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					Jamie S. Barkin, M.D., MACP, MACG, AGAF, FASGE
              Professor of Medicine
  University of Miami, Miller School of Medicine
       Chief, Division of Gastroenterology
             Mt. Sinai Medical Center
Introduction

   Celiac disease is a genetically-determined
    autoimmune condition that can present at any
    age

   It is a permanent intolerance to the gliadin
    fraction of proteins in wheat, barley and rye

   Prevalence 1:100 to 1:150 persons

   Caucasians are more at risk than other races

                  McGough N, Cummings JH. Proc Nutr Soc 2005;64:434-450
                    Marmouz F. Eur Ann Allergy & Clin Immunology 2007;39:23-25
Prevalence of Celiac Disease


Healthy population     -        1:133
1st degree relatives   -        1:18 to 1:22
2nd degree relatives   -        1:24 to 1:39




                       Fasano, et al. Arch Intern Med 2003;163:286-92
Celiac Disease

Three peaks:
      Infancy
      Second to third decade of life
      Fifth to sixth decade of life

Delay in diagnosis – 7 years




                          Ciclitira PJ. Nature Clinical Practice Gastroenterology &
                                                          Hepatology 2007 (4);9:483
The Celiac Iceberg


           Symptomatic                                   Manifest
           Celiac disease                                mucosal
                                                         lesion



                                      Silent celiac
                                        disease




                                 Latent Celiac Disease   Normal
                                                         mucosa
                     Genetic susceptibility – DQ2, DQ8
                            Positive serology



                                        (Adapted) CDHNF - NASPGHAN
         Stages of Celiac Disease

                Symptom   Serology   Histology

Latent             -         +           -

Silent             -         +           +

Diarrhea           +         +           +
         Spectrum of Celiac Disease

  Biopsy                  Symptoms
Villous Atrophy          Malabsorption




                   1%




 IEL                           Atypical/Asymptomatic
Does clinical presentation correlate with
degree of villous atrophy in patients with
celiac disease?
   Classical presentation– diarrhea and weight loss symptoms
   Atypical or silent presentation – anemia, osteoporosis or
    dermatitis herpetiformis

Aim: To evaluate the correlation between the clinical presentation
  of patients with celiac disease and the degree of villous
  atrophy

Results:
 499 patients, more of whom had atypical or silent celiac
  disease than classical presentation – 56% vs. 44%

   Clinical presentation did not correlate with the degree of
    villous atrophy in patients with celiac disease

                                       www.nature.com/clinicalpractice/gasthep
Celiac Disease World-Wide

   Iran - common finding among patients
    labeled as irritable bowel syndrome (11%) in
    Iran
   India - common cause of chronic diarrhea
    both in children and in adults

   Central America/Puerto Rico/South America
    - under-diagnosed
Conditions more common in celiac disease

Diabetes (type 1 – 5% of CD & up to 10% of juvenile diabetes mellitus
Thyroid disorders (autoimmune or Graves)
Adrenocortical failure (Addison's)
Liver disease (raised transaminases in 40% of new CD and primary
biliary cirrhosis)
IgA deficiency
Lymphocytic or microscopic colitis
Down‟s syndrome
Unusual neurologial disorders
Dental enamel defects
Turner syndrome




          (Adaptation) McGough N, Cummings JH. Proc Nutr Soc 2005;64:434-450
Associations of CD

   Hematological: IgA – deficiency, hemolytical anemia,
    thrombopenic purpura

   Nephrological: IgA – nephropathy

   Hepatic and digestive: primary biliary cirrhosis, Crohn‟s
    disease and colorectal bleeding

   Lupus, Sjögren‟s syndrome myasthenia, rheumatoid
    arthritis, polyarthritis

   Atopia, asthma, disease of farmer‟s lung or poultry
    breeders


            Marmouz F. Eur Ann Allergy & Clin Immunology 2007;39:23-25
Pathophysiology of celiac disease

