Celiac disease: Clinical sciences

Celiac disease, also known as celiac sprue or gluten-sensitive enteropathy, is a genetic condition associated with an immune-mediated response to gluten, which is a protein found in wheat, barley, and rye. In genetically susceptible individuals, a component of gluten called gliadin, triggers an immune response within the small intestine, eventually causing local inflammation and production of antibodies against both gliadin and an enzyme called tissue transglutaminase. Over time, local inflammation results in malabsorption of various vitamins, minerals, and other nutrients. In children, celiac disease typically occurs after 6 months of life, because this is the period when caregivers introduce gluten-containing foods to their babies.

Now, if your pediatric patient presents with a chief concern suggesting celiac disease, first perform a focused history and physical examination, and obtain labs, including CBC and CMP. Your patient will commonly present with typical gastrointestinal symptoms that are related to mucosal damage in the small intestines and subsequent malabsorption. These include bloating; abdominal pain; chronic diarrhea; and steatorrhea, which is a greasy, foul-smelling stool that’s difficult to flush; as well as poor weight gain in young children or weight loss in older children and adults. Other historical findings may include extraintestinal symptoms like irritability and changes in their child’s behavior. Additionally, there might be a history of pre-existing autoimmune conditions, such as Type 1 diabetes mellitus or rheumatoid arthritis; genetic conditions, like Down or Turner syndrome; or a positive family history of celiac disease.

As far as the physical exam goes, you might notice abdominal distention; a pattern of short stature on growth charts; as well as signs of failure to thrive, or delayed puberty. Finally, some patients might present with dermatitis herpetiformis, which refers to an itchy, vesicular rash that typically appears bilaterally on the elbows and knees. Meanwhile, lab results often reveal low hemoglobin and elevated transaminases.

Now, here’s a clinical pearl to keep in mind! Some patients may present with atypical gastrointestinal features like constipation and vomiting. There are also a number of atypical extraintestinal effects of celiac disease including oral manifestations, like aphthous ulcers and dental enamel hypoplasia; skeletal manifestations, like arthritis and osteoporosis; and symptoms of iron, folate, and vitamin B12 deficiencies, like fatigue and peripheral neuropathy. In rare cases, children can present with celiac crisis, which is an acute and life-threatening manifestation characterized by profuse diarrhea, dehydration, electrolyte imbalances, and hypoproteinemia.

With these findings, you should suspect celiac disease. Your next step is to order a total serum IgA level and check for IgA antibodies against tissue transglutaminase, or anti-TTG IgA for short. Before you proceed with testing though, make sure your patient continues to consume a gluten-containing diet until you confirm or rule out the diagnosis!

If the total IgA level is normal and anti-TTG IgA antibodies are negative, consider an alternative diagnosis, such as Crohn disease or pancreatic insufficiency.

On the other hand, if the total IgA level is below the reference range and anti-TTG IgA antibodies are negative, then your patient has IgA deficiency. Now, it’s important to identify IgA deficiency, because this condition is much more common in patients with celiac disease, when compared with healthy individuals! And when total IgA levels are low, you can’t rely on anti-TTG IgA antibodies to diagnose or rule out celiac disease. So, in this case, you should look at IgG antibodies and order anti-TTG IgG antibodies and IgG serum antibodies against the deamidated gliadin peptide, or anti-DGP IgG for short.

If anti-TTG and anti-DGP IgG antibodies are negative, consider an alternative diagnosis. However, if either anti-TTG or anti-DGP IgG antibodies are positive, your next step is to order an esophagogastroduodenoscopy, or EGD for short, and obtain duodenal biopsies.