A 14 year old male came to diagnostic clinic for a second opinion concerning loose stools and abdominal pain.
He had had several months of loose stools up to 5-7 times/day which were described as loose and pudding-like without undigested food or blood. He said that sometimes his stool seemed to float on top of the toilet water and smelled bad, but this was not consistent.
About 2-3 months ago he began having abdominal pain that occurred several times per week. Some episodes woke him at night. These could make him cry but he was consolable.
He had no recent travel, pet or antibiotic exposures and he had a chlorinated urban water supply. His family members had been healthy.
The past medical history revealed constipation around the time of toilet training.
The family history was positive for a father with Celiac disease and lactose intolerance.
The review of systems was negative for fevers, excessive fatigue, weight loss, sweats, skin changes, or joint involvement.
The pertinent physical exam showed a gregarious male in no acute distress. His weight was 75% and height 50%. His abdominal examination revealed normal bowel sounds, no hepatosplenomegaly or masses, and a soft abdomen without guarding.
Rectal examination revealed a small amount of liquid stool that was released after the examination. The stool was guiaic negative. He had no edema.
The previous work-up by the local physician included an endomysial, transglutaminase, and antigliadin antibodies, all of which were negative.
He also had a hemoglobin level of 13.2 g/L, platelet count of 210 x 1000/mm2, erythrocyte sedimentation rate that was slightly elevated at 24 mm/hour (normal up to 20 mm/hour). C-reactive protein, total protein, albumin, urinalysis, liver function tests and electrolytes were normal.
Abdominal radiographs showed a non-specific bowel gas pattern. Serial stool examinations were negative for blood, bacteria or parasites.
Repeated laboratory evaluation in the clinic was positive for IgA antigliadin antibody and the patient was referred to a pediatric gastroenterologist.
An upper endoscopy with a small bowel biopsy was performed and showed villous atrophy on 4 of 6 samples.
The diagnosis of Celiac disease was made and the patient was instructed on elimination of gluten from his diet. The parents were very supportive as the father had to follow the same diet restrictions already.
The patient’s clinical course over the next month showed clinical improvement with resolution of the abdominal pain, and the loose stools occurring only 1-2 times/day. He had gained ~1 pound of weight.
The patient was screened again for iron deficiency, Vitamin D, calcium, fasting glucose and thyroid function tests. All were normal.
The patient was to follow up again in 2 months.
Celiac disease (also known as celiac sprue, nontropical sprue or gluten-sensitive enteropathy) is a chronic malabsorption disorder of the small bowel that is caused by exposure to dietary gluten in genetically predisposed individuals.
It is found in people from infancy to late adulthood and is genetically associated with HLA-DQ2 and DQ8. It is more common in Caucasian individuals of northern European descent.
Clinically it can present with many different symptoms including being asymptomatic, abdominal pain, diarrhea with/without hematochezia, constipation, steatorrhea, fatigue, irritability, vomiting, weight loss, failure to thrive (weight and height), muscle wasting, ascites (secondary to hypoproteinemia), and anemia.
Classic stools in children < 2 years are described as pale, water semi-formed, voluminous and foul-smelling.
Differential diagnosis includes:
- Bacterial overgrowth
- Crohn’s disease
- Cow’s milk protein intolerance
- Eosinophilic gastroenteritis
- Status-post viral gastroenteritis
- Tropical sprue
- Zollinger-Ellison syndrome
Treatment is elimination from the diet of gluten, prolamins (ethanol soluble protein) and glutenins (acid/alkali soluble protein). This includes all wheat, rye, barley, and possibly oats. Dairy products may also be a problem as patient may have lactose intolerance too.
They can eat soybean, tapioca, rice, corn, potatoes and buckwheat. Up to 70% of patients will have improvement of symptoms within 2 weeks of being on the diet.
Patients also need to be screened for micronutrient deficiencies including anemia, calcium/Vitamin D, folic acid and Vitamin B12.