   Malabsorption of nutrients, especially iron,
    folate, calcium and vitamin D

   Increased intestinal permeability may permit
    entry of other toxins which might induce
    autoimmune diseases




                                       CDHNF - NASPGHAN
Incidence of autoimmune diseases in celiac
disease (CD): protective effect of the gluten-
free diet
AIM:
  To determine which factors modulate the risk of autoimmune
  disease and to evaluate the effect of gluten-free diet in 924
  celiac patients

Results
 The cumulative risk of autoimmune disease was 8.1% ±1% at
  age 15, and 15.7%± 1.5% at age 30

   Factors associated with an increased risk were family history
    of autoimmunity and diagnosis of CD before age 36


                           Cosnes J, et al. Clinical Gastroenterology and Hepatology
                                                                      2008;;6:753-758
Incidence of autoimmune diseases in celiac
disease (CD): protective effect of the gluten-
free diet
(Cont)
Results
 After CD diagnosis, 55/788 patients developed an autoimmune
  disease

   The cumulative risk of subsequent autoimmune disease was
    lower in patients compliant to a gluten-free diet vs.
    noncompliant patients

   The incidence of autoimmune diseases was 5.4 per 1000
    patient-years during adherence to a gluten-free diet vs. 11.3
    per 1000 patient-years during non-adherence to the diet


                            Cosnes J, et al. Clinical Gastroenterology and Hepatology
                                                                       2008;;6:753-758
Factors in celiac disease

   Genetic susceptibility

   Immune system

   Environment - Gluten in diet
Genetics and pathogenesis of celiac
disease

   Concordance is 75 – 90% in monozygotic
    twins and 10 – 20% in dizygotic twins

   In first-degree relatives the prevalence is
    10% and in second-degree relatives it is 2%

   Patients with CD (95%) carry the human
    leukocyte antigen (HLA, HLA-DQ2 or HLA-
    DRB*4 DQ8)


                   McGough N, Cummings JH. Proc Nutr Soc 2005;64:434-450
Non-dietary factors

   Infections
       Viral infections
         ●   Sequence homology between -gliadin and
             adenovirus type 12 & 7, rubella and human herpes-
             virus 1


       Parasitic infestations
         ●   sequence homology between -gliadin and
             plasmodium yoelli
       Other ?


                                                  CDHNF - NASPGHAN
  Dietary Factors

     Wheat – (15% protein, 75% starch)

                                Gluten
Gliadin                                       Glutenin
(alcohol soluble)                          (alcohol insoluble)
Prolamine




   Rye prolamines – secalines
   Barley prolamines – hordeins
   Oats are safe

                                          CDHNF - NASPGHAN
Mucosal events

   Epithelial cell infiltration
       increased IEL‟s – (>90% CD8, <10% CD4)
       increased mucosal / T cells (nl <10%)
       role of / cells in celiac disease is unknown


   Mucosal surface alterations
       loss of epithelial cells
       proliferation of crypt epithelial cells



                                                  CDHNF - NASPGHAN
Humoral response in celiac disease


   Humoral response
      Enhanced antibody production

         Anti-tissue transglutaminase

         Anti-gliadin

         ? Other auto-antigens (anti-actin)



       Mechanism of antibody production unknown




                                               CDHNF - NASPGHAN
Expanded Definition of celiac disease

   Celiac disease is an autoimmune condition
   Occurs in genetically susceptible individuals
   DQ2 and/or DQ8 positive HLA haplotype is
    necessary but not sufficient
   A unique autoimmune disorder because:
       Both the environmental trigger (gluten) and the
        auto-antigen (tissue transglutaminase) are known
       Elimination of the environmental trigger leads to a
        complete resolution of the disease


                                               CDHNF - NASPGHAN
Celiac Disease and autoimmunity


   Prevalence of autoimmune disorders in celiac
    disease related to duration of gluten exposure
       Diagnosed before 2 years of age: 5%
       Age 2-10 years: 17%
       Greater than age 10 years: 24%


   Increased incidence of autoimmune disease in
    patients with IDDM and „silent‟ celiac disease and
    their first-degree relatives who were EMA+


