induced proctocolitis (FPIP) by high-throughput sequencing.@*METHODS@#A total of 31 children, aged <6 months, who experienced FPIP after exclusive breastfeeding and attended the outpatient service of the Third Affiliated Hospital of Zunyi Medical University from October 2018 to February 2021 were enrolled as the FPIP group. Thirty-one healthy infants were enrolled as the control group. Fecal samples were collected to extract DNA for PCR amplification. High-throughput sequencing was used to perform a bioinformatics analysis of 16S rDNA V3-V4 fragments in fecal samples.@*RESULTS@#The diversity analysis of intestinal flora showed that compared with the control group, the FPIP group had a lower Shannon index for diversity (P>0.05) and a significantly higher Chao index for abundance (P<0.01). At the phylum level, the intestinal flora in both groups were composed of Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes. Compared with the control group, the FPIP group had a significant reduction in the composition ratio of Actinobacteria (P<0.001) and a significant increase in the composition ratio of Proteobacteria (P<0.05). At the genus level, the intestinal flora in the FPIP group were mainly composed of Escherichia, Clostridium, Enterococcus, Klebsiella, and Bifidobacterium, and the intestinal flora in the control group were mainly composed of Bifidobacterium and Streptococcus. Compared with the control group, the FPIP group had a significant reduction in the composition ratio of Bifidobacterium and Ruminococcus (P<0.05) and significant increases in the composition ratios of Clostridium and Shigella (P<0.05).@*CONCLUSIONS@#Compared with the control group, the FPIP group has a reduction in the diversity of intestinal flora and an increase in their abundance, and there are certain differences in several bacterial genera. These results suggest that changes in the composition of intestinal flora at genus level may play an important role in the development and progression of FPIP.

Food protein-induced enterocolitis syndrome: a clinical analysis of 5 cases and literature review / 中华实用儿科临床杂志

Objective:To summarize and analyze the clinical features of food protein-induced enterocolitis syndrome (FPIES).Methods:The medical history and follow-up data of 5 children with FPIES diagnosed in Department of Gastroenterology, Beijing Children′s Hospital of Capital Medical University from July 2018 to September 2019 were collected, and their clinical characteristics were summarized and analyzed.Results:Five children with FPIES were all infants, including 3 females and 2 males.Before the onset of the disease, the cases visited multiple departments and the average number of visits before diagnosis was 3.There were 4 cases of milk protein allergy and 1 case of egg white allergy.The patients had acute vomiting [5 cases (100%)], diarrhea [4 cases (80%)], early shock symptoms [5 cases (100%)], transient fever [2 cases (40%)]. Hematogenous leukocytes were increased in 3 cases (60%), C-reactive protein was increased in 1 case (20%), faecal leukocytes(+ )[2 cases (40%)], occult blood (+ ) [1 case (20%)]. Four cases were tested for food allergen specific IgE, of which 2 cases (40%) were positive for milk protein.After avoiding allergens, 3 patients (60%) needed intravenous rehydration treatment and 2 cases (40%) received oral rehydration treatment.The above 5 cases recovered quickly.Three patients (60%) used antibiotics.Four cases (80%) of the first-degree relatives of FPIES had a clear history of allergy.Families of children with FPIES had low awareness of the disease before the diagnosis was made, and the allergens were strictly avoided according to the doctor′s instructions after the diagnosis was made.Similar allergic reactions did not occur again, and complementary foods were gradua-lly added under the guidance of the doctor.Two patients had multiple food allergies.The body weight and length of 2 children with growth retardation were catching up with each other.Conclusions:FPIES is a serious food allergy related gastrointestinal disease which is easy to be misdiagnosed clinically.The diagnosis requires a combination of the family and personal allergy history, diet records, the characteristic performance of disease onset, the effect of diet avoi-dance and the necessary differential diagnosis.The long-term management and monitoring after diagnosis is also very important.

