A Comprehensive Review of Celiac Disease/Gluten-Sensitive Enteropathies.

Celiac disease is a complex immune-mediated gluten-sensitive enteropathy with protean clinical manifestations. It is manifest in genetically predisposed individuals who ingest gluten in varying amounts. In broad terms, it is thought to affect 1% of the population in the USA. More specifically, the prevalence increases drastically from 1:133 in patients not-at-risk, to 1:56 in symptomatic patients, to 1:39 in patients with a second-degree relative with the diagnosis, and to 1:22 in patients with a first-degree relative with the diagnosis. It may be associated with several immune-mediated phenomena, autoimmune diseases, and complicated by vitamin and other trace element deficiencies, bone disease, and malignancy. Our understanding of celiac disease has evolved rapidly over the past two decades. This has led to several lines of enquiry on the condition and potential treatment options. More recently, several entities including gluten intolerance, non-celiac gluten sensitivity, and seronegative celiac disease have been described. These conditions are distinct from allergies or intolerance to wheat or wheat products. There are challenges in defining some of these entities since a large number of patients self-report these conditions. The absence of confirmatory diagnostic tests poses an added dilemma in distinguishing these entities. The differences in spectrum of symptoms and highlights of the variability between the pediatric and adult populations have been studied in some detail. The role of screening for celiac disease is examined in both the general population and "at risk" populations. Diagnostic strategies including the best available serologic testing, utility of HLA haplotypes DQ2 and DQ8 which are seen in over 90% of patients with celiac disease as compared with approximately 40% of the general population, and endoscopic evaluation are also reviewed. Comprehensive nutritional management after diagnosis is key to sustained health in patients with celiac disease. Simple algorithms for care based on a comprehensive multidisciplinary approach are proposed. Refractory and non-responsive celiac diseases in the setting of a gluten-free diet are examined as are novel non-dietary therapies. Finally, the association of other disease states including psychiatric illness, infertility, lymphoproliferative malignancy, and mortality is explored with special attention paid to autoimmune and atopic disease.

Hit or a miss: Concordance between histopathologic-endoscopic findings in gastric mucosal biopsies.

BACKGROUND: Current literature shows a variable degree of concordance between endoscopic and histopathologic findings in gastric mucosal biopsies. Most prior studies have focused on specific gastric entities such as gastritis in patients with high prevalence of Helicobacter pylori (H. pylori). In this study, we assess concordance between histologic and endoscopic findings in a wide spectrum of targeted as well as non-targeted gastric endoscopic biopsies. METHODS: We retrospectively reviewed pathology database and slides at Hershey Medical Center to identify 630 gastric mucosal biopsies obtained from 525 consecutive patients. The corresponding clinical and endoscopic findings were retrieved from the electronic medical record. RESULTS: The rate of abnormal endoscopic and histologic findings was 72.9% and 74.4%, respectively, with Cohen's ĸ coefficient of 0.24. There were 444 (70.5%) concordant cases and 186 (29.5%) discordant cases (88 cases with abnormal endoscopy but normal histology, and 98 cases with normal endoscopy but abnormal histology). Some endoscopic findings, in particular, mass, polyp, ulcer, and nodule/papule were highly concordant with abnormal histopathologic findings; while other endoscopic findings such as inflammatory changes, normal and prominent folds were associated with normal and a variety of abnormal histopathology. Multivariate analysis showed no significant association between intestinal metaplasia and H. pylori in this study. CONCLUSIONS: Histopathologic-endoscopic correlation in gastric biopsies varies depending on endoscopic mucosal patterns. Intestinal metaplasia may not have a significant association with H. pylori infection in populations with low prevalence of H. pylori.

Terminal Ileitis as a Feature of Henoch-Schönlein Purpura Masquerading as Crohn Disease in Adults.

Henoch-Schönlein purpura (HSP), more recently termed immunoglobulin A (IgA) vasculitis, is a systemic small-vessel vasculitis characterized by perivascular IgA deposition. This disease manifests clinically as palpable purpura, arthralgia, gastrointestinal symptoms, and renal dysfunction. Although ileitis can be seen in HSP, terminal ileitis is virtually pathognomonic for Crohn disease. We present a comprehensive review of the literature on this association, including 2 cases of our own, to demonstrate the importance of considering HSP in the differential diagnosis of ileitis suggestive of Crohn disease. We review the growing body of literature suggesting a pathophysiologic link between the conditions, possibly through an IgA-mediated mechanism.

Lung lining fluid glutathione attenuates IL-13-induced asthma.

GGT(enu1) mice, deficient in gamma-glutamyl transferase and unable to metabolize extracellular glutathione, develop intracellular glutathione deficiency and oxidant stress. We used intratracheal IL-13 to induce airway inflammation and asthma in wild-type (WT) and GGT(enu1) mice to determine the effect of altered glutathione metabolism on bronchial asthma. WT and GGT(enu1) mice developed similar degrees of lung inflammation. In contrast, IL-13 induced airway epithelial cell mucous cell hyperplasia, mucin and mucin-related gene expression, epidermal growth factor receptor mRNA, and epidermal growth factor receptor activation along with airway hyperreactivity in WT mice but not in GGT(enu1) mice. Lung lining fluid (extracellular) glutathione was 10-fold greater in GGT(enu1) than in WT lungs, providing increased buffering of inflammation-associated reactive oxygen species. Pharmacologic inhibition of GGT in WT mice produced similar effects, suggesting that the lung lining fluid glutathione protects against epithelial cell induction of asthma. Inhibiting GGT activity in lung lining fluid may represent a novel therapeutic approach for preventing and treating asthma.