Celiac Disease Is the Focus of New Cleveland Clinic Program

Gastroenterologist Alberto Rubio Tapia, MD, an internationally recognized authority on celiac disease (CD), has joined Cleveland Clinic to create a comprehensive CD treatment and research program.

“I was looking for a place where I can develop a world-class celiac program,” says Dr. Rubio Tapia. “Cleveland Clinic is the perfect place.”

As a clinician and researcher, first at the National Institute of Medical Sciences and Nutrition in his native Mexico and subsequently at Mayo Clinic, Dr. Rubio Tapia has helped significantly advance medical knowledge about the chronic immune-mediated disorder. He was the lead author of the American College of Gastroenterology’s CD guidelines and has published peer-reviewed studies that found:

• One in 141 Americans has CD, the first research to establish the disease’s national prevalence.
• CD is five times more common now in the U.S. than it was in the early 1950s — a dramatic and unexplained increase.
• People with undiagnosed CD have nearly quadruple the mortality risk of those who don’t have the disease.
• Most people on gluten-free diets have not been diagnosed with CD.
• Screening at-risk groups (case finding) is not an effective way to identify CD patients.

At Cleveland Clinic, Dr. Rubio Tapia is assembling a multidisciplinary team of specialists to address CD’s systemic impacts and patients’ medical, nutritional and lifestyle modification needs. Post-diagnosis clinical evaluations at three months, six months and one year will allow team members to assess patients’ progress and respond to new or ongoing issues. He intends to adopt the integrated, patient-centered medical home approach that Cleveland Clinic has successfully employed to overcome fragmentation-of-care issue with inflammatory bowel disease patients.

Shared CD medical appointments are a possible means to efficiently deliver care and patient education while providing group reinforcement. Dr. Rubio Tapia also hopes to assist primary care physicians in the region with testing, diagnosis- and treatment-related issues, emphasizing the need to manage CD as a multi-system disease.

Research-wise, Dr. Rubio Tapia’s plans include seeking improved strategies to identify undiagnosed CD patients; examining the effect of the medical home approach on CD clinical outcomes; establishing a CD tissue and serum registry to support gene-based studies; exploring why CD is uncommon in African-Americans; and probing why the overall U.S. CD prevalence has risen so sharply in the last half-century.

“Our message to CD patients and physicians is that we will deliver high-quality care,” Dr. Rubio Tapia says. “We are developing a systematic way to approach every single patient who comes to us. They will absolutely get what they need.”

Recently, Consult QD had a wide-ranging conversation about CD and the new Cleveland Clinic CD program with Dr. Rubio Tapia. Here are excerpts:

Q: You were a fellowship-trained gastroenterologist in Mexico before coming to the United States to gain additional research experience. How did you become interested in CD?

Dr. Rubio Tapia: I have been dedicated to celiac disease research and clinical care for 20 years. There’s no personal reason, like a family member affected, but it is a personal professional challenge. I just want to make things better for the patients. I started a celiac clinic in Mexico City, and at that time, celiac disease was not well known in Mexico. So I took part in a study there [screening apparently healthy Mexican Mestizo blood donors for the presence of tissue transglutaminase antibody, a marker for CD], that showed the prevalence was the same as in other Western and northern European countries. And it was shocking, not just for Mexico, but for the international community, knowing that CD was that frequent in the Mexican population. I think it’s a very fascinating disease. We know a lot, but still, the only treatment is the gluten-free diet. It’s the only autoimmune disease that we know for sure what the antigen is, and we cannot cure it yet.

Q: You coauthored a 2012 study that was the first to establish the prevalence of CD in the United States. What were the main takeaways?

Dr. Rubio Tapia: We did that study using a survey called NHANES [the National Health and Nutrition Examination Survey]. We tested the serum of the survey patients. One percent is the prevalence in the U S. But that 1% is 2 million people. Only 17% know that they have celiac disease, meaning they are clinically diagnosed. Celiac disease is a global disease, so every single country that checks for the prevalence has found it. The most recent is India. That’s a really big deal, because they have a population of 1.3 billion. One percent of that is a lot of celiac disease.

Q: People with CD may be asymptomatic or have symptoms that are nonspecific or may not involve the gastrointestinal system. How is a diagnosis made?

Dr. Rubio Tapia: Only 30% of patients with newly diagnosed celiac disease have diarrhea. Seventy percent have other clinical presentations that are more systemic. To make a diagnosis, we start with serology, testing for the presence of anti-tissue transglutaminase antibodies. Those are strongly supportive of celiac disease but are not confirmatory. If the serology is positive, the next step is endoscopic biopsy of the small bowel for histologic confirmation.

Q: Is there a genetic marker for CD?

Dr. Rubio Tapia: We know that the HLA haplotypes DQ2 and DQ8 increase the risk of developing celiac disease. If you don’t have those genes, you cannot have the disease. So it’s a test that we use to rule out celiac disease. The complicated part is that 30% of the U.S. population has the DQ2 and DQ8 haplotypes but only 1% develops the disease. So there are more genes that are involved in triggering the condition, and there are also environmental factors. Intestinal infections, delivery by Cesarean section, possibly the amount of gluten in the diet, and some types of surgery increase the risk of developing the disease.

Q: What is the gluten paradox?

Dr. Rubio Tapia: There are about 2 million people in the United States who are following a gluten-free diet without having a diagnosis of celiac disease. And there are about the same number of people who actually have celiac disease and need a gluten-free diet but don’t know it, because they aren’t diagnosed.

