Definitions Associated with Celiac Disease

Leon H. Rottmann, Ph.D., Professor Emeritus, University of Nebraska-Lincoln
Lifeline, Spring 1996, Vol XIV, No 2, pp 1-2

[This article remains in this Library as part of the historic timeline information about celiac disease. Note however, thatHuman Leukocyte Antigen (HLA) region genes have become known as part of the genetic requirement and omega gliadins are no longer totally free of suspect. 2004. Intolerance in the medical community means an adverse response to food not involving the immune system. Foreign translations contine to use the term intolerance to mean "unable to tolerate."]

The following concepts and definitions are offered to relate to requests from celiacs and dietitians for "textbook definitions" related to celiac disease.

Gluten intolerance associated with celiac disease may be identified with a number of alternate names (gluten-sensitive enteropathy, non-tropical sprue, celiac disease - and for dermatitis herpetiformis). It is a condition in which the following situations occur:

  1. actual or potential intestinal malabsorption of virtually all nutrients;
  2. a possible lesion of the mucosa in the small intestine;
  3. and, prompt clinical improvement following withdrawal of certain gluten-containing cereals and toxicants from the diet.

Gluten intolerance is thought to be inherited through a gene match for the individual; it represents a toxic reaction. Small parts of the lining of the first six or seven feet of the small intestine (the jejunum) of persons with this disorder are damaged by a protein fraction of gluten called gliadin. Gliadin (glutenin) is present in wheat, oats, rye, barley and a series of other grains with lower levels of the offending protein. There are two amino sequences in these proteins that have been found to cause the toxic reaction in Alpha, Beta and Gamma gliadins; the Omega gliadins are thought not to cause a toxic reaction.

The same grain stimulus may cause either and intolerance (a toxic reaction) and/or allergic reaction. Allergies are seen as an induced sensitivity; an acquired immunologic state induced in a susceptible subject by an antigen (allergen) which is characterized by a marked change in the subject's reactivity. The term is commonly used to denote the immediate, transient kind of immunologic (allergic) reaction characterized by contraction of smooth muscle and dilation of capillaries due to the release of pharmacologically active substances (histamines, serotonin and slow reacting substances), all classically initiated by the combination of antigen (allergen) with mast cell-fixed antibodies.

A general working definition of gluten-sensitive enteropathy (celiac disease) includes the following points:

  1. Celiac disease is a permanent condition of gluten intolerance;
  2. The initial mucosa lesion is flat, and recovers when the patient is treated with a gluten-free diet;
  3. Reintroduction of gluten into the diet will produce a histologic relapse in the jejunal mucosa within two years.

Application of strict diagnostic criteria has led to the realization that there is a wide clinical spectrum within celiac disease, and has reinforced the need for biopsy to conform the diagnosis in every patient.

Considerable data on celiac disease and on immunoregulation implicate induction of mucosal delayed-type hypersensitivity (DTH) as the underlying abnormality. The factor that leads to sensitization rather than tolerance could be an abnormality of T cells, antigen presentation, or permeability of the epithelium, or an adjuvant effect of coincident infection.

There are no standard methods for detecting the presence of antigen-specific T effector cells. At the moment, the best available method for studying mucosal DTH is based on morphology. A distinct pattern small-intestinal mucosal damage had been observed in models of gut DTH. The features described in some or all of these situations are hyperplasia of the crypts of Lieberkuhn with or without shortening of the villi; and increase in the proportion of goblet cells; brush border enzyme deficiency; increased counts of intraepithelial leukocytes (lymphocytes) (IEL) and mucosal mast cell; an increased mitotic indices of IEL; and expression of class II antigens by crypt enterocytes. All of these occur in the celiac lesion and are well demonstrated when objective methods are used to examine biopsy material.

Indications for the Jejunal Biopsy: malabsorption syndrome: diarrhea; unexplained weight loss; iron deficiency; of no evidence of blood loss, folate deficiency; metabolic bone disease, old rickets; other vitamin and mineral deficiencies, abdominal lymphoma duodenal or jejunal adenocarcinoma; IgA deficiency; hyposplenic blood film with no splenectomy; evidence of other diseases associated with celiac disease.

Celiac Disease and Related Disorders:

Definite Associations: diabetes mellitus; thyrotoxicosis; hypothyroidism; IgA deficiency; sarcoidosis; vasculitis; dermatitis herpetiformis; encephalopathy and cerebellar atrophy; myasthenia; peripheral neuropathy; malignant lymphomas; small-intestine adenocarcinomas; esophageal and pharyngeal squamous carcinoma.

Probable Associations: Addison's disease; rheumatoid arthritis; Sjogren's syndrome; bird fancier's lung; farmer's lung; pernicious anemia; exocrine pancreatic insufficiency; inflammatory bowel disease; primary biliary cirrhosis; collagenous colitis.

Many diseases are found with a higher than normal frequency on larger groups of patients with celiac disease. In particular, there is the cluster of autoimmune disease linked with the HLA-A1, B8 phenotype: diabetes in a patient with celiac disease can produce considerable management difficulties; pernicious anemia requires parenteral injections of vitamin B12 indefinitely; autoimmune Addison's disease may be missed in a patient who seems to require steroids for relief of symptoms attributed to celiac disease; and thyrotoxicosis contributes to diarrhea and weight loss.

Other immune associations with celiac disease that are unexplained include IgA deficiency, in itself harmless, and splenic atrophy. Bizarre neurologic disease may also coexist with celiac disease. Dermatitis herpetiformis (DH) is characterized by a symmetrical pruritic skin rash with subepidermal blisters, and granular subepidermal deposits of IgA in remote, uninvolved skin. Most patients with DH have abnormal small-intestinal biopsy pathology, histologically indistinguishable from that of celiac disease, which returns to normal after dietary exclusion of gluten. An interpretation of these observations is that most patients with DH also have celiac disease but a minority are totally tolerant of gluten. But, for most there is the requirement of dietary gluten for a clinical expression to exist.

Malignant lymphoma in association with celiac disease was described initially as Hodgkin's disease or reticulum cell sarcoma. Later the term malignant histiocytosis if the intestine (MHI) was used, but current evidence suggests that the tumor is a T cell lymphoma, and the suggested nomenclature, "enteropathy-associated T cell lymphoma" (EATCL) is more generally used.

The majority of lymphomas in patients with celiac disease are intestinal, not only in the jejunum, but in any part of the small intestine. There may be ulcers and strictures of nodules or tumor, and occasionally there are only microscopic foci. At this time, a strict adherence to the clinical gluten-free diet is thought to be the best methodology for monitoring celiac disease and for prevention and development of foci, tumors and lymphoma or sarcoma cancers.

 

Sources: Excerpted from writing of Seamus O'Mahony and Ann Ferguson on "Gluten-Sensitive Enteropathy (Celiac Disease)" and from the Doctor of Medicine Thesis by Willem Karel Dicke, University of Utrecht, The Netherlands.


CSA Library Series
CSA Library Series is a collection of articles that pertain to celiac disease and dermatitis herpetiformis. Most of these articles have appeared in CSA’s quarterly newsletter, Lifeline, which all CSA members receive. Historic articles included in these resources may or may not include updated notes. Updated information indicated in red type. Articles represent the work of the author.