Affecting many body systems, celiac disease presents in a multitude of ways – sometimes with no digestive symptoms. Pediatric gastroenterologist Mala Setty, MD, explains the steps to accurate diagnosis, including when biopsy is required. She provides a flowchart for distinguishing celiac from other gluten-related disorders, a timeline for patient improvement on a gluten-free diet, and clarifications on the “gluten-free” product label.
good afternoon, and this is my talk on celiac disease and gluten related disorders. I am Moloch settee. I'm associate professor at UCSF Benioff Children's Hospital, Oakland. Many of you may know me. I do run the celiac clinic in the East Bay. My disclosures I receive royalties from up to date. My objectives today is to review the changing clinical presentations of celiac disease to discuss it and examined the current guidelines for screening and diagnosis, discuss gluten and gluten related disorders, and review the gluten free diet and monitoring challenges. As many of you know, celiac disease is now recognized as a common food intolerance and is noted to be a unique auto immune disease. Found in 1% of the American population. It is an immune mediated and theropod the that has a well recognized environmental trigger of gluten and a well recognized auto antigen tissue. Trans Bhutanese uh, we know that eliminating the trigger leads to complete resolution of the disease, and it occurs in genetically susceptible individuals who carry the H. L. A D two or D Q. Eight molecules. It was first described by Samuel G. Who's credited in 18 88 stating that celiac disease is a kind of chronic indigestion met in persons of all ages but especially apt to affect Children between one and five years of age. Signs of the disease air yielded by the feces and the onset of the disease is usually gradual. Caxias a constant symptom, and the belly is mostly soft, often distended. But it was really in the in this early state that they noted that this was a rare condition, and it was highlighted by this malnutrition and Cacak CIA that carried a high mortality rate in the 19 twenties. It was Sydney Hawes who another pediatrician who recognized that there was a dietary solution in placebo controlled trials. They gave eight Children bananas and two were not treated with us. Onda later died. For decades, this became the treatment of choice and prevented many deaths. This diet, uh, specifically excluded bread, crackers, potatoes and all cereals is really in 1953 Another pediatrician, the setting of World War Two, where there was a severe bread shortage in the Netherlands, they saw that there was a beneficial side effect of improving the mortality rate of celiac disease. This strengthen the link to wheat and he is given the term of pioneer of the gluten free diet worldwide worldwide wheat, rice and maize air, the most widely consumed foodgrains. Introduced over 10,000 years ago, we is now the most widely grown crop and is available as processed wheat flour used in the production of baked goods, pastas, noodles and alcoholic beverages. We contains about 75% protein, which is shown to be mostly glide ins and glutinous, which conform polymers called gluten. It is in various gluten rich cereals that are capable of eliciting the celiac disease. Immuno Jenness ity in patients, both gluten ins angle. I didn't have certain amino acid sequences that act as epitaphs for celiac disease, and these air termed the ImmunoGen IQ peptides or the anti gen peptides, which I will speak of more Laker. In this diagram, you can see how gluten is a very elastic protein. It is the main structural protein in wheat and contains the toxic protein fractions mentioned previously. Glide in and gluten ends. Uh, they form a very elastic consistency to dough and create stability and softness in the small bowel. Gluten is partially digested to glide in peptides and in this diagram, you can see the ville I and where Glidden is gluten is broken into glide and fragments. These are crossing the epithelial barrier and are acted upon by tissue transfer terminates, which create the damn undated glide in which is the ImmunoGen IQ portion of the peptides. It is then recognized by H L E. D two or D Q eight bearing antigen presenting cells that present thes to to the CD four positive T cells. This then leads to activating the CD eight positive inter epithelial lymphocytes, which caused damage to the epithelium, uh, leading to villus atrophy and villas Blunting. This also leads to B cell activation, which develops the auto antibody that is a hallmark of the disease caused called tissue translate Tamponnaise E G. A. It is this auto immune response that leads to the developing the classical severe G. I presentations that were described in early descriptions that are less often seen. Now. Aziz, we are becoming more aware of this condition in these classical G I symptoms. It is chronic recurrent diarrhea, abdominal distension, poor appetite, malnutrition, abdominal