Separate the wheat from the chaff when it comes to food allergy, food intolerance, and celiac disease. Featuring renowned gastroenterologist and current president of the American Gastroenterological Association, Dr. Sheila Crowe MD FRCPC FACP FACG AGAF, we discuss how to differentiate a food allergy from an intolerance, what diagnostic testing is appropriate, and why fructans might be the real culprit in patients with ‘gluten sensitivity’.
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Written by: Sarah P. Roberts, MPH
Guest: Sheila Crowe, MD
Hosts: Matthew Watto, MD; Stuart Brigham, MD; Paul Williams, MD
Producers: Sarah P. Roberts, MPH and Chris Chiu, MD
Editor: Matthew Watto, MD
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- A 40 year old previously healthy woman is evaluated for a six-month history of intermittent abdominal bloating, diarrhea, and fatigue. No recent travel or infectious exposure, and tests are negative for C. difficile and giardia. You suspect celiac disease. Which of these antibodies is the most appropriate first test?
- Serum IgE levels
- Serum IgG levels
- Tissue transglutaminase antibody (tTG)
- Antigliadin antibodies
- Deamidated gliadin peptide (DGP)
- Which of the following food reactions are immune-mediated?
- B and D only
- A and D only
- A 52 year old male presents to your office as a new patient and tells you his past history is significant for hypertension and “celiac disease”. He has long-standing gastrointestinal symptoms of bloating, flatulence and intermittent diarrhea. He eats ice cream regularly without exacerbation of his symptoms. For the past 3 months he notes improved symptoms on a gluten free diet though he admits tTG serology and biopsy for celiac disease were negative earlier this year. What is the most likely diagnosis?
- Lactose intolerance
- Celiac disease
- Fructan intolerance
- Wheat allergy
Answers can be found above links from the show.
Case from Kashlak Memorial:
A 34-year-old woman presents to her primary care physician complaining of frequent gastrointestinal distress, including loose stool, bloating and abdominal cramps. The symptoms have been going on for several months and the patient has lost ~5% of her total body weight. The patient is not pregnant, no recent history of antibiotic use, and no relevant travel history. Her sister is a nutritionist and told her she might have celiac disease and should avoid eating gluten. She wants to know how to get tested for celiac, and if she should stop eating wheat.
Dr Crowe’s take home points:
- There is a difference between a food allergy (which is immune-mediated) vs. intolerance (other underlying mechanisms).
- Send the patient to an allergist when hives, wheezing, asthma or anaphylaxis symptoms are present.
- Family history of autoimmune disease or allergy is important
- Make sure you have a good RD to work with/recommend to your patients
- The difference between a food allergy and an intolerance is its immune basis. e.g. Celiac disease = non-IgE related immune response. Shellfish allergy = IgE mediated. Lactose intolerance = non-immune mediated adverse reaction to food. [Crowe. Am J Gastro 2013]
- Classifying reactions to food: A ‘sensitivity’ is synonymous with ‘intolerance’ while hypersensitivity suggests allergy. -Dr Crowe
- Celiac: Serology and biopsy remains positive for up to 3 years even on a gluten free diet!
- Wheat allergy: IgE mediated release of histamine from mast cells and basophils can cause a serious, even fatal allergic reaction. Typically seen in young children, and most grow out of it by age 14. Rarely, some adults will have wheat allergies. -Dr Crowe
- Non-celiac gluten sensitivity (NCGS): Mechanism is “poorly understood”, may actually be due to fructan intolerance, and often responds to treatment with a low FODMAP diet (Skodje et al. Gastro 2018).
- Peanuts and tree nuts are the major causes of food-allergy related death in the U.S (Bock SA et al. J Allergy Clin Immunol 2001). Top 8 causes include: milk, soy, eggs, wheat, peanuts, tree nuts, fish and shellfish (Allergy Stats AAAAI.org accessed 5/10/18).