                            Ventura et al. Gastro 1999; Not, Diabetologia 2001
Prevalence of celiac disease is higher in
other autoimmune conditions
Type 1 diabetes mellitus            3.5 – 10%
Thyroiditis                         4 – 8%
Arthritis                           1.5 – 7.5%
Autoimmune liver diseases           6 – 8%
Sögren‟s syndrome                   2 – 15%
Idiopathic dilated cardiomyopathy   5.7%
IgA neuropathy                      3.6%




                                         CDHNF - NASPGHAN
Visible Iceberg of CD



       Diarrhea

     Constipation

    Abdominal pain

       Bloating

      Weight loss
Presenting features of celiac
disease
   Adults
      Diarrhea, altered bowel habit including constipation

      Abdominal pain, dyspepsia, bloating

      Aphthous ulcers – mouth

      Anemia (fe or folate and rarely vitamin B-12)

      Weight loss

      Dermatitis herpetiformis

      Malabsorption, edema

      Osteoporosis, low impact fracture




                           McGough N, Cummings JH. Proc Nutr Soc 2005;64:434-450
Invisible Part of the Iceberg

   Hematological: iron deficiency anemia

   Rheumatologic: demineralization, arthralgias fractures

   Neurological: peripheral neuropathy (lack of), epilepsy (and
    cerebral calcifications) ataxia (vitamin E deficiency?), Migraine

   Digestive: stimulating functional, mouth ulcers, unexplained
    increase of transaminases and rare severe hepatopathy

   Gynecological: infertility, amenorrhea, fetal hypotrophy,
    miscarriages


                    Marmouz F. Eur Ann Allergy & Clin Immunology 2007;39:23-25
Increased overall mortality in adult life


Secondary to increased:
     Autoimmune diseases
     Osteoporosis
     Liver diseases
     Cancer




                                  CDHNF - NASPGHAN
COMPLICATIONS
Potential Nutritional Complications in
Untreated Celiac Disease


Low Iron           Low niacin
Low folate         Low B6 (rare)
Low vitamin B-12   Low beta-carotene
Low vitamins       Low zinc
ADEK                Essential fatty acid deficiency
Low thiamine




                                         CDHNF - NASPGHAN
Potential Nutritional Complications in
Untreated Celiac Disease


Prolonged  PT        Hypophosphatemia
Hypocalcemia         Hypomagnesaemia
Elevated PTH         Re-feeding   syndrome
Increased alkaline
 phosphatase




                                          CDHNF - NASPGHAN
Iron deficiency anemia resistant to oral
iron

   One of the most common non-GI manifestation in
    adult studies

   5 – 8% of adults with unexplained iron deficiency
    anemia have celiac disease

   In children with newly diagnosed celiac disease
       Anemia is common
       Little evidence that celiac disease is common in children
        presenting with anemia



                                                    CDHNF - NASPGHAN
Bone Disease in Celiac Disease

         Arthritis
         Osteoporosis
         Osteopenia
         Osteomalacia
         Rickets




                                 CDHNF - NASPGHAN
Bones and Celiac Disease

   CD presenting with classic malabsorptive
    symptoms was the association with bone disease,
    particularly osteomalacia (Bennet et al, 1932)

   Reduced bone mineral density, osteopenia or
    osteoporosis in 20 – 50% of the patients newly
    diagnosed with CD (Butcher, et al 1992; Corazza, et
    al 1995, 1996; Mc Farlane et al, 1995; Kemppainen et
    al, 1999; Cellier et al 2000; Meyer et al 2001)

   The consequences of these bone changes are
    probably an increase in aches and pains
                                                               Cont
                 McGough N, Cummings JH. Proc Nutr Soc 2005;64:434-450
Bones and Celiac Disease

   Increased fracture is reported , but the risk is small

   Patients who presented subclinically with anemia or
    osteopenia or just on screening, the fracture risk is
    not increased compared with the controls