pain, vomiting, irritability and muscle wasting is seen the trending presentations of celiac disease over the years, and especially in research wrist rich countries. We're seeing that the clinical manifestations of celiac disease maybe more heterogeneous, including the typical G I symptoms has seen here with malabsorption tive symptoms of diarrhea, but as well as a myriad of extra intestinal disorders. So with improved testing, recognition and case finding things, particular study noted that two thirds of their patients had normal body mass index. Okay, more of the newly diagnosed we're presenting with the nonclassical diagnosis symptoms rather than the, um, classical malabsorption of symptoms. Uh, and many were actually a symptomatic and found on screening or incidentally. And, uh, in general, these patients were found to have less severe mucosal disease than the classical, uh, celiac patients, and their average age was noted to be higher. This data supports the notion that screening guidelines should not rely on generally malabsorption of symptoms alone in the public arena. It has been raised that screening may may well be a good question if all Children are most Children should be screened, however, due to cost benefit studies that has not panned out as being useful. It is known that, however, that symptomatic or untreated disease is associated with elevated morbidity and mortality and impressive impaired quality of life in Children who are untreated. It can affect their growth, nutrition and pew Bertel development. So with this, I'm gonna start with our first case scenario, a 14.5 year old girl presented to the, uh, the endocrinology clinic with Amon Urea and delayed puberty. She is active in cheerleading and gymnastics. She does suffer from joint and musculoskeletal pains, but she denies all g I symptoms. Uh, in terms of her growth chart, you can see her weight is quite low in her hi appears to be, uh, normal. Uh, laboratory studies were done that noted a normal at CBC, CMP said Ray and CRP a normal beta hCG and thyroid studies. Her FSH was elevated at 98. Within Esther dial less than six. Her T four was normal. Her thyroid peroxide, base antibodies and thorough globulin antibodies were negative. Her tissue transfer Tamponnaise I G A was quite high as well as her total i g a. Being normal with a elevated and a museum antibody. Further studies were done that revealed a normal carry a type 46 x x she did have a G I referral by the endocrinologist and endoscopy confirmed the diagnosis of celiac disease, a gluten free diet, and hormone replacement therapy was initiated. What you can see is a with this therapy, her weight and height improved significantly. There is an increased frequency of celiac disease, ah noted more than the general population, which is 1% currently. Uh, where the general population has a 40% rate of having a chill, a duty to or D Q A. Those with genetic syndromes such as Down's Turners and Williams. There's a much higher rate or frequency of celiac disease up to 12 times and down syndrome, uh, up to three times more in Turner's and Williams up to 10 10% among family members. It is seen that, uh, celiac disease can also increase tenfold up Thio 10% in systemic worldwide Review of data published in 2018. This image represents the worldwide celiac disease zero prevalence rate in the countries that reported data prevalence values were stratified into these four different categories, with the lightest gray being 0 to 25th percentile on all the way up to the 76 to 100 percentile and the lowest and highest percentiles included countries that had very low national prevalence rates of point to 2.8 up Thio 8.5% respectively. So the Sarah prevalence of celiac disease was observed to be highest in these particular countries in Asia, Northern Africa up to 8.5% as noted earlier. Uh huh, the lowest was noted in in sub Saharan Africa, where we know that, um, the there is less prevalence of the D Q two haplotype, uh, as well as lower wheat consumption. In a national pathology database review of four and 50,000 duodenal biopsies, they saw that there was villus atrophy, uh, in in various ethnic groups within this country. Uh, in in this analysis, they found that the prevalence here seen here, um, undergoing duodenal biopsy was an overall rate of 1.7%. So more than than the 1% previously mentioned, um, the risk was lower in patients identified as South Indian East Asian on Hispanic, whereas compared with other Americans such as the North Indian in Jewish Middle Eastern populations, Uh, in terms of the North Indian populations, it was seen in mostly the Punjabi Um subject of the North Indian populations, with a standard of one in 40 that was identified. Other risk factors have been looked at with celiac disease and this a cohort of Type one diabetics studied by the teddy group, the environmental determinants of diabetes type one diabetes. They saw that several environmental factors were, uh, involved