Síndrome de enterocolitis inducida por proteínas alimentarias por ingesta de kiwi como causa de evento potencialmente grave inexplicado en una niña / Food Protein Induced Enterocolitis Syndrome due to ingestion of kiwi causing potentially severe unexplained event in a child

El síndrome de enterocolitis inducida por proteínas alimentarias es una alergia alimentaria no mediada por inmunoglobulina E que se manifiesta clínicamente con vómitos profusos y repetitivos, en ocasiones, asociados a diarrea, y puede llegar a asociar deshidratación y letargia, con riesgo de desarrollo de shock. A pesar de su potencial gravedad, el índice de sospecha de este síndrome es bajo, lo que demora su diagnóstico, especialmente, en aquellos casos que son desencadenados por alimentos sólidos. La presencia de vómitos y la duración de más de un minuto son los datos clave que pueden diferenciarlo de los episodios breves, resueltos e inexplicados. Se presenta el caso de una lactante de 6 meses de vida con diagnóstico final de síndrome de enterocolitis inducida por proteínas alimentarias por ingesta de kiwi.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE food allergy manifesting as profuse, repetitive vomiting, sometimes with diarrhea, leading to dehydration and lethargy that can be severe and lead to shock. Despite the potential severity, awareness of FPIES is low and diagnosis is often delayed, especially in those triggered by solid foods. Presence of vomits and duration of more than 1 minute are the key differential factors to distinguish FPIES from brief resolved unexplained events. We report a case of a 6-month-old infant finally diagnosed as having kiwi induced FPIES.

The diagnostic value of PIVKA-Ⅱcombined with AFP and AST/ALT ratio in the diagnosis of primary liver cancer with HBV infection / 国际检验医学杂志

Objective To investigate the expression level of protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) in serum of primary liver cancer patients with HBV infection and combined with alphafetoprotein (AFP) and AST/ALT ratio in the diagnosis of primary liver cancer with HBV infection.Methods Sera of 68 HBV infection patients with primary liver cancer were collected.Meanwhile, sera of 109 HBV infection patients (8 cases of gallbladder diseases, 94 cases of benign liver diseases, 7 csaes of other organ diseases) were collected as controls.The serum levels of PIVKA-Ⅱand AFP were detected by the method of chemiluminescent immunoassay and electrochemical luminescence respectively.The rate method was used to detect the content of AST and ALT, and the ratio of AST/ALT was calculated.Compared the expression level of tumor markers in each group, and the receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic efficacy of individual and combined application of each index in the diagnosis of primary liver cancer.Results The sera levels of PIVKA-Ⅱ, AFP and AST/ALT ratio in primary liver cancer with HBV infection group were all higher than those in control group (P＜0.01).ROC curve analysis showed that with the critical value of PIVKA-Ⅱ, AFP and AST/ALT ratio in serum were 100.42 mAu/mL, 232.35 ng/mL and 1.571 in the diagnosis of primary liver cancer with HBV infection, the area under the ROC curve (AUC) were 0.942, 0.786 and 0.723 respectively;the sensitivity were 89.70％, 58.80％and 51.50％;the specificity were 91.70％, 88.10％and 79.80％.The AUC of PIVKA-Ⅱcombined with AST/ALT ratio in the diagnosis of primary liver cancer with HBV infection was 0.955, the sensitivity and specificity wree 86.80％and 93.40％respectively.Conclusion The value of PIVKA-II in the diagnosis of primary liver cancer with HBV infection is obviously better than that of AFP and AST/ALT ratio.The combined detection with AST/ALT ratio will be helpful to improve the diagnostic efficacy of primary liver cancer with HBV infection.

Diagnostic value of serum alpha-fetoprotein, alpha-fetoprotein variant and abnormal prothrombin in primary hepatocellular carcinoma / 中华肝脏病杂志

