Celiac disease: Clinical sciences

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Introduction0:00–0:46

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.

Focused H&P, labs0:46–2:57

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.

Suspect celiac disease2:57–3:26

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.

Consider alternative diagnosis3:26–3:38

IgA deficiency3:38–4:45

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.

Anti-TTG IgA positive4:45–5:04

Now, let’s go back one more time to total IgA levels and anti-TTG IgA antibodies! Normal IgA levels and positive anti-TTG IgA antibodies are highly suggestive of celiac disease so you should proceed with EGD and duodenal biopsies.

EGD with biopsy5:04–6:50

In celiac disease, damage to the duodenum can be spotty, so remember to obtain biopsies from multiple sites! The classic findings of celiac disease include villous atrophy, crypt hyperplasia, and an increase in intraepithelial lymphocytes.
WIth these findings you can confirm the diagnosis!Now here’s a clinical pearl to keep in mind! In some children, you can diagnose celiac disease without performing a biopsy as long as they have characteristic signs and symptoms like diarrhea and poor weight gain.
Using shared decision-making with the child’s medical provider, caregivers can choose either a biopsy or a non-biopsy diagnostic approach.
Criteria for a non-biopsy diagnosis include anti-TTG IgA levels 10 times greater than the upper limit of normal, followed by a positive serum endomysial antibody on a separate blood sample.
If the endomysial antibody testing is positive, you can diagnose celiac disease without a biopsy. And here’s one last clinical pearl!
If a patient with celiac disease has started a gluten-free diet before you begin your evaluation, antibody levels and biopsy specimens might be normal, so you can’t rely on them to make a diagnosis.
Instead, you can order genetic testing for HLA-DQ2 or HLA-DQ8. If they’re positive, have your patient consume a gluten-rich diet, and if their symptoms return or get worse, you can diagnose celiac disease.
Keep in mind that you can’t diagnose celiac disease based on positive HLA results alone, since individuals without celiac disease can be positive for HLA-DQ2 or HLA-DQ8; however, negative HLA-DQ2 and HLA-DQ8 rules out celiac disease.
Alright, once you diagnose celiac disease, focus on disease management, which primarily relies on the lifelong adherence to a gluten-free diet.

Celiac disease - treatment6:50–8:29

Because a strict gluten-free diet can be expensive and difficult to maintain, all patients should be referred to a dietician for accurate information about how to recognize and avoid sources of gluten.
A dietitian can also promote optimal nutrition by ensuring the patient’s diet contains an age-appropriate intake of calcium, vitamin D, and other nutrients.
If a patient has a suboptimal response to dietary modifications, they might have a hidden source of gluten in their diet; and in this case, the dietitian can review their diet closely.
Also remember that all patients should take a daily multivitamin supplement, and some children may require caloric supplementation to optimize growth.
Moreover, these children will benefit from a quality of life assessment and consideration of any psychosocial impacts of their diagnosis.
Children with dietary restrictions are sometimes impacted by bullying at school and can feel excluded during typical childhood activities, such as birthday parties and other events where gluten-containing foods are served.
In addition to the dietary recommendations, don’t forget to treat any associated conditions, such as B12 or iron deficiency anemia.
Adults with celiac disease may also require DEXA scanning to identify osteoporosis. Finally, if your patient has dermatitis herpetiformis, consider treatment with dapsone to control pruritus.Alright, as a quick recap… If a patient presents with signs and symptoms suggesting celiac disease, order a total IgA level and TTG-IgA.

Review8:29–9:36

If the total IgA level is below the reference range and anti-TTG IgA is negative, diagnose IgA deficiency and order anti-TTG and anti-DGP IgG antibodies.
If either the anti-TTG or anti-DGP IgG is positive, order an EGD with duodenal biopsies. Finally, normal total IgA levels and positive anti-TTG IgA are highly suggestive of celiac disease so, again, proceed with EGD and duodenal biopsies.
The biopsy findings of villous atrophy, crypt hyperplasia, and an increase in intraepithelial lymphocytes confirm a diagnosis of celiac disease.
Treatment consists of a strict gluten-free diet, along with dietary consultations, and a quality of life assessment. Finally, remember to treat any associated conditions.
Celiac disease: Clinical Sciences: Video, Causes | Osmosis