Correspondence
Celiac Sprue
N Engl J Med 2002; 347:446-448August 8, 2002
- Article
To the Editor:
In the review of celiac sprue by Farrell and Kelly (Jan. 17 issue),1 the suggested diagnostic approach and the information in Table 2 (positive and negative predictive values of diagnostic serologic tests) may be misleading. For antiendomysial antibodies, the positive predictive value of 98 to 100 percent is based on studies of populations in which the prevalence of the disease is about 50 percent2 — that is, there is a high level of diagnostic suspicion. However, the post-test probability (predictive value) for a patient with a positive test for antiendomysial antibodies depends on the pretest probability. The likelihood ratio for both positive and negative test results would be more informative and useful for planning a diagnostic strategy.
When the level of suspicion is low, as in adults with diarrhea, in whom the probability of celiac sprue is about 5 percent,3 a positive test for antiendomysial antibodies (assuming 94 percent sensitivity, 97 percent specificity, and a consequent likelihood ratio of 31 for a positive test2) leads to a post-test probability of 60 percent, a level at which it may be reasonable to perform a confirmatory intestinal biopsy. However, for population screening with a pretest probability of celiac disease of 0.25 percent,1 a positive test for antiendomysial antibodies increases the probability of celiac disease to only 8 percent, with a false positive rate of 92 percent.
3 ReferencesAgostino Colli, M.D.
Ospedale A. Manzoni, 29300 Lecco, Italy
a.colli@ospedale. lecco. it Alice Colucci, M.D.
Dario Conte, M.D.
Ospedale Maggiore, 20122 Milan, Italy1
Farrell RJ ,Kelly CP . Celiac sprue. N Engl J Med 2002;346:180-188
Full Text | Web of Science | Medline2
Cataldo F ,Ventura A ,Lazzari R ,Balli F ,Nassimbeni G ,Marino V . Antiendomysium antibodies and coeliac disease: solved and unsolved questions: an Italian multicentre study. Acta Paediatr 1995;84:1125-1131
CrossRef | Web of Science | Medline3
Hin H ,Bird G ,Fisher P ,Mahy N ,Jewell D . Coeliac disease in primary care: case finding study. BMJ 1999;318:164-167
CrossRef | Web of Science | Medline
To the Editor:
Bone mineral density has been found to be reduced in a substantial number of patients with celiac sprue.1 A gluten-free diet can improve bone mineral density, but in many cases, osteopenia does not resolve.2,3 Recently published guidelines recommend measurement of bone mineral density at diagnosis and treatment in selected cases with a bisphosphonate or calcitonin, in addition to calcium and vitamin D supplementation.1 These guidelines may be helpful in the treatment of patients with celiac sprue.
3 ReferencesFernando Gomollón, M.D.
Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
fgomollon@able.es 1
Scott EM ,Gaywood I ,Scott BB . Guidelines for osteoporosis in coeliac disease and inflammatory bowel disease. Gut 2000;46:Suppl 1:i1-i8
CrossRef | Web of Science | Medline2
Kalayci AG ,Kansu A ,Girgin N ,Kucuk O ,Aras G . Bone mineral density and importance of a gluten-free diet in patients with celiac disease in childhood. Pediatrics 2001;105:E89-E89
CrossRef | Web of Science3
McFarlane XA ,Bhalla AK ,Reeves DE ,Morgan LM ,Robertson DA . Osteoporosis in treated adult coeliac disease. Gut 1995;36:710-714
CrossRef | Web of Science | Medline
To the Editor:
We agree with Farrell and Kelly that lifelong, strict adherence to a gluten-free diet is the cornerstone of treatment for celiac disease. However, their inclusion of wheat starch is controversial at best. Chartrand et al. reported the occurrence of symptoms in 15 of 17 patients with celiac sprue who consumed wheat-starch products with only 0.75 mg of gliadin per 100 g of food.1 The symptoms resolved when the wheat starch was removed. Foods labeled as gluten-free in the United States and Canada are not allowed to contain any wheat starch.2
The recommendation, in Table 3 of the article by Farrell and Kelly, to “use only rice, corn, maize, buckwheat, potato, soybean, or tapioca flours, meals, or starches” unnecessarily restricts the diet. The inclusion of other gluten-free flours and grains, such as quinoa, millet, amaranth, flax, and bean flours, adds not only variety but also nutrients.
