Diagnosis and Management of Celiac Disease Monik Kowalczyk

Objectives       

Epidemiology Pathophysiology Clinical Presentation Diagnosis Management Monitoring Complications

Celiac Disease  

Villous atrophy of the small intestinal mucosa Malabsorption of nutrients after the ingestion of wheat gluten

Epidemiology of Celiac Disease 

The true prevalence remains unknown 

   

1% in US

Occurs primarily in whites of northern European ancestry Also is found in areas to which Europeans have emigrated Increased prevalence in family members Slight female predominance

The Spectrum of Celiac Disease 

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

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Classic or typical celiac disease  Enteropathy with the classic gastrointestinal symptoms of malabsorption Atypical celiac disease  Enteropathy with only extraintestinal symptoms Silent celiac disease  Fully expressed enteropathy found after serologic screening in asymptomatic patient Refractory celiac disease  Does not respond to at least six months of a strict gluten-free diet

The Spectrum of Celiac Disease 

Latent celiac disease Celiac disease was present before, usually in childhood, the patient recovered completely with a gluten-free diet, remaining "silent" even when a normal diet was reintroduced  About 20 percent of such patients continue to have latent disease into adulthood  Others re-develop variable degrees of villous atrophy 

The Spectrum of Celiac Disease

Pathophysiology 



Immune disorder that is triggered by an environmental agent (gliadin) in genetically predisposed persons Results from the interplay of genetic, environmental, and immunologic factors

Pathophysiology 

Genetic 



Environmental factors     



HLA-DQ2 and HLA-DQ8 are the strongest and bestcharacterized genetic susceptibility factors

Gluten Timing of gluten introduction Mode of delivery Duration of breastfeeding Microorganisms

Immunologic 

Adaptive and innate immune systems dysregulation

Endoscopic Appearance   

Absence of duodenal folds Multiple fissures Scalloping of mucosa 

Not specific for celiac disease     



Eosinophilic enteritis Giardiasis Amyloidosis Tropical disease HIV enteropathy

The mucosa of celiac disease often appears normal at endoscopy

1. Severe villous atrophy 2. Crypt hyperplasia 4. Increased lymphocytes in the lamina propria and epithelial cell layer 5. After 6 months on a strict gluten-free diet. Well-formed villi and a return of the mucosal architecture toward normal.

Modified Marsh Classification Increased IEL

Crypt hyperplasia

Villous atrophy

Type 0

no

no

no

Type 1

yes

no

no

Type 2

yes

yes

no

Type 3a

yes

yes

yes (partial)

Type 3b

yes

yes

yes (subtotal)

Type 3c

yes

yes

yes (total)



 



The length of small intestinal involvement varies among individual patients Correlates with the severity of clinical symptoms Proximal intestine is usually the most severely involved Exclusive involvement of the distal small intestine can occur

Clinical Features 

In the past, celiac disease was perceived to be a pediatric disorder, but the diagnosis now is being made increasingly in adults



Mean age at presentation: 45 years



Many adult patients have short stature





Possible that celiac disease can develop for the first time in adult life 25% of cases diagnosed in patients older than 60 years

Gastrointestinal Symptoms 

Diarrhea 

Usually episodic Can have up to 10 BMs per day Steatorrhea



Can suggest the presence of complications

 

    

Vague abdominal discomfort Severe abdominal pain can occur Abdominal bloating/abdominal distention Excessive amounts of malodorous flatus Severe recurrent aphthous stomatitis

Malnutrition   

Weight loss Short stature Deficiencies Fat soluble vitamins: ADEK  Iron  B complex (B12, thiamine)  Folate 

Extraintestinal Symptoms

Skeletal 

Osteopenia/Osteoporosis 

> 70% of patients with untreated celiac disease have osteopenia



Arthritis



Symptoms 



Bone pain

Pathophysiology   

Impaired calcium and Vit D absorption Binding of calcium and magnesium to unabsorbed dietary fatty acids Inflammatory mediators

Hematologic Symptoms 

Anemia 



Coagulopathy 



Iron, folate, vitamin B12, or pyridoxine deficiency

Vit K deficiency

Thrombocytopenia Hyposplenism/Splenic atrophy of unknown cause  Thrombocytosis 

Neurologic Symptoms 

Peripheral neuropathy 

Deficiencies of vitamins such as vitamin B complex vitamins 



Ataxia 

 

