As pediatric gastroenterologist Jennifer Duong, MD, explains in this guide for primary care, celiac disease (CD) is common and can affect many organ systems. Untreated, it increases the risk of serious problems ranging from stunted growth to GI cancers – making early detection and management critical. Duong provides insights on distinguishing CD from similar disorders, such as wheat allergy; clarifies which patients should be screened; and dispels the confusion around serologic testing, giving particulars on specific tests and noting when referral is warranted. She also discusses CD’s impact on quality of life, offering guidance on protecting kids’ mental health. Bonus: Learn when she’ll consider forgoing a biopsy, normally the diagnostic gold standard.
So, um, today we'll be discussing celiac disease. Again, uh, my name is Jennifer Duo, and I'm an assistant professor within the division of Pediatric Gastroenterology. I have no disclosures related to this presentation. We have 4 objectives for today's discussion. First, I'll be reviewing the epidemiology of celiac disease. Secondly, I'll be discussing the presentation of celiac disease and how it differs from other gluten-related disorders. Third, I'll be discussing the screening algorithm for celiac disease and going over who should be referred to GI clinic. And finally, I'll review celiac disease management. So moving on to our first objective. Celiac disease is an immune-mediated neuropathy. It's triggered by gluten ingestion, which is a protein found in wheat, barley and rye. It results in small intestinal inflammation with a wide variety of systemic symptoms. Celiac disease affects 1% of the population and is a common condition. It has variations in prevalence depending on a patient's age, sex, as well as geographic location. In regards to age, it does affect children more so than adults, with two typical peaks, one in childhood, occurring between the ages of 6 to 7, and then the second peak in adults in the 4th decade of life. It also affects females more so than males. There is also regional variation in celiac disease, with a prevalence of about 0.4% in South America, 0.5 in Africa and North America, 0.6% in Asia, and 0.8 in ocean, but in Europe and Oceania. Secondly, we will be discussing the presentation of celiac disease and how it differs from other gluten-related disorders. It's important to remember that celiac is not just limited to the GI tract, and it really is a multi-organ disorder. Celiac disease manifestations can be divided into gastrointestinal and extraintestinal manifestations. In the GI tract, it's the typical symptoms that we know, including diarrhea, abdominal pain and distention, vomiting, or weight gain, and constipation. Celiac can also have neurologic involvement, including headaches, seizures, as well as brain fog, and patients can have behavioral changes and psychiatric disorders as well. A skin finding that is specific to celiac disease is dermatitis or petiformis, which is an itchy, fluid-filled, blistering rash that typically occurs on the elbows, knees, buttocks, and back. In the mouth, you may see dental enamel hypoplasia, as well as recurrent at this mouth ulcers. And patients may have challenges with growth, as well as delay in puberty. Patients can have liver as well as biliary tract involvement, including autoimmune liver disease and benign elevations in their transaminasis. From the hematologic side of things, iron deficiency anemia is a common finding. And then finally, going into the musculoskeletal system, you can see osteopenia, osteoporosis, bone fractures, as well as arthritis and alphalgia. One common area of confusion is distinguishing celiac disease from other gluten-related disorders, including non-celiac gluten sensitivity and wheat allergy. A few ways to distinguish these entities is the timing of symptoms from exposure, as well as the presence of respiratory symptoms. For celiac disease, symptoms typically occur hours to months after exposure, and symptoms include both gastrointestinal and extraintestinal manifestations. These patients do not have respiratory findings, and as mentioned, a unique skin findings of celiac disease is dermatitis herpetiforms. In contrast, non-celiac gluten sensitivity, while having similar symptoms, these symptoms typically manifest earlier in the span of hours to days. Again, these patients don't have respiratory symptoms, and patients with non-celiac gluten sensitivity do not have the rash of dermatitis or petiformis. Finally, with wheat allergy, symptoms occur very soon after exposure, usually minutes to hours after ingestion, and these patients often have respiratory symptoms and can have evidence of anaphylaxis as well. So again, with gluten-related disorders, especially celiac disease and non-celiac gluten sensitivity, it's difficult to distinguish the two given symptoms are very similar, but they are very different entities and should be managed differently. In celiac disease, the pathogenesis is thought to be autoimmunity with an