Celiac disease: Hiding in plain sight

Clinical pearls for frontline PCPs

A 44-year-old man presents as a new patient because he is worried that he has lost weight for no obvious reason and has been noticeably more fatigued recently. He is very worried that he has cancer.

He reports to the medical assistant (MA) that he recently moved to the area and has lost about 8 lbs since he arrived 3 months ago, despite having a normal appetite. After moving to the area, he joined the local newcomer’s volleyball club to meet people. He notes that his stamina has decreased significantly over those 3 months. He is otherwise healthy and is on no medications except for levothyroxine 100 µg daily. Other than the hypothyroidism diagnosed about 1 year ago, he has no significant past medical history. He does not use tobacco products, and although he generally has not consumed much alcohol in the past, he has started drinking three to four beers twice weekly after volleyball games and on the weekends. He has had some bloating and upset stomach in the past few months that he has attributed to the stress of getting settled in. No other symptoms have been noted. His vital signs are normal.

The MA presents the patient’s case to the physician.

“Doc, this is a new 44-year-old patient who comes in reporting unexplained weight loss and being tired all the time. He recently moved to our area and is otherwise healthy. He is really worried that he has a cancer of some kind. His only medication is levothyroxine,” the MA says.

The physician enters the room and notes a healthy but anxious-appearing man. After further questioning, the patient notes a change in his bowel habits; he often feels bloated, gassy and nauseated after going out with the volleyball team after games. He has had more loose stools recently — three to four bowel movements a day on many days.

His bowel movements have been greasier and more foul smelling than he has noted in the past.

On physical exam, the physician noted a few nonspecific mouth ulcers on his buccal mucosa. His skin exam was notable for a rash. The patient adds that he has noticed a red itchy rash for the past 2 weeks. Lung and heart exams are normal. The abdominal exam is notable for borborygmi and mild abdominal distention. The patient’s stool is hemoccult negative.

Labs include the following:

• complete blood count (CBC): white blood cell count (WBC) of 3.5; platelet (PLT) count of 180,000; hemoglobin (Hgb) of 9; and a mean corpuscular volume (MCV) of 85
• thyroid stimulating hormone: 3.5
• comprehensive metabolic panel: glucose of 88; serum glutamic-oxaloacetic transaminase of 70; serum glutamic pyruvic transaminase of 75; alkaline phosphatase of 110; and total bilirubin of 0.8

Subsequent studies are ordered off of the initial blood sample and include:

• iron: 40
• total iron-binding capacity: 350
• ferritin: 40
• B12: 200
• folate: 3.0

Because of the weight loss and iron deficiency anemia, he is referred for colonoscopy and esophagogastroduodenoscopy (EGD).

The colonoscopy is notable for two polyps, each about 1 to 2 cm. Pathology shows tubular adenomas. EGD shows mild gastritis and peculiar appearing small bowel mucosa — the villi are definitely more blunted than normal. Biopsies are taken. The diagnosis based on the symptoms and biopsy is celiac disease. He has an IgA and tissue transglutaminase antibody (TTA Ab) testing done, and these showed a normal IgA Ab (310 mg/dL) result and a TTA result of 250 µg/g — very elevated — confirming the diagnosis of celiac sprue.

Philip A. Bain

The patient is provided information on celiac disease and is referred to the nutritionist for extensive teaching on a gluten-free diet.

The patient returns in 6 weeks, and his bowel pattern returned to his baseline. The previously noted rash and mouth ulcers have resolved. Repeat bloodwork shows the following:

• CBC: WBC of 3.8; PLT count of 210,000; Hgb of 10.5; and MCV of 85
• TTA: 5 µg/g
• IgA: 300 mg/dL

Overall, he is very pleased with his progress, and he is glad that he is feeling better and less fatigued.

He returns in about 6 months, reporting that he felt really good for about 4 months but recently began noting GI symptoms, including nausea, bloating and loose stools. TTA is repeated and is found to be elevated again (200 µg/g). He sheepishly admits to the physician that although he was really motivated early on regarding following the gluten-free diet, he resumed his previous pattern of drinking beer and not paying very close attention to his diet because he was feeling better. The physician explains how common it is for patients with celiac disease to relapse due to not following the gluten-free diet faithfully, which can be challenging. She refers the patient back to the nutritionist to help identify which foods and drinks are likely causing the symptoms. She gives him more resources to help him sort out if specific foods contain gluten.

