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Michael N Marsh

Publications and source records attributed to Michael N Marsh.

2 recordsLinked to original sources

Diagnosis of coeliac disease.

The diagnosis of coeliac disease depends on the finding of characteristic, though not specific changes, of intraepithelial lymphocytosis, crypt hyperplasia and various degrees of villous height reduction identified in duodenal biopsies of individuals ingesting a gluten containing diet, together with symptomatic and histologic improvement on gluten withdrawal. Serologic testing has become the main mode of determining who will undergo biopsy. The IgA endomysial antibody and IgA tissue transglutaminase antibody have approximately 90% sensitivity and specificity, though there are reports of lower sensitivity and specificity in the clinical practice setting. This is due to lower titers of these antibodies in the presence of lesser degrees of mucosal damage. The widespread availability of serologic tests for coeliac disease allows the diagnosis to be considered by any physician. Gastroenterologists will be required to interpret the results of serologic tests and perform duodenal biopsies when indicated. Pathologists likewise need to be better acquainted with the more subtle changes of cell mediated immunity within the mucosa that are suggestive of underlying gluten sensitivity.

Celiac Disease↗

Celiac disease.

Clinically, celiac disease has always been regarded as a wasting, malabsorptive disorder due to disease of the small intestinal mucosa. It has been difficult for clinicians to recognize that this condition is primarily due to sensitization of mesenteric T lymphocytes to wheat protein (gluten) in genetically predisposed (DQ2+) individuals. On contact with dietary-derived gluten in the upper intestine, these sensitized T lymphocytes are activated leading to inflammation of and morphologically altered mucosal architecture: the latter reverts to normal with a gluten-free diet. The circulation of sensitized T lymphocytes to other parts of the intestinal mucosa explains why identical immunopathological inflammation can be induced in ileal and rectal mucosa. It appears, then, that in predisposed DQ2+ subjects, mesenteric T lymphocytes recognize gluten as foreign (non-self) antigen, thereby inducing mucosal pathology secondary to the initiating lymphocyte-protein interaction, analogously to the mucosal lesions that typify graft-vs-host reactions, or nematode or Giaraia infestations. Today, as this article describes, we recognize that celiac disease often exists in a subclinical, or "compensated-latent," form, or with symptoms that do not immediately suggest an origin in the gastrointestinal tract.

Celiac Disease↗