Eosinophilic Esophagitis in Children: Endoscopic Findings at Diagnosis and Post-intervention.

PURPOSE OF REVIEW: The goal of this review is to present and summarize studies on endoscopic findings in eosinophilic esophagitis (EoE), at diagnosis and in response to treatment, utilizing rigorous peer-reviewed literature in children wherever possible and to introduce a recently proposed standardized endoscopic evaluation system. RECENT FINDINGS: Gold standard of diagnosis and assessment of response to therapy in EoE requires multiple endoscopies with biopsies for histology, which allows for observation of the esophageal mucosa. Typical endoscopic findings in patients with EoE include edema, exudate, furrowing, concentric rings, and strictures. Endoscopic findings have been broadly characterized into inflammatory features (edema, exudate, furrowing) and fibro-stenotic features (rings, stricture), in order to better reflect their underlying pathophysiology. Recent studies suggest strong correlations between endoscopic findings, through composite scoring systems, and histology, and therefore may be helpful as part of disease surveillance. The EoE Endoscopic Reference Score (EREFS) classification system was proposed in 2013 as an outcome metric for standardization in reporting endoscopic signs of EoE. Subsequent studies support utility of composite scoring, which utility has similarly been seen in pediatric treatment trials. Endoscopy in children provides insight into the natural history of EoE, with progressively more fibro-stenotic features occurring over time, giving an additional perspective into esophageal remodeling and response to treatment. Recognition of typical endoscopic findings at diagnosis and upon repeat endoscopy has allowed a clinician to monitor visual changes in esophageal mucosal health. Further studies to assess the role of composite scoring in disease management are needed.

IgE-associated food allergy alters the presentation of paediatric eosinophilic esophagitis.

BACKGROUND: Links between food allergens and eosinophilic esophagitis (EoE) have been established, but the interplay between EoE- and IgE-associated immediate hypersensitivity to foods remains unclear. OBJECTIVE: We sought to determine the prevalence of IgE-associated food allergy at the time of diagnosis of EoE in children and to determine whether differences existed in presentation and disease compared to subjects with EoE alone. METHODS: Eosinophilic esophagitis patients were stratified based on the diagnosis of IgE-associated immediate hypersensitivity (EoE + IH vs. EoE-IH). Clinical, histologic, pathologic, and endoscopic differences were investigated using a retrospective database. RESULTS: We found that 29% of the 198 EoE patients in our cohort had EoE + IH. These subjects presented at a younger age than those without IH (6.05 vs. 8.09 years, P = 0.013) and were more likely to have comorbid allergic disease. Surprisingly, the EoE + IH group presented with significantly different clinical symptoms, with increased dysphagia, gagging, cough, and poor appetite compared to their counterparts in the EoE-IH group. Male gender, allergic rhinitis, the presence of dysphagia, and younger age were independently associated with having EoE + IH. Specific IgE levels to common EoE-associated foods were higher in EoE + IH, regardless of eliciting immediate hypersensitivity symptoms. In contrast, IgE levels for specific foods triggering EoE were relatively lower in both the groups than IgE levels for immediate reactions. CONCLUSIONS AND CLINICAL RELEVANCE: Immediate hypersensitivity is common in children with EoE and identifies a population of EoE patients with distinct clinical characteristics. Our study describes a subtype of EoE in which IgE-mediated food allergy may impact the presentation of paediatric EoE.

A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis.

The progressive familial intrahepatic cholestases (PFIC) are a group of inherited disorders with severe cholestatic liver disease from early infancy. A subgroup characterized by normal serum cholesterol and gamma-glutamyltranspeptidase (gammaGT) levels is genetically heterogeneous with loci on chromosomes 2q (PFIC2) and 18q. The phenotype of the PFIC2-linked group is consistent with defective bile acid transport at the hepatocyte canalicular membrane. The PFIC2 gene has now been identified by mutations in a positional candidate, BSEP, which encodes a liver-specific ATP-binding cassette (ABC) transporter, sister of p-glycoprotein (SPGP). The product of the orthologous rat gene has been shown to be an effective bile acid transporter in vitro. These data provide evidence that SPGP is the human bile salt export pump (BSEP).

Identification of a locus for progressive familial intrahepatic cholestasis PFIC2 on chromosome 2q24.

Progressive familial intrahepatic cholestasis (PFIC; OMIM 211600) is the second most common familial cholestatic syndrome presenting in infancy. A locus has previously been mapped to chromosome 18q21-22 in the original Byler pedigree. This chromosomal region also harbors the locus for benign recurrent intrahepatic cholestasis (BRIC) a related phenotype. Linkage analysis in six consanguineous PFIC pedigrees from the Middle East has previously excluded linkage to chromosome 18q21-22, indicating the existence of locus heterogeneity within the PFIC phenotype. By use of homozygosity mapping and a genome scan in these pedigrees, a locus designated "PFIC2" has been mapped to chromosome 2q24. A maximum LOD score of 8.5 was obtained in the interval between marker loci D2S306 and D2S124, with all families linked.

Primary sclerosing cholangitis in Arab children: report of four cases and literature review.