The statement that oats can be consumed daily as long as “the patient has no ill effects” is hard to assess. Many celiac complications, such as decreased bone density, are silent. Oats remain promising, but until it has been demonstrated that long-term consumption of oats is not harmful, especially in children, it remains prudent to await further research on safety.3
Patients need consistent guidelines for a gluten-free diet, such as those issued by the American Dietetic Association and Dietitians of Canada and endorsed by the Gluten Intolerance Group of North America, the Canadian Celiac Association, and the Celiac Disease Foundation.2,4
4 ReferencesEvelyn Tribole, M.S., R.D.
Celiac Disease Foundation, Studio City, CA 91604
etribole@aol.com Cynthia Kupper, R.D., C.D.
Gluten Intolerance Group of North America, Seattle, WA 98166Michelle Pietzak, M.D.
University of Southern California Keck School of Medicine, Los Angeles, CA 900271
Chartrand LJ ,Russo PA ,Duhaime AG ,Seidman AG . Wheat starch intolerance in patients with celiac disease. J Am Diet Assoc 1997;97:612-618
CrossRef | Web of Science | Medline2
American Dietetic Association, Dietitians of Canada. Manual of clinical dietetics. 6th ed. Chicago: American Dietetic Association, 2000.
3
Kalayci AG ,Kansu A ,Girgin N ,Kucuk O ,Aras G . Bone mineral density and importance of a gluten-free diet in patients with celiac disease in childhood. Pediatrics 2001;108:E89-E89
CrossRef | Web of Science | Medline4
Case S. Gluten-free diet: a comprehensive resource guide. Saskatchewan, Canada: Case Nutrition Counseling, 2002. (Accessed July 19, 2002, at http://www.glutenfreediet.ca.)
To the Editor:
Farrell and Kelly discuss the clinical presentations of celiac sprue. We recently saw a patient who presented with pancytopenia as an extraintestinal manifestation.
An 82-year-old woman was hospitalized because of diarrhea that had persisted for six weeks. She had been a vegetarian for many years and did not use supplements. Physical examination revealed an anorectic woman with a fever (temperature, 38.6°C). The examination was otherwise unremarkable. Laboratory tests showed pancytopenia (hemoglobin level, 5.3 g per deciliter; mean corpuscular volume, 103 fl; leukocyte count, 1.9×109 per liter; platelet count, 86×109 per liter, with evidence of hemolysis [lactate dehydrogenase level, 8420 U per liter; haptoglobin level, 6 mg per deciliter]). The vitamin B12 level was less than 0.07 ng per milliliter (normal value, >0.18 ng per milliliter), and the folate level was 0.84 ng per milliliter (normal value, >2.5 ng per milliliter). A test for antigliadin antibodies was positive. Histologic examination of a specimen from a biopsy of the small intestine confirmed the diagnosis of celiac sprue. Radiologic examination of the small bowel ruled out other anatomical abnormalities.
Our patient was treated with hydroxocobalamin and folate and a gluten-free diet. The diarrhea diminished. The pancytopenia resolved, and the lactate dehydrogenase level returned to the normal range within two weeks.
This case shows that the combination of celiac sprue and an inadequate dietary intake can cause pancytopenia and hemolysis. Celiac sprue can cause pancytopenia in an elderly patient, and 20 percent of patients with celiac disease are more than 60 years old when the disease is diagnosed.1
1 ReferencesBernhard W.M. Spanier, M.D.
Barbara Dietz, M.D.
Chris J.J. Mulder, M.D., Ph.D.
