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

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.

Successful endoscopic submucosal dissection of a giant polyp in a 21-month-old female.

Endoscopic submucosal dissection (ESD) is now recognized as the preferred treatment modality for gastrointestinal epithelial lesions. A 21-month-old female was admitted with a giant hyperplastic polyp causing a gastric outlet obstruction. Successful ESD was performed with caution. The post-procedural course was uneventful without a bleeding episode. Although further study of the feasibility of ESD in early children is necessary, ESD could be applied to avoid laparotomy even in young children.

Clonazepam treatment of pathologic aerophagia in children with mental retardation.

PURPOSE: Pathologic aerophagia (PA) may lead to bowel perforation or volvulus in mentally retarded patients. The authors investigated the effects of clonazepam on the management of PA in children with severe to profound mental retardation (MR). METHODS: This study was undertaken as a retrospective case analysis of 21 PA patients with MR who were followed for over 12 months and diagnosed as having PA. Patients were assigned to two management groups, that is, to a clonazepam randomized open-labeled, treatment group or a reassurance group. The following were recorded and analyzed; age, response, remission rate to clonazepam treatment, and the side effect of clonazepam. It was defined positive response (response+) as being symptom-free for a whole week within 1 month of commencing treatment and remission(+) as being symptom-free for a whole month within 6 months of treatment. RESULTS: The average age of the 21 PA children with MR was 10 years and 13 patients were female. Symptom duration before diagnosis of PA was 7 months. Clinical features of the clonazepam-trial group (n=11) and the reassurance group (n=10) were non-significantly different. Response(+) was achieved by 2 patients (18.2%) in the clonazepam-trial group and by no patient in the reassurance group. Remission(+) was achieved by 6 patients (54.5%) in the clonazepam-trial group and by one patient (10%) in the reassurance group (p=0.040). CONCLUSION: When PA children with MR with severe bowel distention are considered for surgical treatment to prevent acute abdomen, a trial of clonazepam could be recommended.

Epstein-barr virus infection with acute pancreatitis associated with cholestatic hepatitis.

Infection-induced acute hepatitis complicated with acute pancreatitis is associated with hepatitis A virus, hepatitis B virus or hepatitis E virus. Although rare, Epstein-Barr virus (EBV) infection should be considered also in the differential diagnosis if the patient has acute hepatitis combined with pancreatitis. We report a case of EBV infection with cholestatic hepatitis and pancreatitis with review of literature. An 11-year-old female was admitted due to 1-day history of abdominal pain and vomiting without any clinical symptoms of infectious mononucleosis. Diagnosis of reactivated EBV infection was made by the positive result of viral capsid antigen (VCA) IgM, VCA IgG, Epstein-Barr nuclear antigen and heterophile antibody test. We performed serologic tests and magnetic resonance cholangiopancreatography to exclude other viral or bacterial infection, autoimmune disorder, and structural problems. The patient's symptoms recovered rapidly and blood chemistry returned to normal with conservative treatment similar to previously reported cases.

Food protein-induced proctocolitis: Is this allergic disorder a reality or a phantom in neonates?

The etiology of small and fresh rectal bleeding in neonates who are not sick is usually unknown; the only known cause is food protein-induced proctocolitis (FPIPC). It has been recently reported that FPIPC is a rare cause of rectal bleeding in newborns, and most cases have been proved to be due to idiopathic neonatal transient colitis. A recommended strategy for diagnosing suspected FPIPC in neonates is as follows. During the early stage, the etiology of small and fresh rectal bleeding in an otherwise healthy newborn need not be studied through extensive investigations. In patients showing continued bleeding even after 4 days, sigmoidoscopy and rectal mucosal biopsy may be performed. Even if mucosal histological findings indicate a diagnosis of FPIPC, further oral food elimination and challenge tests must be performed sequentially to confirm FPIPC. Food elimination and challenge tests should be included in the diagnostic criteria of FPIPC.

The etiology of small and fresh rectal bleeding in not-sick neonates: should we initially suspect food protein-induced proctocolitis?