 

B12 and thiamine

Cerebellar and posterior column damage

Demyelinating central nervous system lesions Seizures Pathophysiology unknown Often irreversible with gluten withdrawal

Muscular 

Atrophy 



Weakness 



Malnutrition due to malabsorption Generalized muscle atrophy, hypokalemia

Tetany 

Calcium, vitamin D, and/or magnesium malabsorption

Gynecologic and Obstetric Symptoms   

Amenorrhea occurs in 1/3 of women Menarche is often delayed Infertility Common to become pregnant shortly after commencing a gluten-free diet  Unfavorable outcomes of pregnancy 

Recurrent spontaneous abortions  Intrauterine fetal growth retardation 

Male Reproductive Problems  

Impotence Abnormally low sperm count

Hepatic 

Mild chronic elevation in serum aminotransferases  

AST 29 to 80 ALT 60 to 130



Hepatic dysfunction usually reverses on gluten-free diet



Associated with advanced liver disease    

Primary biliary cirrhosis Autoimmune hepatitis Primary sclerosing cholangitis Congenital liver fibrosis

Other GI Disorders 

Inflammatory bowel disease



Microscopic colitis Mild small intestinal lymphocytosis and partial villus atrophy are common in both lymphocytic and collagenous colitis  Mild colonic lymphocytosis occurs in many patients with untreated celiac disease and may improve on gluten-free diet 

Dermatitis Herpetiformis  

Intensely pruritic skin eruption characterized by inflammatory papules and vesicles Due to the pruritus, excoriations and erosions are often the most prominent clinical manifestations

Dermatitis Herpetiformis Common sites: 

Elbows



Forearms



Knees



Buttocks



Back



Scalp

Dermatitis Herpetiformis 

Associated with a mild patchy enteropathy indistinguishable from celiac disease  



Tends to be less severe than celiac disease Only a minority of patients have intestinal symptoms

Diagnosis 

Biopsy perilesional skin 



Skin close to a lesion but not affected by blistering

Immunofluorescence of granular or speckled IgA deposits

Dermatitis Herpetiformis 

Two very closely related gluten-sensitive disorders but nonetheless distinct clinical disease entities  



Most patients with DH have at least latent celiac disease Less than 10% of patients with celiac disease have DH

Treatment   

Dapsone Strict gluten-free diet allows most patients to discontinue dapsone Iodine can also exacerbate DH and should be avoided

Follicular Hyperkeratosis and Dermatitis 

Vitamin A malabsorption



Vitamin B complex malabsorption

Idiopathic Pulmonary Hemosiderosis  



Lane-Hamilton syndrome Recurrent episodes of diffuse alveolar hemorrhage Introduction of a gluten-free diet has been associated with remission of pulmonary symptoms

Autoimmune Disease 

Strongly associated with celiac disease 

 

DM-1 Autoimmune thyroid disease 

      

20% in adult patients

Hypothyroidism > hyperthyroidism

IgA nephropathy Interstitial lung disease Systemic lupus erythematosus Sjögren's syndrome Polymyositis Rheumatoid arthritis Sarcoidosis

Other 

Selective IgA deficiency 

2% of celiac disease patients 

20 times the population prevalence

Other 

Down Syndrome



Turner Syndrome

Disorders Possibly Associated with Celiac      

Addison's disease Autoimmune hemolytic anemia Cavitary lung disease Congenital heart disease Cystic fibrosis Immune thrombocytopenic purpura

     

Iridocyclitis or choroiditis Macroamylasemia Myasthenia gravis Polymyositis Schizophrenia Systemic and cutaneous vasculitides

When to Test for Celiac Disease? 

Patients with symptoms or laboratory evidence of malabsorption



Chronic diarrhea Weight loss Steatorrhea Postprandial abdominal pain and bloating



(strong recommendation, high level of evidence)

  



Patients with first-degree family members with confirmed diagnosis of CD  

If they show symptoms of laboratory evidence of CD (strong recommendation, high level of evidence) Consider testing asymptomatic patients (conditional, high level of evidence)

When to Test for Celiac Disease? 



Patients with elevated serum aminotransferase levels when no other etiology is found (Strong recommendation, high level of evidence) Patients with Type I DM if there are any digestive symptoms, or signs, or laboratory evidence suggestive of CD (Strong recommendation, high level of evidence)



What tests should you order if you suspect celiac sprue?