Q: Based on CD prevalence estimates, it’s unlikely that most of those people on a gluten-free diet have undiagnosed CD. Are they gluten-sensitive, and what can be done for them?

Dr. Rubio Tapia: What exactly does being gluten-sensitive mean? I was opposed to that designation. It is not very helpful for patients. The problem is that there is no diagnostic criteria — there’s no specific marker to confirm the diagnosis. If the patient is on a gluten-free diet and is doing well and wants to know if they have celiac disease, we can answer that question. We can give confirmation or rule out the condition. If they’re on a gluten-free diet but are not doing well, they are not gluten-sensitive. Do they have irritable bowel syndrome, a celiac mimicker or another condition that is undiagnosed? We can help there, too.

Q: What are the consequences of untreated CD?

Dr. Rubio Tapia: The goal of treatment is healing of the bowel and the resolution of symptoms and malabsorption. Patients improve if the diagnosis is made early and the gluten in their diet is removed. If you don’t achieve mucosal healing, the long-term consequences may include anemia; malnutrition; bone disease; the development of malignancies, especially lymphoma of the small bowel; peripheral neuropathy; ataxia; dementia; and a moderately increased risk of mortality.

Q: The U.S. Preventive Services Task Force does not currently support universal CD screening, saying it’s not clear that the potential benefits outweigh potential harms. If the majority of CD cases are undiagnosed, how can they be identified?

Dr. Rubio Tapia: The way to identify more people early is by case finding — testing for the condition in high-risk populations. I’m a critic of case finding. It’s not the best way to do it, but it’s the best thing that we have available right now. So I think the research question is how we can move from case finding to a better kind of a strategy.

Q: Where do you expect patient referrals to your CD program will come from?

Dr. Rubio Tapia: The main source is from primary care physicians. Endocrinology and neurology are also frequent referral sources. I’m getting patients from gastrointestinal physicians because celiac disease can cause all kinds of liver issues. When the liver disease is unexplained, it may be celiac hepatitis or celiac disorder of the liver. The diabetes center will be another big referral source because type 1 diabetes and celiac disease are genetically linked; 8% of type 1 diabetics have celiac disease. I’m getting referrals from functional medicine specialists who are seeing patients with difficult-to-explain symptoms.

Q: What should happen after a patient is diagnosed with CD?

Dr. Rubio Tapia: A gluten-free diet is the only treatment for celiac disease at present. But if you tell the patient just to go and be gluten-free, that is not very helpful. Changing dietary habits is extremely complicated and patients have a lot of questions. They make mistakes. There’s a lot of frustration. Implementation of the diet takes three to six months, and that’s three to six months that the intestine isn’t healing.

That’s when they need more support from us. I believe in the concept of working as a multidisciplinary team. We are developing a systematic way to approach every single patient who comes to us. They need to see a dietitian who is knowledgeable about gluten-free diets. Follow-up visits also are important. We have them at three months, six months and one year after diagnosis.

The initial visit with a newly diagnosed patient is very busy and we use a checklist. We discuss what gluten is, where it is found, what foods are not allowed and which are OK. We review the patient’s specific nutritional condition and what needs to be improved. We talk about cross-contamination, how to set up your kitchen to be safe at home, how to eat safely when you dine out.

The three-month visit with the dietitian is to learn about and manage any issues patients are facing with the implementation of their diet. That’s probably the most important visit because that’s when patients have the most questions, and when their difficulties following the diet are becoming evident. We ask questions: Are you following the gluten-free diet, and if not, why? What challenges are you encountering? It may be economics, or that they don’t want to put their whole family on a gluten-free diet because of their own condition, or that they share kitchen and food-storage space with someone who isn’t gluten-free. We need to provide advice and help with practical solutions.

At the six-month visit, autoimmunity should be improving, and at one year you expect the disease to be in remission. However, complete healing of the intestine may take years.

Q: Is accessing gluten-free foods and adhering to a gluten-free diet hard for CD patients?

Dr. Rubio Tapia: There are options. The gluten-free market is expanding, but prepared foods are very expensive — four times more expensive than regular food for the same amount and type. So if the problem for a patient is cost, then they need natural gluten-free food sources, but that requires instruction.

Q: How effective is a gluten-free diet in resolving CD symptoms?

Dr. Rubio Tapia: Initially, it works probably 90% of the time. Long-term, about 30% of the patients who did well at the beginning may have some recurring symptoms, which we then need to assess. The most common reason for persistent symptoms after a period of being well on a gluten-free diet is that they are encountering gluten, somehow. Then the dietitian is key to identifying the potential source of contamination. Sometimes we need to use steroids or immunosuppressants for very specific complications or conditions in celiac disease, such as for refractory celiac disease when the patients are doing everything they can to be gluten-free but severe symptoms continue to be an issue.

Q: Is a vaccine a possibility to treat CD?

Dr. Rubio Tapia: Celiac disease is not an allergy. It’s an immune-mediated disease with complex genetics, and you cannot treat a condition like this with a vaccine in the present way that vaccines are delivered. We need a technological improvement in the way we deliver the antigens to develop tolerance, but right now we are not smart enough to know how to do it. There are efforts in a rat model to deliver gluten peptides to the gut in small amounts on medications that help to decrease inflammation, but how we transition that technology to humans is the challenge. Alternatives beyond the gluten-free diet are urgently needed.