Celiac disease is no longer thought to only affect the gut
A range of symptoms throughout the body need to be recognized and lead to celiac disease testing
Like a dizzying array of sweets in a candy shop, celiac disease presents in so many ways that it’s difficult to pick out the symptoms that belong in the diagnosis bag.
Gastrointestinal symptoms, including diarrhea, constipation, bloating and abdominal pain, as well as weight loss, reflux, osteoporosis and neurological symptoms, including headache, brain fog, fatigue, peripheral neuropathy and ataxia are all symptoms of celiac disease in adults.
In children, gastrointestinal symptoms and short stature, fatigue, headache, delayed puberty, canker sores, dental enamel defects and joint pain can all be signs of celiac disease.
This variety of symptoms complicates diagnosis. In addition to having different symptoms, the severity of the symptoms varies and some people with celiac disease have no symptoms at all.
In a study published as part of the special celiac disease edition of the American Gastroenterological Association Gastroenterology, “Clinical Presentation and Spectrum of Gluten Symptomatology in Celiac Disease,” an international group of researchers describe challenges in diagnosis in light of the way presentation of celiac disease has been evolving. This evolution has taken place alongside advances in disease detection and understanding of the ways the disease develops, persists and is resolved, says the study, which reviewed existing evidence.
Changing views
Celiac disease was historically seen as a pediatric illness characterized by failure of the small intestine to take in the nutrients from food. Now it is seen more as an immune illness that can have effects on the entire body across all ages, lead study author Dawn Adams, MD, of Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues note.
“Appreciation of the evolving presentation of celiac disease in adults and children is important for clinicians, as celiac disease remains greatly underdiagnosed around the world,” the authors wrote. They advise that both gastrointestinal and symptoms that affect other parts of the body, called extraintestinal symptoms, should prompt testing for celiac disease. In fact, extraintestinal symptoms are increasing in both adults and children, the study says.
Today, most patients present with irritable bowel syndrome-like symptoms, anemia, osteoporosis and more or have no symptoms and are diagnosed through random testing, called screening.
In addition to getting diagnosed with celiac disease, symptoms play a role in managing the condition and in clinical trials investigating drugs to treat celiac disease.
Diagnosis lacking globally
Between 50 and 80% of those who have celiac disease remain undiagnosed. Delays in diagnosis are common, averaging from seven to 10 years after the first symptom of celiac disease develops. Still most countries, including the U.S., don’t do widespread screening of the general population, making it critical that doctors are aware of the symptoms of celiac disease to improve its detection.
Signs to look for
There has been a major shift in the understanding of how celiac disease develops as researchers uncover evidence of the role of the immune reaction that results in a t-cell response to gluten in many parts of the body. T-cells are white blood cells that function as the body’s disease fighting soldiers and are part of a coordinated immune system battle. In the case of celiac disease, these soldiers incorrectly read gluten as the enemy, rally the immune response troops and go on the attack.
This broader understanding of the effects of celiac disease has drawn attention beyond gastrointestinal symptoms. About 60% of adults and children are affected by symptoms outside the gastrointestinal tract, including short stature, fatigue and headache as the most common in children and anemia, fatigue, headache and psychiatric disorders as the most common in adults, the study says.
Prior to diagnosis, up to about 60% of adults have normal weight, though about 30% are overweight and about 10% are obese. Adults are more likely to have milder gastrointestinal symptoms, including diarrhea, constipation, abdominal pain, and bloating and may also have lethargy, osteoporosis, neurological issues, reproductive complications, or abnormal liver enzymes.
Physicians, including primary care and specialists, should be on the lookout for all these as potential signs that celiac disease testing is needed. Related autoimmune diseases are also found in those who have celiac disease, including type 1 diabetes, microscopic colitis or autoimmune thyroid disease.
Irritable bowel syndrome (IBS) symptoms overlap with those of celiac disease, in some cases leading to a misdiagnosis of IBS and delay in the diagnosis of celiac disease. However, someone with celiac disease can also have IBS, which contributes to ongoing symptoms even when the gluten-free diet is being followed strictly.
Role of vitamins and minerals
Vitamins and minerals that are not being absorbed properly can also lead to symptoms. One in 31 patients who have iron deficiency anemia also have intestinal damage that indicates celiac disease, according to evidence reviewed for the study. Deficiencies are also found in B and D vitamins, folate, zinc, and copper. Lack of these vitamins and minerals can lead to anemia, bone disease, cognitive, sensory or motor issues, and more.
When calcium and vitamin D are not absorbed, osteoporosis and fractures can occur in those with celiac disease. About 30 to 60% of those newly diagnosed with celiac disease had low bone mineral density, and 18 to 35% had osteoporosis, evidence shows. Arthritis and joint pain without inflammation might also be signs of celiac disease.
