|Effects of Small Amounts of Gluten in the Diet of Celiac Patients|
S. Auricchio and R. Troncone
A diet excluding wheat, oats, rye and barley is the cornerstone of the treatment of coeliac patients. Such a gluten-free diet (GFD) is recommended irrespective of the presence of symptoms. Maintenance of a strict GFD is not a simple matter, as small amounts of gluten capable of causing relapse have been identified in several previously unsuspected sources, thanks to the recent availability of sensitive detection assays. To date there is no definition as to what amount of gluten in the diet might be tolerable. Compliance to the GFD is a problem, particularly in certain groups of patients (e.g. adolescents). Small amounts of gluten in the diet often do not cause clinical symptoms, nor increased serum levels of antigliadin antibody, nor gross changes of the jejunal histology; nevertheless, they seem to be able to activate mucosal cell-mediated immunity. This finding represents a warning in view of the recently reported protective effect of GFD against malignancies. In conclusion, all present evidences give strong support for advising all patients to adhere to a strict GFD for life.
Since the identification of gluten as aetiologic factor in coeliac disease (CD), a strict gluten-free diet (GFD) has become the cornerstone of the management of such patients. Their diet should exclude wheat, oats, rye, and barley; rice and maize are nontoxic and are usually used as wheat substitutes. The GFD is recommended for both symptomatic and asymptomatic CD patients. Although it is standard practice to treat all CD patients by dietary means, two main issues are still questioned by some Authors. How strict should the diet be? Should it be for life?
Maintenance of a strict GFD is not a simple matter. Avoidance is not always easy, as small amounts of gluten capable of causing relapse have been identified in several previously unsuspected sources, e.g. some pharmaceutical preparations and Communion waters. On a weekly basis a daily communicant may consume up to 35 mg gliadin. Unsatisfactory growth and intestinal partial villous atrophy have documented in an 8-year-old boy, since he started to take Holy Communion once a week. In fact, the presence of wheat in the Host may represent a real problem for patients who attend Holy Communion regularly. According to the New Testament a wheat-free host is unacceptable, but it might be theologically acceptable for patients to take Holy Communion in the form of Christ's Blood (consecrated wine) instead of the Body. More recently, the availability of sensitive methods of detection (RIA, ELISA) has permitted to reveal that commercial gluten-free products themselves may represent an unsuspected vehicle of small amounts of gliadin. In fact, up to 1 mg of gliadin/100 g dry product has been shown to be present in foods labeled as gluten-free. Moreover, 4 out of 10 patients presented symptoms, who had ingested with such products a daily amount of 1-2 mg of gliadin regularly for 6 weeks. To date there is no definition as to what amount of gluten in the diet might be tolerable. The issue is so far without answer because of the noticeable lack of clinical studies, and the large variability of gluten sensitivity from patient to patient. Nevertheless, present evidences (some discussed below) strongly support the view that restriction of gliadin and related prolamines should be complete for all patients.
Compliance to the gluten-free diet is a problem particularly in certain groups of patients. Most studies show poor dietary compliance in coeliac teenagers, with only 50% adhering to a GFD; it is likely that the rate of compliance is even lower, as many of those declaring maintenance of a strict GFD reveal significant mucosal abnormalities. Yet, most are asymptomatic with normal haemato-logical and biochemical parameters. Since so many are apparently well, some researchers have questioned whether firm dietary restriction is really necessary. In view of these findings, a low gluten-containing diet (2.5-5 g/day) has been advocated as a more realistic treatment for some patients. With the aim of assessing compliance with the GFD in a cohort of teenager coeliacs, and the clinical, immunological and histological consequences of different amounts of gluten present in their diet, we have recently investigated 123 CD patients diagnosed in the first years of life and followed-up for at least ten years. The amount of dietary gluten symptoms associated diseases were assessed and antigliadin antibodies (AGA) measured.
In 36 patients who underwent jejunal biopsy a morphometric evaluation was also carried out by a computerized image analysis system. Eighty (65%) patients were found to be on a GFD, 29 (23.6%) were on a gluten-containing diet (average daily gluten content: 15 g), while 14 (11.4%) were on a GFD with occasional intake of small amounts of gluten, ranging from 0.026-2 g/day (average 0.73 g/day). Of these, 9 ingested 1 g/day and 5 approximately 1-2 g/day. Clinical symptoms occurred more frequently in patients on a gluten-containing diet, but not in patients on a semistrict diet. For the semistrict GFD group, neither symptoms nor AGA levels were found to be reliable markers of gluten ingestion. By the computerized image analysis we were able to show a significant decrease in surface epithelial volume, and a significant increase in crypt epithelial volume passing from the GFD group to the gluten-containing diet group. Surface intraepithelial lymphocytes (IEL) significantly decreased from the GFD group to those on a gluten-containing diet, while crypt epithelium showed a significantly inverse pattern. Patients ingesting small amounts of gluten (less than 1 g daily) showed not obvious alterations in routine mucosal architecture, yet they presented increased absolute number of crypt IEL. These results are in agreement with those of other Authors who have demonstrated that patients on a low gluten-containing diet (2.5-5 g/day) show increased IEL counts in the absence of gross morphological changes and significant AGA response. Taken as a whole, these observations suggest that small amounts of gluten are able to activate mucosal cell-mediated immunity.
Although the need of a lifelong treatment with GFD is generally accepted, also this issue has been questioned. Some Authors have decided not to prescribe GFD to coeliac adolescents who showed a definitive mucosal relapse if they did not show clinical symptoms. Of 29 cases, 19 maintained severe mucosal damage at bioptic follow-up, while four showed a "total" mucosal recovery and six a "partial" recovery after 4 to 6 years of normal diet. These Authors suggest that the condition of gluten sensitivity may be only transient.
The long-term significance of "minor" histologic changes observed in adolescent coeliacs on a semistrict GFD, or even on an entirely normal diet, is uncertain, but these findings represent a warning in view of the recently reported protective effect of gluten-free diet against malignancies. There is in coeliac disease a two-fold increase in overall mortality, and much is accounted for by malignancies. The data available show that for coeliac patients who have taken a gluten-free diet for five years or more the risk of developing cancer over all sites is not increased when compared with the general population. The risk is increased in those taking a reduced gluten or a normal diet, with an excess of cancer of the mouth, pharinx, oesophagus, and particularly of lymphoma (relative risk: 77.8). The enteropathy-associated T cell lymphoma arising in coeliac patients is likely to be a tumor of mucosal T cells, possibly the intraepithelial T cell component. But strict dietary compliance is to be recommended to avoid also other long-term risks associated with coeliac disease: poor general health, developmental retardation, infertility, malabsorption, bone disease, deterioration of the condition during pregnancy.
In conclusion, all present evidences give strong support for advising all patients to adhere to a strict GFD for life. The diet should be based on natural food prepared with non-toxic cereals. That represents a sound alternative to special food based on protein-free wheat derived flours. The latter carry the risk of being contaminated by small amount of gliadin. Furthermore, these products available upon prescription can be perceived by patients as drugs. On the contrary, a diet exclusively based on maize and rice as cereals could be implemented by the rest of the family. A precocious education of the taste of patients diagnosed in early childhood may significantly contribute to a better compliance to GFD later in life.
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.