Diagnosis of Celiac Disease 

IgA anti-tissue transglutaminase antibody (TTG) 



Preferred single test for detection of CD

Total IgA level

Diagnosis of Celiac Disease 

If IgA deficinecy has been identified/likely 

IgG-based testing  





IgG deaminated gliadin peptides (DGPs) IgG TTG

Antibodies against native gliadin are not recommended for primary detection of CD Combining several tests marginally increases sensitivity, but reduces specificity and is not recommended in lowrisk populations

Diagnosis of Celiac Disease 

Duodenal biopsy should be performed even if serologic testing is negative if suspicion is high

Diagnosis of Celiac Disease 





All testing must be done on gluten-containing diet Weakly positive individual may become negative within weeks of strict adherence to GFD 80% of subjects will test negative after 6-12 months on GFD

Diagnosis of Celiac Disease 

Histological abnormalities of CD can be patchy



Multiple biopsies should be performed



Duodenal Biopsy   

One or two biopsies from the bulb At least four from distal duodenum Bulb biopsies should be clearly labeled to help take into account the different architecture of the bulb and avoid false positive reports of villous atrophy

Diagnostic Testing Algorithm

Other Causes of Villous Atrophy   

Tropical sprue SIBO Infectious enteritis  

         

Giardia Intestinal TB

Autoimmune enteropathy Hypogammaglobulinemic sprue Drug enteropathy (Olmesartan) Whipple’s Collagenous sprue Crohn’s Eosinophilic enteritis Intestinal lymphoma GVHD AIDS enteropathy





45 yo Caucasian male with PMH of IBS-D now with worsening diarrhea x 3 months. Has a sister with celiac disease. His symptoms resolve completely on self prescribed gluten free diet. His diarrhea returns when he is exposed to wheat or rye. Does he have celiac disease?

Diagnosis of Celiac Disease 

Improvement of symptoms on GFD cannot accurately differentiate CD from other common gastrointestinal disorders  



PPV 36% GFD improved symptoms if 60% of pt with IBS-D

Clinical exacerbation after re-introduction of gluten  

PPV of 28% Re-introduction of gluten in healthy patients can cause GI symptoms

Non-celiac Gluten Sensitivity 





Condition in which individuals do not have the diagnostic features of CD but develop symptoms upon exposure to dietary gluten Symptoms alone cannot reliably differentiate CD from non-celiac gluten sensitivity Objective tests are needed to differentiate between the two disorders (Strong recommendation, moderate level of evidence)

Non-celiac Gluten Sensitivity 





Knowledge of the pathogenesis is limited Is not associated with malabsorption or nutritional deficiencies Not associated with any increased risk for autoimmune disorders or intestinal malignancy

Non-celiac Gluten Sensitivity 

Important to differentiate it from CD: The risk for nutritional deficiencies  The risk for complications of CD  The risk in family members  Influence adherence to diet (Conditional recommendation, moderate level of evidence) 



The patient does not want to stop gluten-free diet. What do you order to r/o celiac disease?



HLA Typing DQ2  DQ8 

 

The most important genetic risk factor for CD is presence of HLA-DQ heterodimers DQ2  



DQ8 



95% Present in 30% of white population 5%

Both negative = NPV >99%

HLA-DQ2/DQ8 testing should not be used routinely in the initial diagnosis of CD (Strong recommendation, moderate level of evidence)







HLA-DQ2/DQ8 genotyping testing should be used to effectively rule out the disease in selected clinical situations (Strong recommendation, moderate level of evidence)

When to use HLA Typing? 









Equivocal small-bowel histological finding (Marsh I-II) in seronegative patients Evaluation of patients on a GFD in whom no testing for CD was done before GFD Patients with discrepant celiac-specific serology and histology Patients with suspicion of refractory CD where the original diagnosis of celiac remains in question Patients with Down’s syndrome





The patient is on GFD and typing shows that the patient is + HLA DQ2 What do you do next?

