Coeliac disease

CORRESPONDENCE

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and natural killer cells in the epithelium of the gut distinguishes two different coeliac diseases. Gut 1992; 33: 767–72. Bürgin-Wolff A, Gaze H, Hadziselimovic F, et al. Antigliadin and antiendomysium antibody determination for coeliac disease. Arch Dis Child 1991; 66: 941–47. Bürgin-Wolff A, Hadziselimovic F. Screening test for coeliac disease. Lancet 1997; 349: 1843–44.

Authors’ reply SIR—We believe that we discussed the genetic, immunological, and pathogenetic features of coeliac disease sufficiently. A more detailed immunological review would have been beyond the scope of the seminar. The abortive form of coeliac disease described by F Hadziselimovic and colleagues in 19921 could be included in extensive reviews of coeliac disease, but it is not such an unequivocal clinical entity that it should be commented on in seminars like ours. We do not agree that small-bowel biopsy is useless in the latent form of coeliac disease and unnecessary in silent coeliac disease. We discussed the importance of detecting silent coeliac disease in the section on screening policy and diagnosis. Hadziselimovic says that we do not discuss in sufficient detail when small-bowel biopsy is required for diagnosing coeliac disease. However, we stated: “Small-bowel biopsy is essential and the diagnosis should not be based on serology only”. This can also be seen in our diagnostic algorithm, and we believe that the initial biopsy is mandatory. Another point is that gluten sensitivity is no longer restricted to villous atrophy, but we did not recommend to change the current clinical diagnostic criteria. We also disagree with Hadziselimovic and Bürgin-Wolff that serological tests are enough for the diagnosis of coeliac disease. The sensitivity and specificity of these tests depend on the population tested. Positive gliadin, but also reticulin and endomysial antibodies, are common in individuals with normal mucosal villous morphology. On the other hand, a negative serology does not exclude coeliac disease. In September, 1996, we had a panel discussion at the Seventh International Symposium on Coeliac Disease, Tampere, Finland, entitled “Zero or how many biopsies?” The importance of the initial diagnostic biopsy was generally agreed.2 We do not appreciate the algorithm of Hadziselimovic and Bürgin-Wolff which alters the worldwide current diagnostic policy for coeliac disease. It would be interesting to learn results from clinical studies in which the proposed algorithm has been

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used. Children and adults may get symptoms on gluten challenge before seroconversion of antibodies and development of a clear-cut mucosal injury. If the challenge is stopped, we have no biopsy result to rely on. The findings of initial biopsy are essential for routine clinical practice. *Markku Mäki, Pekka Collin Coeliac Disease Study Group, Institute of Medical Technology, University of Tampere, PO Box 607, FIN-33101, FInland 1

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Hadziselimovic F, Emmons RL, Schaub U, Signer E, Burgin-Wolff A, Krstic R. Occurrence of large granular lymphocytes and natural killer cells in the epithelium of the gut distinguishes two different coeliac diseases. Gut 1992; 33: 767–72. Walker-Smith JA. Discussion of diagnostic criteria for coeliac disease at Tampere meeting. In: Mäki M, Collin P, Visakorpi JK, eds. Coeliac disease. Proceedings of the Seventh International Symposium on Coeliac Disease, September 5–7, 1996. Tampere: Coeliac Disease Study Group (in press).

Diagnosis of Alzheimer’s disease with cerebrospinal fluid tau protein and aspartate aminotransferase SIR—In Mattias Riemenschneider and colleagues’ report (Sep 13, p 784)1 of tau and aspartate aminotransferase (AST) concentrations in cerebrospinal fluid (CSF), their suggestion that these markers are useful in distinguishing Alzheimer’s disease from other forms of dementia is premature. Their study contains a number of design flaws. In their first paragraph they say that the original postulate is that AST might be a useful marker of Alzheimer’s disease provided that other disorders “such as brain ischaemia”, which also raise CSF AST concentrations, are excluded, yet they then proceed to compare two cases of cerebrovascular dementia with “other dementias”. They do not mention the amount of correlation between the degree of dementia (as determined by scores on the Mini Mental State Examination) and CSF concentrations of the markers. Neither is there any mention of the degree of cognitive impairment in the other-dementia cases, and why is the number in this group much smaller than the other two? A particular concern is the inclusion of two cases of unclassified dementia—which could have been atypical presentations of Alzheimer’s disease. Riemenschneider and colleagues do not seem to have made any attempt to match cases and controls for age, which

is a serious omission since neurofibrillary tangles containing tau protein can be found in the brains of elderly patients with no evidence of dementia. Thus, Riemenschneider’s study is an observation, which could be enlarged upon in a larger and better designed study to substantiate their claims before CSF concentrations of AST or tau can be used in the diagnosis of Alzheimer’s disease. Thomas Esmonde Directorate of Neurosciences, Royal Victoria Hospital, Belfast BT12 6BA, UK 1

Riemenschneider M, Buch K, Schmolke M, Kurz A, Guder WG. Diagnosis of Alzheimer’s disease with cerebrospinal fluid tau protein and aspartate aminotransferase. Lancet 1997; 350: 784.

Author’s reply SIR—We agree with Thomas Esmonde that the potential of tau and aspartate aminotransferase (AST) for the differential diagnosis of Alzheimer’s disease needs corroboration by further study of greater number of patients with other dementias. Our working hypothesis was that AST activity does not differ significantly from control values in most patients with nonAlzheimer’s disease dementia. We expected increases in AST in acute ischaemia and subarachnoid haemorrhage. Acute ischaemia may be temporarily present in cerebrovascular disease so that AST may imperfectly differentiate cerebrovascular dementia from Alzheimer’s disease. However, all six patients with cerebrovascular dementia we have studied so far have normal AST activities. The severity of dementia in our other dementia group is mild to moderate, as in the Alzheimer’s disease group, indicated by a mean Mini Mental State Examination (MMSE) score of 21. Our other dementia group also included two patients whose dementia was unclassified at the time of publication. Subsequent diagnostic work-up revealed depression and normal pressure hydrocephalus as causes of their cognitive impairment. As we reported previously,1 we did not find an association between tau concentrations and MMSE scores. Our present data show that there is also no significant correlation between AST and cognitive impairment (Spearman’s rank correlation coefficient r=0·17). The fact that our cognitively healthy controls had a non-significant lower mean age than the groups of patients with Alzheimers disease does not account for the difference in tau values. In controls, CSF tau values are not significantly associated with age,2 and

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