#89: Celiac Disease – The Great Mimicker

July 20, 2023 | By Sam Masur

Audio

Summary:

TTG IGA, DGP IGG, IGG EMA…do you ever feel like you’re making alphabet soup trying to diagnose Celiac Disease? Listen to our episode with our special guest, Dr. Dale Lee from Seattle Children’s, as he teaches us how to diagnose, manage, and treat Celiac Disease. Dr. Lee will teach us how almost any symptom can mimic Celiac, and why going gluten-free is so important!

Celiac Disease Pearls

1. Have a very low threshold to test for Celiac, and don’t feel discouraged about getting negative celiac serologies! You are doing the right thing by sending them off because Celiac has such a variable presentation.
2. The diagnosis of Celiac by endoscopic biopsy requires that the patient be actively consuming gluten.  Don’t ask them to avoid gluten after a positive TTG IgA until their endoscopy.
3. The dieticians at your institution are your best collaborators and sources of knowledge! They are key to successful treatment of Celiac Disease. 
4. Management of Celiac is important even if someone is asymptomatic because ongoing inflammation can cause complications in the future, including development of autoimmune diseases, malignancies, and anemias.

Celiac Disease Notes

DEFINITION

• Celiac Disease (CD) is an immune-mediated enteropathy to gluten, which is a protein found in wheat, barley, and rye. Gluten is the protein that gives soft elasticity to bread products.
• Symptoms are due to inflammation. Inflammation leads to malabsorption, causing osmotic effects such as bloating.
• Celiac disease develops after exposure to gluten. Thus, it is not seen before 6-12 months (introduction of solid food)

Celiac vs. Gluten/Wheat Sensitivity vs. Gluten/Wheat Allergy

Symptoms may look very similar between all 3; however, gluten/wheat sensitivity would not show any increased inflammatory markers or abnormal biopsies. A gluten/wheat allergy might have some serologic inflammation but no GI tract inflammation on biopsy.

CLINICAL PRESENTATION

Bimodal presentation: In childhood around ages 8-10 and in adulthood around ages 30-40

Wide variety of presentations – our expert guest calls Celiac the Great Mimicker. Symptoms can be very diverse, e.g.:

– GI: abdominal pain, discomfort, distention, constipation, but NO hematochezia

– Neuro: difficulty focusing, migraines

– MSK: rash, joint pain, bone fractures

– Constitutional: faltering growth

– Asymptomatic (at least 10%)

In adults, Celiac often presents with vague symptoms and providers do not think about growth as much. Can be misdiagnosed as IBS or MSK etiology.

Family history is very important! 1st degree relatives with Celiac Disease increases your chance of developing CD to 5-11%, so all 1st degree relatives of a new diagnosis should be screened. Other family history of autoimmune diseases also elevates risk, but it’s unclear exactly how much.

DIAGNOSIS

In most practice, serology is used for screening and endoscopic biopsies are used as the definitive test. Per Dr. Lee, the threshold to test should be super low because screening is easy and the symptoms can be so variable. 

Serology

• Gold standard for screening (95% sensitive/specific): TTG IgA with a total IgA. If the IgA level is low, the TTG IgA test cannot be used. However, this is rare.
• Deamidated Gliadin DGP IgG, TTG IgG: Acceptable tests if low total IgA, but not as sensitive/specific. If IgA is normal, proceed with TTG IgA as above and ignore positives in the IgG testing.
• Anti-endomesial antibody – usually a sendout. Interestingly, in Europe, some guidelines will accept a serologic diagnosis of Celiac if the 1st TTG IgA > 10x normal level, and anti-endomesial antibody is positive (i.e. don’t need a scope). Can potentially follow these titers for disease monitoring.  
• Anti-gliadin antibodies: not very sensitive/specific – high likelihood of false positive

Without 100% sensitivity, there will always be serology-negative celiac disease. Therefore, negative serology should not stop further testing if celiac is still suspected.

Endoscopy and Biopsies

• Endoscopic biopsies definitively diagnose celiac disease. However, the patient needs to be consuming gluten for the biopsies to be accurate. Therefore, after a positive serologic screen, do not ask families to abstain from gluten while waiting for their GI appointment.
• GI wait times can be long! Coordinate with your local gastroenterologists for a more prompt endoscopy if you are concerned. 
• Expert Practice: In addition to duodenal biopsies, Gastroenterologists will  also biopsy gastric and esophageal mucosa to look for comorbidities such as H. Pylori and eosinophilic esophagitis.

Related Screening

• CBC: check for nutritional deficiencies e.g. iron deficiency anemia
• Vitamin D level
• Liver Function 
• DEXA: only if Celiac is poorly controlled
• Screening for other autoimmune diseases, e.g. Type 1 Diabetes, autoimmune thyroid disease, and autoimmune hepatitis

Providers often screen for celiac with new diagnoses of other autoimmune diseases, such as type 1 diabetes. However, the TTG IgA may be falsely elevated due to high levels of inflammation from the new autoimmune disease. Unless it’s an extreme elevation, the PCP or endocrinologist can trend this titer over a few months to see if it resolves before referring to GI because it could be a false positive.  