Patients have a higher risk of gastrointestinal malignancies, skin disorders, and autoimmune diseases including Diabetes type 1, arthritis, Hashimoto’s thyroiditis and Grave’s disease.
Various laboratory tests are available to help confirm or exclude the diagnosis. Laboratory testing of blood may be normal even in people with symptoms and intestinal biopsy proven disease.
The sensitivity and specificity of a test itself cannot be used to estimate the probability of disease individual patients. Individual test results using likelihood ratios can be helpful though, especially if the results are not consistent between tests or over time. For a more extensive discussion of this please see the To Learn More articles below especially Akobeng’s article which uses Celiac disease as an example.
IgG antibody tests are available but in various studies there is a great deal of heterogeneity in the sensitivity and specificity. IgG antibody tests have poor sensitivities of 40-90% but specificities are 98-100%. As IgA antibody tests are usually also available these are usually preferred.
IgA endomysial antibody
- Direct immunofluorescence test where endomysial antibodies bind to connective tissue surrounding smooth muscle cells
- Highest diagnostic accuracy: sensitivity is 96-98% and highly specific at 95-97%
- In certain circumstances, a positive endomysial antibody is considered diagnostic and may obviate the need for confirmatory small bowel biopsy
IgA transglutaminase antibody
- ELISA test – antibodies to tissue transglutminase enzymes are released by inflammatory cells, endothelial cells and fibroblasts because of the inflammation and irritation from the gluten
- Test is fairly diagnostic: sensitivity of 93%, and 96-99% specificity
- A positive test is fairly diagnostic
IgA antigliadin antibody
- ELISA test – antibodies bind to gliadin which is a component of gluten
- IgA has a sensitivity of 80% and specificity of 80-90%
- A positive test is not specific enough to be diagnostic so generally requires a biopsy to confirm or exclude the diagnosis
Small bowel biopsy
- Considered as the gold standard as histology will show vilous atrophy
- Problem is that the atrophy may be patchy and therefore biopsy may miss involved areas
- Villous atrophy can also be seen in many other diseases too therefore it is not specific for Celiac disease
- Some recommend a repeat biopsy 3-4 months after beginning a gluten-free diet to show histologic improvement
Questions for Further Discussion
1. What skin disorders are more common with Celiac disease?
2. What gastrointestinal malignancies are more common with Celiac disease?
3. What histological changes are seen on intestinal biopsy with Crohn’s disease?
4. Explain sensitivity, specificity and likelihood ratios?
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
To view current news articles on this topic check Google News.
To view images related to this topic check Google Images.
Rostom A, Dube C, Cranney A, et.al. The diagnostic accuracy of serologic tests for celiac disease: A systematic review.
Vallee PA, Guandalini S. Sprue. eMedicine.
Available from the Internet at http://www.emedicine.com/ped/topic2146.htm (rev. 2/8/2006, cited 6/13/2007).
Mearin ML. Celiac disease among children and adolescents. Curr Probl Pediatr Adolesc Health Care. 2007 Mar;37(3):86-105.
Akobeng AK. Understanding diagnostic tests 2: likelihood ratios, pre- and post-test probabilities and their use in clinical practice. Acta Paediatrica. 2007;96(4);487-491.
ACGME Competencies Highlighted by Case
1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
2. Essential and accurate information about the patients’ is gathered.
3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
4. Patient management plans are developed and carried out.
5. Patients and their families are counseled and educated.
7. All medical and invasive procedures considered essential for the area of practice are competently performed.
8. Health care services aimed at preventing health problems or maintaining health are provided.
9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.
10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.
13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
14. Knowledge of study designs and statistical methods to appraisal clinical studies and other information on diagnostic and therapeutic effectiveness is applied.
23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
25. Quality patient care and assisting patients in dealing with system complexities is advocated.
26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.
Donna M. D’Alessandro, MD
Professor of Pediatrics, Children’s Hospital of Iowa
July 30, 2007