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Gluten sensitivity: a many headed hydra

BMJ 1999; 318 doi: (Published 26 June 1999) Cite this as: BMJ 1999;318:1710

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Gluten sensitivity: a many headed hydra and a Trojan horse

EDITOR - Hadjivassiliou's editorial "Gluten sensitivity: a many headed hydra" 1 underlines and clearly illustrates the diverse clinical presentation of coeliac disease and strongly defend the hypothesis that the gut is not the sole protagonist in this disease.

This is a very important concept and has wide clinical implications. It gives a solution to patients with obscure neuromuscular disorders who respond very well to a gluten-free diet. This also explains to a certain extent why paediatricians diagnose coeliac disease more often than the gastroenterologist dealing with adult patients.

There are two points that deserve wider comment. As Hadjivassiliou has correctly pointed out, coeliac disease has one of the strongest HLA associations of any immune disease (HLA DQ2 and HLA DQ8). Therefore, patients with positive for antigliadin or antiendomysium antibodies with this genotype are in all likelihood coeliacs even when the duodenal and/or jejunal mucosa is morphologically normal. He also quotes his previous work that 85% of patients with neurological disorders associated with gluten sensitivity have an HLA genotype in keeping with coeliac disease compared with 25% of the normal population 2. This statement introduces a Trojan horse in the difficult arena of what is coeliac disease in the absence of histological features of the small intestine. In this situation, HLA typing should be mandatory in these complex clinical problems although many clinicians do not ask for this investigation mainly due to the relative high expensive laboratory techniques which is mainly done in Blood banks or transplantation centres. Modern technology of HLA-DQ typing is refining the definition of the heterodimers specifically associated with coeliac disease and will probably reduce the costs 3.

The other issue that I would like to raise concerns his observation that the typical clinical expression of a patient with gluten sensitivity where the sole manifestation is neurological is cerebellar ataxia, with a peripheral neuropathy, what he has previously named gluten ataxia 4 has not been confirmed by another group 5. The message is that for the time being serology and clinical response is not enough to make the diagnosis of gluten sensitivity, particularly in the absence of morphological abnormalities of the small intestine, HLA-DQ typing should be part of the diagnosis.

I think, however, that Hadjivassiliou's editorial is excellent and will contribute to disseminate the new findings on coeliac disease to other clinicians than the gastroenterologist and will stimulate further research.

Amado Salvador Peña, Professor of Gastrointestinal immunology
Free University Hospital, Amsterdam, The Netherlands, E-mail:

1. Hadjivassiliou M, Gr#newald RA, Davies-Jones GA. Gluten sensitivity: a many headed hydra. Heightened responsiveness to gluten is not confined to the gut. Bmj 1999;318(7200):1710-1711.

2. Hadjivassiliou M, Chattopadhyay AK, Davies-Jones GA, Gibson A, Grunewald RA, Lobo AJ. Neuromuscular disorder as a presenting feature of coeliac disease. J Neurol Neurosurg Psychiatry 1997;63(6):770-5.

3. Crusius JBA, Mulder CJJ, Mearin ML, Peña AS. Value of the HLA-DQ heterodimer as a genetic marker of the predisposition to coeliac disease. Neth J Med 1994;45:A13.

4. Hadjivassiliou M, Grunewald RA, Chattopadhyay AK, Davies-Jones GA, Gibson A, Jarratt JA, et al. Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia. Lancet 1998;352(9140):1582-5.

5. Pellecchia MT, Scala R, Filla A, De Michele G, Ciacci C, Barone P. Idiopathic cerebellar ataxia associated with celiac disease: lack of distinctive neurological features. J Neurol Neurosurg Psychiatry 1999;66(1):32-5.

Competing interests: No competing interests

26 June 1999
Amos Salvador Pe??
Professor of Gastrointestinal immunology
Free University Hospital