Celiac Disease

Educational Objectives

The goal of this program is to improve diagnosis of celiac disease. After hearing and assimilating this program, the clinician will be better able to:

1. Apply serum and genetic testing to diagnose celiac disease.
2. Recognize extraintestinal (ie, nonclassic) symptoms of celiac disease.
3. Cite American College of Gastroenterology guidelines on diagnosing celiac disease.

Summary

Overview: Celiac disease (CeD, or sprue) is present in 1% of the US population; the classic presentation of celiac disease (including diarrhea and abdominal cramping) has been surpassed by dozens of nongastrointestinal (GI) manifestations; antibody and genetic tests are now available to help make the diagnosis; risk factors include first- and second-degree relatives with CeD and presence of type 1 diabetes mellitus or autoimmune thyroiditis

Whom to test: assess patients with diarrhea, malabsorption, weight loss, pain, and bloating for CeD; these symptoms are also present in irritable bowel syndrome (IBS) and a host of other GI illnesses

Nonceliac gluten sensitivity: represents a variety of poorly understood reactions to gluten or other food elements in patients not diagnosed with CeD; estimated prevalence is 0.55%

Differential diagnosis of CeD: includes lactose intolerance, IBS, hyperthyroidism, inflammatory bowel disease (IBD), small intestinal bacterial overgrowth (SIBO), infections, and many other illnesses; diagnosis of CeD can take years because of the large differential diagnosis associated with diarrhea and abdominal pain

Gluten-free diets: consuming a gluten-free diet usually increases a person’s intake of fats and sugars; it also may be low in fiber, iron, folates, and B vitamins; most Americans with CeD are overweight; oats do not contain gluten (unless the product is produced in a factory that just processed wheat); ≤20% of patients with CeD do not have a full response to a gluten-free diet because of nonadherence, inadvertent ingestion of gluten, and difficulty in determining the true gluten status of foods when dining out; some patients with CeD do not respond at all; in addition to oats, individuals with CeD can consume rice, quinoa, and soy

Extraintestinal symptoms: neuropsychiatric issues (eg, depression, “brain fog,” anorexia nervosa, anxiety, attention-deficit/hyperactivity disorder, schizophrenia), autoimmune disease, and elevated transaminases may be manifested in CeD; fever is not a manifestation; other nonclassic features include fatigue, short-term memory loss, irritability, and reduced bone density

Dermatitis herpetiformis: diagnostic for CeD; manifested by itchy blisters occurring on the extensor surfaces of the limbs, but may also appear elsewhere; ≈10% of patients with CeD have this condition (many do not have GI symptoms); skin biopsy can confirm diagnosis; resolving dermatitis herpetiformis with a gluten-free diet can take months, but treatment with dapsone offers immediate relief

Diagnostic tests: tissue transglutaminase IgA (tTG-IgA) is the first-line serum test for CeD; it is 96% to 98% sensitive and 88% to 100% specific; the antigliadin antibody (AGA) test is no longer used because of inaccuracies; the antiendomysial antibody (EMA) test is a high-technology, high-cost test with 75% to 98% sensitivity and 99% to 100% specificity; it may be considered when tTG-IgA test results are questionable; false-positive tTG antibody tests are rare, but may occur in patients with IBD, connective tissue diseases, febrile illnesses, or type 1 diabetes

Total immunoglobulin A (IgA) test: the speaker recommends a total IgA test because 2% to 5% of patients with CeD may be IgA deficient; IgA deficiency is 10 to 15 times more common in individuals with CeD than in those without it; IgA deficiency is asymptomatic, and it requires special workup for CeD that includes an antideamidated gliadin peptide (anti-DGP) test, which is generally more accurate than tTG-IgA for evaluating CeD in IgA-deficient individuals; anti-EMA tests are often falsely negative in IgA-deficient individuals

Human leukocyte antigen (HLA) DQ2 and DQ8 haplotypes: carried by 35% to 40% of the US population; associated with autoimmune disease and type 1 diabetes; when assessing HLA DQ2 and DQ8, one is looking for negative results

Nonceliac gluten sensitivity: a series of poorly understood reactions to gluten, fructans, or another element that is not CeD; controversial topic because the pathophysiology is not established; 45% of patients with self-reported wheat sensitivity actually have IBS

Distinguishing nonceliac gluten sensitivity from IBS: exclude celiac disease; instruct patient to follow a gluten-free diet for ≥6 wk; waxing and waning symptoms usually indicate IBS; symptoms that are mostly well-controlled suggest nonceliac gluten sensitivity

Nutritional deficiencies in CeD: iron deficiency anemia can occur in 33% of men and 19% of women with CeD; folate deficiency can occur in 12%, and B12 deficiency in 5%; the duodenum and upper jejunum absorb iron and folate, and the ileum absorbs vitamin B12; the proximal small bowel is the area most commonly affected by CeD