Objective@#To explore the diagnostic value of single or combined detection of serum tumor markers alpha-fetoprotein (AFP), α-fetoprotein (AFP)-L3 and abnormal clotting (PIVKA-II) in the primary hepatic carcinoma.@*Methods@#Serum AFP, AFP-L3 and PIVKA-II of 56 cases with primary hepatic carcinoma, 46 cases with cirrhosis, 45 cases with other liver disease and 41 healthy persons (control group) were examined by chemiluminescence method, and the differences in the levels of AFP, AFP-L3 and PIVKA-II in each group were compared.@*Results@#Serum level of AFP, AFP-L3 and PIVKA-II in patients with primary liver cancer was significantly higher than that of the cirrhosis, other liver disease and control groups, and the difference was statistically significant (P < 0.05). The receiver operating characteristic curve analysis showed that the areas under the curve for the diagnosis of primary hepatic carcinoma by AFP, AFP-L3 and PIVKA-II were 0.887, 0.846 and 0.885, respectively. The combined use of the three tumor markers for the diagnosis of primary hepatic carcinoma increased the area under the curve to 0.899. Among the single detection, AFP had the highest sensitivity of 91.07% and PIVKA-II had the highest specificity at 88.63%. In the combined detection, AFP/PIVKA-II combination had the highest sensitivity of 94.64 %, while the AFP + AFP-L3 + PIVKA-II combination had the highest specificity at 98.48%.@*Conclusion@#Combined detection of AFP, AFP-L3 and PIVKA-II could improve the diagnostic specificity and the sensitivity of primary hepatic carcinoma; thereby make up the deficiency of single detection and improve the early diagnosis rate.

Marcadores de inflamación y desarrollo de tolerancia en la proctocolitis alérgica / Markers of inflammation and tolerance development in allergic proctocolitis

Antecedentes: Con el incremento de la proctocolitis alérgica inducida por proteínas de la dieta (PAIPD), son necesarios estudios que aclaren su fisiopatología y determinar marcadores no invasivos y sencillos para el diagnóstico y la evaluación del desarrollo de tolerancia. No hallamos estudios publicados sobre la función del índice de neutrófilos/linfocitos (INL) y el volumen plaquetario medio (VPM), que son marcadores no invasivos fácilmente medibles, en pacientes con PAIPD. Objetivos: Determinar la relación entre el INL y el VPM con el diagnóstico y desarrollo de tolerancia en niños con PAIPD. Métodos: Estudio transversal retrospectivo, los datos se obtuvieron del sistema de registros médicos, los síntomas y los resultados de laboratorio de los pacientes con diagnóstico de PAIPD fueron controlados en los consultorios de alergia y gastroenterología. Se compararon valores del hemograma al momento del diagnóstico con el grupo de niños sanos de edad y sexo similares. Resultados: Entre los 59 pacientes con diagnóstico de PAIPD, los varones representaron el 47,4% y las niñas, el 52,6%. El VPM y el volumen plaquetario relativo (VPR) eran significativamente más altos entre los pacientes con PAIPD en comparación con el grupo de referencia (n: 67) (p < 0,001). Asimismo, VPM y el VPR fueron significativamente elevados en pacientes que no desarrollaron tolerancia comparados con los que la desarrollaron (p= 0,01). Con el INL no hubo diferencias entre los grupos. Conclusiones: El VPM y el VPR se consideraron marcadores adecuados para predecir el pronóstico de los pacientes con PAIPD dado que son rápidos, costo-efectivos y fáciles de medir.

Background. Today, as a result of an increase in the frequency of food protein-induced allergic proctocolitis (FPIAP), there is a need for studies not only to enlighten the pathophysiology of the disease but also to determine simple, non-invasive markers in both diagnosis, and evaluation of the development of tolerance. No study has been found in the literature about the place of neutrophil/lymphocyte ratio (NLR) and mean platelet volume (MPV), which are easy to calculate and non-invasive markers. Objectives. The purpose is to determine the relation between NLR and MPV with the diagnosis and development of tolerance in children with FPIAP. Methods. In this retrospective cross-sectional study, clinical, demographic symptoms and laboratory findings of patients, monitored with FPIAP diagnosis in allergy and gastroenterology clinics, were acquired from the patient record system. Hemogram values at the time of diagnosis were compared with the values of healthy children of the same age and gender. Results. Among 59 patients diagnosed with FPIAP, males constitute 47.4% and females constitute 52.6%. MPV and platelet crit (PCT) values were significantly high when compared to the control group (n: 67) in FPIAP cases (p <0.001). Also, MPV and PCT values were significantly high in non-tolerance developing cases when compared to developing ones (p= 0.01). Conclusions. Contrary to NLR, MPV and PCT values have been considered to be good markers in predicting prognosis in cases with FPIAP since they are quick, cost effective and easy to calculate.

