<<Disclaimer: Verify this information before applying it to your situation.>> Since there were quite a few people interested in responses to my query, I offer this summary. A number of you mentioned that two days was not a sufficient challenge with gluten to see villous atrophy. I agree, although I was happy at the time not to have to go through a longer torture period. My GE repeatedly assured me that the gut reaction happens very quickly. Maybe not. I am beginning to suspect that this "gold standard" is not all that golden. Others with negative diagnoses also felt as I do that the pain of going through more testing was not worthwhile. Better to stay healthy on the diet. For some the challenge/testing may be worthwhile, such as to determine potential problems in offspring, or for proof of a need for accommodation. Recall that my questions were: "Are these two conditions, celiac sprue and gluten intolerance, two points on a continuum or two entirely different diseases? Is the prognosis for gluten intolerance different? Are any researchers studying this difference?" Most responses addressed the first question. Several people provided examples indicating that the severity of the disease varies greatly, from smooth villi with no symptoms, to normal mucosa with symptoms. So a continuum exists. It would be great if genetic testing could identify the disease, but here again, both false positive and negatives occur. Actually it may be that the tests aren't so much false, but that the disease varies so much for each individual and we're not looking for the right things. One list member tested positive for the "celiac gene" and positive on the IgG antibody test, but negative on the biopsy. It appears that no tests today are entirely reliable. Alternatively, others indicated that gluten intolerance symptoms may result from other conditions. Some list members have been diagnosed with other conditions such as irritable bowel syndrome, eosinophilic gastroenteritis, and microscopic colitis. I was directed to the Websites of the Celiac Sprue Association ( http://www.csaceliacs.org/infocenter.html) and the Celiac Group Support Page (http://www.celiac.com/). This led (through a buried link) to my rummaging around the Environmed Research website ( nutramed.com/digestion/celiacallergy.htm). They state that: "We think that people diagnosed with celiac disease are a sub-population of a much larger group with gluten allergy... Often, an assortment of related whole-body problems accompanies celiac disease. We think the related problems are typical of delayed pattern food allergy and use celiac disease research information to create a model of food allergy." This site provides information on immediate (IgE), delayed and auto-immune reactions. RAST is used to detect immediate IgE allergies to gluten (this is the same allergy reaction as hay fever and can result in anaphylactic shock in some persons allergic to nuts, for example) One listmember also fell into the gray area between a negative celiac diagnosis (and negative RAST) and obvious reactions to gluten. Therefore, it appears that for some, gluten intolerance can be due to diseases other than celiac sprue. On the other hand there appears to be a continuum in manifestations of celiac sprue. But many will not meet the textbook definition. Harrison's (13th ed) rigorous definition is as follows: 1) evidence of malabsorption 2) abnormal small-bowel biopsy showing blunting and flattening of villi and changes in the surface epithelium 3) clinical, biochemical, and histologic improvement after instituting a gluten-free diet. This definition indicates that celiac disease is primarily a malabsorption phenomenon (due to an auto-immune reaction) as opposed to a food allergy or intolerance. But for the present, as far as treatment goes, I may just as well have celiac sprue. Regarding the second question, I plan on trying bread again after a year or so. If I don't really have celiac disease, maybe I'll get better at some point. Regarding the third question, a quick search of the literature (MedLine) produced hundreds of relevant articles from 1990 to now. I haven't time now to be thorough, but I didn't see any findings that answer my question on gluten enteropathy due to an autoimmune effect versus a gluten allergy. One study suggested that sub-clinical gluten enteropathy is quite common (Gut 1992 Feb 33:2 194-7) Another article found that gluten-sensitive celiac-like symptoms may occur in patients with serum antiendomysium antibodies, apparently normal intestinal mucosa, and HLA typing not commonly associated with celiac disease [only 10 patients looked at](Gastroenterology 1996 Sep 111:3 608-16). Some authors suggest that because of the recognized clinical heterogeneity of celiac disease, the definition (as above) should be changed (Ann Allergy 1993 Jul 71:1 29-32). I'll keep at this after I get back from vacation next week. At least we can take heart that our problem is not being ignored by researchers. Thanks for the feedback. Reimar in Toronto