in the incidence rates of celiac disease, including geography, seasonality, the amount of gluten intake, uh, infectious episodes, their genetics, female gender and first degree relatives. Further evaluation of these of this particular study group showed the d R three or did you to home ozai Ghous having the highest risk factor. Um, Dick, you ate first degree relatives in this. This was primarily being Swedish, um, female. The amount of gluten that was being intake and those born in spring. And then you start seeing some negative risk factors. A swell, Um, yeah, So our next case scenario and we will have our poll question after this. In this case, this is a 15 year old girl she presented with fatigue, rapid waking poor school performance for the past 1.5 years on, and with occasional abdominal pain. constipation, bloating. She also complains of some cold intolerance and muscle aches on some sleep issues. Great. So in this, uh, a, uh, full panel was sent on, and agreeably, this is not the classic symptoms that you would see with celiac disease. However, in this case, celiac panel was sent and was found to have a tissue. Translator terminates I G A of greater than 100 as well as, ah, auto antibodies for, uh, thyroid peroxide days and an elevated TSH referrals were made thio, gastroenterology and endocrinology. She had an upper endoscopy that confirmed the diagnosis of celiac disease. She was started on thyroid hormone replacement and a gluten free diet. So we see an increased prevalence of celiac disease, an autoimmune conditions. In fact, up to 15 25% in some studies of celiac disease have, uh, autoimmune thyroid itis, and 40% will have anti thyroid antibodies. Are there conditions that are seeing or type one diabetes up to 10% a Z mentioned thyroid itis not immune. Hepatitis up to 8%. Addison's disease a swell as arthritis. Uh, other autoimmune liver diseases, uh, show grand syndrome can be up to 15% Andi idiopathic dilated cardiomyopathy. A swell as I G and F apathy. A common denominator tends to be that they all have h l a d d two or D. Q. Eight. Our next case scenario is an 11 year old girl who has a several year history of recurrent abdominal pains, known lactose intolerance and increase crap gas. And she's been seeing her pediatrician for several years. For these conditions, she has normal growth parameters. And finally, lab work was done showing a tissue shone through. Tamponnaise idea of 25 An end a medial antibody i g A. That was negative and a total i g a of 81. She has a family history of thyroid disease. No family history of celiac disease on a referral was placed to see the gastroenterologist. Uh, endoscopy was done, and she had, uh, visual findings of furrowing and oedema in the esophagus and histology that showed over 200 years. And it fills per high power field in the distal eyes, esophagus and 50 years NFL's per high power field in the mid and proximal esophagus, knowing that normally there is zero s NFL's. Um, this is what what we call us NFL Like esophagitis, her duodenal biopsies were completely normal. So establishing the diagnosis the North American Guidelines, which is from the a g A and NASA, began, uh, require a positive celiac serology while on a gluten containing diet which includes tissue translate terminates I g a and A total I g a the d m undated glide and I g is, uh, important in less than two year olds and the tissue chance contaminates i g is important. Thio add thio i g a deficient, um Children. The endoscopy with biopsy should be done while on a gluten containing diet where 4 to 6 biopsies are obtained from the distal duodenum and separate biopsies were obtained from the bulb of the which is the first part of the small intestine characteristic his do pathology of partial or complete villus atrophy. A crypt hyperplasia and increased intra epithelial lymphocytes should be identified on these biopsies. Mhm. So again, initial testing is a total i g a. With the tissue transfer contaminates i g A, which is more accurate than other test combinations. Children who have the tissue transfer terminates i g a below 10 times the upper limit of normal should undergo biopsies to decrease the risk of false positives. Uh, the European society put out guidelines several years ago recommending that those who had elevated T T g I G over 10 times the upper limit of normal could be considered to go without biopsy at. So we here in North America have not embraced those guidelines, mainly because the increased, um, incidents in Europe allows them to have a bit more flexibility in this. Whereas here we do see frequently false positives and so do need to still consider doing a biopsy. Eso Who can we diagnose without biopsy? A symptomatic child who has a high serum i g a level with with a tissue transfer terminates i g a greater than 10 times the upper limit of normal A and a musical antibody i g a. That's positive, along with another tissue transferred 10 minutes i g. A on a second serum sample. But