Chylomicron Retention Disease: Failure to Thrive and Abdominal Distention in an Infant.

This case report describes an infant with failure to thrive and progressive abdominal distention that ultimately led to a rare diagnosis of chylomicron retention disease at 1 year of life. Laboratory abnormalities included increased qualitative stool fat, along with low apolipoprotein B, high-density lipoprotein, low-density lipoprotein (LDL), and total cholesterol in blood. In chylomicron retention disease, diarrhea has been reported as the most common presenting symptom followed by failure to thrive and vomiting. Diarrhea and vomiting before 6 months of life have been described in cases of chylomicron retention disease reported in the literature; however, this patient did not present with either of those symptoms. This case report uniquely demonstrates that lack of early or persistent digestive symptoms of diarrhea or vomiting does not exclude a diagnosis of chylomicron retention disease.

Immunophenotyping of peripheral eosinophils demonstrates activation in eosinophilic esophagitis.

BACKGROUND AND AIM: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder characterized by upper gastrointestinal symptoms and the presence of high numbers of eosinophils in the esophagus. Although eosinophils in the esophagus have been found to be activated in subjects with EoE, detailed studies of intracellular signaling pathways involved in the mechanism of activation of eosinophils in EoE have heretofore been limited. The aim of the study was to assess whether any surface molecules or transcription factors are activated in peripheral eosinophils in subjects with EoE. METHODS: Eosinophils and CD3+ lymphocytes were identified directly from 50 µL of whole blood of EoE and control subjects. Using Hi-FACS, levels of surface activation markers, including CD66b, and intracellular phosphoepitopes, including phosphorylated forms of signal transducer and activator of transcription (phospho-STAT) 1 and 6, were measured within each cell subset. RESULTS: Levels of surface CD66b as well as levels of intracellular phospho-STAT1 and phospho-STAT6 in peripheral blood eosinophils were significantly higher for untreated subjects with EoE vs healthy controls (P < 0.05). Levels of phospho-STAT1 and phospho-STAT6 in peripheral blood eosinophils were lower in subjects with EoE on therapy versus untreated subjects with EoE (P < 0.05). CONCLUSIONS: Levels of phospho-STAT1 and phospho-STAT6, transcription factors involved in inflammatory processes, were both significantly higher in peripheral eosinophils from untreated (ie, newly diagnosed) subjects with EoE versus subjects with EoE on therapy, healthy controls. Blood-based measurements of CD66b and phospho-STAT levels in peripheral eosinophils may be beneficial for identifying EoE.

Increased HLA-DR expression on tissue eosinophils in eosinophilic esophagitis.

OBJECTIVE: The aim of the study was to investigate whether eosinophils have increased human leukocyte antigen (HLA)-DR expression in subjects with eosinophilic esophagitis (EoE) compared with controls. PATIENTS AND METHODS: Patients who were undergoing an upper endoscopy with biopsies for suspected gastroesophageal reflux disease (GERD) or EoE at Lucile Packard Children's Hospital were enrolled. In total, the blood and tissue samples of 10 healthy controls (HC), 11 subjects with GERD, and 10 with EoE were studied. Multiple tissue staining to identify eosinophils (via eosinophil cationic protein-clone EG2) and major histocompatibility complex class II cell surface receptors (via HLA-DR) was performed via immunohistochemistry. The peripheral blood was analyzed using flow cytometry to detect eosinophil HLA-DR expression among these subjects. RESULTS: In the tissue, a greater proportion of eosinophils expressed HLA-DR among the subjects with EoE (mean 0.83 +/- 0.14, n = 9) relative to those with GERD (mean 0.18 +/- 0.19, n = 8, P < 0.01) and HC (mean 0.18 +/- 0.13, n = 6, P < 0.01). In total, 6 participants (4 HC subjects and 2 subjects with GERD) did not have any eosinophils identified on tissue staining and were unable to be included in the present statistical analysis. In the blood, there was no statistically significant difference in eosinophil HLA-DR expression among HC subjects (mean 415 +/- 217, n = 6), subjects with GERD (mean 507 +/- 429, n = 2), and those with EoE (mean 334 +/- 181, n = 6). CONCLUSIONS: These data demonstrate that the eosinophils from the esophagus of subjects with EoE have increased HLA-DR expression within this tissue.

Increased number of regulatory T cells in children with eosinophilic esophagitis.