   BMD does improve with a GFD but may not return to
    that seen in a matched population (Corraza et al.
    1995; McFarlane et al 1995; Sategna-Guidetti et al.
    2000; Pazianas et al. 2005)
Risk of cancer in celiac disease


              Increased                             Decreased
Definite*
    Non-Hodgkin's lymphoma – T>B                        Breast
    Small bowel adenocarcinoma

Possible                                                Lung?
   Esophagus
   Melanoma
   Large bowel
   Liver
   Oropharyngeal
   Pancreas

   *Diminishes with time from diagnosis
   except NHL & only in those with
   dietary compliance

         (Adaptation) McGough N, Cummings JH. Proc Nutr Soc 2005;64:434-450
“Hepatitis” and Celiac Disease


   Evidence for elevated serum transaminases
    (ALT, AST) in adults with untreated celiac
    disease
    ●   Up to 9% of adults with elevated ALT, AST may
        have silent celiac disease

    ●   Liver biopsies in these patients showed non-
        specific reactive hepatitis – may simulate NASH

    ●   Liver enzymes normalized on gluten-free diet


                                              CDHNF - NASPGHAN
Celiac disease screening amongst
women of reproductive age
 A Swedish cohort study compared 2078 births by
  women diagnosed with celiac disease prior to or
  after the birth of an infant with the background
  child-bearing population
Result:
 Undiagnosed maternal celiac disease at birth was
  strongly linked to low or very low infant birth weight,
  lower placental weights and higher Cesarean
  section rate



                   Ludvigsson JF et al. Gastroenterology 2005;129:454-463
Dermatitis Herpetiformis

●   Erythematous macule >urticarial papule > tense
    vesicles
●   Severe pruritus
●   Symmetric distribution
●   90% no GI symptoms
●   75% villous atrophy
● Gluten sensitive

                               Garioch JJ et al. Br J Dermatol 1994;131:822-6
                             Fry L. Baillieres Clin Gastroenterol 1995;9:371-93
                                Reunala T, et al. Br J Dermatol 1997;136:315-8
Diagnostic principles of celiac disease

   Confirm diagnosis before treating
       Diagnosis of celiac disease mandates a strict gluten-free
        diet for life
            following the diet is not easy
            QOL implications


   Failure to treat has potential long-term adverse
    health consequences
       Increased morbidity and mortality




                                                    CDHNF - NASPGHAN
Role of serological tests in Celiac
Disease

   Identify symptomatic individuals who need biopsy

   Screening of asymptomatic “at risk” individuals
    who need a biopsy

   Supportive evidence for the diagnosis

   Monitoring dietary compliance




                                            CDHNF - NASPGHAN
Serological tests

 Antigliadin antibodies (AGA)
 Antiendomysial antibodies (EMA)
 Anti-tissue transglutaminase
  antibodies (TTG)
       First generation (guinea pig recombinant
       Second generation (human recombinant)
   HLA typing

                                        CDHNF - NASPGHAN
Serological Test Comparison



                   Sensitivity %               Specificity %
   AGA-IgG             69 – 85                     73 – 90
   AGA-IgA             75 – 90                     82 – 95
   EMA (IgA)           85 – 98                    97 – 100
   TTG (IgA)           90 - 98                     94 – 97




               Farrell RJ, Kelly CP. Am J Gastroenterol 2001;96:3237-46
Anti-gliadin antibodies (AGA)

   Sensitivity and specificity do not exceed
    80%

   The specificity of AGA IgA is approximately
    50%

   False positive results can be found in
    patients with esophagitis, gastroenteritis,
    inflammatory bowel diseases

                              Basso D, et al Lupus 2006;15:462-465
Serology diagnosis of celiac disease


   Tissue transglutaminase is the serological test of choice for
    the diagnosis of CD

   Selective IgA deficiency is found in 2-3% of individuals with CD
    and affects not only tTg IgA antibodies but also EMA and AGA
    IgA antibodies

