MIAMI — Ataxia, peripheral neuropathy, and epilepsy are among the extraintestinal manifestations of celiac disease when it presents in a child over age 15 months. The bowel symptoms of diarrhea, nausea, and abdominal pain are more common in younger children.

Other extraintestinal or atypical symptoms include dermatitis herpetiformis and other skin disorders, osteopenia and osteoporosis, iron-deficient anemia resistant to oral iron treatment, liver and biliary tract disease, and delayed puberty. Also, short stature can be a presenting sign. “In fact, 10% of children who walk into endocrinologist's office for short stature have celiac disease,” Dr. Stefano Guandalini said during a pediatric update sponsored by Miami Children's Hospital.

A meeting attendee asked Dr. Guandalini if celiac serology should be routine in the work-up of patients with failure to thrive. “Yes, that is a big presentation for celiac disease, as long as the child has gluten in their diet,” he said. “Residents sometimes will suggest this in a 3-month-old who has never had solid food.”

There is even growing recognition that dental enamel defects in permanent teeth are a sign of the condition, Dr. Guandalini said.

“All the specialties are touched by this condition, even general pediatrics,” said Dr. Guandalini, pediatric gastroenterologist and professor of pediatrics at the University of Chicago.

Celiac disease also can present with other autoimmune conditions, Dr. Guandalini said. For example, an estimated 4%–10% of patients with type 1 diabetes mellitus also have celiac disease, as do 4%–8% of those with thyroiditis, and 2%–8% of those with arthritis.

“We tested one individual who had type 1 diabetes and found six relatives in the extended family with celiac disease,” Dr. Guandalini said. “Celiac disease is much more prevalent if you are related to a celiac disease patient.”

A child will, on average, visit eight pediatricians before being diagnosed, according to the Celiac Disease Center at the University of Chicago Web site, www.celiacdisease.net

A meeting attendee asked if screening asymptomatic relatives of people with celiac disease is worthwhile. “Yes,” Dr. Guandalini said. “The prevalence in first-degree relatives is between 10% and 25%. [These are] very high numbers.”

A negative genetic test rules out celiac disease for life because it features a 100% negative predictive value. However, the test only has a 5% positive predictive value, so “a positive test means nothing,” Dr. Guandalini said.

This “fascinating autoimmune disease” is triggered in genetically susceptible individuals by ingestion of gluten, the protein in wheat, rye, and barley. “We think that many, if not all celiac disease individuals, might have a problem with how they regulate their intestinal permeability,” Dr. Guandalini said. Increased intestinal permeability allows more gluten to enter, attach to receptors, and present as antigens (non-self) to the immune system. This process can lead to damage of intestines, primarily the small intestines, including duodenal mucosa. Multiple childhood infections also are implicated in the possible etiology, he added.

In the early 1980s, diagnosis primarily was based on GI symptoms such as diarrhea, vomiting, and weight loss, but currently, only about 8% of patients are diagnosed with these symptoms alone, Dr. Guandalini said. Diagnosis has changed over time toward more asymptomatic adults being detected through screening (Am. J. Med. 2006;119:e9–14).

“Every time you screen for celiac disease, test for [tissue transglutaminase] antibodies and total serum IgA, and confirm with a biopsy,” Dr. Guandalini said. Some suggest that direct visualization of intestinal damage, including villous atrophy or blunting, is diagnostic. However, he said, “You cannot distinguish by visual findings if someone has celiac disease or not. You need to take a biopsy to an experienced pathologist—changes can be subtle.” Dr. Guandalini had no relevant disclosures.

Early introduction of gluten into the diet of children at risk might be protective. For example, the timing of gluten introduction made a difference in a prospective study of 1,560 children at risk (JAMA 2005;293:2410–2). Specifically, the researchers found a protective window between 4 and 6 months of age.

Another study demonstrated that breast-feeding is beneficial to prevent or delay celiac disease (Arch. Dis. Child. 2006;91:39–43). Only one study included in this meta-analysis report showed no protective effect, Dr. Guandalini said.

“So you can recommend breast-feeding, and introduce gluten at 4–6 months along with breast-feeding in children at risk to minimize risk of celiac disease,” he commented.

The only treatment for celiac disease is a diet free of gluten. However, “research is ongoing to find ways to remove gluten from wheat, degrade the enzyme, or to keep the gates tight,” Dr. Guandalini said. “So there is hope that someday they will be able to eat at least some gluten.”

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'You cannot distinguish [celiac disease] by visual findings … takea biopsy to an experienced pathologist.' DR. GUANDALINI

Update on Diagnosing, Managing Celiac Disease : Short stature and dental enamel defects are added to the existing list of extraintestinal symptoms.