Cereal Grain Proteins
The diagnosis of celiac disease is made by a history of illness that suggests gluten allergy and is confirmed by small intestine mucosal biopsy, which demonstrates atrophy of the absorptive surface. In the typical case, biopsy of the distal duodenum and/or jejunum reveals villous atrophy, inflammatory infiltrate of the lamina propria and degeneration of the surface epithelium. I emphasize that an intestinal biopsy is not definitive to decide proper patient care and is not required before a symptomatic person begins diet revision.
Celiac disease, as defined by the small intestinal biopsy result, represents a specific endpoint for gluten reactions, one of many possible effects of wheat allergy. Most medical textbooks dogmatically state that an intestinal biopsy must be done and must show typical changes before the diagnosis is made and before a gluten free diet is prescribed. We think that this is an old and dogmatic position that has no current validity. You can say to the dogmatic MD that you he or she might define CD by the biopsy result, but you have to allow for another and larger group of patients with gluten-caused disease who are not biopsied celiacs, but share many, if not all the disease features of patients with CD.
The diagnosis of celiac disease is often missed and patients may present to physicians with symptoms for several years before the diagnosis is made. In one study, fourteen patients (39%) had been referred to the hospital a total of 30 times with features suggestive of celiac disease without being diagnosed. The average delay between initial referral and diagnosis was 6 years in nine of these patients.
The intestinal biopsy allows a pathologist to examine microscopically the surface of the small intestine. The surface of the small intestine is covered by a dense mat of villi, projecting nipples that shed cells containing digestive enzymes and absorb food molecules. In long-standing celiac disease, the villi are blunted and the surface is smoothed-out. The Marsh classification is used by pathologists to assess that degree of intestinal pathology. Marsh 1 and 2 changes show increased lymphocyte activity in the villa, but no agreement has been reached about the significance of these changes. Marsh 3 is considered to be definitive pathology and can be further divided into three groups from A to C; Marsh IIIC being complete villous atrophy.
While the biopsy is a useful procedure, it has several drawbacks and is not definitive in the diagnosis of all forms of gluten allergy. Many patients develop gluten-driven immune disease without an abnormal jejunal biopsy result. Significant gluten protein allergy and increased bowel permeability may exist despite normal appearance of the jejunal lining under the microscope. Biopsy is a procedure with a small incidence of complications, especially bowel perforation. A biopsy is a very small tissue sample and may miss patchy, irregular and intermittent bowel changes. Patients with diagnosed CD in remission or with intermittent symptoms may have normal biopsy results but remain sensitive to gluten. Patients on a gluten free diet conversely may improve symptomatically but show little or no improvement on follow-up biopsy.
Wahab et al reported: In a long-term follow-up study of 158 patients with celiac disease in our hospital, the histologic recovery after starting a gluten-free diet takes time (more than 2 years in 35.4% of patients) and is incomplete or absent (10.1% villous atrophy in long-term follow-up) in a substantial subgroup of patients. Considering the morbidity of the malabsorption condition and the risk for secondary complications such as osteopenia and malignant neoplasm, these results imply the need for a systematic follow-up of patients with celiac disease.
I have often reviewed the history of patients with chronic diarrhea and associated abnormalities, who have been "thoroughly investigated" in an academic center and left untreated because their biopsy result was normal. When a biopsy is reported as "normal", they are told, "You do not have celiac disease; eat anything you like." This diagnostic rigidity manifests the classic error of "treating the lab result" and not the patient. The logical fallacy is that while a normal biopsy argues against the diagnosis of CD, simply because CD has been defined by the biopsy result, the normal biopsy result in no way suggests that the sick patient can eat anything he or she likes.
Patients with chronic diarrhea and other symptoms suggestive of celiac disease often have milk and wheat "allergy" until proven otherwise and benefit from diet revision, regardless of the biopsy result. Physicians who make therapeutic decisions solely based on biopsy results are not serving the best interests of their patients who simply want to be better. Investigations that do not lead to effective therapy are of no value to patients.
Diagnosis of gluten-sensitivity in all disorders may be facilitated in the near future by better immunological laboratory tests, including measurement of circulating serum antibodies directed against these proteins, and of circulating immune complexes which contain food antigens. The best simple blood test is the measurement of auto antibodies directed against tissue transglutaminase (anti-tTG antibodies). The antibody type is IgA, measured by solid phase ELISA, a quantitative, automated and more reproducible method that permits comparison of results from qualified laboratories.
If the Biopsy is Negative, Gluten Allergy has not been ruled out; Too many patients have been dismissed without proper Diet Revision Therapy. When a biopsy is reported as normal, they are sometimes told, You do not have celiac disease; eat anything you like. This diagnostic rigidity manifests the classic error of "treating the lab result" and not the patient. Patients with chronic diarrhea and other symptoms suggestive of celiac disease often have milk and wheat allergy and benefit from Diet Revision Therapy, regardless of the biopsy result.
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