Spaarne Ziekenhuis Heemstede, 2100 AJ Heemstede, the Netherlands
b.w. mspanier@freeler. nl 1
Jansen TL ,Mulder CJJ ,Karssen PHZ ,Wagenaar CGJ . Epidemiological survey of the Dutch Coeliac Disease Society: an update 1992. Eur J Gastroenterol Hepatol 1993;5:73-78
CrossRef | Web of Science
Author/Editor Response
The authors reply:
To the Editor: We agree with Colli and colleagues that the predictive value of a serologic test for IgA antiendomysial antibodies will vary depending on the prevalence of celiac sprue in the study population. The data in our article are based on published studies. The estimated diagnostic accuracy in other populations can be calculated on the basis of the characteristics of the assay (its sensitivity and specificity) and the expected prevalence of the disease. The possibility of a false positive result of a test for antiendomysial antibodies underlies our recommendation that a small-bowel biopsy be performed in all cases to obtain histologic confirmation of celiac enteropathy before dietary treatment is started.
Dr. Gomollón highlights the well-documented association between celiac sprue and osteopenia. We do recommend measurement of bone mineral density in patients with newly diagnosed celiac sprue. An evaluation of bone mineral density is especially important in patients with clinical evidence of nutritional deficiency and in those with abnormal serum levels of calcium, inorganic phosphate, alkaline phosphatase, or vitamin D at presentation. If osteopenia is identified, it should be treated and monitored as it would in patients who do not have celiac sprue. The effects of a gluten-free, and possibly lactose-free, diet on dietary calcium intake should also be considered, and appropriate oral supplements given.
We thank Tribole and colleagues for their helpful comments on the continually evolving guidelines with regard to cereals that can safely be included in a gluten-free diet. As we stated in our review, wheat starch should be included only if it is gluten-free. Wheat starch containing detectable gliadin should not be labeled as gluten-free and should be avoided. The inclusion of a variety of less well known grains, such as quinoa and millet, is a welcome advance. Although oats were previously considered unsafe, more recent studies indicate that they are well tolerated and do not appear to induce intestinal immune activation in children or adults with celiac sprue.1-4 The important caveat, as we explained, is that oat products may be contaminated by gluten from wheat, barley, or rye either in the field or during processing. Thus, if oats are to be consumed, they must come from a reliable source and be introduced into the diet with caution. Because of these valid concerns about purity, many dietitians continue to exclude oats from the recommended gluten-free diet.
In our article, we duplicated portions of the text and Figure 3 that had appeared in another review we published, on the diagnosis of celiac sprue.5 This occurred because our article on diagnosis was used as a basis for our general review of celiac sprue. We did not appropriately inform the Journal and its readers of this duplication and apologize for our error.
5 ReferencesRichard J. Farrell, M.D.
Ciaran P. Kelly, M.D.
Beth Israel Deaconess Medical Center, Boston, MA 02215
rfarrell@caregroup.harvard. edu 1
Janatuinen EK ,Pikkarainen PH ,Kemppainen TA , et al. A comparison of diets with and without oats in adults with celiac disease. N Engl J Med 1995;333:1033-1037
Full Text | Web of Science | Medline2
Hardman CM ,Garioch JJ ,Leonard JN , et al. Absence of toxicity of oats in patients with dermatitis herpetiformis. N Engl J Med 1997;337:1884-1887
Full Text | Web of Science | Medline3
Picarelli D ,Di Tola M ,Sabbatella L , et al. Immunologic evidence of no harmful effect of oats in celiac disease. Am J Clin Nutr 2001;74:137-140
Web of Science | Medline4
Vader LW ,de Ru A ,van der Wal Y , et al. Specificity of tissue transglutaminase explains cereal toxicity in celiac disease. J Exp Med 2002;195:643-649
CrossRef | Web of Science | Medline5
Farrell RJ ,Kelly CP . Diagnosis of celiac sprue. Am J Gastroenterol 2002;96:3237-3246
CrossRef | Web of Science
- Citing Articles (2)
Citing Articles
1
A. C. Hofer, R. T. Tran, O. Z. Aziz, W. Wright, G. Novelli, J. Shay, M. Lewis. (2005) Shared Phenotypes Among Segmental Progeroid Syndromes Suggest Underlying Pathways of Aging. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60:1, 10-20
CrossRef2
G. E. M. Reeves. (2004) Coeliac disease: against the grain. Internal Medicine Journal 34:9-10, 521-525
CrossRef