Addressing patients’ questions: in speaker’s experience, it is exceedingly rare for filler in pills or capsules to exacerbate CeD; IBS and CeD can coexist; CeD and microscopic colitis can coexist (≤33% of patients with CeD have findings suggestive of microscopic colitis); this is especially important if patient remains symptomatic after truly adhering to a gluten-free die; investigate further with colonoscopy and biopsy; duodenal biopsies are not useful for patients on self-imposed gluten-free diets because the villi will have regenerated

Treatment: currently, the only way to manage CeD is to consume a gluten-free diet; peptide vaccinations and enzymes may be part of future therapeutics

Considerations and scenarios: CeD in the presence of negative tTG-IgA is possible but very unlikely; false-negative results may occur with mild disease; IBS is more likely; small-bowel biopsy — modified Marsh classification system is used to evaluate histologic components beyond villi appearance; type 0 is normal (CeD highly unlikely); type 1 has a large differential diagnosis, including CeD; type 2 is very rare; may include CeD with dermatitis herpetiformis; type 3 indicates symptomatic CeD; per American College of Gastroenterology guidelines (2019), all tTG-IgA-positive patients with suspected CeD require a small-bowel biopsy; guidelines state that a high level of transglutaminase antibodies, >10 times the upper limit of normal, is a reliable and accurate test for diagnosing active celiac disease; when such a strongly positive transglutaminase antibody is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for CeD is virtually 100%; can be caused by many other conditions (eg, SIBO, malnutrition, autoimmune enteropathy, giardia, Crohn disease, HIV, tuberculosis); in pediatric patients, biopsies are considered optional under certain circumstances; more scenarios — a capsule endoscopy to assess CeD may be considered for extraordinary symptoms such as bleeding or severe pain; tTG-IgA testing may be considered to monitor diet compliance; a gluten rechallenge is not required for patients with a diagnosis of CeD; the US Preventive Services Task Force (2017) recommends against routine screening of asymptomatic family members; outdated AGA test — a patient with a positive AGA test from many years ago may or may not have CeD, as the original test was “notoriously inaccurate”; in such a patient, HLA (genetic) testing should be performed; if negative, the patient does not have and will never have CeD; if positive, gluten challenge for 12 mo with follow-up blood test would be appropriate

CeD and other diseases: lymphoma — patients with CeD have an increased risk for lymphoma (≈1 in 8000); CeD that is refractory to diet restrictions may indicate lymphoma or other malignancy; leaky gut — presence has been demonstrated in CeD and many other illnesses, but the clinical significance is not clear

Positive tTG-IGA test and negative small-bowel biopsy: in such a patient, the first question is how thorough the biopsy was; current approach to small-bowel biopsy calls for 2 biopsies from the duodenal bulb, which may detect very early disease and increases the yield of diagnosis by 13%; in addition, 4 biopsies should be performed in the second duodenum; false-positive tTG-IGA is rare; can use anti-EMA antibodies, anti-DGP, and genetics for diagnosis

Final considerations: nonresponse to gluten-free diet — patient may have microscopic colitis, IBS, or IBD; controlled type 1 diabetes with abdominal pain, bloating, and diarrhea — potential associated conditions include gastroparesis, diabetic bowel, SIBO, and CeD; conditions associated with CeD — include type 1 diabetes, elevated transaminases, Down syndrome, autoimmune thyroid diseases, and many others: genetically modified wheat — there is no definitive answer as to whether genetic modification is a source of increased CeD and nonceliac gluten sensitivity

Readings

Cabanillas B. Gluten-related disorders: Celiac disease, wheat allergy, and nonceliac gluten sensitivity. Crit Rev Food Sci Nutr. 2020;60(15):2606-2621; Domsa EM et al. Celiac disease: A multi-faceted medical condition. J Physiol Pharmacol. 2020;71(1); Hujoel IA, Murray JA. Refractory celiac disease. Curr Gastroenterol Rep. 2020;22(4):18; Husby S et al. AGA clinical practice update on diagnosis and monitoring of celiac disease-changing utility of serology and histologic measures: expert review. Gastroenterology. 2019;156: 885–889; Lebwohl B et al. Epidemiology, presentation, and diagnosis of celiac disease. Gastroenterology. 2021;160(1):63-75; Rostom A et al. The diagnostic accuracy of serologic tests for celiac disease: a systematic review. Gastroenterology. 2005;128:S38–46; Rubin JE et al. Celiac disease. Ann Intern Med. 2020;172(1):ITC1-ITC16; Serena G et al. Celiac disease and non-celiac wheat sensitivity: state of art of non-dietary therapies. Front Nutr. 2020;7:152.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose. In his lecture, Dr. Buch presents information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Buch was recorded exclusively for Audio Digest using teleconference software in compliance with social-distancing guidelines during the COVID-19 pandemic. Audio Digest thanks the speakers for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

GE350802

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.