Clinical Practice Update | Diagnosing and Managing Refractory Celiac Disease

Refractory Celiac Disease wp10 best-practice recommendations to guide gastroenterologists in diagnosing and managing refractory celiac disease.

  • Donavyn Coffey, 1

Experts from across the country have assembled the first American Gastroenterological Association clinical practice update for refractory celiac disease, a rare condition that often requires extensive workup to rule out co-conditions and gluten contamination.

The practice update addresses how gastroenterologists should diagnose and manage this rare form of celiac disease, offering 10 best-practice recommendations covering areas such as use of corticosteroids as first-line therapy and heightening surveillance of type 2 refractory patients for lymphoma (Gastroenterology 2022;163[5]:1461-1469).

Reevaluate the Diagnosis

With refractory celiac disease, patients continue to experience significant symptoms, such as diarrhea and weight loss, even though they adhere to a gluten-free diet. Intestinal biopsies reveal significant inflammation and damage, putting these patients at high risk for complications.

However, it’s critical to remember that refractory celiac disease is rare, according to the lead author of the practice update, Alberto Rubio Tapia, MD, a gastroenterologist and celiac expert at Cleveland Clinic in Cleveland. So, proper diagnosis is crucial and the main focus of the practice update.

“It is very easy to assume refractory from the beginning,” Dr. Rubio Tapia said. “[But in] most referrals of refractory, when I do the evaluation, it’s actually that the original diagnosis was not correct or [there’s] obvious gluten contamination.”

1. When a patient presents as unresponsive to a gluten-free diet, the first step, according to Dr. Rubio Tapia and his co-authors, is to reevaluate their diagnosis. “Review the biopsy to make sure all conditions of celiac disease are met,” Dr. Rubio Tapia said. On second look, it may be that another condition mimicked the markers for celiac disease, such as lactose intolerance, pancreatic insufficiency or irritable bowel syndrome.

2. If the diagnosis is confirmed, the most common problem is accidental gluten contamination. Dr. Rubio Tapia estimated that 50% of patients referred to him with suspected refractory celiac disease actually have gluten contamination in their diet.

3. If the diagnosis is confirmed and contamination is ruled out, it’s likely that other conditions alongside celiac disease are the culprit. The review authors recommend a systematic evaluation of other potential symptom drivers, such as IBS, pancreatic insufficiency, lactose intolerance and microscopic colitis.

Distinguishing Types

Noting that refractory celiac disease affects only 0.1% to 0.3% of celiac patients, Carol Semrad, MD, a gastroenterologist specializing in small bowel diseases and nutrition at the University of Chicago Celiac Disease Center, said the value of the new practice update is that it addresses refractory celiac disease while also offering advice on how to approach other patients who aren’t fully responsive to a gluten-free diet, she said.

4. Only once a misdiagnosis, dietary issues and other conditions are systematically excluded can you move forward and distinguish between types 1 and 2 refractory celiac disease. At what point a physician should refer a potential refractory celiac disease patient “depends on how confident they feel doing a systematic evaluation.”

5. But the testing required to distinguish between types 1 and 2 refractory celiac disease is not available everywhere. General gastroenterologists should partner with centers that have the clinical and technical expertise to make the diagnosis because distinguishing between types 1 and 2 is critical to patient management. Type 2 is especially dangerous, putting patients at significant risk for lymphoma in the intestinal tract and mortality.

6. These patients are usually extremely ill with diarrhea, weight loss, vitamin and mineral deficiencies, and low protein levels, said Dr. Semrad, who was not involved in the new guidelines. Although “you don’t see them that often, you must recognize and treat the refractory celiac patients quickly,” Dr. Semrad said. It’s critical that they be admitted for nutrition support, rapid evaluation and management. Reach out to a local hematopathologist or celiac center for help, “even if it’s just a phone call,” she said.

7. If type 2 refractory celiac disease is diagnosed, small bowel imaging should be used to assess for signs of enteropathy-associated T-cell lymphoma or ulcerative jejunoileitis. Then a detailed macro- and micronutrient intake is critical to identifying and correcting deficiencies, she said. Corticosteroids are typically the first-line therapy for patients with types 1 and 2 refractory disease.

Collaboration and Connection

8. Once the official diagnosis has been made, the primary gastroenterologist and celiac disease expert can work together to treat the patient. In his practice, Dr. Rubio Tapia sees referrals from a number of different states and countries. After confirming the diagnosis and starting treatment, he collaborates with local gastroenterologists for regular follow-ups, he said.

9. “Televisits have improved this model significantly,” Dr. Rubio Tapia said. It’s now much simpler to stay connected to complex patients and their local doctors.

10. If the standard treatment of steroids doesn’t work for a patient, the next step is for a celiac disease expert to reevaluate the treatment and potentially connect the patient to a clinical trial.