Diagnosis on GFD 



Serology and intestinal biopsy should not be relied upon to exclude CD in patients already adhering to a GFD (Strong recommendation, high level of evidence) Formal gluten challenge should be considered, where necessary, to diagnose or exclude CD in patients already adhering to a GFD (Strong recommendation, high level of evidence)

Diagnosis on GFD 





If the duration of GFD has been brief (less than 1 month), serology and histology are often still abnormal and can be used to diagnose CD Normal serologic and histologic findings on a GFD cannot be used to exclude CD definitively HLA-DQ2/DQ8 testing should be performed prior to embarking on a formal gluten challenge

Gluten Challenge 



Patient reverts to a normal, gluten-rich diet, under medical supervision, to enable diagnostic testing Diet     



Containing at least 3 g (previously 10g) of gluten per day Average gluten-containing diet contains roughly 10-40 grams Slice of bread 3-5 grams of gluten Serving of pasta 6 grams of gluten 6–8 weeks

Patients who develop severe symptoms following gluten ingestion are not suitable candidates for gluten challenge

Gluten Challenge



 



After 8 weeks of gluten challenge the patient develops diarrhea and abdominal bloating. TTG + Patient does not want to undergo endoscopy with duodenal biopsy What endoscopic procedure can help you make the diagnosis?



Capsule endoscopy

The Role of Capsule Endoscopy 

Capsule Endoscopy   

Sensitivity 89% Specificity 95% Better at detecting macroscopic atrophy than EGD

The Role of Capsule Endoscopy 

Indicated in patients with  

Positive celiac serology Who are unwilling or unable to undergo upper endoscopy with biopsy (Strong recommendation, moderate level of evidence)

Capsule Endoscopy 

   

Considered for the evaluation of small-bowel mucosa in patients with complicated CD (Strong recommendation, moderate level of evidence) Stenosis Erosions Ulcerative jejunitis Lymphoma



Type I refractory celiac disease



Mucosal ulceration and severe villous atrophy



Circumferential ulceration and stricture in type II refractory celiac disease



What if the patient is unwilling or unable to undergo a gluten challenge?

 

Some patients will opt to continue on a strictly GFD without undergoing formal gluten challenge Such patients should be managed in a similar fashion to those with known CD (Conditional recommendation, low level of evidence)





However, this approach will include unnecessary monitoring, therapy, and expense Therefore the patient should be aware of the ongoing availability of definitive testing should they so desire

Management of Celiac Disease 



Strict avoidance of all products containing gluten (Strong recommendation, high level of evidence) Adhere to a gluten free diet for life   

Huge lifestyle change $$$$ Causes significant anxiety

Management of Celiac Disease 



Patients should be referred to a registered dietitian who is knowledgeable about CD to receive nutritional assessment and education (Strong recommendation, moderate level of evidence) Testing and treatment for micronutrient deficiencies 

Iron, folic acid, vitamin D, and vitamin B12 (Conditional recommendation, low level of evidence)

Gluten Free Diet

Gluten Free Diet 

Gluten -protein found in: Wheat  Rye  Barley  Triticale 

Wheat       

Breads Baked goods Soups Pasta Cereals Sauces Salad dressings

Barley     

Malt Food coloring Soups Vinegar Beer

Rye  

Rye bread (pumpernickel) Cereals

Triticale 

Hybrid of wheat and rye 

  

Grown to have a similar quality as wheat while being tolerant to a variety of growing conditions

Breads Pasta Cereals

Gluten Free Diet 

There is considerable variation in patients ability to tolerate gluten Some can ingest small amounts of gluten without symptoms  Gliadin shock or celiac crisis 



Severe diarrhea with dehydration

Gluten Free Diet 





Patients might have accompanying lactase deficiency secondary to damage to surface epithelial cells Milk and dairy products should be avoided upon initiation of a gluten-free diet Reintroduced after the disease responds to the diet

Oats 









Oat is an important source of nutrients/vitamins Moderate amounts of oats are not toxic to majority of patients with celiac disease Can contain significant amounts of other grains, especially wheat, because of contamination Avoided until remission is achieved on a glutenfree diet Later 2 ounces of oats per day from a reliable source may be introduced







The gluten-free diet often contains inadequate iron, calcium, vitamin D, and B vitamins Daily gluten-free multivitamin supplement is recommended to avoid deficiency states Avoiding gluten often leads to inadequate fiber intake and constipation

Common Foods that Contain Gluten             

Pastas Noodles Breads and Pastries Crackers Baked Goods Cereal & Granola Breakfast Foods Breading & Coating Mixes Croutons Sauces & Gravies Flour tortillas Beer Malt beverages