UNLABELLED: This study was performed to identify the cause and frequency of food protein-induced proctocolitis (FPIPC) in not-sick neonates with small and fresh rectal bleeding and to verify the effectiveness of oral food elimination and challenge test (ECT) as a diagnostic method of FPIPC. We prospectively analyzed neonates with small and fresh rectal bleeding who were clinically normal. We investigated age at symptom onset, feeding at onset of bleeding, the time of bleeding disappearance, stool smear and culture, endoscopic findings, and histopathologies in the biopsy specimens of 16 not-sick neonates. We performed food ECT in cases with over 4 days of persistent rectal bleeding in the absence of any other etiology. In 16 not-sick neonates with rectal bleeding, the median age at symptom onset was 8.5 (1-43) days. Endoscopic abnormalities were observed in all 16 patients, and in 10 cases satisfying the pathological guidelines for FPIPC, two (12.5 %) were confirmed as FPIPC by food ECT. In the other 14 (87.5 %) cases, rectal bleeding spontaneously disappeared after on average at 4 (1-8) days and thus was diagnosed as idiopathic neonatal transient colitis (INTC). CONCLUSIONS: FPIPC is rare as a cause of small and fresh rectal bleeding in not-sick newborns and most of cases proved to be INTC. Although clinical findings are suspected as its symptoms and histological results satisfy its diagnostic criteria, FPIPC should be carefully confirmed through food ECT.

Cytomegalovirus-associated esophageal ulcer in an immunocompetent infant: When should ganciclovir be administered?

Cytomegalovirus (CMV)-associated esophageal ulcer is rare in immunocompetent infants. The presence of inclusion bodies and immunohistochemical staining for CMV in biopsy specimens obtained during esophagogastroduodenoscopy (EGD) indicate that such ulcers occur because of CMV infection. A 7-week-old female infant who experienced frequent vomiting and feeding intolerance was diagnosed with a massive CMV-associated ulcer in the distal esophagus. The ulcer improved after conservative treatment using proton-pump inhibitors; however, ganciclovir was not administered. In a follow-up EGD biopsy specimen, no CMV inclusion bodies were present, and immunohistochemical staining results for this virus were negative. The presence of CMV inclusion bodies indicates active viral replication. If persistent inclusion bodies or positive immunohistochemical staining for CMV is observed in follow-up biopsy specimens, ganciclovir may be used to treat CMV-associated esophageal ulcers.

Acute Pancreatitis Induced by Azathioprine and 6-mercaptopurine Proven by Single and Low Dose Challenge Testing in a Child with Crohn Disease.

We report here a case of drug-induced acute pancreatitis proved by elimination and single, low dose challenge test in a child with Crohn disease. A 14-year-old boy with moderate/severe Crohn disease was admitted due to high fever and severe epigastric pain during administration of mesalazine and azathioprine. Blood test and abdominal ultrasonography revealed acute pancreatitis. After discontinuance of the medication and supportive care, the symptoms and laboratory findings improved. A single, low dose challenge test was done to confirm the relationship of the adverse drug reaction and acute pancreatitis, and to discriminate the responsible drug. Azathioprine and 6-mercaptopurine showed positive responses, and mesalazine showed a negative response. We introduce the method of single, low dose challenge test and its interpretation for drug-induced pancreatitis.

What is the 'objective' differential factor of diarrhea in infancy?: Normal state versus diarrheal illness in infants with chronic frequent and loose stool.

PURPOSE: This study aimed to identify 'objective' differential factors for normal frequent loose stool (NFLS) and diarrheal illness with dehydration and nutritional deficiency (DIDN) among infants with chronic frequent loose stool (CFLS). METHODS: Data were analyzed from infants under 2 years of age with CFLS who had been transferred from general pediatricians. These 46 patients were divided into 2 groups (NFLS versus DIDN). Nocturnal stool was defined as evacuation between 10 pm and 6 am. Maximal stool amount/day (measured using the mother's hand) was specified as the highest score during the period of CFLS obtained by adding up each evacuation's score (range, 0-2 points). RESULTS: There were 36 cases of NFLS and 10 of DIDN. A failure to gain weight (P=0.0001), fever (P=0.0079), colic/abdominal pain (P=0.0014), gross blood in stool (except allergic proctocolitis) (P=0.0113), nocturnal stool (P=0.0001), and the score of stool amount (P=0.0001) were found to significantly differentiate the groups. A failure to gain weight was observed in 39% of even NFLS. The frequency, mucus content, and microbiological findings of stools, as well as diaper dermatitis were not found to significantly differentiate the groups. CONCLUSION: NFLS was more common than DIDN in infants with CFLS. The most 'objective' differential factors were nocturnal stool and the score of stool amount (≥7 points/day).