Research advances in the diagnosis and treatment of food protein-induced enterocolitis / 中华实用儿科临床杂志

Food protein-induced enterocolitis (FPIES) is a non-IgE mediated food allergy that occurs primarily in infants and children.Although the hypotension or even shock occurs and might need to go to emergency department in severe patient with FPIES,there is an overall lack of knowledge about FPIES.Misdiagnosed or delayed diagnosis might be due to the absence of non-invasive diagnostic biomarker or diagnostic program specifically for FPIES,an overall lack of understanding of FPIES,and a combination of nonspecific symptoms.A clinical history and oral food challenges are the main diagnostic tools.Take care to exclude other potential causes before diagnosis established in the case of the history unclear.Avoidance of trigger food is the main treatment.During a acute episode,intravenous fluids may be required,and the complications need to be treated as well.

Accuracy of des-γ-carboxy prothrombin(DCP) for diagnosis of primary hepatocellular cancer: a Meta-analysis / 临床检验杂志

Objective To carry out a systematic evaluation for the diagnostic accuracy of Des-γ-carboxy-prothrombin(DCP) in primary hepatocellular cancer(PHC) by Meta-analysis.Methods The published international and domestic studies on DCP in the diagnosis of PHC were searched in multiple databases from its inception until December 2016.A total of seventeen studies were finally selected,among which 1 970 cases of PHC group and 2 588 cases of control group were included.The control group was composed of chronic hepatitis,cirrhosis,tumors in other systems and healthy subjects with physical examination.A meta-analysis was performed using Stata 12.0.Results The overall pooled results of the analysis and the 95％ confidence intervals were as follows:the sensitivity(SEN) was 0.79 (0.74 to 0.83),the specificity (SPE) was 0.90 (0.87 to 0.93),the positive likelihood ratio(PLR) was 8.1 (5.8 to 11.1),the negative likelihood ratio(NLR) was 0.24(0.19 to 0.29),the diagnostic odds ratio(DOR) was 34(21 to 55) and the area under the summary receiver operator characteristic curve (SROC) was 0.91 (0.89 to 0.93).The sensitivity combined the detections of AFP and DCP in the diagnosis of PHC was 0.90 with 0.94 of AUCROC and 56 of DOR.Conclusion The serum DCP may exhibit a relatively higher diagnostic specificity for PHC.The combined detections of AFP and DCP could improve the sensitivity and diagnostic accuracy.

Severe forms of food allergy / Formas graves de alergia alimentar

Abstract Objectives: To guide the diagnostic and therapeutic management of severe forms of food allergy. Data sources: Search in the Medline database using the terms "severe food allergy," "anaphylaxis and food allergy," "generalized urticaria and food allergy," and "food protein-induced enterocolitis syndrome" in the last ten years, searching in the title, abstract, or keyword fields. Summary of data: Food allergy can be serious and life-threatening. Milk, eggs, peanuts, nuts, walnuts, wheat, sesame seeds, shrimp, fish, and fruit can precipitate allergic emergencies. The severity of reactions will depend on associated cofactors such as age, drug use at the onset of the reaction, history and persistence of asthma and/or severe allergic rhinitis, history of previous anaphylaxis, exercise, and associated diseases. For generalized urticaria and anaphylaxis, intramuscular epinephrine is the first and fundamental treatment line. For the treatment in acute phase of food-induced enterocolitis syndrome in the emergency setting, prompt hydroelectrolytic replacement, administration of methylprednisolone and ondansetron IV are necessary. It is important to recommend to the patient with food allergy to maintain the exclusion diet, seek specialized follow-up and, in those who have anaphylaxis, to emphasize the need to carry epinephrine. Conclusion: Severe food allergy may occur in the form of anaphylaxis and food-protein-induced enterocolitis syndrome, which are increasingly observed in the pediatric emergency room; hence, pediatricians must be alert so they can provide the immediate diagnosis and treatment.

