Research has uncovered several seemingly unrelated conditions linked to coeliac. Just a few years ago, doctors may have only looked for gastrointestinal symptoms to indicate potential coeliac, but it’s now widely accepted that many other health conditions are related. Some are well known, such as osteoporosis and anemia. Others, such as liver disease and oral inflammation, are less likely to be connected to coeliac. This review will describe some less-frequently recognised conditions, highlight recent research and discuss benefits of the gluten-free diet.
Nonalcoholic fatty liver disease (NAFLD) is a common form of liver disease. It is most frequently found in people who are overweight or obese and those with diabetes or high cholesterol. The liver performs many vital functions in the body, including detoxification and energy storage. It also stores fat, which, in the right amounts, isn’t a problem. When patients have too much accumulation of fat in the liver, however, NAFLD can develop. In most people, NAFLD does not present with any symptoms. But in some it can progress to more severe conditions, including fibrosis and cirrhosis.
NAFLD is also seen more frequently in patients with celiac, according to a study published in 2015. Researchers from the U.S. and Sweden found that of 26,816 celiac patients, 53 were eventually also diagnosed with NAFLD. This risk was highest in the first year after diagnosis. According to lead researcher Dr. Norelle Reilly, assistant professor of pediatrics and director of pediatric celiac disease at Columbia University Medical Center, “The rationale for exploring the risks of NAFLD in individuals with celiac disease may demonstrate unexpected or undesirable weight gain following the initiation of the gluten-free diet.” This weight gain, cautions Reilly, may increase the risk of developing NAFLD for patients with newly diagnosed celiac. Also, Reilly states that processed gluten-free food, which is often higher in fat and calories, may play a role.
Celiac link theory
Why some with celiac disease go onto develop NAFLD remains a bit of a mystery. But there is one theory, Reilly explains. “One possible route, proposed by Ludovico Abenavoli and colleagues, is that increased gut permeability, sometimes referred to as ‘leakiness,’ may be triggered by conditions associated with celiac disease, such as small intestinal bacterial overgrowth (SIBO). This can lead to exposing the liver to bacterial toxins, which can lead to injury and stress that can trigger the development of the condition.”
Most people with NAFLD are unaware they have the condition, and this is no different for those who have celiac. “NAFLD may have no symptoms, but at this point, screening is not recommended for average adults, with or without celiac disease,” says Reilly. “However, in any patient with elevated liver transaminases, NAFLD should certainly be considered among many disorders, and an appropriate evaluation is then warranted.”
Can NAFLD be prevented or treated? Because the condition is very much related to lifestyle choices, healthy eating can go a long way. “Maintaining a healthy diet and body weight with plenty of (gluten-free) whole grains, fruits and vegetables is associated with many health benefits, not just related to NAFLD,” advises Reilly. “Following regularly with a registered dietitian is recommended for all with coeliac disease to help in maintaining this balance. Even among those who have already developed NAFLD, the mainstay of treatment involves lifestyle modifications and weight loss in those patients who are overweight.”
“Oral symptoms that suggest celiac disease may be present include aphthous ulcers, otherwise known as canker sores,” states Dr. Maureen Leonard, clinical director at the Center for Celiac Research and Treatment at Massachusetts General Hospital. “Dental enamel hypoplasia or tooth discoloration can be a sign, which generally affects children younger than 7 years of age. Finally, patients may present with glossitis or inflammation of the tongue.”
Recurrent aphthous stomatitis (RAS) is relatively common, affecting about 10 to 20 percent of the population. These mouth ulcers can be particularly painful and affect the ability to eat, brush teeth properly, speak or swallow. Family history, injury to the mouth, stress, immune system changes, hormones and nutritional deficiencies may increase the risk of developing RAS.
Research shows that RAS can also be a sign of undiagnosed celiac disease. A 2008 study found that these mouth sores were found more frequently in children with celiac (22.7 percent vs. 7.1 percent of healthy controls). Other studies have found similar results. A 2014 study showed that RAS was more common in patients with celiac who didn’t have other gastrointestinal symptoms. They may also result from dietary deficiencies that have developed due to celiac. “Mouth sores may be due to immune or inflammatory conditions, or from a secondary folate deficiency, which can occur due to malabsorption in celiac disease,” notes Leonard.
Geographic tongue (GT), a form of glossitis, causes chronic or long-term inflammation of the tongue. A healthy tongue is covered in pink-white bumps called papillae. But in those with GT, some of these papillae are missing, and the tongue is instead covered in red, patchy areas. These areas can heal and then reappear on other areas of the tongue. The condition is called geographic tongue because the red regions give the appearance of a map. Symptoms of GT may be mild and might only be noticeable when eating spicy or acidic foods.
GT may be more common in those with coeliac, research suggests. A 2016 study found that nine out of 60 (15 percent) of patients with GT were later diagnosed with coeliac. Study authors noted that, like RAS, many of the patients diagnosed with coeliac did not suffer from other gastrointestinal symptoms. GT may develop from nutritional deficiencies found in those with newly diagnosed coeliac disease, notes Leonard. “Tongue inflammation is most likely secondary to a vitamin B12 deficiency, which is a secondary problem due to malabsorption.”