- It’s safe for the patient with celiac disease to eat a cow or chicken that has consumed gluten! -Dr Crowe
Definitions and Classification
- Food intolerance: Many underlying mechanisms including metabolic (e.g. lactose), physiological (e.g. legumes, fatty foods), psychological, food toxicity (e.g. food borne pathogen), or idiosyncratic (Crowe. Gastro 2013).
- Take a thorough history: Ask about dietary intake: fructose, gluten, dairy? What symptoms are you experiencing? What triggers your symptoms? Any rashes? Time of day? Family history of food allergy? Personal or family history of autoimmune disease? -Dr Crowe
- Common food allergy/intolerance symptoms are bloating, diarrhea, nausea, dyspepsia, abdominal pain, and cramping. Note: Nocturnal symptoms, rectal bleeding, unintentional weight loss above 10% bodyweight = red flags suggesting a non-functional disorder. –Dr Crowe
- Celiac disease: A non-IgE mediated food allergy w/symptoms that overlap with irritable bowel syndrome (IBS), and other functional bowel disorders (Crowe. Gastro 2013). Differential diagnoses are lactose intolerance, giardia, fructose intolerance, or post-infectious enteropathy. -Dr Crowe
- Extraintestinal manifestation of celiac disease (from DynaMed Plus) are common and may include: failure-to-thrive, stunted growth, delayed puberty, chronic anemia, decreased bone mineralization (osteopenia/osteoporosis), dental enamel defects, irritability, chronic fatigue, peripheral neuropathy, gluten ataxia, arthritis/arthralgia, amenorrhea, increased AST, ALT (Curr Gastroenterol Rep 2006 Oct;8(5):383)
- Dermatitis herpetiformis (DH) – extensor rash (elbows, back of head, buttocks, over the knees), very itchy, and often excoriated at time of presentation. Confirm by biopsy. Pathognomonic for celiac.
- Gluten ataxia warrants a neurology consult.
- Even if the patient is already eliminating gluten from their diet, there is still a wide window for serology testing/pathology; many people following a strict gluten free diet will still have abnormal pathology results for 1-3 years. -Dr Crowe
- Check CBC, CMP. Take a focused history including triggers and what patient has tried so far. Check tTG IgA as first step. Avoid tTG IgG, which is much less sensitive. Only check tTG IgG (along with deamidated gliadin peptide (DGP)) if patient has IgA deficiency. Antigliadin antibody is no longer used due to poor sensitivity/specificity. Positive serology can be followed to track disease activity. -Dr Crowe’s expert rec
- To differentiate celiac from non-celiac conditions, keep in mind that a biopsy done on a non-celiac patient would not show blunting of the villi nor a positive TtG result.
- Rule out lactose intolerance: by having patient drink skim milk, which has lots of lactose but not fat. Some people have intolerance to the fat present in milk, triacylglycerol. If the patient can drink 8-12 ounces of skim milk and doesn’t get diarrhea within an hour, then it is not true lactose intolerance.
- Genetic testing helpful in three settings: 1.) for children of patients with celiac disease to see if they have the genes; 2.) patients who have suspected refractory celiac disease. If genes for celiac are absent then patient probably has another enteropathy that is mimicking celiac e.g. drug-induced enteropathy. -Dr Crowe
- The antihypertensive, Olmesartan, is associated with drug induced enteropathy that presents as “refractory celiac disease”. As soon as a patient discontinues the drug, their symptoms improve! –Dr Crowe
- Food allergy testing: Start by taking a good history. Supplemental food allergy testing may include: skin prick testing and in-vitro testing for specific IgE-antibodies, and oral food challenges (Gerez IF. Singapore Med J 2010).
- If you think the patient has an allergic disorder, send them to allergist. If you think it’s GI related, send them to a gastroenterologist. For all these diseases, a registered dietitian (RD) is very important when enacting diet changes.