Common Foods that Contain Gluten         

Energy bars/granola bars Fries Potato chips Lunch meats Candy Soup (cream-based soups) Multi-grain tortilla chips or tortillas Salad dressings and marinades Starch

Common Foods that Contain Gluten       

Brown rice syrup Meat substitutes (vegetarian burgers, tempeh, vegetarian sausage, imitation bacon, imitation seafood) Soy sauce Self-basting poultry Pre-seasoned meats Cheesecake Eggs served at restaurants 



Restaurants put pancake batter in their scrambled eggs and omelets

Baking powder 

Some brands of baking powder contain starch to prevent clumping

Alcoholic Beverages that Contain Gluten 

Most distilled alcoholic beverages and vinegars are gluten-free 



      

Gluten is filtered during distillation process

Wines and hard liquor/distilled beverages are gluten-free Beers Ales Lagers Malt beverages Malt vinegars Not distilled - not gluten-free There are several brands of gluten-free beers available

Cross-Contamination        

Toasters Flour sifters Deep fried foods cooked in oil shared with breaded products Shared containers Condiments (double-dipped) Wheat flour can stay airborne for many hours in a bakery/house Oats Pizza

Medications 

Not all medicines and vitamins are gluten-free

Naturally Gluten Free      

Fruits Vegetables Meat and poultry Fish and seafood Dairy Beans, legumes, and nuts

Major National Celiac Support Groups 







With information on local groups Gluten Intolerance Group; 206-246-6652; www.gluten.net Celiac Disease Foundation; 818-990-2354; www.celiac.org Celiac Sprue Association-USA; 402-558-0600; www.csaceliacs.org

Books 



Gluten-Free Diet - A Comprehensive Resource Guide by Shelley Case, B.Sc., RD; www.glutenfreediet.ca Pocket Dictionary: Acceptability of Foods and Food Ingredients for the Gluten-Free Diet Canadian Celiac Association, 2005; www.celiac.ca

The Gluten-Free Gourmet-Living Well Without Wheat Cookbook by Bette Hagman; www.best-cooking-books.com/search_Bette_Hagman/searchBy_Author.html 





Wheat-Free, Gluten-Free Cookbook for Kids and Busy Adults by Connie Sarros; www.gfbooks.homestead.com Gluten-Free Quick and Easy by Carol Fenster; www.savorypalate.com

Magazines  

Gluten-Free Living; www.glutenfreeliving.com Sully’s Living Without Magazine; www.livingwithout.com





On August 2, 2013, the Food and Drug Administration (FDA) announced its long-awaited gluten-free food labeling rule Gluten free 

 



< 20 parts per million (ppm) of gluten

Manufacturers have until August 5th, 2014 Naturally gluten-free products can be labeled as such (i.e., water or fresh produce) There will be no symbol to identify foods that are gluten-free

20 parts per million  





20 parts per million = .002% 20 milligrams of gluten per 1 kilogram of food 1-ounce (28.35 grams) slice of gluten free bread containing 20 parts per million gluten would contain 0.57 milligrams of gluten Regular slice of bread 3-5 grams of gluten

Why < 20 ppm 





No analytical methods available to reliably detect gluten below 20 ppm In line with standards in other countries 10 milligrams per day of gluten consumption is a safe level for the vast majority of individuals with celiac disease 1/8 of a teaspoon of flour  18 slices of bread with each slice containing 20 ppm of gluten 



Covered   



All FDA-regulated foods Dietary Supplements (vitamins, minerals, herbs, amino acids) Imported food products that are subject to FDA regulations

Not Covered:     

Restaurant foods Meat, poultry and unshelled eggs (and any other products regulated by the USDA) Distilled spirits and wines Malted beverages made with malted barley or hops Regulated by Alcohol and Tobacco Tax and Trade Bureau (TTB)



 

The patient with CD confirmed by TTG and duodenal biopsy returns after 4 months on gluten free diet. His diarrhea improved significantly with initiation of GFD. He currently reports loose stools about 3 times per week (previously diarrhea TID) and intermittent abdominal pain and bloating. Labs: +TTG What do you do next?



