Evaluating patients suspected of having celiac disease, including

patients with compatible clinical symptoms, patients with atypical

symptoms, and individuals at increased risk (family history,

previous diagnosis with associated disorder, positivity for HLA DQ2

and/or DQ8)

Screening test for dermatitis herpetiformis, in conjunction with

endomysial antibody (EMA) test

Monitoring adherence to gluten-free diet in patients with

dermatitis herpetiformis and celiac disease

Celiac disease (gluten-sensitive enteropathy, celiac sprue)

results from an immune-mediated inflammatory process following

ingestion of wheat, rye, or barley proteins that occurs in genetically

susceptible individuals. The inflammation in celiac disease occurs

primarily in the mucosa of the small intestine, which leads to villous

atrophy. Common clinical manifestations related to gastrointestinal

inflammation include abdominal pain, malabsorption, diarrhea,

and constipation. Clinical symptoms of celiac disease are not

restricted to the gastrointestinal tract. Other common manifestations

of celiac disease include failure to grow (delayed puberty and short

stature), iron deficiency, recurrent fetal loss, osteoporosis, chronic

fatigue, recurrent aphthous stomatitis (canker sores), dental enamel

hypoplasia, and dermatitis herpetiformis. Patients with celiac

disease may also present with neuropsychiatric manifestations

including ataxia and peripheral neuropathy, and are at increased

risk for development of non-Hodgkin lymphoma. The disease is

also associated with other clinical disorders including thyroiditis,

type I diabetes mellitus, Down syndrome, and IgA deficiency.

Celiac disease tends to occur in families; individuals with family

members who have celiac disease are at increased risk of

developing the disease. Genetic susceptibility is related to

specific HLA markers. More than 97% of individuals with celiac

disease in the United States have DQ2 and/or DQ8 HLA markers,

compared to approximately 40% of the general population.

A definitive diagnosis of celiac disease requires a jejunal biopsy

demonstrating villous atrophy. Given the invasive nature and cost

of the biopsy, serologic and genetic laboratory tests may be used

to identify individuals with a high probability of having celiac

disease. Subsequently, those individuals with positive laboratory

results should be referred for small intestinal biopsy, thereby

decreasing the number of unnecessary invasive procedures

(see "Celiac Disease Diagnostic Testing Algorithm" in Special

Instructions). In terms of serology, celiac disease is associated

with a variety of autoantibodies, including endomysial (EMA),

tissue transglutaminase (tTG), and deamidated gliadin

antibodies. Although the IgA isotype of these antibodies usually

predominates in celiac disease, individuals may also produce IgG

isotypes, particularly if the individual is IgA deficient. The most

sensitive and specific serologic tests are tTG and deamidated

gliadin antibodies.

The treatment for celiac disease is maintenance of a gluten-free

diet. In most patients who adhere to this diet, levels of associated

autoantibodies decline and villous atrophy improves. This is

typically accompanied by an improvement in clinical symptoms. 

See "Celiac Disease Diagnostic Testing Algorithm" in Special

Instructions for the recommended approach to a patient suspected

of celiac disease.

An algorithm is available for monitoring the patient's response

to treatment, see "Celiac Disease Routine Treatment Monitoring

Algorithm" in Special Instructions.

For your convenience, we recommend utilizing cascade testing for

celiac disease. Cascade testing ensures that testing proceeds in

an algorithmic fashion. The following cascades are available;

select the appropriate one for your specific patient situation.

Algorithms for the cascade tests are available in Special Instructions.

#89201 "Celiac Disease Comprehensive Cascade": complete testing

including HLA DQ

#89199 "Celiac Disease Serology Cascade": complete testing

excluding HLA DQ

#89200 "Celiac Disease Comprehensive Cascade for Patients on a

Gluten-Free Diet": for patients already adhering to a gluten-free diet"

To order individual tests, see "Celiac Disease Diagnostic Testing

Algorithm" in Special Instructions.

<4.0 U/mL (negative)

4.0-10.0  U/mL (weak positive)

>10.0 U/mL (positive)

The finding of tTG-IgA antibodies is specific for celiac disease and

possibly for dermatitis herpetiformis. For individuals with moderately

to strongly positive results, a diagnosis of celiac disease is likely

and the patient should undergo biopsy to confirm the diagnosis.

If patients strictly adhere to a gluten-free diet, the unit value of

IgA-anti-tTG should begin to decrease within 6 to 12 months of

onset of dietary therapy.

This test should not be solely relied upon to establish a diagnosis

of celiac disease. It should be used to identify patients who have

an increased probability of having celiac disease and in whom a

small intestinal biopsy is recommended.

Affected individuals who have been on a gluten-free diet prior to

testing may have a negative result.

For individuals who test negative, IgA deficiency should be

considered. If total IgA is normal and tTG-IgA is negative, there

is a low probability of the patient having celiac disease and a

biopsy may not be necessary.

If serology is negative or there is substantial clinical doubt

remaining, then further investigation should be performed with

endoscopy and bowel biopsy. This is especially important in

patients with frank malabsorptive symptoms since many

syndromes can mimic celiac disease. For the patient with frank

malabsorptive symptoms, bowel biopsy should be performed

regardless of serologic test results.

The antibody pattern in dermatitis herpetiformis may be more

variable than in celiac disease; therefore, both EMA and tTG

antibody determinations are recommended to maximize the

sensitivity of the serologic tests.

1.   Green PH, Cellier C:  Celiac disease. N Engl J Med 2007;357:

      1731-1743

2.   Harrison MS, Wehbi M, Obideen K:  Celiac disease:  More

      common than you think. Cleve Clinic J Med 2007;74:209-215

3.   Rose C, Dieterich W, Brocker EB, et al:  Circulating autoantibodies

      to tissue transglutaminase differentiate patients with dermatitis

      herpetiformis from those with linear IgA disease. J Am Acad Dermatol

      1999;41:957-961

4.   Update on celiac disease:  New standards and new tests.

      Mayo Communique 2008