association to HLADQ2 and HLADQ8. On lab testing, these patients typically have positive autoantibodies, as well as evidence of a neuropathy on intestinal biopsies. In addition, these patients often have coexisting conditions such as type one diabetes and thyroid disease, and can have long-term complications of untreated disease such as malignancy. In contrast with non-celiac gluten sensitivity, the pathogenesis is thought to be innate immunity with no HLA association. These patients do not have positive autoantibodies and do not have a neuropathy present on their biopsies. These patients do, don't have any um co-existing conditions and there are no long-term complications um from non-celiac gluten sensitivity. Finally, wheat allergy is an allergic process with short-term complications of anaphylaxis and, and allergy complications, again without autoantibodies and without a neuropathy. So, after you have a patient that you suspect with celiac disease, then the question becomes, what are the next steps as far as screening? The diagnosis of celiac disease relies on high-risk groups to screen, serologic testing, and then duodenal biopsies. Groups to screen are those patients that are symptomatic, as we've discussed, those with associated conditions and first degree relatives. Screening is done with serologic testing, with the preferred test being total IGA and TTG IGA or tissue transglutaminase IGA. And if the patient is found to have elevations in their TTGIGA, we then proceed with EGD with biopsies. Typical findings include increased intraepithelial lymphocytes, crypt hyperplasia, and villas lnting. So let's go into our groups that are high risk for screening. Specific conditions to consider testing for celiac disease include first degree relatives. I usually recommend starting this screening, starting at 2 to 3 years of age. And usually screening about every 2 years or so until patients reach puberty to maximize growth and avoid delays um in diagnosis and puberty. After puberty, screening can often be done every 3 to 5 years, depending on risk factors and the presence of symptoms. Those with autoimmune conditions, especially type one diabetes and thyroid disease, also should be screened for celiac disease. As well as genetic conditions, including Down syndrome, Turner syndrome, and Williams syndromes. And then finally, patients with IgA deficiency should also be screened. So next, let's go into the serologic testing of celiac disease, which often um creates a little bit of confusion. The initial screening test for celiac disease is a total IGA and tissue transglutaminase IGA or TTGIGA, which is a very specific and sensitive test. The sensitivity is about 95 to 98% with the specificity of 94 to 95%. The important thing about this test, it it's important that the child is consuming gluten at the time of this screening protocol. For those who have an IgA deficiency, an IgG-based test, such as deaminated glitin peptide, anti-endomesal antibody, or a TTG IgG should be performed as the second step. Finally, for those children who are under 2 years of age, the initial screening algorithm usually includes, again, the total IGA and TGGIGA, as well as the deaminated ble and peptide IgG. In regards to the don'ts for serologic testing, In general, it's recommended using alternative tests as the first screening test. So, I would avoid using uh endomesal antibody, deaminated glutin peptide, and anti-glutin antibodies as the first initial test. What about routine HLA testing for DQ2 or DQ-8? Usually, this is not recommended as the initial test. Um, I'll sometimes use it, use it in the GI clinic in a situation where um a case is difficult or I'd like to rule out celiac disease. And the reason for that is having a negative HLA makes celiac disease highly unlikely. It's also important to know that a positive result does not confirm the diagnosis, so you can't rely on positive HLA testing uh to make a diagnosis of celiac disease. Um, this is the recommended algorithm from the European Society of Pediatric Gastroenterology, or EBA for short. Um, these are the most recent guidelines from 2020, and so these, this is a nice, um, useful resource if you're having some questions about how to perform the screening. Again, the first step is starting with the clinical suspicion for celiac disease or um being of a celiac disease high-risk group, and again, measuring the TTG IGA and a total IGA. If your TTGIGA is positive, then that is easy because the patient just then gets referred to us, um, in pediatric uh GI for an endoscopy. However, what do you do if your TCGIGA is negative? Well, then you would want to check your total IGA. If your total IGA is low, then as we discussed before, I would recommend obtaining an IgG based test, and if that test is positive, referring to us in pediatric GI. If the total IGA is normal, then we'll have to consider the possibility of a false negative test, which typically I've seen in the setting of if a patient isn't consuming enough gluten, or if they have primarily