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Protean Manifestations of CD Serological Testing, Dr. Joseph Murray,
------------------------------------------------  Mayo Clinic,
Rochester, MN.  Dr.  Murray opened the first Celiac clinic in the USA
at the University of Iowa.

Dr. Murray noted that today, celiac disease (CD) has a widening
spectrum in the way it presents, the symptoms that improve on a
gluten-free (GF) diet and the serologic information that is available.
While CD may be the source of MANY symptoms, it is not the source of
ALL of our symptoms.  Inflammatory bowel disease, Crohn's disease, and
other autoimmune diseases hide many cases of CD.

The classic definition of malabsorption has now been expanded to
include such areas as anemia, folate deficiency and hypocalcemia as
well as fat-soluble vitamin deficiency, raised alkaline phosphates and
prolonged prothrombin time (bruising and bleeding).  How much of the
intestine is actually involved in the malabsorption and how much of
the rest of the intestine compensates for the problem is an unknown at
this time.

Celiacs can have many presentations: upper GI symptoms, constipation,
iron deficiency, diarrhea either with or without steatorrhea, or
lactose intolerance.  (Parenthetically, Dr. Murray noted that
conditions like floating stools with a typical smell can be caused by
such simple inputs as apples and/or metamucil.)  Many celiacs can
present with only one symptom such as failure to thrive, abdominal
pain or short stature.  In the Sudan, for example, rickets is often
the only presentation while in Denmark, dental enamel defects may be
the only presentation.  And oftentimes celiacs have had previous
diagnoses including irritable bowel syndrome (Crohn's, etc.), primary
lactose syndrome, psychiatric problems, menstrual blood loss, diabetic
diarrhea, giardia, inflammatory bowel disease, pernicious anemia,
peptic ulcer, pancreatitis and/or fibromyalgia.

Dr. Murray used the iceberg analogy in describing the types of
celiacs: the small group of classic celiacs at the top of the iceberg;
a larger group of atypical celiacs currently being diagnosed; a much
larger group, currently undiagnosed, with silent celiac disease; and
the base of the iceberg with a very large group of people with latent
gluten sensitivity.  However, the iceberg is not the same in every
country.  In Sweden, most celiacs are known and it is common for the
diagnosis to occur in childhood.  In Europe, maybe half the celiacs
are known and only a quarter to a third are discovered in childhood.
In the U.S., a smaller percentage of the celiacs are diagnosed.

In order to diagnose CD, Dr. Murray believes a 3-prong focus is
necessary.  First, a liberal duodenal biopsy policy is required.  That
is, biopsy more rather than less often; don't hesitate to biopsy.
Second, all high risk groups should have at least the blood screening
test.  These would include those with a family history of CD;
diabetics; those with thyroid problems or Down's syndrome; and
patients with either persistent diarrhea or IGA Deficiency.  And
finally, all lactose intolerant Caucasians should be biopsied.

Dr. Murray discussed a study that was done on 216 patients at the
University of Iowa in the 1990's.  The patients ages ranged from 1 to
90 with 80% being 18 years or older and a 3:1 ratio of females to
males.  Before diagnosis and the GF diet, over 80% of the patients had
abdominal pain; bloating was common; approximately 75% had weight
loss; and 50% had daily diarrhea.  After being on the GF diet, 20 to
25% still had daily diarrhea.  And even though the diarrhea cleared up
for many within a week to a month, it took much longer for many
others.  In addition, abdominal pain and bloating dropped
significantly but almost 20% developed constipation from the GF diet
due to lack of fiber.  Also, nausea and stomach emptying were still a
problem.

Other observations from the study included:

  * Patient pain covered a broad spectrum but showed dramatic
    improvement on the GF diet.

  * Patient pain could either be in the lower abdomen or diffuse.

  * 46% of the patients' pain worsened with eating.

  * 60% of the patients' pain improved with defecation.

  * 46% of the patients met the Rome 2 symptomatic criteria for
    Irritable Bowel Syndrome (IBS).

  * Bone pain improved on the GF diet but joint pain showed no change.

  * Fatigue, headaches and weight loss improved on the GF diet.

  * Arthritis pain medication was reduced on the GF diet.

  * The Body Mass Index, 50% thin; 25% normal; 12% overweight; and 11%
    severely obese before the GF diet, returned to the same spread
    within 6 to 18 months.

  * Non-GI symptoms were common.

Dr. Murray offered several comments concerning the status of current
CD testing:

  * Serologic testing allows for screening of asymptomatic patients.

  * A recent study on tissue transglutaminase indicates that the
    sensitivity is significantly reduced in cases of partial villus
    atrophy.

  * Initial comparison testing of endomysial antibody and tissue
    transglutaminase tests indicates no significant difference.

  * Serologic testing for follow-up is not useful for occasional
    gluten ingestion.