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."

and

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. 

and: 

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. 

                   Sources:

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   

9. Ilyas et al "NON-HODGKIN'S LYMPHOMA, COELIAC DISEASE, AND 
EPSTEIN-BARR  VIRUS: A STUDY OF 13 CASES OF ENTEROPATHY-ASSOCIATED
T- AND  B-CELL LYMPHOMA" _Journal of Pathology_ 1995; 177: 115-122   

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