Protein losing enteropathy in severe atopic dermatitis in an exclusively breast-fed infant.

We first report a case of protein losing enteropathy in severe atopic dermatitis in an exclusively breast-fed 5-month-old infant. Protein losing enteropathy was confirmed by fecal alpha1-antitrypsin clearance test and imaged successfully by 99mTc-human serum albumin scintigraphy. The present case highlights that protein losing enteropathy in severe infantile atopic dermatitis is being a topic of concern and also an issue even in exclusive breast feeding patients.

Diffuse microscopic angiodysplasia and nodular lymphoid hyperplasia in an infant with obscure massive lower gastrointestinal bleeding: a diagnostic challenge.

The authors report a rare case of diffuse microscopic angiodysplasia and nodular lymphoid hyperplasia involving the distal ileum and total colon in a 13-month-old girl who had recurrent episodes of massive lower gastrointestinal bleeding of obscure origin. Colonoscopy showed multiple nodular hyperplasia and mucosal erosions, and all other diagnostic studies were negative. At laparotomy, intraoperative transluminal endoscopic transillumination was of benefit in identifying the bleeding foci but could not detect every angiodysplastic lesion.

The significance of gastric juice analysis for a positive challenge by a standard oral challenge test in typical cow's milk protein-induced enterocolitis.

This study was performed to investigate the significance of gastric juice analysis (GJA) as a diagnostic criterion of a positive challenge in a standard oral cow's milk challenge (OCC) to confirm typical cow's milk protein-induced enterocolitis (CMPIE). Data from 16 CMPIE patients (aged 14 to 44 days) were analyzed. A standard OCC was openly executed using 0.15 g/kg of protein. Three symptoms (vomiting, lethargy, and bloody or pus-like stool), and four laboratory findings (GJA [3 hr], changes in peripheral blood absolute neutrophil count [ANC] [6 hr], C-reactive protein [6 hr], and stool smear test for occult blood or leukocytes) were observed after OCC. Before OCC, baseline studies were conducted; a stool smear test, blood sampling, and GJA. Positive OCC results were; vomiting (87.5%) (observed 1-3 hr after OCC), lethargy (62.5%) (1-3 hr), bloody or pus-like stool (43.8%) (6-10 hr), abnormal GJA (93.8%), an ANC rise >3,500 cells/microL (93.8%), and an abnormal stool smear test (75.0%). A single GJA test after a standard OCC is a sensitive diagnostic criterion of a positive challenge, and may provide an early confirmatory diagnosis of CMPIE. An investigation of positive OCC outcomes helps to find out a diagnostic algorithm of criteria of a positive challenge in CMPIE.

Indexes of suspicion of typical cow's milk protein-induced enterocolitis.

This study was performed to identify clinical factors that facilitate the diagnosis of typical cow's milk protein-induced enterocolitis (CMPIE). Data from 142 consecutive patients (aged 15 to 45 days, cow's milk formula- or cow's milk and breast milk mixed-fed) admitted due to vomiting and/or diarrhea were retrospectively analyzed. These 142 subjects were divided into three groups: the CMPIE, infection, and non-infection group. Each group was composed of 16 (11.3%), 102 (71.8%), and 24 (16.9%) patients, respectively. On admission, poor weight gain (p=0.003), hypoalbuminemia (p=0.035), peripheral leukocytosis (p=0.012), and metabolic acidosis (p=0.015) were found to be more significant in the CMPIE group than those in other two groups. In CMPIE, serum albumin levels decreased from 3.3+/-0.9 g/dL on admission to 2.6+/-0.3 g/dL during admission (p<0.05), and methemoglobinemia was observed in 3 patients (18.8%) (p=0.012). Multiple logistic regression analysis showed that the independent predictors of CMPIE versus the infection group were failure to gain weight (OR, 10.75 [95% CI, 1.53-66.12]) (p= 0.014) and hypoalbuminemia (OR, 9.53 [95% CI, 1.62-49.01]) (p=0.010). The early recognition of indexes of suspicion for CMPIE may be of help in the diagnosis and treatment of this disorder.

12-O-tetradecanoyl phorbol 13-acetate induces the expression of B7-DC, -H1, -H2, and -H3 in K562 cells.