- “Voodoo” testing: Beware of pseudoscientific tests for food allergies. The NIH/NIAID Guidelines J Allerg Clin Immunol 2010 section 184.108.40.206. on nonstandardized and unproven procedures states:
Guideline 12: The EP recommends not using any of the following nonstandardized tests for the routine evaluation of IgE-mediated FA:
- Basophil histamine release/activation138,139
- Lymphocyte stimulation140,141
- Facial thermography142
- Gastric juice analysis143
- Endoscopic allergen provocation144–146
- Hair analysis
- Applied kinesiology
- Provocation neutralization
- Allergen-specific IgG4
- Cytotoxicity assays
- Electrodermal test (Vega)
- Mediator release assay (LEAP diet)
- First, ask the patient what they have tried so far.
- A recent RCT of IBS patients assigned to eat three types of food bars–gluten, placebo bar, fructan bar showed that patients who had the worst symptoms were those who consumed the fructan bar (Skodje et al. Gastro 2018). This suggests that patients who lack the genetic, serologic, or histologic markers for celiac disease, but improve on a gluten free diet probably have fructan intolerance.
- Elimination diets: Not intended to be permanent. Alter the microbiome by cutting out starches/sugars, then gradually re-introducing foods to identify a patient’s triggers. Once they feel well, patients reintroduce foods to maintain a diverse diet. -Dr Crowe
- Examples of elimination diets include the low FODMAP diet and the paleolithic/’caveman’ diet. Dr Crowe recommends consultation with a registered dietician to enact these complex diet changes.
- FODMAP diet: Low in lactose, gluten, sugars and starches. The downside of the low FODMAP is that we don’t have the data yet to understand long term outcomes.
- 00:00 Disclaimer
- 03:35 Getting to know our guest, book recs, and career advice
- 10:35 Clinical case
- 11:40 Defining allergy, intolerance
- 14:05 Food intolerance and FODMAP
- 18:02 Taking a history in patient with potential food allergy vs intolerance
- 21:34 Dermatitis herpetiformis, gluten ataxia, and extraintestinal manifestations of celiac
- 26:12 Diagnosing celiac disease
- 30:53 Next steps if celiac testing is negative; lactose, fructose intolerance, IBS
- 33:48 Non-celiac gluten sensitivity (NCGS)
- 37:48 Study of NCGS
- 40:41 Olmesartan and drug-induced enteropathy
- 43:38 Dieticians, dietary recs, elimination diets
- 48:10 “Voodoo” testing
- 52:36 Counseling patients on diet
- 54:35 Take home points
- 55:50 Outro
Disclosures: Dr. Crowe reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
Goal: Listeners will gain a working knowledge of how to identify and treat common types of food allergies/intolerance, including celiac disease.
After listening to this episode listeners will…
- Differentiate between a food allergy and a food intolerance or sensitivity
- Describe enteropathic and non-enteropathic symptoms of food allergy
- Distinguish celiac disease from non-celiac gluten sensitivity
- Order the appropriate tests when celiac disease is suspected
- Differentiate lactose intolerance from triacylglycerol intolerance
- Provide basic recommendations to modify a patient’s diet when food allergy or intolerance is present
Answers: 1) c, tTG 2) f, A and D only 3) c, Fructan intolerance (probably mistakenly called non-celiac gluten sensitivity)
Links from the show:
- Celiac Disease for Dummies by Dr. Sheila Crowe and Dr. Ian Blumer
- Skodje, Gry I. et al. Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-Reported Non-Celiac Gluten Sensitivity. Gastroenterology , Volume 154 , Issue 3 , 529 – 539.e2
- Celiac disease article DynaMed Plus
- Dietary Proteins and Functional Gastrointestinal Disorders by Boettcher and SE Crowe Am J Gastroenterol 2013
- Stanford University Medical Center Low FODMAP diet handout
- Review of refractory celiac disease
- Study on Olmesartan association with refractory celiac disease
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