The Difference Between Celiac Disease & Gluten Sensitivity
A 2021 update for providers and patients
What is the difference between celiac disease and gluten sensitivity in 2020? The gluten-free diet is still everywhere. While awareness of the term “gluten-free” has increased, the understanding of the difference between gluten sensitivity and celiac disease is lagging behind. As we all live online more and more, the influence of the internet plays a more important role. Confusion and misinformation about celiac disease and non-celiac gluten sensitivity are still widespread.
As health care providers, we have the opportunity to correct misperceptions and identify patients with these common and underdiagnosed conditions. We need to respond to patient questions with accurate information and a well-informed diagnostic plan.
I have a large number of patients in my practice with celiac disease (CD) or non-celiac gluten sensitivity (NCGS). The disparity in diagnosis and treatment from other providers is astounding. There is confusion on countless fronts. Misinformation stems, in part, from internet lore and well-meaning friends. These are variables that are difficult to control. However, I also see many people whose providers have given them misinformation, or no information, about CD and NCGS. This shortfall is accompanied by the trend of provider recommendations to start a gluten-free diet to “see if it helps” without first testing for CD. While well-intended, this approach can be detrimental to patients and their families.
I hope that by reading this article, the medical community and patients will gain a clear understanding of the following:
- The difference between CD and NCGS.
- The importance of testing for CD before starting a gluten-free diet.
- Reliable resources on CD and NCGS for both you and your patients.
Celiac disease is common. A 2003 landmark study found the incidence of CD in people donating blood to be 1/133. More recent information shows that the number is now closer to 1/100. If someone is symptomatic or has a celiac-related disorder such as anemia, diabetes, osteoporosis, short stature, infertility, or Down’s syndrome, the incidence of CD increases to 1/25. If there is a first degree relative with CD, the incidence increases further to 1/22, irrespective of whether or not the relative showed any symptoms.
CD is an autoimmune, genetic, lifelong condition that can present at any age. It causes damage to the villi of the intestinal mucosa because of an abnormal immune reaction to gluten. Gluten is a protein found in wheat, barley, and rye. With continued ingestion of gluten, a person with CD develops malabsorption and subsequent complications. These include (but are not exclusive to): anemia, vitamin deficiencies, heart disease, osteoporosis, infertility, and neurologic symptoms. Celiac disease is a multi-organ system disorder that can affect the thyroid, liver, heart, and reproductive organs, as well as the musculoskeletal system and brain.
Symptoms are different than people think
The presentation of celiac disease has changed dramatically over the last decade. This disease is a chameleon whose presentation varies from person to person. Once thought to be a “wasting” disease, we now know that 40% of CD patients are overweight or obese at diagnosis. Another common misconception is that gastrointestinal symptoms are required in order to initiate a diagnostic evaluation. However, gastrointestinal symptoms only occur in 30–40% of celiac patients at diagnosis. Their absence should not preclude an assessment.
“Atypical” presentations for CD are now common, including factors such as anxiety, depression, anemia, fatigue, osteopenia, rashes, dental enamel defects, and aphthous ulcers. For a more complete list of celiac symptoms click here.
One or more of these may qualify as the presenting symptom. I would like to reemphasize that only 30-40% of patients actually have GI symptoms at diagnosis. For example, I have frequently seen newly diagnosed celiac patients with only anxiety or only joint pain. They have no other symptoms – emphasis on no other symptoms. These were their “gluten-reaction” symptoms.
Also changed is the belief that CD is found primarily in Northern European Caucasians. The ethnic boundaries of CD are now blurred, as the disease appears to be equally common in other ethnic groups.
Active Celiac Disease
Three factors must be present to have active celiac disease.
1. Genetic predisposition. Forty percent of the population carries one of the at-risk genes for celiac disease. Of that 40%, only 5% have active celiac disease. The reason for this is being investigated. Patients must carry teither he HLA-DQ2 or the HLA-DQ8 gene to be at risk for celiac disease. You are at risk if you have either. You do not need both to be at risk. But, the presence of these genes is not diagnostic. The presence of either DQ-2 or DQ-8 only indicates a predisposition. If neither marker is present, celiac disease can be ruled out. Researchers are currently evaluating other genes for their involvement in celiac disease. Of note, there are currently no scientifically validated genes associated with NCGS.
2.Gluten. Patients must be consuming gluten for CD to be active.
3.Environmental trigger. Not all triggers are known but identified triggers include early/repeated infections, pregnancy, and GI infections, antibiotic use at an early age.
Testing for Celiac Disease
Patients must be consuming gluten for screening tests to be valid.
Basic screening for celiac disease includes a serum TTG IgA and total serum IgA. Total serum IgA needs to be done in order to rule out IgA deficiency which occurs in about 10% of celiac patients. If IgA deficiency is present, the TTG IgG must be used but is less accurate. Further testing may be needed in those situations.
Some labs include a DGP-IGA and EMA in their celiac screen/panel or do these tests as a reflex. The confirmatory test is an endoscopic biopsy. The biopsy is indicated if tests are positive and are required for diagnosis.
Of note, many celiac centers and practitioners follow a more extensive evaluation process involving screening antibodies, genetic testing, clinical response to a gluten-free diet, and endoscopy. These protocols and other testing algorithms are beyond the scope of this article
Treatment for CD
Currently, the only treatment for CD is a strict, lifelong gluten-free diet—100% of the time. Pharmaceutical treatments currently in clinical trials may aid in the digestion of gluten or in decreasing intestinal permeability. Current over-the-counter digestive enzymes marketed for digesting gluten are not appropriate for people with CD.