BACKGROUND: The prevalence of primary sclerosing cholangitis, a rare progressive liver disorder, is increasing with the advent of endoscopic retrograde cholangiography in the investigation of children with obscure liver disease. The etiology of primary sclerosing cholangitis is not known, clinical presentation is variable, treatment is only of limited success and long-term studies on prognosis in children are incomplete. Primary sclerosing cholangitis has not been described in Arab children. METHODS: To describe detailed clinical, laboratory, histologic and radiological features in 4 children with primary sclerosing cholangitis identified over a 2-year period at a tertiary referral center in Riyadh Saudi Arabia. RESULTS: Four children, all females, between the ages of 4 and 11 years with primary sclerosing cholangitis are identified. The diagnosis was suggested by the histology and confirmed by the characteristic cholangiographic findings. Clinical findings were itching in all 4 children, hepatomegaly in 3 and splenomegaly in 4 patients. Three of 4 patients had portal hypertension and 2 of these three variceal hemorrhage. Antinuclear and smooth muscle antibodies were negative in all four patients. None had clinical manifestations of chronic inflammatory bowel disease but microscopic colitis was documented in all 4 patients. CONCLUSIONS: Primary sclerosing cholangitis is present in Arab children with a prevalence rate of 5% in our study population.

Locus heterogeneity in progressive familial intrahepatic cholestasis.

Progressive familial intrahepatic cholestasis (PFIC or Byler disease) is a rare autosomal recessive form of severe and fatal cholestatic liver disease. A locus for PFIC has recently been mapped to chromosome 18q21-q22 in the original Byler pedigree. This region harbours the locus for a related phenotype, benign recurrent intrahepatic cholestasis (BRIC), suggesting that these traits are allelic. Linkage analysis was undertaken in five consanguineous PFIC pedigrees from Saudi Arabia using marker loci (D18S69, D18S41, D18S64, D18S38, D18S42, D18S55, D18S68, and D18S61) which span the Byler disease/BRIC region on 18q21-q22. In this family set the disease locus was excluded from this region, showing that locus heterogeneity exists for the PFIC phenotype.

Progressive familial intrahepatic cholestasis (Byler's disease) in Arab children.

The clinical, biochemical and histological characteristics in six Arab children with progressive familial intrahepatic cholestasis (PFIC) (Byler's disease) are described. The autosomal recessive mode of inheritance is established. Jaundice and pruritus were early symptoms, with onset in the 1st 3 months in all patients. Other features included growth failure, developmental delay, ataxia, areflexia, gall-stones and epistaxis. Gamma-glutamyl-transpeptidase and cholesterol were normal, but total bile acid levels were uniformly elevated in all patients. Histology showed features of hepato-canalicular cholestasis, lack of bile duct proliferation and fibrosis or cirrhosis in all patients. Five patients who were followed up were alive at a mean age of 75.8 months.

Phosphorylase b kinase deficiency glycogenosis with cirrhosis of the liver.

We describe an Arab girl with complete absence of phosphorylase b kinase activity in the liver, symptomatic hypoglycemia, and persistently elevated serum aminotransferase values whose symptoms did not lessen with age; sequential liver biopsies showed progression to cirrhosis. Cirrhosis could not be ascribed to any other known cause. We conclude that type IX glycogenosis is not always associated with a benign outcome.

Congenital chloride diarrhea. A study in Arab children.

Congenital chloride diarrhea (CCD) is a common metabolic disorder in Saudi children with an incidence of 1 in 5,500. The present retrospective study from Saudi Arabia, over 7.5 years, presents the clinical, biochemical, and treatment details in 10 children with CCD. The perinatal characteristics of maternal polyhydramnios, prematurity, abdominal distention, and diarrhea were seen in 100% and hyperbilirubinemia in 90% of patients. Hypokalemic hypochloremic metabolic alkalosis was a feature in 50% of the children and acidosis in both neonates. Fecal chloride greater than 100 mmol/L in 100% and fecal chloride greater than the sum of fecal sodium and potassium were found in 55% of patients. The mean age at the time of diagnosis was 10 months and the mean duration of follow-up for the group was 38 months (range 2-89 months). Eight of the nine patients treated with continuous oral electrolyte solution demonstrated "catch-up" physical growth. Mental subnormality, growth retardation, and renal impairment were seen in one patient who failed to comply with the treatment. Cerebral palsy in another child was due to neonatal intraventricular hemorrhage.

Pulmonary hemorrhage in association with autoimmune chronic active hepatitis.

Extrahepatic manifestations have been reported in a majority of patients with ACAH. We describe an 11-year-old girl with CAH who developed life-threatening AH and was successfully managed with mechanical ventilation and high-dose steroids. Although a number of pulmonary manifestations have been described in association with AICAH, this article is the first showing its association with AH.

Childhood shigellosis in Saudi Arabia.

In this study 234 children with shigellosis were evaluated during a 6-year period. The ages ranged from 2 days to 13 years (mean, 3.4 years). Sixty percent of the children were in the 1- to 4-year age group. One hundred four children were hospitalized and 130 were outpatients. Most cases of shigellosis presented during the months of April-May and September-November. Shigella flexneri accounted for 44% and Shigella sonnei for 43% of the isolates. Susceptibility testing showed that 54% were resistant to ampicillin, 72% to trimethoprim-sulfamethoxazole and 77% to tetracycline. Eighty percent were resistant to two or more antimicrobial agents. Morbidity and mortality was higher in children who were initially treated with antimicrobials to which the organism was resistant than in those treated with antimicrobial agent to which the organism was susceptible.