Elevated liver enzymes, infertility, adverse pregnancy outcomes, and other autoimmune diseases such as type 1 diabetes and autoimmune thyroid disease are also potential indications of celiac disease. About 5% of the general population has autoimmune diseases compared to 16% of those who have celiac disease, the review study says.
No symptoms
Recent studies based on patients diagnosed through random testing found that 10 to 27% had no symptoms or symptoms that were unrecognized, the review study says. However, these patients had intestinal damage, blood test results, response to the gluten-free diet and commitment to following it comparable to those diagnosed because they had symptoms.
“The mechanism of why some patients with celiac disease are asymptomatic is not understood and is an important research question,” the authors wrote. One recent study found that asymptomatic patients were taller, had lower levels of antibodies to gluten and less severe intestinal damage.
Broad testing for celiac disease to diagnose it in those without symptoms is controversial, according to the authors. One reason is that it is less clear that those without symptoms benefit as much from the gluten-free diet. “The burden of a strict, lifelong gluten-free diet is high, and some have questioned whether this treatment outweighs the health risk in asymptomatic disease,” the review study says.
Although those detected through random testing can be less satisfied with the diagnosis, studies and clinical trials have found that they often report improvement on the diet. In some cases, they only recognize their symptoms after improvement on the gluten-free diet.
The review study authors suggest a low threshold for celiac disease testing even when someone does not have overt complaints since symptoms poorly predict who has celiac disease.
The U.S. Preventative Services Task Force does not recommend screening for celiac disease in the general population or those who don’t have symptoms because there is currently not enough evidence to assess the balance of harm and benefit. The task force is a panel of experts in disease prevention that works to improve the health of Americans by making evidence-based recommendations about routine screenings, check-ups and patient counseling to prevent illnesses, diseases, or other health problems. Meanwhile, Italy in 2024 launched the first nation-wide population screening program for celiac disease and type 1 diabetes in children. The review study notes this may influence practices in other countries in the future.
Symptoms after diagnosis
Although the gluten-free diet can resolve some or all symptoms, acute reactions can be triggered when someone with celiac disease eats gluten inadvertently or on purpose. An acute reaction is sudden and more severe than chronic symptoms, which occur over a long period.
Of those with celiac disease participating in studies with a gluten challenge, 60 to 90% report acute symptoms including nausea, bloating, vomiting, diarrhea, constipation, abdominal pain, lethargy and headache. Some describe confusion, forgetfulness, difficulty concentrating and mental sluggishness, a group of cognitive symptoms called brain fog.
Exposure to gluten while on the gluten-free diet is common, usually inadvertently when someone eats out or eats a product they don’t realize contains gluten. Tests that can detect gluten in stool and urine have shown that 25 to 89% of those with celiac disease have consumed some gluten, frequently without knowing it. When gluten gets into the diet, abdominal pain and diarrhea are the most common symptoms reported. On average, it takes about an hour for symptoms to begin and they last for about 24 hours.
People with celiac disease fearful of being accidentally exposed to gluten sometimes develop hypervigilance of the gluten-free diet. This restricts their lifestyle and reduces their quality of life, the review study says.
Drug development and symptoms
Interest in developing drugs to treat celiac disease has focused attention on symptoms and how to monitor and measure them when testing new treatments. Measurement of the elevation of Interleukin 2, (IL-2) a cytokine signaling molecule in the immune system, correlates with the start and magnitude of gastrointestinal symptoms.
Cytokines are small, secreted proteins released by cells that have a specific effect on the interactions and communications between cells.
IL-2 is the earliest and most sensitive biomarker, or red flag, of acute gluten exposure, the review study says. Research has shown that acute gluten exposure causes nausea and vomiting and IL-2 elevation. These symptoms are common with acute gluten exposure but aren’t reported as often before someone is diagnosed with celiac disease, which the review study authors say is an important distinction between chronic and acute symptoms in celiac disease.
Overall, acute reactions to gluten vary widely, according to the review study. Symptoms can be affected by age, previous reactions to gluten, anxiety and depression, and frequency of gluten exposure. In studies where gluten is consumed for a number of days in a row, acute symptoms are reduced.
Meanwhile, many patients who have no symptoms before diagnosis report increased sensitivity to inadvertent gluten in the weeks and months after they are diagnosed and go on the gluten-free diet.
These variations between symptoms that stem from chronic gluten exposure before diagnosis and acute gluten exposure afterward are not fully understood. Objective biomarkers, including IL-2, will likely be used to increase understanding of symptoms related to gluten exposure and to develop better ways for patients to report symptoms.
Better understanding of the mechanism of gluten induced symptoms is needed, including symptoms that are not gastrointestinal, the review study concludes. Approval of drugs to treat celiac disease will also depend on better ways to measure and monitor symptoms.
Support groups
There are a number of support groups for caregivers and patients with celiac disease. Reach out to your gastroenterologist, dietitian, local hospital or community center for more details.
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Written by
Amy Ratner
Director of Scientific Affairs
Beyond Celiac
