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PATHOPHYSIOLOGY OF CELIAC DISEASE
Celiac disease, a simple model of association with the HLA system, occurs in a specific genetic context: 95% of patients express the DQ2 molecule. Rare, non DQ2 patients express the HLA-DQ8 antigen. These molecules, DQ2 or DQ8, present peptide fragments of gluten modified by an enzyme, tissue transglutaminase to CD4 T lymphocytes of the chorion. Other genetic factors are still to be determined, in particular those which participate in the predisposition to this disease, the age of onset or its severity.
WHEN SHOULD CELIAC DISEASE BE SUSPECTED ?
- In infants, the usual clinical signs of celiac disease occur after weaning, when cereals are introduced in the diet: growth retardation associated with apathy, muco-cutaneous pallor, anorexia. In an infant with frequent liquid stools, the abdomen is distended and hypotonic. In an older child, the symptoms are often more varied, frequently with anemia or growth retardation. Gastro-intestinal symptoms sometimes are of secondary importance: chronic diarrhea, abdominal pain, bloating which is sometimes severe, nausea or vomiting.
- In adults, it is possible to observe the usual signs, i.e. chronic diarrhea or weight loss, together with abdominal pain, nausea or vomiting. Often, this involves incomplete clinical forms manifested by a deficiency syndrome, more atypical manifestations (see table 1) or by a neoplastic complication such as gastro-intestinal lymphoma. Frequently, these minor symptoms do not cause concern to the patient who does not consult a physician. If stress or pregnancy occur, the clinical presentation may be altered and be the occasion in which the diagnosis is established. Very often in patients with celiac disease, their height is smaller than their relatives, menarche occurs at a later age and menopause at an earlier age.
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- The diagnosis for celiac disease may also be established in combination with other disorders such as dermatitis herpetiformas, insulin-dependent diabetes, thyroiditis, Sjögren syndrome or primary biliary cirrhosis. In these cases, any clinical sign or other laboratory abnormality which is not part of the context of the disease considered should lead to search for celiac disease.
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DIAGNOSTIC METHODS
Diagnosis is based on a constellation of evidence. Serologically, IgG and IgA antigliadin antibodies are relatively sensitive and specific (screening using ELISA test). They gradually give way to anti-endomysium antibodies, with nearly total sensitivity and specificity. However the screening technique (immunofluorescence) is delicate and costly. Screening for anti-transglutaminase antibodies (very specific because transglutaminase is the main autoantigen of the disease) is not used in everyday practice.
Upper gastro-intestinal endoscopy is necessary; it reveals villous atrophy with a mosaic pattern in the duodenum. This presentation is found when crossing into the small intestine and in addition the physician will look for associated lymphoma, in particular in adults and in the elderly. Histologically, the diagnosis is confirmed by the feature of total or sub-total atrophy which associates the disappearance of villi hyperplasia of crypts and infiltration of the mucosa with immune cells and in particular with T lymphocytes.
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THE GLUTEN-FREE DIET
Total and definitive exclusion of gluten from the diet is the basis of treatment of celiac disease. The principle is simple: elimination of all foods containing at least 1 of 4 toxic cereals and their substitution by other cereals, mainly rice and corn. One study has suggested that oats are well tolerated in the short term, but this result needs to be confirmed in the long-term.
There are two objectives to a gluten-free diet: clinical recovery and prevention of complications of celiac disease.
Recovery is obtained in children in one year: this diet produces normalization of height and weight. Laboratory tests (anti-endomysium antibodies) become negative within about 6 months and histological findings in one year.
In adults, the improvement can be slower. The prevention of nutritional complications (osteoporosis, anemia, malabsorption syndrome) and lymphoma, require that diet be followed for life even though celiac disease appears to be latent.
How to initiate a gluten-free diet?
Theoretically, this, no doubt, involves one of the simplest medical prescriptions. In practice, application of a gluten-free diet is very constraining and can be a true obstacle to a normal social life. Indeed, gluten exists in all foods which contain wheat, such as bread and pasta, and in a very large number of products produced by the food and agricultural industry, in particular, prepared foods, sweets and some desserts. Additives containing gluten are used in prepared foods as texture or stabilizing agents. A dietician who is experienced in explaining the constraints of a gluten-free diet will give the patient a list of foods which are authorized and unauthorized. She/he will also teach the patient to read the labels and to prohibit preparations containing starch, modified starch or plant-based starching substances.
Recent European guidelines require the specific labelling as to whether such substances contain gluten or not. Most often it will be necessary to see the dietician again to specify points which may lead to confusion. It is also necessary to know that a certain number of medications contain gluten. Apart from its constraining character, a gluten-free diet proves costly, and is estimated at 800 FF (120 euros). per month and per household. Indeed for obvious practical reasons, often the entire family adopts the replacement products, which are not cheap. However, since 1996, the partial payment of such a diet by the Social Security System facilitates compliance.
Resistance to a gluten-free diet
The absence of a prompt response to a gluten-free diet should first lead the physician to suspect poor compliance with the diet, whether voluntary or not. Indeed, the dose level below which gluten may no longer be toxic has not been clearly established, all the more since there are probably wide variations between subjects. A detailed dietary questionnaire sometimes makes it possible to detect deviations sometimes ignored by the patient her/his self.
After eliminating poor compliance, the absence of a clinical and histological response after three to six months of a strict gluten-free diet makes it possible to define true resistance to such a diet. In a rare context, about 5% of cases, it is necessary to screen for a cause of primary or secondary resistance such as the ingestion of medications containing gluten, the occurrence of collagenous sprue which is sometimes associated with ulcerations of the small intestine, irreversible, small lesions of the mucosa, or even lymphoma of the small intestine. The latter three conditions require management in a specialized setting and require a study of epithelial lymphocytes by immunohisto-chemistry. Cortocosteroid therapy or the use immuno-suppressant agents are often necessary.
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CONCLUSION
Celiac disease is the only clinical condition in gastro-enterology whose treatment is based on a dietary prescription which is simple in principle, i.e. a gluten-free diet, but difficult to implement considering the social constraints which it imposes. Medical support, but especially dietetic support by trained staff sensitive to this problem is essential. Patient associations are of primary aid for success in this approach.
Dr Benoit Coffin
Hôpital Louis Mourier, Colombes
Hôpital Louis Mourier, Colombes
References:
Ciclitira P.L.
AGA Technical review on coeliac sprue. Gastroenterology, 2001 ; 120 : 1526-1540.
Janatuinen E.K, Pikarainen P.H, Kemppainen T.A et al.
Comparison of diets with and without oats in adults with coeliac disease.
N. Engl. J. Med. 1995 ; 333 : 1033-1037.
Collin P, Reunala T, Pukkala E et al.
Coeliac disease-associated disorders and survival. Gut 1994 ; 35 : 1215-1218.
Fine K.D, Meyer R.L, Lee E.L
The prevalence and causes of chronic diarrhea in patients with celiac sprue treated with a gluten-free diet. Gastroenterology 1997 ; 112 : 1830-1838.
Cellier C, Delabesse E, Helmer C et al.
Refractory sprue, coeliac disease, and enteropathy associated T cell lymphoma. Lancet 2000 ; 356 : 203-208.
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