   Both IgA and IgG AGA antibodies are present in the sera of
    patients with CD, although they are not specific because
    gliadin crosses the normal gut mucosa, and approximately 5 -
    10% of the healthy population will be positive, particularly
    older individuals


                       McGough N, et al Proceedings of the Nutrition Society
                                                           2005;64;434-450
Biopsy diagnosis of celiac disease


Histological Features:
     Increased IEL‟s (>30/100 enterocytes)
     Loss of nuclear polarity
     Change from columnar to cuboid
     Lamina propria cellular infiltrate
     Crypt elongation and hyperplasia
     Increased crypt mitotic index
     Progressive villous flattening

                                       CDHNF - NASPGHAN
Role of “Routine” Small Bowel Biopsy at
Endoscopy

   Current practices by pediatric GI physicians

   Rationale:
       Celiac disease is common and endoscopic appearance may look
        normal
       Era of open access endoscopy

   Routine biopsy in high-risk groups
       Family members
       Chronic liver disease
       IBS, IDDM, IBD, Sjögren syndrome
       Down‟s syndrome
       Patients with atypical symptoms
Mucosal Differential Diagnosis of
Immunopathology
   Celiac
   Giardiasis
   Milk intolerance
   Tropical sprue
   GVHR




                       Marsh, Gastroenterol 1992;102:330-354
Two main problems when considering
screening

   ~25 – 30% of individuals with positive screening
    serological tests may have normal biopsies. It is
    unclear whether these individuals have early or mild
    celiac disease, false positive tests or variable
    production of autoantibody of unclear prognostic
    value

   Compliance with gluten-free diet is poor when
    symptoms are mild or absent and when diagnosis is
    made beyond childhood


                     Liu E, et al Clin Gastroenterol Hepatol 2003;(1):356-362
TREATMENT
Gluten-Containing Grains to Avoid


Wheat          Bulgar                Filler
Wheat Bran     Couscous              Graham flour
Wheat Starch   Durum                 Kamut
Wheat Germ     Einkorn               Matzo
Flour/Meal     Barley                Emmer
Semolina       Barley Malt/Extract   Faro
Spelt          rye                   Triticale



                                     CDHNF - NASPGHAN
Ingredients that may contain gluten

   Seasonings and spice blends or mixes
   Modified food starch
   Malt/malt extract/flavoring
   Modified hop extract and yeast-malt sprout
    extract
   Dextrin
   Caramel color


                                      CDHNF - NASPGHAN
Other items to consider


   Lipstick/gloss/balms
   Mouthwash/toothpaste
   Play dough
   Stamp and envelope glues
   Vitamin, herbal and mineral preparations
   Prescription or OTC medications



                                     CDHNF - NASPGHAN
Gluten-Free Grains and Starches

Amaranth                  Potato
Arrowroot                 Quinoa
Buckwheat                 Rice
Corn                      Sorghum
Flax                      Tapioca
Millet                    Teff
Montina                   Flours made      from nuts, beans
                            and seeds
Oats*

 *for possible cross-contamination with gluten -containing grains

                                                      CDHNF - NASPGHAN
Can oats be taken in a gluten-free diet (GFD)?
A systematic review
Results
 10 studies involving 165 patients


   Only 1 patient was shown to have histological damage as a
    result of consuming oats

Conclusions
 Celiac patients can, to some advantage, include oats in a GFD


   Recommend adding oats to their GFD when they are
    established on a conventional GFD


                    Garsed K, Scott BB. Scand J Gastroenterol 2007;42:171-78
Safe Ingredients

   Starch

   Maltodextrin
       Made from cornstarch, potato starch, or rice starch,
        but not from wheat

   Vinegar and alcohol
       Distilled vinegar and distilled spirits are gluten-free,
        however avoid malt vinegar and malt beverages (e.g.
        beer)


                                                   CDHNF - NASPGHAN
Health beliefs of adults with celiac
disease

   Survey of 100 people in celiac disease support group (Buffalo,
    NY)
      Number of people who agreed with following statements:

         ”If I eat less gluten I will have less intestinal damage”

