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Serological Testing May Offer New Hope for the Chronically Ill
by Ron Hoggan
Dec 9, 1996

Celiac disease is at the root of many painful and deadly diseases. Perhaps due to the common perception that celiac disease is rare, the medical profession in North America is currently quite resistant to testing for celiac disease. Some hope has been offered by recent research. Investigators using antibody testing have discovered that celiac disease is quite common, occurring in about 1 in 250. But that incidence is among *healthy* blood donors, not patients suffering from gastrointestinal complaints. Surely the incidence would be much higher in this group.

Actually, there is considerable evidence that this disease is much more frequent in some specific high-risk groups, including those demonstrating gastrointestinal symptoms:

Cucchiara et al (1) say:
"It is concluded that celiac disease frequently affects the motor behavior of the gut and that its effects may be reversed by appropriate diet."


Usai et al (2) say:
"This confirms previous studies suggesting that gastrointestinal motor abnormalities should probably be added to the clinical spectrum of the disease."

Here is a list of a few of the recent publications where the reported experience of researchers working in this area, supporting the notion that a full panel of celiac blood tests increases the accuracy and hence, the value of such testing:

Cataldo et al (3) say:
"Combined determination of EMA and AGA showed an increased predictive value....."

Mascart-Lemone & Lambrechts (4) state:
"Only a combination of anti-gliadin IgG and anti-endomysium IgA affords a 100% sensitivity for coeliac disease."

Kumar (5)

Presented a taxonomy indicating that anti-reticulin antibodies, while not very sensitive, were 100% specific to celiac disease.

Valdimarsson et al (6) say:
"Based on these data, we suggest that small bowel biopsy is not necessary to diagnose celiac disease in symptomatic adults with IgA antiendomysium antibodies."

Vazquez et al (7) state:

"Furthermore, combination of EmA and ARA has shown the best specificity and positive predictive value."

I could go on, but I think the point is clear. Full panel blood testing is consistent with the findings of the published experts in this area.

Some members of the medical profession raise the possibility of false positives reducing the economic and diagnostic value of such testing. At the Nov. 9 Conference at the Mt. Sinai Center, New York, NY, this issue was addressed by Dr. Kumar, and several other researchers working in this area. It seems that in cases where false positives have been carefully investigated, the histologies show an increased presence of ICAM. These adhesion molecules are the first stage in the celiac disease-associated immune response. Follow-up of these patients reveals celiac disease when gluten intake is increased. The so-called false positives then, are an earlier indicator of celiac disease than villous atrophy.

Given the very high incidence of lymphoma in untreated celiac disease, screening tests among people demonstrating gastrointestinal symptoms, seem prudent and reasonable. What are the costs of treating lymphoma? How many cases would need to be prevented, to make such screening economically viable? This, of course, ignores the humanitarian issue which, to some of us, is much more compelling.

There is also a sentiment that celiac disease, when mild, does not pose a threat of the more serious hazards associated with the more obvious, and therefore, diagnosed cases of celiac disease. Again, this position is at odds with the experts:

Barry et al (8) indicate that the untreated, asymptomatic cases of celiac disease, which are only detected in familial screening, are at higher risk of developing malignancy.


Ilyas et al (9) say:
"Thus, a change in symptoms in patients with previously unrecognized latent CD may lead to the diagnosis of lymphoma."

Freeman et al (10) say:
"....the associated celiac sprue is sometimes mild and may remain undetected..."

At the N.Y. conference in November, it was repeatedly stated by the presenters, that the clinical presentation of celiac disease, in a large minority of cases, is *not* usually diarrhea. In many cases it was constipation. Three of these presenters indicated that more than 90% of celiac disease is undiagnosed in the U.S.A.

This is viewed as irrelevant by some. They see no hurry in diagnosing the cases of silent and latent celiac disease. This view is also at odds with the published investigators:

Corazza et al (11) say:
"It is important that even subclinical and silent forms are diagnosed as early as possible."

Also Mascart-Lemone et al (4) state:
"This is of major interest in order to begin early dietary treatment of these patients in order to avoid development of malignant disorders."

If the public ever finds out about the relative risk factors for lymphoma and other malignancies in celiac disease, and that an accurate screening tool like the EMA test is available, but eschewed by some members of the medical profession because it is too expensive, the public outcry may be deafening.

Several mass screening studies have been conducted in Italy, resulting in the early diagnosis of many celiacs. Catassi et al and Cataldo et al have both demonstrated the economic viability of such screening. And yet many North American practitioners resist screening high risk patients.

We are talking about testing that could well reduce the incidence of lymphoma and other cancers by a substantial degree. It is a test that costs under $100. There are a lot of people who could die from old age, rather than cancer. I think that anyone demonstrating gastrointestinal symptoms should be tested for celiac disease. I also think it is irresponsible to keep ignoring the research in this area.

Especially with the economies of scale that would be associated with mass screening, and the rapidly declining costs due to innovations in substrate materials used, the tests promise to become more and more affordable.

Almost 20% of patients with neurological illness of unknown aetiology have demonstrated celiac disease (Hadjivassiliou et al). About 10% of diabetes mellitus patients have demonstrated celiac disease (Sorensen et al). Screening high risk populations offers a high yield. Since Cucchiara et. al. and Usai et. al. are identifying gastrointestinal motor abnormalities in celiac disease, that would make patients with gastrointestinal symptoms a high risk group. It would also indicate the need for screening tests for patients with gi complaints.


  1. Cucchiara et al "Upper gastrointestinal motor abnormalities in children with active celiac disease" _J. Pediatr. Gastroenterol. Nutr_ 1995; 21(4): 435-442
  2. Usai et al "Oesophageal motility in adult coeliac disease" _Neurogastroenterol. Motility_ 1995; 7(4): 239-244
  3. Cataldo et al "Antiendomysium antibodies and coeliac disease: solved and unsolved questions." _Acta Paediatr_ 1995; 84(10): 1125-1131
  4. Mascart-Lemone & Lambrechts "Serology of coeliac disease: early diagnosis and therapeutic impact" _Acta Gastroenterol Belg_ 1995; 58(5-6): 388-396
  5. Kumar "Predictive Value of Serology Testing" CSA conference Nov. 9, 1996, Mt. Sinai Center, New York, NY.
  6. Valdimarsson et al "Is small bowel biopsy necessary in adults with suspected celiac disease and IgA anti-endomysium antibodies? 100% positive predictive value for celiac disease in adults" _Dig Dis Sci_ 1996; 41(1): 83-87
  7. Vazquez et al "Screening for asymptomatic celiac sprue in families" _J Clin Gastroenterol_ 1995; 21(2): 130-133
  8. Barry et al "Coeliac disease and malignancy. The possible importance of familial involvement" _Scand J Gastroenterol_ 1971; 6: 205-207
  10. Freeman et al "Primary Abdominal Lymphoma" _The American Journal of Medicine_ 1977; 63: 585-594
  11. Corazza et al "Coeliac disease in adults" _Baillieres Clin Gastroenterol_ 1995; 9(2): 329-350
  12. Sorensen et al "Risk of estimation of disorders associated with coeliac disease: a 16 year Danish nationwide follow-up study based on hospital discharge data: implications for screening" _Int J Risk Safety Med_ 1996; 8(2): 137-140
  13. Hadjivassiliou et al "Does gluten sensitivity play a part in neurological illness?" _Lancet_ 1996; 347: 369-371
  14. Catassi et. al. "Coeliac disease in the year 2000: exploring the iceberg" _Lancet_ 1994; 343: 200-203