Resumo Objetivos: Abordar o manejo diagnóstico e terapêutico das formas graves de alergia alimentar. Fontes dos dados: Busca ativa na base de dados Medline dos termos severe food allergies, anaphylaxis and food allergy e food protein-induced enterocolitis nos últimos dez anos e com busca nos campos título, resumo ou palavra-chave. Síntese dos dados: A alergia alimentar pode ser grave e ameaçadora à vida. Leite, ovo, amendoim, castanha, noz, trigo, gergelim, crustáceo, peixe e frutas podem precipitar emergências alérgicas. A gravidade das reações vai depender de fatores associados, tais como idade, uso de medicamentos no início da reação, persistência de asma e/ou rinite alérgica grave, história de prévia anafilaxia, exercício e doenças intercorrentes. Para anafilaxia, a adrenalina intramuscular é uma indicação bem estabelecida. Para o tratamento da síndrome da enterocolite induzida pela proteína alimentar na fase aguda no setor de emergência, fazem-se necessárias a pronta reposição hidroeletrolítica e a administração de metilprednisolona e odansetrona IV. Importante recomendar ao paciente com o diagnóstico de alergia alimentar grave que mantenha a dieta de exclusão, procure acompanhamento especializado e, naqueles que apresentaram anafilaxia, enfatizar a necessidade de portar adrenalina. Conclusão: Alergia alimentar grave pode se manifestar como anafilaxia ou síndrome da enterocolite induzida por proteína alimentar em fase aguda, as quais, por serem condições cada vez mais presentes e reconhecidas no setor de emergência pediátrica, demandam diagnóstico e tratamento imediatos.

Progresses in diagnosis and treatment of food protein-induced enteropathy / 国际儿科学杂志

Food protein-induced enteropathy (FPE)is a series symptom of chronic diarrhea, malabsorption, hypoproteinemia, malnutrition caused by non-IgE mediated food allergy.The pathogenesis of FPE remains unclear, and may be related to gut mucosal barrier, intestinal bacteria, gastrointestinal immunity, oral tolerance and genetic, etc.Histology performance of FPE is characterized by flat atrophy of the small intestine.Diagnosis of PFE relies on history, mucosal histological changes, and oral food challenges.Food eliminate is the mainstay of FPE management.The paper reviews the pathogenesis, clinical manifestation, diagnosis and treatment of FPE to improve the recognition of clinicians.

Food protein-induced enterocolitis syndrome / 国际儿科学杂志

Food protein-induced enterocolitis syndrome(FPIES) is a series symptoms of recurrent vomiring and diarrhea caused by non-IgE-mediated food allergy to cow milk and soy in infants.The most common causative foods of FPIES are cow milk,soy and rice.Symptoms start within first days to 12 months of life.The sensitivity is usually outgrown by 3 years of age.The most common clinical symptoms observed include recurrent vomiting,diarrhea,fecal bloody,lethargy,pallor,etc.The diagnosis relies on history,clinical features,food eliminate,and oral food challenges.The food elimination is the mains treatment of FPIES management.

The diagnostic value of protein induced by vitamin K absence or antagonist-ii in non-infant patients with acquired deficiency of vitamin K-dependent coagulation factors / 中华内科杂志

Objective To explore the diagnostic value of protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) in non-infant with acquired deficiency of vitamin K-dependent coagulation factors (ADVKCF).Methods PIVKA-Ⅱ levels were measured by ELISA in 50 patients with ADVKCF on day 0,3,7 after vitamin K treatment.Prothrombin time(PT),APTT,FⅡ ∶ C,FⅦ∶ C,FⅨ∶ C,and FⅩ∶ C were analyzed simultaneously.Twenty healthy subjects were enrolled as controls.Results The average level of PIVKA-Ⅱ in ADVKCF group was (3.83 ± 1.40) μg/L,while (1.30 ± 0.54) μg/L in the control group (P ＜ 0.05).The PIVKA-Ⅱ levels on day 0 and 3 did not show significant difference [(3.83 ± 1.40) μg/Lvs (3.79 ± 0.66) μg/L,P ＞ 0.05],but decreasing significantly on day 7 compared to the control group (P ＜ 0.05).The PIVKA-Ⅱ level was (3.78 ± 1.30) μg/L in patients receiving plasma transfusion,while (3.91 ± 1.49)μg/L in no-plasma-transfusion group (P ＞ 0.05).Coagulation factors Ⅱ,Ⅶ,Ⅸ and Ⅹ activity which decreased significantly before treatment returned to normal range after one week use of vitamin K,leading to complete correction of prolonged APTT and PT (＞ 100 seconds).Conclusions The PIVKAⅡ level in ADVKCF patients is significantly higher than that of healthy subjects within one week treatment of vitamin K,which is not influenced by plasma transfusion.This study suggests that PIVKA-Ⅱ is a more sensitive parameter than APTT,PT and the activity of coagulation factor,which could be a valuable factor in the early diagnosis of ADVKCF.

