Changes in mucosal IgG4+- and IL-10+-cell frequencies in adults with eosinophilic esophagitis on a two-food elimination diet.

Eosinophilic esophagitis (EoE) is increasingly diagnosed in patients with dysphagia. Type-2 immunity can induce EoE histopathology via non-IgE-dependent mechanisms, possibly involving IgG4 and IL-10. To elucidate the contribution of this response to EoE pathogenesis, we examined its association with clinical and histologic endpoints in adult EoE patients given a two-food elimination diet. IgG4- and IL-10-expressing cells were counted in esophageal biopsies and serum food-specific IgG4 measured at baseline and follow-up. Variables were correlated with histologic measures of disease activity. Patients exhibited significant reduction in esophageal eosinophilia and overall histology. A significant decrease in IL-10+-cell frequencies correlated with histologic changes. In contrast, a decline in serum and esophageal IgG4, while substantial, did not correlate with IL-10+-cell frequencies or histologic parameters. These results suggest a critical role of IL-10 in EoE pathogenesis. Conversely, IgG4 expression, while reflecting exposure to food antigens, is not obviously related to EoE histopathology or IL-10 expression.

Food Allergy and Intolerance: A Narrative Review on Nutritional Concerns.

Adverse food reactions include immune-mediated food allergies and non-immune-mediated intolerances. However, this distinction and the involvement of different pathogenetic mechanisms are often confused. Furthermore, there is a discrepancy between the perceived vs. actual prevalence of immune-mediated food allergies and non-immune reactions to food that are extremely common. The risk of an inappropriate approach to their correct identification can lead to inappropriate diets with severe nutritional deficiencies. This narrative review provides an outline of the pathophysiologic and clinical features of immune and non-immune adverse reactions to food-along with general diagnostic and therapeutic strategies. Special emphasis is placed on specific nutritional concerns for each of these conditions from the combined point of view of gastroenterology and immunology, in an attempt to offer a useful tool to practicing physicians in discriminating these diverging disease entities and planning their correct management. We conclude that a correct diagnostic approach and dietary control of both immune- and non-immune-mediated food-induced diseases might minimize the nutritional gaps in these patients, thus helping to improve their quality of life and reduce the economic costs of their management.

The overlap syndrome of urticaria and gastroesophageal reflux disease.

BACKGROUND: One-quarter of systemic symptoms associated with chronic spontaneous urticaria (CSU) are related to gastrointestinal complaints (GICs). OBJECTIVES: To investigate the prevalence and features of urticaria-overlapping GICs. METHODS: In this retrospective cross-sectional survey, 1426 consecutive outpatients were observed at our University Department. Only patients suffering from urticaria or GICs with a complete diagnostic work-up including serum total IgE level (Tot-IgE), differential blood count and urticaria activity score (UAS), were evaluated. RESULTS: Among different GICs, gastroesophageal reflux disease (GERD) was the most frequent syndrome observed (15.4%; 95%CI: 13.6-17.3). The prevalence of overlap syndrome for urticaria and GERD was 5.9% (95%CI: 4.7-7.2). In urticaria-patients, the prevalence of GERD was four-fold higher than in patients without hives (44% vs. 11%, p<0.001). UAS was significantly higher in urticaria and GERD overlap syndromes vs. isolated urticarias. In patients with GERD or acute/chronic urticaria or overlap syndrome, Tot-IgE and eosinophil blood count (EBC) differed significantly, with a stepwise increase in their values; from the subgroup of patients with GERD only, to that with overlap of CSU to GERD. Prevalence values for urticaria overlapping with GERD were three- and two-fold higher in CSU and in long-duration GERD cases respectively compared to acute urticaria or short-duration GERD cases. Similar to Th2 pathology models, CSU and GERD overlap syndrome was significantly and independently associated with Total-IgE ≥100IU/ml or EBC ≥250/mmc compared to CSU or GERD. Endoscopic/bioptic findings of non-erosive reflux disease (NERD) or Barrett's esophagus (BE) were more frequent in chronic overlap syndrome than in GERD-patients. CONCLUSIONS: GERD was the most frequent GIC in patients with urticaria. Overlap syndrome was more frequent among patients with CSU, where this syndrome was associated with higher values of UAS, Tot-IgE, EBC and frequencies of NERD and BE. These results suggest that overlap syndrome is frequently a chronic syndrome with a Th2-like profile.

Telaprevir may induce adverse cutaneous reactions by a T cell immune-mediated mechanism.

The HCV protease inhibitor telaprevir associated with peginterferon-alpha and ribavirin, was widely used in the recent past as standard treatment in HCV genotype-1 infected patients. Telaprevir improves the sustained virology response rates, but at the same time increases the frequency of adverse cutaneous reactions. However, mechanisms through which telaprevir induces cutaneous lesions are not yet defined. A 50-year-old woman, affected by HCV genotype 1b, was admitted to our Department for a telaprevir-related severe cutaneous eruptions, eight weeks after starting a triple therapy (telaprevir associated with Peginterferon-alpha and ribavirin). Mechanisms of cutaneous reactions were investigated by skin tests with non-irritating concentrations of telaprevir and by activating in vitro T lymphocyte with different concentrations. Immediate and delayed responses to skin testing were negative, but the drug-induced lymphocytes activation was significantly higher as compared to patient's baseline values and to parallel results obtained in three healthy subjects (p < 0.05). In conclusion, adverse cutaneous reactions of our patient were caused by a telaprevir-induced T-cell dependent immune mechanism.