Some of the most promising pharmaceuticals under investigation are aimed at decreasing the symptoms that occur from cross-contamination, such as when dining out. They will not be a cure, but their development will be helpful in addressing the social and psychological issues surrounding CD. The social aspect of celiac disease is not commonly discussed in the medical community. Amongst patients, however, it comes second to their symptoms in overall concern regarding the disease.
The use of nanoparticle technology is currently being evaluated as a treatment for celiac disease. Early results are promising.
Non-Celiac Gluten Sensitivity
In 2011 researchers began addressing the presence of reactions to gluten in patients who did not have CD. Subsequently, a consensus panel developed the following definition of NCGS: “Non-celiac gluten sensitivity is a term that relates to one or more of a variety of immunological, morphological, or symptomatic manifestations that are precipitated by gluten in individuals in whom celiac disease has been excluded.”
In short, If someone has been properly evaluated and ruled-out for CD but gets symptoms when eating gluten, they are given the diagnosis of ‘Non-celiac gluten sensitivity”
The pathophysiology of NCGS is the subject of intense study. It appears as if NCGS may encompass several different entities rather than one discrete disorder. In some patients, their reaction may be due to the carbohydrate component of gluten, such as in FODMAP intolerance. In other patients, the reaction may be due to proteins, such as amylase trypsin inhibitors. NCGS pathophysiology is a rapidly evolving area of knowledge with many unknowns. The sensitivity does not appear to be autoimmune in nature. It is unknown if there is a genetic component or an environmental trigger.
What is clear is that a gluten-free diet is beneficial to these patients and can bring on much-needed relief of their symptoms.
How do you diagnose NCGS?
There is no validated test to diagnose NCGS. Some online labs offer blood, saliva, or stool tests for gluten sensitivity, but they are invalidated and not recommended.
It is impossible to develop a test when the mechanism of NCGS has not been determined. Diagnosis is made by ruling out CD and wheat allergy while the patient is on a gluten-containing diet. Once both are ruled out, a gluten elimination diet is prescribed. If symptoms improve, the patient is deemed to have NCGS. Using a response to initiation of a gluten-free diet as a prognostic indicator will give inaccurate results, as both celiac and NCGS can have similar responses to a gluten-free diet.
How do you treat NCGS?
At this point, a gluten-free diet may not be the starting point for NCGS patients. Many cases of NCGS are due to FODMAP intolerance. Once an evaluation is done to assure no other conditions are responsible for symptoms, a low FODMAP diet may be indicated. Referral to a dietitian familiar with the Low FODMAP diet is recommended.
Once studies clarify what NCGS truly is, more targeted and individualized therapies will be developed. It is not clear how strict the gluten-free diet needs to be or what the long term complications are. These are both areas currently under investigation.
The Importance of Testing
The blood tests and biopsy used to test for CD require a patient to be consuming gluten to obtain valid results.
If a patient is started on a gluten-free without first evaluating for CD, it becomes very difficult to diagnose celiac disease appropriately. Patients who experience clinical improvement on a gluten-free diet will rarely restart a gluten-containing diet to get an appropriate diagnosis. They finally feel well, and returning to being sick is just not an option. The importance of testing cannot be overemphasized. Consider these factors:
CD is lifelong, but we don’t know about NCGS. It is wrong to subject someone to a lifelong, strict gluten-free diet if they don’t need it. The social and psychological implications can be vast.
CD requires a strict gluten-free diet. Those with NCGS may not be treated by a gluten-free diet. They may require a low FODMAP diet. This difference of utilizing the proper diet can be life-changing to some patients.
CD is genetic. If you miss a diagnosis of CD, you may also miss or delay diagnosis in their child, sibling, or parent.
CD has long-term risks and complications. These parameters may be different for NCGS. We simply don’t know yet. Appropriate diagnosis is necessary for proper follow-up care of celiac patients and those with gluten sensitivity.
Insurance reimbursement can be more challenging without a diagnosis. You and your patients are more likely to get insurance reimbursement for a diagnosis of CD that would otherwise be missed if never tested for.
Accommodations. In order to obtain ADA accommodations, students need documentation stating they have a diagnosis of CD or food allergies. At this time, NCGS does not appear to be covered under the ADA.
I hope this information clarifies the rapidly evolving topic of gluten-related disorders. Unfortunately, according to current estimates, only 17% of American patients with CD are actually diagnosed. Please help change that statistic by considering celiac disease more often and in situations other than gastrointestinal symptoms. Don’t recommend a gluten-free diet without testing for celiac disease and please share what you’ve learned.
Beth Israel Deaconess Celiac
Celiac Community Foundation of
Celiac Disease Foundation
Columbia University Celiac Center:
University of Chicago Celiac
THIS ARTICLE IS COPYRIGHTED BY AMY BURKHART, MD, RD.
Dr. Amy Burkhart is a doctor (M.D.), Registered Dietitian, R.D., and fellowship-trained in integrative medicine. She specializes in treating chronic digestive disorders from an integrative/functional medicine perspective. She is a specialist in celiac disease and gluten/wheat-related disorders.