MANAGEMENT

Why is managing Celiac important, especially if the patient feels well? 

It can be difficult to convince a patient to adhere to a strict gluten-free diet if they feel asymptomatic. However, gluten leads to continuous inflammation, which can affect growth, nutrition, bone mineralization, small bowel cancers, and elevated risk of other autoimmune conditions (Gastroenterology 1999).

Gluten-Free Diet

Gluten in concentrations of over >20 PPM is considered significant (according to the National Celiac Association). This equates to about 10mg of gluten a day, which is the minimum level for continuous villous atrophy (American Journal Clinical Nutrition 2007). To put this in perspective, a slice of bread contains approximately 3,500mg of gluten. Thus, the mainstay of treatment is to remove gluten entirely. Patients should also be aware of cross-contamination or cross-contact (studies ongoing to determine specific inflammatory risk of cross-contamination in these small amounts).

Examples of cross-contamination:

• Using the same knife to spread from a jar of nut butter onto wheat bread, then gluten-free bread
• A restaurant making pizza dough with wheat flour that is airborne
• A restaurant with ingredients they dip into repeatedly (e.g. a fast casual burrito place spreading beans onto a wheat tortilla) 

What about at school?

• School should be a safe place. They are mandated to provide the foods that their students need, but space and knowledge might not be where it needs to be.
• Expert Practice: Advise parents to talk directly with the school and the food services. Establish a 504 plan, which schools must legally support. 

Cultural Considerations

• Although not every cuisine revolves around bread products as a centerpiece, gluten can be hidden in many processed foods like chips or popsicles.
• Other cuisines may have staples that contain obvious or hidden gluten, like soy sauce. Examples of foods in other cuisines that are gluten free are tamari/gluten-free soy sauce and injera which is made from teff. However, both of these products are sometimes made or cut with wheat, so it’s still important to read the label.

Expert opinion: A gluten-free diet can be very restrictive. It is a tricky balance between reducing gluten (to reduce inflammation and its sequelae), and also supporting our patients, being careful not to induce disordered eating or anxiety around foods. It’s important to learn the principles, but acknowledge and validate that no one can be perfect.

Monitoring

Expert practice: There are “4 pillars” of Celiac management and monitoring if a patient is responding to a gluten-free diet:

1. Symptom Improvement: Sometimes patients may immediately feel better. Other times, it may take weeks to months to see change, especially in regards to growth. 
2. Labs: Changes in TTG IgA titer over time. Need to take this in context – there are cases where the labs normalize but EGD biopsies still show active disease. Dr. Lee also recommends performing annual screening for comorbidities (CBC, 25-hydroxy D, thyroid tests, and nutritional testing if not growing well)
3. Dietician involvement – regular appointments with a dietician to check in on the gluten-free diet, answer any questions, and discuss barriers
4. Repeat endoscopy (optional) – if the patient reports active symptoms with abnormal labs, a scope may be helpful to acquire more data. It might not be required in children if the first 3 pillars are going well, but in adults, it is routine to do a repeat EGD 12-18 months after diagnosis.

Refractory Celiac Disease – adherence to a gluten-free diet without improvement – is very rare in pediatrics. This can happen in adults as a separate T-cell mediated immunologic process. If a child isn’t responding to the gluten-free diet, it is more likely they are either a) intentionally or unintentionally including gluten in their diet, or b) have a concurrent infection, such as H. Pylori.

What’s on the Horizon?

Currently there are no pharmacological treatments for Celiac Disease. Some places may sell enzymes that digest gluten, but these need more research and are not approved for wider use as of summer 2023. There are many drug trials in process, with mechanisms that either degrade gluten, bind it to keep it in the intestinal lumen, prevent absorbing it, or alter the body’s immunologic response.

Links

• National Celiac Association

Goal

Listeners will explain the serologic and pathologic diagnosis, treatment, and monitoring progress of Celiac Disease in the outpatient setting.

Learning Objectives

After listening to this episode listeners will…  

1. Recognize the similarities and differences between Celiac Disease, and gluten/wheat sensitivity and allergy.
2. Describe the different serologic approaches to diagnosis and any additional screening at time of a positive diagnosis.
3. Translate the importance of a gluten-free diet for Celiac Disease in accessible language.
4. Appreciate the possible barriers to successful adherence to a gluten-free diet.

Disclosures

Dr Lee has been a consultant for Takeda Pharmaceuticals and Schiper Medicine. No trade names have been used and all discussion is not relevant to consulting work. The Cribsiders report no relevant financial disclosures. 

Citation

Zhang AY, Lee D, Masur S, Chiu C, Berk J. “#89: Celiac Disease – The Great Mimicker”. The Cribsiders Pediatric Podcast. https:/www.thecribsiders.com/ July 19, 2023.