extraintestinal manifestations. So if you have a high clinical suspicion for celiac disease, despite a patient having negative serology and a normal IGA, when in doubt, just refer to us in GI. So we talked about some reasons that TTGIGA may be falsely negative, but it's important to know that there are also false positives too. So some false positive causes include Crohn's disease, type one diabetes, liver disorders, infections, as well as connective tissue disorders. So again, these are the patients that should be referred to us, the positive T TTG IGA, and if you have concerns for celiac disease, um, even if a patient has negative serologies. And as mentioned, when in doubt, um, please consult with our team. So what happens when a patient comes to us uh in the GI clinic? Usually, um, we do additional testing such as screening for comorbid, um, Celiac disease such as iron deficiency anemia or we think of um other potential causes of their GI symptoms. So sometimes we even obtain fecal calprotectin, inflammatory markers, thyroid um serologies. We usually discuss endoscopy, which is the gold standard for diagnosis. And for those who have stopped um gluten consumption, uh, we discuss gluten reintroduction as this is required um for, for performing the endoscopy. What is considered sufficient gluten intake? Sufficient gluten intake is considered to be 3 to 6 g of gluten per day for 4 to 12 weeks. To give you a sense, one slice of bread is about 2 to 3 g of gluten, so ideally, patients should be consuming about 2 slices of bread daily to have considered um sufficient intake of gluten. There's many different ways to introduce, um, reintroduce gluten to a child who's been restricting. Um, unfortunately, there's no sort of um consensus guideline, but there are some general recommendations in the pediatric population. The key thing to remember is that um what you may do for an asymptomatic child may differ dramatically from one that you may do for a child who has severe symptoms, even after a few days of exposure. It's usually a bit of a clinician discretion on how to reintroduce gluten, but it's usually recommended that um you obtain baseline serologies. Um, and then after introduction, um, having a formal visit with the patient in 4 to 6 weeks to reassess serologies and symptoms. And then after that, having the child remain on gluten as long as they can tolerate, up to 12 weeks prior to performing the endoscopy. The other thing I generally recommend is that if celiac serologies are positive at the primary care office, it is helpful to have the child continue to consume gluten if they can tolerate it until they can be seen by us, and that way we don't have to reintroduce gluten in order to perform the endoscopy, as sometimes that can create some delays in diagnosis. If you're interested in learning more, um, I recommend reading this article that was published in uh JPGN, um, regarding the recommendations for gluten Challenge in pediatric patients, um, which was published in 2023. This is the official journal of the North American Society of Pediatric Gastroenterology. So their guidance is very helpful. So now we're proceeding with endoscopy, and so on endoscopy, what we see with celiac disease is typically flattened or absent duodenal folds, and sometimes we even see what we call scalloping, which is a wavy appearance to the lining of the small intestine. So shown in the picture at the top is normal, whereas the picture at the bottom is celiac disease, and so the arrows are sort of pointing to that area of scalloping. There, um, while these are sort of the classic endoscopy findings, sometimes a scope can look normal or non-specific with celiac disease as well. on pathology, um, the key findings are increased intraepithelial lymphocytes or IELs, crip hyperplasia, as well as via plenting. The key thing to know about pathology is during our endoscopy, um, we typically take 5 to 6 biopsies um in the duodenum, including one in the duodenal bulb, as celiac disease is often a patchy um diagnosis or a patchy disorder. And so having sufficient samples is important to make sure we don't miss the diagnosis. With the pathology, we use the Marsh classification to grade celiac disease, and it uses the three components that I discussed, which is the IELs, rip hyperplasia, and villus atrophy. So in March type one, the patient has just increased IELs. Marsh type 2 includes increased IELs as well as crip hyperplasia. In March 3 is increased IELs, crip hyperplasia, and phylu atrophy. So, when is a biopsy not needed? This is a really hot topic in PGI, and the answer may differ depending on how you ask. Again, I want to emphasize that the gold standard for diagnosis is with endoscopy and biopsy, and the reason for that is you really want to be sure of this diagnosis before um lifelong implementation of a gluten-free diet. That being said, um, in 2020, Espagan, or the European Society for Pediatric GI released these no biopsy guidelines. According to them, um, a biopsy is not needed if the following