This article is more than 5 years old. Information may no longer be current.
AGA President: 7 new developments in celiac disease, wheat sensitivity
Click Here to Manage Email Alerts
CHICAGO — At the AGA Presidential Plenary at Digestive Disease Week, newly appointed AGA President Sheila Crowe, MD, from University of California, San Diego, highlighted the latest developments in celiac disease and wheat sensitivity disorders.
“Celiac disease remained a rare disease until this century, [but] disease susceptibility is no longer restricted to Western and Northern Europeans,” she said. “When I went to medical school we talked about people from Ireland and the Netherlands and Northern Europe. Now this disease affects all of Europe, the Middle East, South Asia and North Africa.”
Increased prevalence
The prevalence of celiac disease has increased in the U.S. and worldwide, according to Crowe.
“The prevalence [has] increased from one in 5,000 ... up to one in 100 in the U.S., and this is a similar prevalence in all of the genetically susceptible parts of the world,” she said.
Altered expression
The expression of celiac disease has also changed over time, she continued.
“In the past century, celiac disease was an overt malabsorptive condition [with] diarrhea, low BMI, bone disease, malnutrition, infertility and anemia,” but atypical celiac disease is now common, with non-GI presentations like neurological issues, depression and migraines.
Many patients also lack an overt clinical manifestation — the so-called “silent celiac disease,” which is often detected during screening of first degree relatives and other at-risk patients, Crowe said.
Updates in pathogenesis
There have been a number of advances in the understanding of the pathogenesis of celiac disease over the past few decades, regarding the host genotype, which is currently restricted to the HLA genes, the delivery mode of gluten, type of feeding, time of feeding, and antibiotics modulating the microbiome.
“The DQ2 genes are necessary but they’re not sufficient to explain the development of celiac disease,” Crowe said. “It is thought that about 40% of the burden of celiac disease is related to the HLA-DQ2.2, 2.5 and 8 genes. In spite of many genome-wide association studies, no key molecules have been identified that are playing a significant role in causing the disease at this time.”
Further, interest in the association of enteric infections and celiac disease has emerged in the last 5 years, she added.
“People are exposed to gluten from childhood and now it’s not really a child’s disease; the average age of diagnosis of celiac disease in modern times is somebody in their mid-40s, and they’ve been eating gluten all their life, so it’s not clear why and when people develop celiac disease,” she said. “This concept of enteric infection being a trigger has been postulated, modulating the immune system, the breaches in the mucosal barrier and alterations of the microbiome.”
She cited as examples a study recently published in Science supporting the role of reovirus as a trigger for celiac disease, and results from the TEDDY study group published in Clinical Gastroenterology and Hepatology suggesting that rotavirus vaccination could reduce celiac disease autoimmunity in susceptible children.
The latter study findings could factor into “changing how we deal with infants who are genetically susceptible; up until now we have not found that sweet spot of [when to introduce] gluten in infancy,” she said.
Nonceliac gluten sensitivity
While the mechanisms underlying nonceliac gluten sensitivity or wheat sensitivity are still unclear, the terms “encompass individuals who report symptoms or alterations in health that are related to perceived gluten or wheat ingestion,” Crowe said. However, these symptoms could stem from fructose or fructans (FODMAPs) in wheat starch, which could lead to symptoms similar to irritable bowel syndrome or other functional GI disorders.
Testing for nonceliac gluten or wheat sensitivity is difficult as the mechanisms are unknown, and thus prevalence cannot be established. However, North American data show “that more and more people without a diagnosis of celiac disease are having more exposure to gluten-free products,” she said.
Researchers have postulated that the pathophysiology of these conditions could include activation of the innate immune system, increased permeability, mucosal inflammation, basophil and eosinophil activation, anti-gliadin antibody elevation and wheat amyloid trypsin inhibitors, but data have been inconsistent.
The recommendation for diagnosing nonceliac gluten or wheat sensitivity is a double blind gluten placebo controlled trial to assess gluten-induced symptoms after excluding celiac disease or wheat allergy, but “unfortunately, in North America, we don’t really have this,” Crowe said.
Screening, diagnosing celiac disease
Although celiac disease has previously been considered to meet criteria for early detection and treatment, the recent USPSTF recommendations do not support screening for asymptomatic celiac disease. Case detection remains the main diagnostic strategy, but recent studies suggest that patients with IBS-D should be screened for celiac disease, she said.
Drawbacks of gluten-free diet
Despite being very expensive, the gluten-free diet is “the most popular diet ever,” but recently some drawbacks have emerged, Crowe said.
These include an increased risk for cardiovascular disorders linked to the gluten-free diet, according to a recent study published in BMJ, and increased levels of harmful heavy metals found in rice, according to a recent study published in Epidemiology.
The latter study “showed increased levels of arsenic, cadmium, lead and mercury in urine and blood, and it is thought that the insecticide that is put on rice contains these heavy metals that are poisonous to the insects and not good for humans either,” Crowe said.
Emerging treatments
A number of trials of therapeutic alternatives to the gluten-free diet are ongoing, Crowe said.
First, prolyl endopeptidases that degrade gluten in the intestine are being developed, but “unfortunately a recent study published in Gastroenterology with ALV-003 [showed] there was no difference in symptoms nor in histology between the drug and the placebo.” Researchers also reported data on a European agent based on the same concept, AN-PEP, at DDW.
Additionally, trials of larazotide and the gluten vaccine, which may hold the most promise, Crowe said, are ongoing.
“Much has been learned but new knowledge is needed,” she concluded. “We need to identify other pathogenic factors that drive the disease ... capitalize on the recent information about enteric viruses ... develop treatments beyond the gluten-free diet, [and] understand more about the nonceliac [gluten and wheat] disorders.” – by Adam Leitenberger
Reference:
Crowe S, et al. Sp590. Presented at: Digestive Disease Week; May 6-9, 2017; Chicago.
Disclosures: Crowe reports financial relationships with UpToDate, Ferring and Otsuka.