Gluten sensitivity: a many headed hydra
BMJ 1999; 318 doi: https://doi.org/10.1136/bmj.318.7200.1710 (Published 26 June 1999) Cite this as: BMJ 1999;318:1710
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Dear Sirs
Dr Hadjivassiliou and colleagues (1) (June 26th) are not correct in
invoking dermatitis herpetiformis (DH) as being analogous to the
neurological disorders which they attribute to gluten sensitivity.
Firstly, all patients with DH do in fact have demonstrable gluten
sensitivity of the small intestine. Thus, although only two-thirds of
patients with DH have a degree of villous-atrophy on a routine diagnostic
single biopsy, if appropriate criteria are used, nearly 100% have
demonstrable gluten sensitivity. Brow et al. (2) showed that if multiple
biopsies are taken, the incidence of villous atrophy rises to 95%. Also,
lymphocytic infiltration of the epithelium occurs in 90% of patients with
DH irrespective of villous architecture, and this abnormal lymphocytic
infiltration resolves with gluten withdrawal (3). Further, it has been
shown that in DH patients without villous atrophy, histological damage is
seen on gluten challenge (4). Thus, all patients with DH do have gluten
sensitivity of the intestine. Second, in DH, a clear and a direct
relationship between the intestine and skin has been demonstrated. Dermal
IgA deposits are the hallmark and do not occur in its absence. After many
years of gluten withdrawal, the IgA will disappear from the skin but
returns with re-introduction of gluten in the diet (4).
By contrast, the putative role for gluten in the cases of ataxia
/neuropathy described by Hadjiivassiliou et al, remains speculative. The
acid test, namely clear and unequiviocal clinical and or imaging /
neurophysiological improvement following gluten free diet, is still
lacking. In the editorial, the authors quote their own previous work
despite the fact that their previous paper actually provided no evidence
for effectiveness of diet. We accept that an unusually high proportion of
their patient are HLA DQ2 and this may well point to an
immunopathogenesis. But, remembering that HLA DQ2 is also associated
with a range of non-gluten sensitive autoimmune conditions, it need not be
gluten related. Neurological case selection rested largely on the finding
of IgG anti-gliadin antibody. But IgG anti-gliadin is extremely common
even in normal individuals. If the hypothesis is correct, what
explanation is given for the absence of neurological defects in the
overwhelming majority of individuals, including the many with coeliac
disease or DH, despite their HLA DQ2 and IgG gliadin antibody positive
status ? Whatever disease process underlies these neurological cases, it
would appear to be different to that leading to skin lesions in DH.
Yours sincerely
Dr D J Unsworth PhD.MRCPath. FRCP
CONSULTANT IMMUNOLOGIST
Southmead Hospital, Bristol. BS10 5ND.
Professor L Fry MD FRCP
EMERITUS PROFESSOR OF DERMATOLOGY
C/O St. Mary's Hospital.
Paddington. London W2 1NY.
References
1 Hadjivassiliou M, Grunewald RA, Davies-Jones GAB. Gluten
sensitivity: a many headed hydra BMJ 1999; 318: 1710-1.
2 Brow J, Parker F, Weinstein W, Rube CE. The small intestinal
mucosa in dermatitis herpetiformis: severity and distributions of the
small intestinal lesion and associated malabsorption: Gastroenterol 1972;
60:355-61
3 Fry L, Seah PP, Hayer PG, Hoffrand AV, McMinn RMH. The small
intestine in dermatitis herpetiformis J.Clin. Path. 1974; 27: 814-27
4 Weinstein WM Latent coeliac sprue. Gastroenterol. 1973 ; 64 : 489-
493.
5 Leonard JN, Haldenton GP, Tucker W, Unsworth DJ, Swain AF, McMinn
RMH. Holborrow EJ, Fry L. Gluten challenge in dermatitis herpetiformis
NEJM. 1983: 308: 816-19.
Competing interests: No competing interests
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: as.pena@azvu.nl
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
Struggling with Celiac
In December of 1996 I was diagnosed with Celiac. I immediately took
on a gluten free diet including the absence of oats. In June of 1999 I
had minor knee surgery and was given several different anti-inflamatories,
along with the conventional over the counter pain killing medication. I
was very disturbed to learn that there is gluten in the inactive
ingredients of the medication I was taken. In August 1999 I my gluten
levels were tested again and it was at 12, where the normal range is <4
-0.
I have read some specualtion that eggs are also a culprit in the
celiac sufferer's diet. I have been eating eggs for the last two years,
and, I am not on any gluten medication. Can these innocent eggs be enough
to incite the gluten levels?
Your answer to this question and future articles such as this one are
very appreciated. Thank you for your research and forum that you present
on your website. Unfortunately the general public is very uneducated about
this condition.
Thank you,
Steve Falkowitz
Competing interests: No competing interests