          (51%)
         “I‟ve lived this long eating gluten, how much will the

          gluten-free diet really help me now?” (33%)
         “my doctor should be the one to tell me when I need

          follow-up testing” (26%)
         “Scientist/doctors still haven‟t proven that gluten really

          hurts them” (16%)



                                                     CDHNF - NASPGHAN
Dietary adherence: A common Problem


   Only 50% of Americans with chronic
    illness adhere to their treatment
    regimen including:
       Diet
       Exercise
       Medication
   Dietary compliance can be the most
    difficult aspect of treatment

                                 CDHNF - NASPGHAN
Barriers to Compliance

   Time pressure – time to plan, prepare food is longer

   Planning – work required to plan meals

   Competing priorities – family, job, etc.

   Assessing gluten content in foods/label reading

   Eating out – avoidance, fear, difficult to ensure food
    is safe

                                               CDHNF - NASPGHAN
Barriers to Compliance

   Social events – not wanting to look/be
    different

   Support of family and friends – “just a
    little bit – it won‟t hurt you”



                                  CDHNF - NASPGHAN
Treatment of Celiac Disease

Gluten-free diet
     Compliance problems due to palatability,
      variations in food labeling and possible
      cross-contamination of other foodstuffs by
      gluten are common




                 Ludvigsson JF et al. Gastroenterology 2005;129:454-463
Factors that Improve Adherence

   Knowledge about the gluten-free diet
   Understanding the risk factors and serious
    complications can occur to the patient
   Ability to break down big changes into smaller steps –
    ability to simplify or make behavior routine
   Ability to reinforce positive changes internally
   Positive coping skills
   Ability to recognize and manage mental health issues
   External test results are motivational, especially in
    asymptomatic individuals




                                                  NASPGHAN
Possible Causes of GI Symptoms on a Gluten-
Free diet


Food  intolerance to   Alternate flours made   from
 fructose                beans or nuts
Sorbitol               Food allergens such as

Olestra
                         milk, protein, soy, nuts,
                         egg, corn
Guar gums
                        Foodshigh in salicylates
Antibiotics             and amines
Lactose




                                        CDHNF - NASPGHAN
Dietary triggers of IBS

   Fermentable Oligosaccharides, Disaccharides,
    Monosaccharide and Polyols (FODMAP)

   FODMAPs can include fructose and lactose, polyols
    (such as sorbitol) and fructo-oligosaccharides
    (fructans)

   Major dietary FODMAPs include fructose and
    fructans; fructose are fruits, honey and high
    fructose corn syrup, and of fructans they are wheat
    and onions


                      Shepherd SJ, et al Clinial Gastroenterology & Hepatology
                                                                2008;6:765-771
Lactose Intolerance & Celiac Disease:
Incidence

   Secondary lactase deficiency is estimated to
    be 20% - 40%

   Increasing lactose intolerance with delayed
    diagnosis

   Increased incidence in patients with GI
    symptoms in celiac disease

   Decrease calcium and vitamin D intake in
    lactose intolerance

                                       CDHNF - NASPGHAN
Causes of poor response to gluten-free
diet
 Wrong diagnosis              IBD
 Gluten ingestion*            Collagenous sprue
 Lactose intolerance*         Ulcerative jejunitis
 Pancreatic insufficiency*    Autoimmune enteropathy
 Microscopic colitis*         Adenocarcinoma
 Bacterial overgrowth*        EATL
 Other food intolerances      Refractory sprue (+/-
 (fructose, milk, soy)         clonal T cell populations
 Collagenous colitis



    *common                                 Peter Green, M.D.
Resources

Reputable websites
     Celiac.com (www.celiac.com)
     National Institutes of Health (www.niddk.nih.gov)
     American Dietetic Association (www.eatright.org)
Local Support Groups
     Celiac.com (www.celiac.com)
National Support Groups
     The Gluten Intolerance Group – GIG (www.gluten.net)
     Celiac Disease Foundation – CDF (www.celiac.org)
Research and Information
     Center for Celiac Research (www.celiaccenter.org)
Resources