OBJECTIVES: There are limited data on the role of regulatory T cells (Treg) in the disease pathology of eosinophilic esophagitis (EoE). We tested the differences in Treg in subjects with EoE compared with those with gastroesophageal reflux disease (GERD) and healthy controls (HC). PATIENTS AND METHODS: Pediatric patients evaluated by endoscopy were recruited for our study. Participants were categorized into 3 groups: EoE, GERD, and HC. RNA purified from esophageal biopsies were used for real-time quantitative polymerase chain reaction assays and tested for forkhead box P3 (FoxP3) mRNA expression. Treg were identified as CD4+CD25hiCD127lo cells in peripheral blood and as CD3+/FoxP3+cells in esophageal tissue. RESULTS: Forty-eight subjects were analyzed by real-time quantitative polymerase chain reaction: EoE (n = 33), GERD (n = 7), and HC (n = 8). FoxP3 expression was higher by up to 1.5-fold in the EoE group compared with the GERD and HC groups (P < 0.05). Protein levels of FoxP3 in blood and tissue were then investigated in 21 subjects: EoE (n = 10), GERD (n = 6), and HC (n = 5). The percentage of Treg and their subsets in peripheral blood were not significant between groups (P > 0.05). The amount of Treg in esophageal tissue was significantly greater in the EoE group (mean 10.7 CD3+/FoxP3+cells/high power field [HPF]) compared with the other groups (GERD, mean 1.7 CD3+/FoxP3+cells/HPF and HC, mean 1.6 CD3+/FoxP3+cells/HPF) (P < 0.05). CONCLUSIONS: We show that Treg are increased in esophageal tissue of EoE subjects compared with GERD and HC subjects. The present study illustrates another possible mechanism involved in EoE that implicates impairment of immune homeostasis.

Eotaxin and FGF enhance signaling through an extracellular signal-related kinase (ERK)-dependent pathway in the pathogenesis of Eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by the inflammation of the esophagus and the infiltration of eosinophils into the esophagus, leading to symptoms such as dysphagia and stricture formation. Systemic immune indicators like eotaxin and fibroblast growth factor were evaluated for possible synergistic pathological effects. Moreover, blood cells, local tissue, and plasma from EoE and control subjects were studied to determine if the localized disease was associated with a systemic effect that correlated with presence of EoE disease. METHOD: Real-time polymerase chain reaction from peripheral blood mononuclear cells (PBMC), immunohistochemistry from local esophageal biopsies, fluid assays on plasma, and fluorescence-activated cell sorting on peripheral blood cells from subjects were used to study the systemic immune indicators in newly diagnosed EoE (n = 35), treated EoE (n = 9), Gastroesophageal reflux disease (GERD) (n = 8), ulcerative colitis (n = 5), Crohn's disease (n = 5), and healthy controls (n = 8). RESULT: Of the transcripts tested for possible immune indicators, we found extracellular signal-regulated kinase (ERK), Bcl-2, bFGF (basic fibroblast growth factor), and eotaxin levels were highly upregulated in PBMC and associated with disease presence of EoE. Increased FGF detected by immunohistochemistry in esophageal tissues and in PBMC was correlated with low levels of pro-apoptotic factors (Fas, Caspase 8) in PBMC from EoE subjects. Plasma-derived bFGF was shown to be the most elevated and most specific in EoE subjects in comparison to healthy controls and disease control subjects. CONCLUSION: We describe for the first time a possible mechanism by which increased FGF is associated with inhibiting apoptosis in local esophageal tissues of EoE subjects as compared to controls. Eotaxin and FGF signaling pathways share activation through the ERK pathway; together, they could act to increase eosinophil activation and prolong the half-life of eosinophils in local tissues of the esophagus in EoE subjects.

Refeeding syndrome.

Refeeding syndrome (RFS) is the result of aggressive enteral or parenteral feeding in a malnourished patient, with hypophosphatemia being the hallmark of this phenomenon. Other metabolic abnormalities, such as hypokalemia and hypomagnesemia, may also occur, along with sodium and fluid retention. The metabolic changes that occur in RFS can be severe enough to cause cardiorespiratory failure and death. This article reviews the pathophysiology, the clinical manifestations, and the management of RFS. The key to prevention is identifying patients at risk and being aware of the potential complications involved in rapidly reintroducing feeds to a malnourished patient.