I think the most important part is the third, which is those who are prepared to commit to the treatment. Um and, uh, and often this is a dyke. This is a discussion that we have in our clinic in terms of long term, uh, need for confirmation have this chronic condition, so controversies still exist. The endoscopy is important in terms of clarifying the degree of inflammation, but also ruling out other conditions that seem to be found in co occurrence with celiac disease, such as a Crohn's disease and Eastern filic G I conditions. The endoscopy with biopsy shows duodenal scalloping A scene here, a swell a SSM mosaic pattern. You will see occasionally flattened folds. Um, we do get 46 biopsies from the distal duodenum and the characteristic history pathology of partial villus atrophy, crypt hyperplasia and the the excess pinkish color, which is the increased interrupted Thalia lymphocytes, should be seen under my my cross api in order to confirm this diagnosis. When should we do the genetic test? The genetic test is done to allow celiac disease to be ruled out, so it's important to do. In screening are first degree relatives. So if a child is diagnosis, then all siblings and parents are recommended to also undergo testing, including the T T G. I. G. A. And the genetic test will help to rule out the potential, um, for long term need for screening in doubtful cases. We use this, uh, if the biopsies don't correlate well with the with the serology tests, and we can do it to see if there is a need for further testing When the patient presents to us already on a gluten free diet, uh, endoscopy can sometimes be reveal a very patchy sort of disease and maybe missed. Um, the genetic test will allow us to determine if a patient should be put back on gluten in order to proceed with an endoscopy, uh, knowing the genetic and sometimes help provide risk estimates based on the ideals that are present. So we know that homo zegas D U two appears to have a 30 time increased risk as compared Thio uh, the, you know, non Hamas. Agus, uh, the hetero Zika's D two has an eight time increased breast of this estimated prevalence, so it can give you guidance in terms of a long term follow up on how you know how likely is a parent or ah, family member to develop celiac disease. The negative test has a very strong negative predictive value and can help you rule out the potential for developing celiac disease. So challenges to establishing the diagnosis in i g a deficient Children who actually have an increased risk of developing celiac disease to 2%. Uh, d amity, glide and peptide i g and the T t g i G can be used These air not as good as the ttg a but can provide some, um, help in terms of ruling in this condition and those who are already on a gluten free diet, it can be challenging Azaz. Uh, often it is requires several weeks to months in order to, um, show Cyril Lodge serology positive on, um, blood work. Eso a gluten challenge is recommended up to four. 4 to 6 weeks prior to endoscopy is an ideal time point. More is always better. Uh, and in terms of blood, work alone. If if you want to challenge somebody, it should be a least 12 weeks prior to doing blood work to see if they develop antibodies. Potential celiac disease is seeing really in the G. I, um, clinic. They are a serology positive, but have normal biopsies. Uh, and in this subset, we often screen regularly, as it has been shown, up to 40% can progress to active disease. Celiac disease is a multi systemic disease. It affects many different systems. Skin growth. Dentition bone, uh, can affect blood, liver, neurologic issues, joint issues, psychiatric disorders as well as, um, kidneys. Anemia, most commonly as a result of iron deficiency, has been reported in 12 to 60% of newly diagnosed patients. It is the most common systemic manifestation in adult studies. UH, 5 to 8% of adults and up to 12% of Children have, uh, have iron deficiency anemia, and we think it's because of reduced absorption of iron. Vitamin B 12 and folate G I blood loss. Hamal, ASUs and other conditions such as Paradox in Deficiency and Leighton Hamilton Syndrome, which is a lung condition uh, with lung hemorrhage is, um, very rare, Uh, and in in these Children who do have iron deficiency anemia, it's more prevalent in those with severe atrophy In their biopsies versus mild in theropod, the Orel manifestations is quite common. Dental enamel defects, air seen in up to 50% of cases with celiac disease, especially during the onset. If the onset is prior to eruption of of these secondary permanent teeth, eso below seven years of age, so most of this is occurring on permanent teeth. Um, it may be the only manifestation in some of these Children. Recurrent at the stomach. Titus zero Estonia Uh, delayed eruption of primary and secondary teeth is also noted. Kill itis or make a traffic class itis is also seen. Up to 60% of newly diagnosed celiac disease have elevated Trans Am Ennis's um 9% of adults with elevated L