   Cookbooks
       Hagman, Bette, “The Gluten-Free Gourmet Cooks Fast and
        Healthy”
       Saros, Connie, “Wheat-free Gluten-free Cookbook for Kids
        and Busy Adults”
       Books and Magazines
       Case, Shelly, “Gluten-Free Diet: A comprehensive
        Resource Guide”
       Gluten-Free living
       Sully‟s Living Without (www.livingwithout.com)

   Product information
       www.glutenfreemall.com


                                                        NSPGHAN
Selected support groups and websites


Children‟s Digestive Health        www.celiachealth.org
and Nutrition Foundation

National Institutes of Health      www.nlm.nih.gov/medlineplus/celiacdisease.html

Gluten intolerance Group           www.gluten.net

Celiac Foundation                  www.celiac.org

Celiac Sprue Association           www.csaceliacs.org




                                Liu E, et al Clin Gastroenterol Hepatol 2003;(1):356-362
Dietary Factors

   33 amino acid peptide in gliadin contains critical
    epitopes – high in glutamine and proline

   Resistant to digestion in lumen

   Penetrates epithelial barrier

   Modified by the enzyme tissue transglutaminase
       Deaminates glutamine residues to glutamic acid

   Resulting higher affinity binding to HLA DQ2
    molecule on the surface of antigen-presenting cells


                                                  CDHNF - NASPGHAN
Long-term follow-up of 61 celiac patients diagnosed in
childhood: Evolution toward latency is possible on a
normal diet

Introduction:
   The question still remains as to whether the maintenance of a
   life-long gluten-free diet is necessary in all celiac children or
   whether in some of them a gluten-containing diet can be safely
   reintroduced

Aim:
  To retrospectively analyze the clinical and biological status of
  adult celiac patients diagnosed in childhood, who remained on
  a normal diet after gluten challenge and were clinically silent




                                  Matysiak-Budnik T, et al Gut 2007;56:1379-1386
Long-term follow-up of 61 celiac patients diagnosed in
childhood: Evolution toward latency is possible on a
normal diet

(Cont)
Results:
 61 patients had resumed a normal diet and were asymptomatic

   48 showed different degrees of villous atrophy (silent CD); 13
    had no detectable atrophy (latent CD) on duodenal biopsies

Conclusion:
 Long-term latency developed in about 20% of CD patients who
  remained symptom free after gluten reintroduction

   Silent celiac – risk of osteoporosis necessitates gluten-free
    diet


                                   Matysiak-Budnik T, et al Gut 2007;56:1379-1386
Budesonide in the treatment of refractory
celiac disease
POP
 29 patients (72% female) received budesonide for a mean of 6.7
  ± 8.5 months

Results
 12 of 15 had complete response to Budesonide


Conclusion
 Response occurred in those who had refractory disease and in
  those with type II disease, irrespective of the presence of
  microscopic colitis (N = 7)




                       Brar P, et al. Am J Gastroenterol 2007;102:2265-2269
 Budesonide and concomitant medication use
 in relation to budesonide response

Therapy                        No. of Complete Moderate Poor
                               patients Response Response Response
Budesonide alone                  15              12                               3
Budesonide + S                     3               1              1                1
Budesonide + S + A                 7                              5                2
Budesonide + A                    4                3                                1
Total                        29 (100%)            55%            21%              24%

 S – systemic steroids;   A - azathioprine




                                       Brar P, et al. Am J Gastroenterol 2007;102:2265-2269
Response to hepatitis B vaccination in
patients with celiac disease
   Non-responsiveness to hepatitis B virus (HBV)
    vaccination is related to genetic features

   Strong relationship between CD and these human
    leukocyte antigen (HLA) genotypes

   Responsiveness to HBV vaccination was observed
    in 17 (68%) CD patients and all (100%) control
    subjects (P = 0.006)



                             Ahishali A, et al. Dig Dis Sci 2008;53:2156-2159

				
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