Correspondence

Absence of Toxicity of Oats in Patients with Dermatitis Herpetiformis

N Engl J Med 1998; 338:1470-1471May 14, 1998

Article

To the Editor:

In their report on the absence of a toxic effect of oats on patients with dermatitis herpetiformis, Hardman et al. (Dec. 25 issue)1 conclude that moderate quantities of oats can be safely included in the diet of such patients. This conclusion is in agreement with the results of a recent study of adult celiac disease.2 We believe, however, that it is currently unwise to advise gluten-sensitive patients that oats are safe.

The absence of a toxic moiety in oats has not been clearly demonstrated. Hardman et al. state that the sequence glutamine – glutamine – glutamine – proline –phenylalanine–proline, which may be part of a toxic epitope in gluten, is not found in oats. However, the sequence glutamine–glutamine – glutamine – proline – phenylalanine is present. Monoclonal antibodies to enterotoxic wheat peptides have cross-reactivity with oat peptides.3 Oat prolamins can also stimulate an immune reaction in intestinal-biopsy specimens.4

Although the apparently nontoxic nature of oats may be due to the low percentage of oat prolamin present, with only large quantities therefore being harmful, some patients may have an exquisite sensitivity, as is the case with the well-known variable sensitivity to gluten among patients with celiac disease. The small numbers of patients in these studies1,2 may be insufficient to detect such an effect. In a larger, Finnish study,5 of the patients consuming oats, two with dermatitis herpetiformis withdrew with worsening of itching (often the first sign of an exacerbation), and two withdrew with abdominal symptoms.

Hardman et al.1 and Srinivasan et al.2 used oats tested for, and determined to be free of, gluten contamination with the use of several molecular biologic methods. These methods are clearly not available to gluten-sensitive patients, who are unable to tell which oat preparations have been contaminated with gluten during harvesting or milling. Even a small degree of contamination may precipitate a relapse, as is demonstrated in patients with celiac disease who are given gluten “micro-challenges.” 2

The advice that a “moderate” quantity of oats is safe can lead only to misinterpretation and confusion, with the possibility that it becomes generally accepted among gluten-sensitive patients that oats themselves are safe. Some patients may consume large quantities of oats in many different forms, with various amounts of gluten contamination, in order to improve a restricted diet. Until the absence of toxicity can be conclusively proved, and oat products labeled as free of gluten contamination, patients should be advised to avoid oats.

Nick Parnell, M.R.C.P.
H. Julia Ellis, Ph.D.
Paul Ciclitira, M.D., Ph.D.
St. Thomas' Hospital, London SE1 7EH, United Kingdom

5 References

1. 1

   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 | Medline

2. 2

   Srinivasan U, Leonard N, Jones E, et al. Absence of oats toxicity in adult coeliac disease. BMJ 1996;313:1300-1301
   CrossRef | Web of Science | Medline

3. 3

   Ellis HJ, Doyle AP, Day P, Ciclitira PJ. Coeliac disease: measurement of a toxic wheat peptide in gluten-free foods. Gut 1995;36:Suppl 1:A65-A65 abstract.
   

4. 4

   Leone NA, Mazzarella G, Ciacci C, et al. Oats prolamines in vitro activate intestinal cell-mediated immunity in coeliac disease. In: Collin P, Maki M, eds. Seventh International Symposium on Coeliac Disease, Tampere, Finland, September 5–7, 1996. Tampere, Finland: Lege Artis, 1996:69.
   

5. 5

   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 | Medline

Author/Editor Response

The authors reply:

To the Editor: The cross-reactivity of a monoclonal antibody to enterotoxic wheat peptides with oat peptides does not prove toxicity. Antibodies may develop to peptide epitopes having as few as six amino acid residues. The antibodies to a 19-residue gliadin peptide may not be specific for the part of the peptide that is active in celiac disease, since the smallest known active peptide has only 12 amino acid residues.1 Furthermore, Ellis et al. found that an antibody to a similar, but slightly larger, active gliadin sequence, which included the 19-residue peptide mentioned above, showed a stronger reaction to oat peptides than to Fraser fraction III.2 Thus, this particular antibody was not likely to be reacting primarily with the celiac disease–active moieties of gliadin peptides.

It does not follow that because oat prolamins can induce antibody production in intestinal-biopsy specimens in vitro, they necessarily induce an enteropathy. Peptides from many different proteins are likely to be more readily absorbed in patients with celiac disease and give rise to antibody production, but there is no evidence as yet that these antibodies (or the peptides) have a primary pathogenic role.

Parnell et al. state that various degrees of sensitivity to gluten occur in patients with celiac disease, and they are concerned that the patients with greater sensitivity may be at risk from the consumption of oats. However, all patients have some changes (at least an increase in intraepithelial lymphocyte counts, if not a decrease in villus and epithelial-cell heights) in the intestinal mucosa with a gluten challenge. In our study and those previously reported with oats, changes in the intestinal mucosa have not been noted.

We are surprised by the comment about the inability of patients to establish the contamination of oats. It is not up to patients to test the purity of oats; the companies selling oats and their products should do the testing, and this has already been demonstrated to be feasible.

Parnell and colleagues state that the absence of a toxic moiety in oats has not been demonstrated. More important, we have not demonstrated any toxic effect of oats on the skin or intestine in patients with dermatitis herpetiformis. If such an effect exists, it remains to be demonstrated.

Catherine M. Hardman, M.R.C.P.
Lionel Fry, M.D.
St. Mary's Hospital, London W2 1NY, United Kingdom

2 References

1. 1

   Marsh MN, Morgan S, Ensari A, et al. In vivo activity of peptides 31-43, 44-55, 56-68 of α-gliadin in gluten sensitive enteropathy (GSE). Gastroenterology 1995;108:Suppl:A871-A871 abstract.
   Web of Science

2. 2

   Ellis HJ, Doyle AP, Day P, Wieser H, Ciclitira PJ. Demonstration of the presence of coeliac-activating gliadin-like epitopes in malted barley. Int Arch Allergy Immunol 1994;104:308-310
   CrossRef | Web of Science | Medline

Citing Articles (7)

Citing Articles

1. 1

   Diana Bolotin, Vesna Petronic-Rosic. (2011) Dermatitis herpetiformis. Journal of the American Academy of Dermatology 64:6, 1027-1033
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2. 2

   Flavia Fedeles, Michael Murphy, Marti J. Rothe, Jane M. Grant-Kels. (2010) Nutrition and bullous skin diseases. Clinics in Dermatology 28:6, 627-643
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3. 3

   E. K. Arendt, F. Dal Bello. 2008. Functional cereal products for those with gluten intolerance. , 446-475.
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4. 4

   Tricia Thompson. (2001) Case Problem. Journal of the American Dietetic Association 101:5, 586-587
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5. 5

   William Harford. (2000) Celiac sprue and related diseases. Current Treatment Options in Gastroenterology 3:2, 159-170
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6. 6

   Nick Parnell, Paul J. Ciclitira. (1999) Celiac disease. Current Opinion in Gastroenterology 15:2, 120
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7. 7

   PARNELL, CICLITIRA. (1999) Review article: coeliac disease and its management. Alimentary Pharmacology and Therapeutics 13:1, 1-13
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