T and S T have been shown to have a silent celiac disease. The liver enzymes usually normalized on the gluten free diet. After about six months, I thought to be due to increase intestinal permeability and inflammation as well as bacterial. Despite aosis in the intestine, it too is associate ID with a severe villus atrophy and malnutrition. It is also seen, uh, in 46% of autoimmune hepatitis, so this too should be evaluated for celiac disease effects bone structure. This manifests with low bone mineral density and early onset of osteo paralysis on osteo Malaysia, even in those who don't have intestinal complaints. So, uh, malabsorption nutritional deficiencies secondary hyper parathyroid is, um um and autoimmune diseases affecting the B. M D are thought to be the primary drivers. Over 60% of adults have low bone mineral density, with the 20% in the osteo product range. Gluten free diet and kids have shown to be very effective in reversing low bone mineral density. Um, in addition to physical activity and proper nutrition dermatitis, her better formas is actually a skin presentation of celiac disease. There are granular i g a. Deposits, uh, in the skin. It's more common in adults and older teenagers on its characterized by these symmetric Perrin dick blisters followed by erosions excoriation, sometimes hyperpigmentation, it's usually seen on the elbows, knees, shoulders, barrack, a sacred region and face. The diagnosis depends on demonstrating the typical i g a deposits on skin biopsies. And it is the epidermal TG three that is the target or translate terminates three. Um, you will also find they have tissue transfer terminates I g a positive in their blood on. And they do have, uh, villus atrophy on biopsy on. And like celiac disease, they have a risk of B cell lymphomas. Gluten ataxia is rare. It may have a slight male predominance on onset is typically in middle age on the oh. There are rare case reports of younger ages. There are cerebellum changes, uh, in in these leading to a tax sick symptoms in either upper lower limb gait. Ataxia and dis are three. Uh, in this condition, there is an auto immune response leading to antibody deposition in brain tissue. You can see all ago clonal bands and the CSF and Sara Bell are inflammation. Uh, uh, Anti perkin G cell antibodies and anti tissue transit terminates Six antibodies are seen in blood. There is some improvement with a gluten free diet. However, residual damage may be present even after this eso early diagnosis and recognition is important. So management of celiac disease, a strict gluten free diet is really the, uh, only treatment for this condition. Currently avoiding wheat right and barley is very important. Dietitian and nutrition counseling has shown to be a important part of maintaining good adherence to this therapy routine Follow up is recommended at least annually. Um, as noted in, uh, John ciders, uh, paper published in pediatrics monitoring growth development and bone health. Micro nutrient levels, serology testing psychological assessments, uh, and symptom evaluation as well. Azaz, uh, testing for other autoimmune conditions is clinical remission possible? So this is an important question that we, uh, consider as an open question. There is no validated tools for measurement of endurance in clinical practice. Serology is the only common assessment, but is really validated for diagnosis and not for follow up. So in a recent meta analysis, they showed that 38% of patients had persisting n theropod the at two years after gluten free diet. In this population that had a repeat endoscopy in this, um, the tissue transmit happiness was elevated and or only 43% of that 38. So the tissue transfer terminates and the Indonesia antibody did not correlate very well with dietary compliance reports and raise the questions, um for Is clinical remission possible? So the Sierra logic markers, unfortunately, do not reflect complete healing of the mucosa. Other tests that are now in studies and also in practice is the gluten ImmunoGen IQ Peptide assessment, which is a stool test that is more of a point of care, test to assess presence and concentration of gluten peptides in the stool. It's only a single time point assessment, so that is its main limitation, but it can give you a sense of whether gluten has been ingested. Um, there is no other non invasive measure of endurance available. Currently, recent large gales to systemic review of 49 pediatric studies cited that adherence rates were between 23 98% over time. There's been no increase in rate of endurance over time. Despite the improvement in accessibility. Some of the barriers that have been noted are taste and lack of availability of foods, higher expenses for gluten free alternatives. Parents will knowledge seemed to play a role in the adherence membership to groups or societies and close physician follow up barriers that seem thio be noted were misunderstandings about the disease. Difficulty in educating