Send the patient to dietitian to review adherence to diet







After starting a gluten-free diet, most patients improve within a few weeks In many, substantial symptomatic improvement is noticed within 48 hours The speed and eventual degree of histologic improvement are unpredictable, but they lag behind the clinical response





Return of villous architecture toward normal might not be evident for two or three months In some patients histologic resolution can take up to two years 

Usually because of exposure to gluten



Lack of declining values and/or persistently positive serology up to 1 year after starting a GFD strongly suggest gluten contamination

Monitoring 

Patients should be monitored regularly   



Residual or new symptoms Adherence to GFD Assessment for complications (Strong recommendation, moderate level of evidence)

Follow-up with health-care practitioner with knowledge of CD (Strong recommendation, moderate level of evidence)

Monitoring 

Monitoring of adherence  

History Serology (IgA TTG or IgA (or IgG) DGP antibodies (Strong recommendation, moderate level of evidence)



Upper endoscopy with biopsies 



Lack of clinical response or relapse of symptoms on GFD (Strong recommendation, moderate level of evidence)

Check for normalization of laboratory abnormalities detected during initial laboratory investigation (Strong recommendation, moderate level of evidence

Monitoring of Celiac Disease Patients

 

2: CBC, LFTs, A, D, E, B12, Cu, Zn, carotene, folic acid, ferritin, iron 3: Check what was abnormal in the past

Non Responders 

Other etiologies for ongoing symptoms Other food intolerances (including lactose and fructose intolerance)  Small-intestinal bacterial overgrowth  Microscopic colitis  Pancreatic insufficiency  Irritable bowel syndrome 





2 years after starting GFD patient develops weight loss, abdominal pain, and diarrhea. Patient is a dietitian herself and is religious about gluten-free diet. What is you diagnosis and what do you do next?



Concerning for refractory celiac disease



Check EGD





Patients with persistent or recurrent symptoms despite GFD require additional work-up to investigate the presence of disorders commonly associated with NRCD It is reasonable to do a follow-up biopsy in adults after 2 years of starting a GFD to assess for mucosal healing

Non Responders 



Persistent symptoms, signs or laboratory abnormalities typical of CD despite 6–12 months of dietary gluten avoidance 7 to 30% of patients

Other Causes of Villous Atrophy   

Tropical sprue SIBO Infectious enteritis  

         

Giardia Intestinal TB

Autoimmune enteropathy Hypogammaglobulinemic sprue Drug enteropathy (Olmesartan) Whipple’s Collageanous sprue Crohn’s Eosinophilic enteritis Intestinal lymphoma GVHD AIDS enteropathy

Non Responders 

Other etiologies for ongoing symptoms Inadvertent gluten ingestion (the most common cause)  Other food intolerances (including lactose and fructose intolerance)  Small-intestinal bacterial overgrowth  Microscopic colitis  Pancreatic insufficiency  Irritable bowel syndrome 

Refractory Celiac Disease 

Type I Lymphocyte infiltration that is similar to that seen in untreated CD  In the US Type I more common  5-year survival 93% 

Refractory Celiac Disease 

Type II  

Abnormal clonal T-cell expansion within the small-bowel mucosa T cells have abnormal immunophenotype with lack of expression of CD8 

    

CD8 is a normal cell surface differentiation marker

Symptoms are more severe and less likely to respond to therapy Malnutrition may require TPN These T-cell abnormalities are associated with a significantly less favorable prognosis 5-year survival 44% Causes of death included lymphoma, malnutrition, and sepsis

Type I Treatment  

No published randomized, controlled trials Steroid therapy Prednisone  Budesonide 



Immunosuppressive agents Azathioprine  Mesalamine 

Type II Treatment No published randomized, controlled trials of therapy  Corticosteroids  Budesonide  Azathioprine or 6-mercaptopurine  Methotrexate  Cyclosporine  anti-TNF  Cladribine  Used to treat hairy cell leukemia and multiple sclerosis  Caution: malnourished and hyposplenic 

Complications   

Ulcerative Jejunoileitis Collagenous Disease Malignancy

Ulcerative Jejunoileitis 



Characterized by ulceration and strictures of the small intestine Symptoms: Recurrent episodes of GI bleeding  Obstruction  Weight loss despite adherence to diet  Perforation with peritonitis 

Ulcerative Jejunoileitis Diagnosis:  Enteroscopy  UGIwSBFT  Abdominal CT  Enterography  Capsule endoscopy  Laparotomy

Treatment 

Some patients respond to a gluten-free diet



Glucocorticoids and azathioprine



Surgical excision of the worst affected segments of small intestine most effective



High risk for transition to lymphoma



Five-year survival rate: