Response to Dr. Cuoco et al

AJG – May, 2000

Letters to the Editor

intestinal metaplasia or atrophic gastritis, which are markers of long-standing chronic infection by H. pylori (5), are sporadic in this population. Gastric mucosa-associated lymphoid tissue (MALT), lymphocytic gastritis, and atrophic gastritis with achlorydria are widely described in celiac (2, 4, 6) and dermatitis herpetiformis (7) patients, and also in patients with autoimmune disorders such as autoimmune thyroiditis (8) and Sjo¨gren’s syndrome (9), which are often associated with CD. We believe that gastric mucosa is involved in the immune response to environmental antigens (such as H. pylori, dietary gluten, and EBV), which, in these genetically susceptible hosts, can lead to lymphoproliferation constituting follicular B-cell gastritis or classical T-cell lymphocytic gastritis. Thus, a more accurate mapping of gastric mucosa in celiac patients is necessary to define more exactly the real presence of lymphocytic infiltrate in the stomach wall. Lucio Cuoco, M.D. Giovanni Cammarota, M.D. Regina Anna Jorizzo, M.D. Italo De Vitis, M.D. Giuseppe Fedeli, M.D. Giovanni Gasbarrini, M.D. Institute of Internal Medicine Department of Gastroenterology Catholic University Rome, Italy

REFERENCES 1. Diamanti A, Maino C, Niveloni S, et al. Characterization of gastric mucosal lesions in patients with celiac disease. A prospective controlled study. Am J Gastroenterol 1999;94:1313–9. 2. Cuoco L, Cammarota G, Tursi A, et al. Disappearance of gastric mucosa-associated lymphoid tissue in coeliac patients after gluten withdrawal. Scand J Gastroenterol 1998;33:401–5. 3. Maki M, Collin P. Coeliac disease. Lancet 1997;349:1755–9. 4. Cammarota G, Fedeli G, Tursi A, et al. Coeliac disease and follicular gastritis. Lancet 1996;347:268. 5. Kuipers EJ, Klinkenberg-Knol EC, Vandenbroucke-Grauls CMJE, et al. Role of Helicobacter pylori in the pathogenesis of atrophic gastritis. Scand J Gastroenterol 1997;32(suppl 223): 28 –34. 6. Wolber R, Owen D, Del Buono L, et al. Lymphocytic gastritis in patients with coeliac sprue or spruelike intestinal disease. Gastroenterology 1990;98:310 –5. 7. Gillberg R, Kastrup W, Mobacken R, et al. Gastric morphology and function in dermatitis herpetiformis and coeliac disease. Scand J Gastroenterol 1985;20:133– 40. 8. Cammarota G, Tursi A, De Marinis L, et al. Gastric mucosaassociated lymphoid-tissue in autoimmune thyroid diseases. Scand J Gastroenterol 1997;32:869 –72. 9. Ferraccioli GF, Sorrentino D, De Vita S, et al. B-cell clonality in gastric lymphoid tissue of patients with Sjo¨gren’s syndrome. Ann Rheum Dis 1996;95:311– 6.

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Reprint requests and correspondence: Lucio Cuoco, M.D., Istituto di Medicina Interna e Geriatria, Universita` Cattolica del Sacro Cuore-Roma, Largo A. Gemelli, 8 – 00168 Rome, Italy. Received July 8, 1999; accepted Oct. 25, 1999.

Response to Dr. Cuoco et al. TO THE EDITOR: We thank Dr. Cuoco et al. for their interest in our report on the characterization of gastric mucosal lesions for patients with celiac disease (1). As they stated, our study presented results different from those previously reported. We observed that chronic gluten ingestion in gluten-sensitive patients produces inflammation of the gastric mucosa (intraepithelial lymphocyte infiltration), and that damage can be augmented by the combined effect of another environmental antigen (Helicobacter pylori [H. pylori]). In our opinion, criticisms raised by Cuoco et al. of some aspects of our study deserve further comment. First, although the number of treated patients is relatively scant, they have been incorporated in the study as a disease control population to assess the effect on the mucosal inflammation of the exclusion of one of the offending antigens (gliadin). Second, diagnosis of celiac disease was based on current criteria consisting of the combination of clinical, histological, and serological features of the disease. We have no doubt that all of those patients included in the study fulfill these modern criteria, and that they are effectively celiac patients. In our extensive experience with adult patients with malabsorption syndromes, a complete intestinal villous atrophy, such as that in our celiac patients, was never attributed to the infestation with Giardia Lamblia. We agree with Cuoco et al. on that the presence of a positive serology for H. pylori does not mean current bacterial infection. However, there are several reasons that histology may not be the most appropriate means of diagnosis of H. pylori infection. The analysis of our data based only on the histological evidence of H. pylori had results similar to those reported in the article using a more global criterion. Thus, histology detected H. pylori infection in 48% of patients and in 51% of nonceliac controls, and no difference was observed between treated and untreated patients. Surprisingly, intraepithelial lymphocyte counts, according to the histological H. pylori status, were not different from those reported by combined histological and serological analysis (data not shown). A third point of discussion is the use of a limited sampling of the gastric mucosa. We agree with Cuoco et al. that a wider sampling would improve accuracy. However, this was a source of systematic bias in most other studies. In conclusion, our results detected a limited mucosal inflammation in the stomach of celiac patients that could be related to the cumulative effect of H. pylori infection and

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Letters to the Editor

gluten sensitivity. The prevalence of lymphocytic gastritis was very low and histological evidence of atrophic gastritis was not detected. These findings could provide an explanation for the very low prevalence of gastric malignancies reported for celiac disease. Julio C. Bai, M.D. Eduardo Maurin˜o, M.D. Gastroenterology Hospital “Dr. Carlos Bonorino Udaondo” Universidad del Salvador Buenos Aires, Argentina

REFERENCE 1. Diamanti A, Maino C, Niveloni S, et al. Characterization of gastric mucosal lesion in patients with celiac disease: A prospective controlled study. Am J Gastroenterol 1999;94:1313–9.

Reprint requests and correspondence: Julio C. Bai, M.D., Gastroenterology Hospital “Dr. Carlos Bonorino Udaondo,” Universidad del Salvador, Caseros 2061, 1264 Buenos Aires, Argentina. Received Oct. 19, 1999; accepted Oct. 25, 1999.

AJG – Vol. 95, No. 5, 2000

Celiac disease is a permanent intolerance to gliadin that results in intestinal villous atrophy. Sensitivity and specifity of serological tests for the screening and diagnosis of celiac disease are variable. Among them, the sensitivity and specifity of EMA are the highest and are related to the degree of mucosal atrophy. Previous studies showed that positivities of AGA IgA and EMA were 62–96% and 90 – 100% (3–5), respectively, in celiac patients. On the other hand, not all children with positive EMA has celiac disease (3). As the authors mentioned, we performed jejunal biopsy only on children who had a positive test for at least one serology. Although our study did not reflect the real sensitivity of serology, it is lower in patients without intestinal atrophy. The Rostami et al. study is very important and suggestive to show that jejunal biopsy should be performed on symptomatic patients even if they do not have positive serological tests, and that if the histopathological findings are consistent with celiac disease, they should be followed with a gluten-free diet. However, another point is the asymptomatic individuals who are in a high risk group for celiac disease and have negative serological tests. Clearly, is it ethical to perform biopsy on all of them? More sensitive and specific screening tests should be developed for this group. Aysel Yu¨ce, M.D. Hu¨lya Demir, M.D. Nurten Koc¸ak, M.D. Figen Gu¨rakan, M.D. ¨ zen, M.D. Hasan O Division of Gastroenterology Department of Pediatrics Hacettepe University Faculty of Medicine Ankara, Turkey

Antiendomysium and Antigliadin Antibodies for the Diagnosis of Celiac Disease TO THE EDITOR: We read with great interest the study by Rostami et al. (1), in which they investigated the diagnostic value of antigliadin (AGA) and antiendomysial antibodies (EMA) in untreated celiac disease with regard to the degree of histological abnormalities in jejunal biopsies according to Marsh’s criteria (2). Briefly, the sensitivity of EMA was found to be 100% in patients with total villous atrophy and 31% in patients with subtotal villous atrophy. Total sensitivity of AGA was 62%. None of the first degree relatives with Marsh I and II had positive EMA. They concluded that negative serology should be interpreted carefully and that EMA and AGA have only limited value in screening celiac disease. We have also evaluated the sensitivity of AGA and EMA in 87 children with celiac disease (78 had Marsh III and nine Marsh I or II histology). Three of the patients with Marsh III were diagnosed during the screening of 56 siblings. Sensitivity of IgA AGA and EMA was 77% (60 of 78) and 92% (72 of 78) respectively in patients with type III lesion. Sensitivity of both tests was 66% (six of nine) in symptomatic patients with Marsh I and II histology who improved with a gluten-free diet.

REFERENCES 1. Rostami K, Kerckhaert J, Tiemessen R, et al. Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: Disappointing in clinical practice. Am J Gastroenterol 1999;94:888 –94. 2. Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunologic approach to the spectrum of gluten sensitivity. Gastroenterology 1992;102: 330 –54. 3. Chan KN, Phillips AD, Mirakian R, et al. Endomisial antibody screening in children. J Ped Gastroenterol Nutr 1994;18:316 – 20. 4. Bu¨rgin-Wolff A, Gaze H, Hadziselimovic F, et al. Antigliadin and antiendomysium antibody determination for celiac disease. Arch Dis Child 1991;66:941–7. 5. Bu¨rgin-Wolff A, Berger R, Gaze H, et al. IgG, IgA and IgE gliadin antibody determination as screening test for untreated coeliac disease. Eur J Pediatr 1989;148:496 –502.