The patient returns in about a year, feeling well, having adjusted to the dietary changes and a normal follow-up TTA (3 µg/g).

Lessons learned

1. Celiac disease is relatively common, affecting 1% of the global population and potentially greater than 1% of the American population. Many patients with celiac disease may go undiagnosed or have minimal or no symptoms. Like many other autoimmune diseases that are rising worldwide, the increase in celiac disease is likely related to shared environmental factors that may trigger the disorder.
2. It is caused by the consumption of gluten-containing foods and drinks in a susceptible person causing an immune reaction resulting in the production of specific antibodies that bind to receptors in various organs — especially in the small intestine, where it results in blunting of the fingerlike projections, or villi. This leads to malabsorption of calories, nutrients and vitamins.
3. Gluten is a protein present in wheat, rye and barley grains.
4. Many people in the United States assume that they or members of their family have celiac disease and needlessly follow a strict gluten-free diet, which can be quite restrictive at times. Some people are “gluten sensitive” — ie, they have symptoms after eating gluten-containing foods but do not have the pathological changes associated with celiac disease.
5. Symptoms associated with celiac disease include nausea, abdominal bloating, loose stools and oily/foul-smelling stools. Unexplained weight loss can be seen, as well as various nutritional deficiencies, including iron deficiency anemia, B12/folate deficiency and low vitamin D levels.
6. Numerous non-GI-related symptoms including headache, fatigue and delayed puberty can be seen. Celiac disease often presents differently in children and adults.
7. Certain conditions are seen with greater frequency in patients with celiac disease, including type 1 diabetes, rheumatoid arthritis in adults, dermatitis herpetiformis, pregnancy loss, ovarian failure, autoimmune thyroiditis, osteoporosis, Down and Turner syndromes and aphthous ulcers. First- and second-degree relatives of patients with documented celiac disease are at increased risk for the disorder.
8. The diagnosis depends a lot on the pretest probability of the disorder being present. If there is a low pretest probability, testing can begin with IgA and TTA Ab testing. Note that about one in 500 people in the U.S. are IgA deficient, which could lead to a falsely low TTA Ab test. Also, the testing should not be done on a gluten-free diet because this also could produce false-negative testing. If the pretest probability is high or the initial TTA level is elevated, the diagnosis should be confirmed with EGD and small bowel biopsy. Physicians are relying less on biopsies to diagnose celiac disease if patients have the characteristic symptoms and their serologies are very elevated — especially among pediatric patients.
9. Currently, the only true treatment for this disorder is to follow a strict gluten-free diet. It is imperative that the patient and family members who buy and cook the meals be referred to a nutritionist for teaching because avoiding gluten can be difficult. Numerous novel therapeutic interventions are being evaluated for patients who are unable to easily follow or tolerate a gluten-free diet.
10. There are unusual cases of TTA/IgA-positive and -negative small bowel biopsies, as well as positive small bowel biopsies and negative TTA/IgA levels. These patients are likely best served by referral to a gastroenterologist.
11. Compliance can be monitored by following TTA levels. If symptoms recur, it is important to recheck the TTA levels.
12. Following a gluten-free diet can be challenging. If the patient can follow a gluten-free diet, the long-term prognosis is good. Unfortunately, many people are unable to follow or continue to follow the diet long term. These patients often continue to feel poorly long term and have a lower quality of life.

References:

• Celiac Disease Foundation. What is celiac disease? https://celiac.org/about-celiac-disease/what-is-celiac-disease/. Accessed June 11, 2024.
• Immune Deficiency Foundation. Selective IgA deficiency. https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/selective-iga-deficiency. Accessed June 18, 2024.
• Posner EB, Haseeb M. Celiac Disease. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441900/.
• Rubin JE, Crowe SE. Ann Intern Med. 2020;doi:10.7326/AITC202001070.