others, um, and adolescence. Complications of untreated celiac disease include persistent G I symptoms. Risk of developing other autoimmune diseases. Uh, in some rare cases, into susceptible has been seen. Do you do the intestinal inflammation? Osteo opinion, Osteoporosis? Uh, refractory. Celiac disease is where the inflammation thio trigger no longer requires gluten presence for celiac inflammation to persist on. This is seen often in the middle aged population that have not been a adherent to their diet on then cancer risks, of course, exist, such as the inter apathy associate ID T cell lymphoma, um, and other cancers like non Hodgkin's anthem on. This shows an increased overall odds ratio for the interrupted the associate ID T cell lymphoma. There's also an elevated mortality rate that has been shown and diagnosed patients who chose not to follow the diet. There was this X fold increase in the systemic mortality rate and undiagnosed patients. Subjects who had elevated anti TTG had a significantly increased mortality rate up to three times. Um, mostly due to intestinal cancers. Follow up mortality studies indicate no change, unfortunately into the a systemic mortality rate in recent years. Which of the following statements about the gluten free lifestyle is false? Patient compliance is a concern. Sources of gluten are always easily detected. Individuals with celiac disease require ongoing education and support individuals with celiac disease and their families should be encouraged to participate in support or advocacy groups. Yes, very true. So you guys did great sources of gluten are always, uh, easily detected is absolutely false. Okay, eso what is gluten free? The FDA labeling standards were determined in 2004 with the Food Allergen Labeling and Consumer Protection Act. It permitted the voluntary use of gluten free on packaged goods. So it's really only for packaged goods, uh, and voluntary meaning they can. If they want Thio, get the their food product, test it. It has to be an official test. A sandwich Eliza test has a cut off of sensitivity of 20 parts per million of gluten, Um, and so those that have the particular label, which they're currently in. A transition phase of this certified gluten free to this certified gluten free label, um, have been tested through the FDA protocol. The gluten free diet is costly, complex and can be challenging, uh, and requires strict avoidance of these sources of wheat, right and barley as well as cross contamination. The gluten free diet has many benefits for celiac patients that air seen in early, medium and long term uh, stages in the early stages. Some of the G I symptoms are noted to be reduced. Um, there are increased food costs that are often brought up. Well being is often improved but may also be impaired. Um, there's food related anxiety that seems to her on DSO requires a lot of, uh, kind of counseling through that in the medium term, what we see is a lot of the deficiencies are corrected. Uh, and we start seeing some symptom response in some of the non G I sort of symptoms such as headaches or joint pains or fatigue or canker sores. Many often at that point start regaining their weight. Um, in the long term, we do note some improvement in bone health eso we do try to monitor that there is a decreased fracture risk associated with that. Um and, of course, the, uh, more remote kind of long term issues. There's decreased risk that has been shown in long term studies for cancer, lymphoma, increased survival rates. Theoneste Fortunate side effects air the weight gain that sometimes seen, um, and needs to be also counseled with, uh, trying not to replace every gluten product with a gluten free product. As these are often double and calories and social restrictions and isolation, um, is often a discussion point with, with our adolescence, a common discussion point with patients include how much gluten is safe. So in uh, controlled studies, it was seen that 10 mg of gluten was sufficient to cause, uh, endoscopy diagnosed intestinal inflammation on dso. This remains the standard 10 mg on this is ah in this website, which I think is on the on the last page as well, which I'll share with you, uh, shows a visual approximation of what 10 mg of gluten can look like compared to quarter. The role of the dietitian is crucial in monitoring and reinforcing the diet is this is really the only current treatment for this chronic condition the dietitian addresses. Um, the psycho social status on helps with counseling. Um, and we also have a social worker that follows up with patients on. Does some screening? Uh, well, Azaz assists with financial constraints and family support will be routinely monitor nutritional status and review common sources of cross contact, which is quite detailed. It can be even in fields where grains are grown in adjacent fields, factories where processed foods can sometimes cross contaminate on at home shared toasters, cutting boards, etcetera, as well