Pancreatitis, or inflammation of the pancreas, is usually caused by excess alcohol consumption or gallstones. The pancreas is a gland found on the right side of the abdomen. It is attached to the top of the small intestine, also known as the duodenum. The pancreas performs many functions in the body, including the production of insulin, which helps regulate blood sugar. It also produces digestive enzymes that assist with the breakdown of nutrients in the small intestine. Symptoms of acute pancreatitis include severe upper abdominal pain, nausea, vomiting and fever. These symptoms usually resolve in a few days, but patients with acute pancreatitis often need to recover in the hospital.
A 2012 study in Sweden found that those with coeliac had an increased risk of developing pancreatitis. According to Leonard, “Pancreatic manifestations of coeliac disease are uncommon but possible. While the etiology of this is unclear, inflammatory processes or a transient (temporary) obstruction have been identified as possible factors.” Swedish researchers cited malnutrition and chronic inflammation that led to changes in the structure and function of the pancreas, in addition to shared immunological markers. Leonard advises patients to be aware of symptoms, especially if they are not improving on the gluten-free diet. “Patients with nonresponsive celiac disease should speak with their physician about the need for testing related to pancreatic function as the source of the persistent symptoms.”
According to the National Down Syndrome Society (NDSS), “approximately 1 in every 700 babies in the United States is born with Down syndrome, making Down syndrome the most common chromosomal condition.” Those with Down syndrome have an extra copy (full or partial) of chromosome 21. According to the NDSS, some of the identifying physical characteristics of the condition include “low muscle tone, small stature, an upward slant to the eyes and a single deep crease across the center of the palm—although each person with Down syndrome is a unique individual and may possess these characteristics to different degrees, or not at all.”
Those with Down syndrome may also be at increased risk for developing celiac. According to Brian Skotko, MD, MPP, medical geneticist at Massachusetts General Hospital and assistant professor at Harvard Medical School, “Unfortunately, a large population-based database does not exist for patients with Down syndrome. As such, our clinical and research community does not have an accurate way of measuring the prevalence of co-occurring celiac disease—or any other diagnosis. But previous research has suggested that the prevalence in people with Down syndrome might range from 3 percent in the U.S. to 16 percent in Sweden.”
Because of this increased risk, parents of children with Down syndrome should be on the lookout for symptoms. Screening is also recommended. “The American Academy of Pediatrics recommends serologic screening for coeliac disease in symptomatic patients with Down syndrome at each preventative care visit, beginning at the age of 1. For adults with Down syndrome, experts recommend similar screening,” states Skotko. “Parents should consider asking their child’s physician to screen for coeliac disease if their son or daughter has otherwise unexplained diarrhea, bloating, large bulky stools, abdominal discomfort, growth failure or excess gas.” However, Skotko notes that sometimes children with Down syndrome may have a difficult time expressing gastrointestinal discomfort and that parents should be on the lookout for behavioral symptoms that may indicate an issue, including moodiness, irritability and crankiness.
Autism or autism spectrum disorder (ASD) is likely caused by a combination of genetic and environmental factors. More common in boys, those with autism exhibit challenges in social skills, speech and communication difficulties, and often display repetitive behaviors. It affects approximately 1 in 68 children in the U.S. “While children with autism frequently have gastrointestinal complaints, to date, autism has not been associated with a higher frequency of celiac disease than the general population in large studies,” notes Dr. Leonard. However, there remains intense interest in the gluten-free, casein-free (GFCF) diet as a potential treatment.
In 2016, a group of researchers conducted a small, double-blind study to determine potential benefits of the GFCF diet in children with autism. Study participants ate a GFCF diet for four to six weeks. After this initial period, they were assigned to receive either GFCF or gluten/casein-containing snacks and meals for the next 12 weeks. Because the study was double-blinded, neither the researchers nor the parents/caregivers knew which children were receiving the GFCF food so that there was no influence on expectations. Parents were asked to keep detailed records of behavior, bowel movements and sleep patterns. Researchers found no significant differences between the two groups, although they did note that the study had a small number of participants and that larger, similarly double-blinded studies are needed to confirm the results.
“We still have a lot to learn about autism, non-celiac gluten sensitivity and intestinal permeability,” states Leonard. “It seems likely that different factors contribute to the development of autism and therefore different subsets of children with autism may respond to different interventions. Some may respond to the GFCF diet, but until we can understand these subsets of children with autism, it will be difficult to predict which intervention is best for each child.”
Parents interested in trying the GFCF diet shouldn’t go it alone, advises Leonard. “I suggest that they see their primary care physician or a gastroenterologist so [the child] can be evaluated clinically with blood testing for celiac disease. I would then recommend that they meet with a registered dietitian nutritionist (RDN) to discuss how to initiate a gluten-free or gluten-free, casein-free diet while ensuring their child is still getting the proper nutrients and calories for growth.”
Leonard encourages parents to reevaluate the effectiveness of the diet after a few weeks. “I would suggest meeting with the physician before and after a trial period of two to six weeks, to discuss whether the goals of the diet were met. Then the family and physician can discuss together whether they should continue with a long-term trial of the diet or if social difficulties or nutritional deficiencies outweigh the benefits of continuing.”