Download celiac sprue - UCSF | Department of Medicine

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CELIAC SPRUE
Key Points:
1. Celiac sprue is a disorder causing intestinal mucosal damage due to patient sensitivities to gluten
products.
2. Many patients have subclinical disease.
3. The gold standard for diagnosis is a small bowel biopsy, but IgA endomysial antibodies and antitissue transglutaminase antibodies have a high sensitivity and specificity for the disease.
4. Treatment consists of a gluten-free diet and can eliminate symptoms and potential complications.
A little history… First described in 1888 although reports suggest its entity as early as 2nd century AD!
Cause identified during WWII when patients with diarrhea improved during the bread shortage and then
worsened after the war when bread supplies returned. The actual bowel lesion was reported in 1954, finally
confirming gluten enteropathy.
Epidemiology: Mostly affects Northern Europeans with a prevalence of 1:300; in the US this number is
slightly decreased. Has been reported in other areas such as India and is referred to as “summer diarrhea”
because this is the season when wheat replaces maize. Used to be considered a disease of childhood but
now many present between ages 10-40. Ratio of silent carriers to symptomatic disease is 7:1, leading to the
concept of the “celiac iceberg”.
Is there a genetic predisposition? Considered an HLA-associated condition with HLA-DQ2 +/- DQ8 gene
loci being most implicated. 36% of siblings develop sprue in families where one child has the disease.
Clinical manifestations:
Classic presentation has 3 characteristics:
1) villous atrophy
2) symptoms of malabsorption such as weight loss, diarrhea, anemia, nutrient or vitamin deficiencies
3) resolution of lesions and symptoms after being on gluten-free diet
Subclinical disease: Symptoms can be mild and non-specific such as fatigue, borderline iron deficiency,
unexplained elevations in transaminases, or a child’s small stature. According to the American
Gastroenterological Association Medical Position Statement on sprue, this diagnosis should be considered
in any patient with unexplained deficiencies of folic acid, B12, iron, or albumin; osteomalacia/osteoporosis;
growth failure in children; and infertility or miscarriages.
Non gastrointestinal manifestations:
• Neuropsychiatric disease: depression, anxiety, ataxia, seizures. Evidence of serologic markers may be
present in these patients and symptoms have been shown to improve with gluten-free diet.
• Arthritis: A study of 200 adults with sprue showed 26% had arthritis.
• Iron deficiency: In a study of 93 patients with iron deficiency anemia, 12% had small bowel findings
consistent with gluten enteropathy. Occult GI bleeding is also associated with this disease.
• Bone disease: Commonly occurs in patients without GI symptoms. When compared to control
patients, significant decreases in bone densities are seen in lumbar spine and femoral neck.
Associations:
• Dermatitis herpetiformis: a papulovesicular rash on the extensor surfaces caused by IgA deposits on
basement membrane. Approximately 85% of pts with this skin disorder have evidence of sprue on
mucosal biopsy. Usually responds to dietary changes.
• Diabetes mellitus Type I: 3-8% of pts with DM Type I have gluten enteropathy. Thought to be due to
similar genetic foci.
• Down syndrome: prevalence of sprue in these patients as high as 16%
• Infertility: Increased menstrual abnormalities and infertility. Untreated pregnant women with sprue
have threefold risk of low birth weight as compared to controls.
• Others: thyroid disease, IgA deficiency
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Diagnosis:
Goal standard is small bowel biopsy with 3 samples evaluated. Characteristic changes include decreased
villous height to crypt depth, decreased epithelial surface cell height, and increased lymphocytic infiltration
of the mucosa. These findings should then improve on repeat biopsy 4-6 months after being on gluten-free
diet. Repeat biopsy is usually not performed because patients improve clinically and diagnosis is not in
question.
Serologic markers:
a) IgA endomysial antibodies: considered the “best” serologic marker by the AGA. Sensitivity 97100% and specificity 98-99%. Of note, 2-3% of patients with sprue have IgA deficiency, so IgA
levels should be tested in patients with a negative test where clinical suspicion is high.
b) Anti-tissue transglutaminase antibodies: a newer ELISA test with sensitivity and specificity of 9495%. Less costly and easier to perform than the IgA anti-endomysial test.
c) Antigliadin antibodies (IgA and IgG): Sensitivity and specificity lower than above tests. Low
predictive value in low-risk patients.
How do I interpret these tests?
In a low-risk patient, a positive IgA endomysial test should be followed by a small bowel biopsy. In a high
risk patient (where suspicion of disease is deemed to be greater than 5%), most should still get a small
bowel biopsy, although it has been argued that in the appropriate clinical setting, a biopsy is not needed. In
general, antigliadin antibodies have a high false positive rate, so in patients with high or low likelihood of
disease, a positive test needs to be confirmed by a small bowel biopsy.
Treatment:
Patients should be placed on gluten-free diet, meaning avoidance of wheat, rye, and barley. While oats are
okay, many commercial oat products are contaminated with wheat gluten. Effective treatment is
demonstrated by improved symptoms and improved or resolved mucosal changes of the small bowel
mucosa within a few weeks. Can also follow IgA endomysial antibody levels to verify response.
*Dietary indiscretion or unknown sources of gluten should be considered in patients where symptoms
persist. When appropriate, it is advisable for patients to join a celiac sprue support group or use the internet
services for dietary suggestions.
*In severe acute cases, steroids can be used initially while dietary changes are implemented.
Why should celiac patients be treated, especially if they are minimally symptomatic?
• Increased risk of malignancy, especially of intestinal lymphoma (RR of non-Hodkin lymphoma 40)
and adenocarcinoma. Risk of these cancers falls to that of normal population when on gluten-free diet
for five years.
• Ulcerative jejunitis: can lead to strictures, perforation, obstruction.
• Nutritional deficiencies: B12, folate, iron, and vitamin deficiencies can lead to a number of health
problems
• Pregnancy and childhood problems: Poor intrauterine growth and childhood development. Mortality
as high as 12% in untreated children with serious disease.
Resources for clinicians and patients:
Celiac Disease Foundation: website is http://www.celiac.org