Food protein-induced enterocolitis syndrome caused by cow's milk protein allergy in an infant：case report and review of literature / 临床儿科杂志

To discuss clinical diagnosis and treatment of cow’s milk protein allergy and cow’s milk protein-induced FPIES (food protein induced enterocolitis syndrome). Methods We retrospectively analyzed clinical data of one infant with milk protein allergy-induced FPIES. Results A 67 days old female on mixed breast and formula feeding developed recurrent diarrhea, abdominal distension, vomiting, mucousy and bloody stools, feeding dififculty, anemia, and failure to thrive since 2 weeks after birth. Laboratory studies showed anemia, increased CRP level and elevation of peripheral white blood count and eosinophil proportion. Milk-speciifc IgE was negative. She was previously hospitalized 4 times, all with admitting diagnosis of“necrotizing enterocolitis”. We treated her with milk protein elimination for 4 weeks and all symptoms were resolved. Milk protein re-challenge test was positive, consistent with clinical features of cow’s milk protein allergy-induced infant FPIES. Conclusions Cow’s milk protein allergy and cow’s milk protein-induced FPIES can present with non-speciifc and variable clinical symptoms and signs, and should be considered in the differential diagnosis.

Is This Symptom Even a Food Allergy?: Clinical Types of Food Protein-induced Enterocolitis Syndrome / 대한소아소화기영양학회지

Food protein-induced enterocolitis syndrome (FPIES) is an under-recognized non-IgE-mediated gastrointestinal food allergy. The diagnosis of FPIES is based on clinical history, sequential symptoms and the timing, after excluding other possible causes. It is definitively diagnosed by an oral food challenge test. Unfortunately, the diagnosis of FPIES is frequently delayed because of non-specific symptoms and insufficient definitive diagnostic biomarkers. FPIES is not well recognized by clinicians; the affected infants are often mismanaged as having viral gastroenteritis, food poisoning, sepsis, or a surgical disease. Familiarity with the clinical features of FPIES and awareness of the indexes of suspicion for FPIES are important to diagnose FPIES. Understanding the recently defined clinical terms and types of FPIES is mandatory to suspect and correctly diagnose FPIES. The aim of this review is to provide a case-driven presentation as a guide of how to recognize the clinical features of FPIES to improve diagnosis and management of patients with FPIES.

Síndrome de enterocolitis inducido por proteínas de la dieta: reporte de casos / Food protein Induced enterocolitis: two case reports

A propósito de 2 casos clínicos de pacientes con antecedente de enterocolitis neonatal, se presenta el temade síndrome de enterocolitis inducido por proteínas de la dieta. Este es un tipo de alergia alimentaria no mediada por Ig E, de presentación severa, con incidencia y prevalencia desconocidas y cuya sospecha clínica, diagnóstico y manejo oportuno, se anteponen al desarrollo de complicaciones severas que incluso pueden llevar a la muerte.

Two case reports of patients with neonatal enterocolitis present the topic of Food Protein-Induced EnterocolitisSyndrome (FPIES). FPIES is a type of food allergy which is not mediated by IgE and which has a severe presentation.Its incidence and prevalence are unknown. Clinical suspicion, diagnosis, and timely management are important in light of likely development of severe complications which can even lead to death.