conditions are met. If TTG IGA is greater than 10 times the upper limit of normal, If on a 2nd specimen, the patient has a positive EMA IGA, which is a highly specific test for celiac disease, And this must be done on 2 samples taken on 2 separate occasions. This differs from previous guidelines from 2012, in which HLA testing was also required, as well as the presence of symptoms. This no biopsy approach really should be done in consultation with a pediatric gastroenterologist and after shared decision making with the family and the child. The challenge that I want to emphasize with this no biopsy approach is that by avoiding an endoscopy, you may miss other pathologies or diagnoses. For instance, patients with celiac disease have high comorbidity with eosinophilic disorders, as well as H. pylori. So the and also the confirming the diagnosis with biopsy may make them eligible to be enrolled in celiac disease-specific studies, and the risk of endoscopies are overall low. So I often will encourage my patients um to undergo endoscopy, um, but I always have conversations with families about this uh as a potential option, um, if they feel very strongly against endoscopy. Finally, let's talk about the management of celiac disease. So, of course, treatment of celiac disease relies on gluten avoidance. And avoidance of gluten containing grains, um, found in wheat, barley, rye, and cross-contaminated oats. It's really important um to follow this diet in consultation with a dietitian familiar with celiac disease, um, to ensure that there aren't um other sort of nutritional deficiencies as a consequence of being on a gluten-free diet. Beyond just the diet, um, it's important that these patients be screened for comorbid diseases, undergo micronutrient screening, and they require mental health support. So disease screening includes checking TTGIGA usually every 3 to 6 months until the labs are normalized, and then usually once the labs are normalized and the patient is asymptomatic, um, this lab is checked on a yearly basis. Um, checking CBC, TSH, and ALT yearly to look for those core morbid conditions. And DEXA scan if celiac serologies remain elevated, to look for complications such as osteopenia and osteoporosis. Annually, a patient should have vitamin D, calcium, their CBC, iron, and vitamin B12 monitored. Finally, it's important to address the mental health challenges for this population. It's been reported that patients with celiac disease actually have worse quality of life and increased risk of anxiety and depression, even compared to patients with ulcerative colitis. So it's really important to perform quality of life assessments and to provide mental health supports with the social worker and um through celiac disease support groups. What are the complications of untreated celiac disease? It increases the risk of intestinal cancers, including lymphomas. It may result in stunted growth and delays in puberty. Nutrient deficiencies. Osteoporosis. Infertility And other autoimmune disorders. So again, it's very important to make the diagnosis and to encourage gluten-free um diet once that diagnosis has been made. So here are our takeaways from today's discussion. We talked about celiac disease prevalence. It is common, affecting 1% of the population. Celiac disease, again, is a multi-organ disorder with both GI and extraintestinal manifestations. Celiac disease diagnosis relies on screening at-risk individuals. serologic testing as well as do adrenal biopsies, which is the gold standard for diagnosis. The initial screening test is the TTG IGA and total IGA. And it's again really important that patients are consuming an adequate amount of gluten for serologic testing and endoscopy, which is usually 2 slices of bread a day for 3 to 6 g of gluten for um at a minimum 4 weeks, um, and then up to 12 weeks. While following, uh, because following a strict gluten-free diet can be challenging, it can certainly contribute to mental health challenges within this population, so it's important to keep that in mind. If you're interested in learning more about celiac disease, I would recommend the GI Kids website, um, which is, um, through the North American Society of Pediatric Gastroenterology. Um, it has really good resources, uh, for families, uh, clinicians, um, gluten-free diet recipes and recommendations. Other celiac disease resources include the Celiac Disease Foundation and Beyond Celiac, which focuses on the education, treatment, and research within celiac disease, and additionally provides really helpful patient resources. Uh, for families who are looking for gluten-free friendly restaurants and reviews, the Find Me Gluten Free is a really nice app. And then the gluten intolerance group um provides help for finding local celiac disease support groups and other resources for managing celiac disease. And then, of course, if you have any questions, um feel free to ask our celiac disease program, which includes clinicians, dieticians, and our celiac disease social workers. Thank you.