Induction of the B7 family molecules by 12-O-tetradecanoyl phorbol 13-acetate (TPA) has been reported, however, the mechanism by which TPA up-regulates these molecules remains poorly understood. In this study, the expression of B7-DC, -H1, -H2, and -H3 in response to TPA was markedly induced in K562 cells. TPA also induced activation of ERK, p38 mitogen-activated protein kinase (MAPK), JNK, phosphatidylinositol-3-kinase (PI-3K), or nuclear factor (NF)-kappaB. Pre-treatments with protein kinase C (PKC) inhibitors significantly inhibited TPA-induced expression of B7-DC, -H1, -H2, and -H3 mRNA as well as TPA-induced phosphorylation of ERK, p38 MAPK, JNK, and PI-3K. TPA-induced expression of B7-DC, -H1, -H2, and -H3 mRNA was abrogated by pre-treatments with inhibitors of ERK and p38 MAPK. However, inhibition of PI-3K and JNK only caused decrease of TPA-induced B7-DC mRNA and B7-H3 mRNA, respectively. TPA-induced degradation of IkappaB-alpha was markedly abrogated by treatments with PKC inhibitors, but not by treatments with inhibitors of ERK, p38 MAPK, JNK, or PI-3K. NF-kappaB inhibitors significantly attenuated the expression of B7-DC, -H1, -H2, and -H3 mRNA in response to TPA. These results suggest that TPA induces the expression of B7-DC, -H1, -H2, and -H3 mRNA in K562 cells via activation of PKC, ERK, p38 MAPK, and NF-kappaB. Distinctly, the expression of B7-DC mRNA and -H3 mRNA in response to TPA is also PI-3K- and JNK-dependent, respectively.

Clonazepam treatment of pathologic childhood aerophagia with psychological stresses.

The treatment of pathologic aerophagia has rarely been discussed in the literature. In this retrospective study, the authors investigated the effects of clonazepam on the management of pathologic childhood aerophagia (PCA) with psychological stresses (PS), but not with mental retardation. Data from 22 consecutive PCA patients with PS (aged 2 to 10 yr), who had been followed up for over 1 yr, were reviewed. On the basis of videolaryngoscopic views, the authors observed that the pathology of aerophagia was the result of reflex-induced swallowing with paroxysmal openings of the upper esophageal sphincter due to unknown factors and also observed that these reflex-induced openings were subsided after intravenous low dose benzodiazepine administration. Hence, clonazepam was administered to treat paroxysmal openings in these PCA patients with PS. Remission positivity was defined as symptom-free for a consecutive 1 month within 6 months of treatment. The results of treatment in 22 PCA patients with PS were analyzed. A remission positive state was documented in 14.3% of PCA patients managed by reassurance, and in 66.7% of PCA patients treated with clonazepam (p=0.032). Thus, clonazepam may produce positive results in PCA with PS. Future studies by randomized and placebo-controlled trials are needed to confirm the favorable effect of clonazepam in PCA.

Advanced criteria for clinicopathological diagnosis of food protein-induced proctocolitis.

The clinicopathological findings in previous studies concerning food protein-induced proctocolitis (FPIPC) are quite diverse in terms of results and conclusions. The aim of this study was to suggest advanced clinicopathological diagnostic criteria that facilitate the early confirmation of FPIPC. Data of 38 FPIPC patients, who had received sigmoidoscopy and biopsy, was analyzed. Microscopic findings were compared with observations of previous studies. Feeding at onset of bleeding was exclusively breast-fed (94.7%) and formula-fed or mixed-fed (5.3%). Endoscopic abnormalities were observed in all patients; nodular hyperplasias with circumscribed and/or central pit-like erosions in 94.7% and erythema in 5.3%. Histopathological findings were; lymphoid aggregates in 94.7%, eosinophils in lamina propria of >or=60 cells/10 HPF in 97.4% and of >20 cells/HPF in 63.2%, epithelial or muscularis mucosa eosinophil infiltration in 97.4%, and crypt abscess in 2.6%. The majority of FPIPC patients are exclusively breast-fed and nodular hyperplasias with erosions may be a disease specific endoscopic finding. Histologic diagnosis of FPIPC is compatible with eosinophils in the lamina propria of >or=60 cells/10 high power fields; however, >20 cells/HPF is not an appropriate diagnostic criterion.