as restaurants where serving utensils and food handling can be a common source of cross contamination. Gluten related disorders has been the overarching, um, kind of classifications system described in 2012 by, uh, Onasa pony. They they attempted to describe the other immune portion, which is what we've discussed already from allergy and then the non auto immune or non allergic groups. Um, so I will talk a little bit about this as well as this. We allergy is an I g. A mediated process. It's primarily directed towards the wheat proteins and the Emily strips and inhibitors that air in wheat. And these are not necessarily in other grains like rye or barley, although there can be cross reactivity, uh, in wheat allergy, you have a teach to sell response that leads to Aisle four, Aisle five and I'll 13. They will have local manifestations. A zoo well, a severe with the potential for severe systemic symptoms as well. Eso vomiting, abdominal pain but also er, to carry a and geo deem a handful axis. Uh, this is, uh, worked up typically by the allergist. Um, and some patients carry a EpiPen. It's quite rare in comparison, Thio Celiac Disease, Baker's asthma is a type of wheat allergy. Were inhaled wheat leads, Thio asthma symptoms and, uh, we dependent exercise induced and a full axis is uh uh also fairly rare condition, but it is sometimes identified if there's index of suspicion where there's ingestion of wheat and followed by mild exercise that leads to an an awful Actiq reaction. Eso the dose of the protein. Introgen does play a role. The tests, uh, that air done or to look for specific I g against wheat and specific wheat allergens. A swell azi Ah, in office placebo controlled we exercise challenge done by the allergists. Non celiac gluten sensitivity has a bs like symptoms that occur after ingestion of gluten or wheat hover in this condition. They have negative allergy tests to wheat negative celiac serology Normal histology, though occasionally have anti glide in antibody positive. There are clinical symptoms that overlap with celiac disease and wheat allergy. Uh, in this condition, there is resolution with a gluten free diet and, uh, confirmatory, uh, diagnosis is with a double blind placebo controlled diet. There is some suspect suspicion that it is ah, faud map sort of response to wheat fruit towns, which are a Z wheat, has a tremendous amount of carbohydrate fraction in it, um, and so may trigger gas production through that the gluten free search trend is very popular. As you can see, it's very sustained. Uh, this is a Google search term, and it can tell you that overall gluten free has been searched several times more than celiac disease, which is the Orange Line. And so the the general population is very interested. The gluten free diet eyes thought to be healthy and without a downside, is that fact or fiction. We say it's false, and the reason is only 5% of gluten free breads were fortified with all four mandatory fortification nutrients such as calcium, iron, nice and anti Simon. 9% of gluten free bread products were fortified with three of those, uh, these micro nutrients, and 28% were fortified with two. Uh, the other belief is gluten is toxic. That, too, is false. It is a important protein in our diet and provides essential nutrients and immuno assets. A gluten free diet is appropriate for first degree family members and for infants at risk for developing celiac disease. Also false as it can sometimes mask the development, absolutely act disease. So take home points whom to screen screen all first degree family members, uh, screen Down syndrome Type one diabetics, Hashimoto's Turner Syndrome, iron deficiency anemia and those with persistently elevated liver enzymes. How do you screen the T T G I G. A and Total I G A. The Children Lesson To would also need the G p i G for I J deficient. The TTG is recommended, and if you do have a positive screen test result, please refer to G I before having them start a gluten free diet to confirm diagnosis. Long term follow up is a a challenge where up to 50% have been shown to be lost. To follow up, we recommend annual or twice yearly routine monitoring, as this has shown to be good for adherence to the diet and for long term morbidity and mortality risks. Dietitian and psychologist leads Eliot clinics have shown to be the most helpful in reinforcing adherence. There is no single validated tool to measure this on. We know poor adherence leads to poor growth outcomes. So are open questions, which I've mentioned previously at how to best follow up celiac disease patients. This remains open. How many have persistent villus atrophy on what is the morbidity risks related to this the roles of medical therapies. There's many drugs on therapeutics in trials, um, in the adult population and potential in the pipeline as well, as well as other alternative complementary strategies s such as probiotics, etcetera. This is, um U C S F pediatric G I yeah, team and how to refer.