The Characteristics and Diagnostic Methods of Food Protein Induced Proctocolitis / 대한소아소화기영양학회지

Food protein induced proctocolitis (FPIPC) is a non-IgE mediated food allergy. FPIPC occurs exclusively among breast-fed infants within the first months of life. FPIPC is often diagnosed clinically in normal-conditioned infants with rectal bleeding. But FPIPC among infancy with rectal bleeding is less general than conceived. The endoscopic findings reveal an edematous and erythematous mucosa with superficial erosions or ulcerations, bleeding and lymphoid nodular hyperplasia. The prominent eosinophilic infiltrates in the rectosigmoid mucosa are important for the histopathologic diagnosis of FPIPC. However, in explaining eosinophilic infiltration within the lamina propria of the mucosa, it is necessary to differentiate whether it is a part of normal findings or occurs due to inflammatory reactions. Oral food challenge and elimination test is performed to identify the same clinical reaction as the symptom of FPIPC by the administration of a specific type of food to infants. The most common causal food is cow's milk. Thus oral food challenge and elimination test can be the effective way of confirming FPIPC, reducing the possibility of misdiagnosis. The purpose of this report is to identify the characteristics of FPIPC, to introduce its diagnostic methods, and to suggest the future direction of research.

Apoptosis and upregulation of TNF-alpha and TRAIL receptor 1 (DR4) in the pathogenesis of food protein-induced enterocolitis syndrome / 소아과

PURPOSE: Expression levels of tumor necrosis factor (TNF)-alpha expression on the mucosa of the small intestine is increased in patients with villous atrophy in food protein-induced enterocolitis syndrome (FPIES). TNF-alpha has been reported to induce apoptotic cell death in the epithelial cells. We studied the TNF family and TNF-receptor family apoptosis on the duodenal mucosa to investigate their roles in the pathogenesis of FPIES. METHODS: Fifteen infants diagnosed as having FPIES using standard oral challenge test and 5 controls were included. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to identify the apoptotic cell death bodies. Immunohistochemical staining of TNF-alpha, Fas ligand (FasL) for TNF family and TNF-related apoptosis-including ligand (TRAIL) receptor 1 (DR4), TRAIL receptor 2 (DR5), and Fas for TNF-receptor family were performed to determine the apoptotic mechanisms. RESULTS: TUNEL+ was significantly more highly expressed in the duodenal mucosa of FPIES patients than in controls (P=0.043). TNF-alpha (P=0.0001) and DR4 (P=0.003) were significantly more highly expressed in FPIES patients than in controls. Expression levels of FasL, Fas, and DR5 were low in both groups and were not significantly different between the 2 groups. CONCLUSION: These results suggest that FPIES pathogenesis is induced by apoptosis, and that TNF-alpha expression and DR4 pathway may have an important role in apoptosis.

Milk-induced enterocolitis in monozygotic twin neonates.

Reports of milk protein-induced enterocolitis are increasing, but few describe the condition in twins. Twin Japanese girls developed bloody diarrhea on day 4 and were transferred to the NICU in our hospital. Surgical disorder and infection were initially suspected, but the correct diagnosis was reached after 12 days of hospitalization.

The Clinical and Histopathologic Findings of Lymphonodular Hyperplasia of the Colon in Infancy and Childhood / 대한소아소화기영양학회지

PURPOSE: Lymphonodular hyperplasia of the colon (LNHC) is a rare finding in children and its significance as a pathologic finding is unclear. The aim of this study was to investigate the clinical significance of LNHC by analyzing clinical and histopathologic findings in children with LNHC. METHODS: We analyzed data from 38 patients who were confirmed to have LNHC by colonoscopy. We checked age, birth history, past history, family history, and clinical symptoms. A hematologic exam, stool exam, and image studies were performed and biopsy specimens were examined by a pathologist. All patients were asked to have short- and long-term follow-up. RESULTS: The mean age of the patients was 12.5+/-14.4 months. All patients presented with complaints of bloody stool. They appeared healthy and the hematologic findings were within a normal range, with the exception of one case. There was no other identified source of bleeding. On histologic exam, 36 patients (94.7%) had lymphoid follicles and 34 patients (84.5%) fulfilled the criteria of allergic colitis. Regardless of diet modification and presence of residual symptom, there was no recurrence of bloody stool through long-term follow-up in all patients. CONCLUSION: LNHC is more common in infants who are affected by allergic colitis, but it can appear even after infancy. LNHC should be regarded as the etiology when there are any other causes of rectal bleeding, especially in healthy children. We suggest that LNHC has a benign course regardless of diet modification and it might not require excessive concerns.