Each of my children have, at several times in their lives, returned home from the doctor with a negative blood sample--and short of sending them back to the teacher telling them, "This is just not acceptable!" I've followed the recommendation that those at high risk should continue to be tested once yearly to watch for the onset of the disease.
http://www.ncbi.nlm.nih.gov/pubmed/15185855
Our family has seronegative tendencies.
Eventually two of the three have tested positive and were diagnosed with CD--for whatever good that did. This just confirmed what I already suspected from their various symptoms .
Meanwhile, the following article could be helpful... to someone... somewhere... sometime.
The letter was pulled from Huntsman Cancer Institute web page I can't reference it now...wouldn't you know. AND its a long one filled with medical references, so buckle in.
THE Cliff Notes: You can have the disease and show negative on bloodwork.
To: John J. Zone M.D.
Huntsman Cancer Institute and Department of Dermatology
2000 Circle of Hope; Rm 5242
Salt Lake City, UT 84112
Phone: 801-585-9427
Fax: 801-585-7477,
Phone: 01 801 587-9300
Serological Diagnosis of Celiac Disease by Vijay Kumar, MD
Vijay Kumar, MD, Research Associate Professor at the University of Buffalo and President and Director of IMMCO Diagnostics
I enjoyed reading J. Murray's comments related to the diagnosis of celiac disease and agree that taking multiple biopsies is still the gold standard of diagnosing celiac disease. However, I am sure he will agree that there are limitations in the histopathological methods of diagnosing celiac disease.
As we know, histological features occur in continuum, with flat lesions at one end of the spectrum and a mucosa with normal villus and crypt architecture but abnormally high density or count of villus intraepithelial lymphocytes at the other, which may be reported normal.
In addition, patients with silent, atypical or occult celiac disease may exhibit normal or mild villous atrophy and histopathology may not be diagnostic. The best example would be patients with dermatitis herpetiformis (DH). As we know, all DH patients have gluten sensitive enteropathy, but only 60-70% of DH patients exhibit characteristic histopathology diagnostic of gluten sensitive enteropathy.
In this regard, there has been a constant effort to put forth a simple serological method that is a specific and sensitive indicator of gluten sensitive enteropathy.
There are basically three antibody markers (ARA, AGA and EMA) that could be used for diagnosing celiac disease and DH. Our studies indicate and corroborate with the others that the AGA test is a sensitive but not very specific marker of celiac disease. On the other hand, ARA is very specific but not sensitive. We described in 1984 the endomysial antibody test and we felt very comfortable reporting that this EMA test has >99% specificity and sensitivity for gluten sensitive enteropathy. We reported cases of DH who were biopsy negative but EMA positive in which the histopathological changes consistent with celiac disease could be induced on an increased gluten intake indicating thereby the sensitivity of EMA tests.
The following table is a summary of our studies on the utility of various serological methods of diagnosing celiac disease. Comparison of Sensitivity, Specificity, Positive and Negative Predictive Value of AGA, ARA, and EMA in Active Celiac Disease:
(this table was all messed up when it came over to my blog so I deleted it, Terina)
I shall be glad to discuss the utility of serological methods in diagnosing celiac disease with anyone interested.
IgA class Reticulin antibodies are found only in Celiac disease and dermatitis herpetiformis. These antibodies are found in approximately 60% of celiac disease patients and 25% of DH patients. This test is falling into disuse because of the limited utility and the availability of better tests. IgA class endomysial antibodies are very specific, occurring only in celiac disease and DH. These antibodies are found in approximately 80% of patient with DH and in essentially 100% of patients with active celiac disease. IgA endomysial antibodies are more sensitive and specific than either reticulin or gliadin antibodies for diagnosis of celiac disease. Antibody titers are found to parallel morphological changes in the jejunum and can also reflect compliance with gluten-free diets. Titers decrease or become negative in patients on gluten free diets and reappear upon gluten challenge.
The purpose of testing for anti-gliadin antibodies includes, in addition to diagnosis of gluten sensitive enteropathy, monitoring for compliance to a gluten free diet. IgA gliadin antibodies increase rapidly in response to gluten in the diet, and decrease rapidly when gluten is absent from the diet. The IgA anti-gliadin antibodies can totally disappear in 2-6 months on a gluten-free diet, so they are useful as a diet control. By contrast, IgG anti-gliadin antibodies need a long time, sometimes more than a year, to become negative.
The reverse is also true. That is, a patient with celiac disease who has been on a gluten-free diet and tests negative for IgA anti-gliadin antibodies, will show a rapid increase in antibody production when challenged by gluten in the diet. Approximately 90% of challenged patients will yield a positive IgA anti-gliadin result within 14-35 days after being challenged. The test results you reported are consistent with a patient who is conforming to a gluten-free diet.
Methods of Testing for Dermatitis Herpetiformis
Iodine testing for DH: This is an old procedure used to create DH blisters. By applying a 30 percent solution of iodine as a patch, a DH outbreak can be created. This may be applicable in some patients when a biopsy is needed and no blisters are available.
Immunofluorescence: The indirect immunofluorescence test shows that the serum of a patient contains specific antibodies that bind to different areas of the epithelium. The direct immunofluorescence tests by a skin biopsy shows a specific diagnosis pattern of DH.
Traditionally this biopsy is obtained from the buttocks. If no outbreaks are observed in this area, the biopsy is recommended for another area where the itching is observed. DH Drugs: The common drugs used to initially control the blisters are: Dapsone, Sulfoxone, and Sulfapyridine. Each one has different advantages/disadvantages or availability in the treatment of DH. Dapsone changes the life span of red blood cells from an average of 120 days to 30 days. Dapsone is known for possible hematologic changes as a common side effect.
CELIAC TESTING
It is recommended to perform a full serological test-panel in patients with suspected celiac disease. These tests measure antibodies belonging to both the IgA and IgG classes of immunoglobulins. The incidence of selective IgA deficiency is much higher in celiac patients than in the general population. In patients with selective IgA deficiency only the IgG antigliadin antibody may be present, however, this antibody is less specific. It means that the IgG-type antigliadin antibody may be present in otherwise normal individuals.
If somebody had a positive endomysial antibody test at the time of diagnosis he/she may choose to use only this antibody test to monitor the effect of the diet. There are individual differences in the disappearance of serum antibodies.
The following is excerpted from an article that was published in the American Celiac Society newsletter by Joseph A. Murray, MD of the Mayo Clinic Rochester, MN, who is a gastroenterologist who specializes in treating Celiac disease
Those patients for whom there is a high suspicion for celiac disease should have a small bowel biopsy which can be obtained by an experienced endoscopist in the distal duodendum. The best noninvasive tests available for screening for asymptomatic celiac disease are the specific serological tests. These are of several varieties: the anti-gliadin, anti-endomysial, or anti-reticulin antibodies. Our experience and the literature support the use as of endomysial antibody test as the single most specific and probably most sensitive for celiac disease. This test has now become available in specialty laboratories as well as in a small number of academic institutions.
All of the tests should be done with the subjects on a normal gluten containing diet. A combination of endomysial and gliadin testing would seem to be the most sensitive as a screening method. A positive test is not, however, considered to be diagnostic and would usually require a small bowel biopsy for confirmation. A trial of dietary exclusion of gluten is *not* recommended as a diagnostic test without a prior abnormal biopsy.
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