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Celiac talk

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Intolerance to gluten proteins from wheat and to related proteins ... Primary biliary cirrhosis. Down syndrome (3-12%) Turner syndrome. Rheumatoid arthritis ... – PowerPoint PPT presentation

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Title: Celiac talk


1
Celiac Disease
Moncton, May 27, 2007
F. Schweiger MD
2
Celiac sprue - Definiton
  • Intolerance to gluten proteins from wheat and to
    related proteins from barley or rye
  • Presents with characteristic histopathological
    changes of the jejeunal mucosa
  • Consequences from asymptomatic to global
    malabsorption and an increased risk to develop GI
    malignancies
  • Manifestation by genetic, environmental,and
    immunological factors

3
Mortality of celiac sprue
  • Before introduction of gluten-free diet
  • 544 children 12
    Hardwick 1939

  • (malabsorption and infection)
  • After introduction of gluten-free diet (Dickie
    1951)
  • 485 children 0.4
    Sheldon 1969
  • 653 adults 2 x increased
    Logan et al 1989
  • 335 adults on GFD no increase
    Collin et al 1994

4
Prevalence of Celiac Disease
  • USA / Canada 1 in
    100
  • Irish
    1 in 152
  • Italians with dyspepsia 1 in 103
  • Swedish blood donors 1 in 256
  • Brazilians 1
    in 680
  • Baltimore (USA) 1 in 300
  • Rare in Afro-Caribbean, Chinese, Japanese
  • Mild female preponderance (21 at most)

5
Triggers of celiac disease
Infectious (viral bacterial)
Diatetic (gluten)
Genetic HLA-DQ2
Autoimmunity
Immune-maturation Th2 Th1
Sprue
6
  • Family Gramineae
  • Subfamily Festucoideae
    Panicoideae
  • Tribe Triticeae Aveneae
    Oryzeae Andropogoneae Paniceae
  • Subtribe Triticineae Hordeinae
    Tripsacinae Anthrxoninae
  • Genus Triticum Secale Hordeum Avena Oryza
    Zea Sorghum Pennisetum
  • Wheat Rye Barley Oats Rice
    Corn Sorghum Millet

7
Toxic wheat proteins
  • Glutelins (glutenins of wheat)
  • Soluble in acids and bases
  • 45 Glu
  • Prolamines (gliadins of wheat)
  • Soluble in 50 70 ethanol
  • 30 56 Glu, 15 30 Pro
  • Alpha, beta, gamma, delta gliadins
  • Toxic peptides PSQQ, QQQP

Gluten
8
Environmental Factors OATS
  • Oats may be tolerated by patients
  • Oats contain less QQQPF (toxic fraction in wheat
    gliadin)
  • Prolamines in oats have less glutamine and
    proline
  • Tolerance to oats depends on the amount consumed
    (less than 40 gm)

9
Genetic factors
  • Concordance in monozygotic twins 75
  • Risk to first degree relatives 2 15 (10 )
  • Risk to 2nd degree relatives 3 5

10
Familial clustering of celiac disease/dermatitis
herpetiformis
  • 1.degree relatives number sprue/DH
    prevalence
  • Parents 521
    22 4.2
  • Sisters/brothers 368 51
    13.8
  • Offspring 54
    7 12.9
  • 2.degree relatives 54 3
    5.6
  • Total 997
    83 8.3

11
Relatives Who and How to Screen ?
  • Index case has proven celiac disease
  • Relative is interested in being screened
  • Relative is willing to undergo diagnostic testing
  • Relative is willing to undergo treatment
  • Relative will derive benefit from treatment
  • If relative is symptomatic, approach is
    diagnostic not screening

S. Crowe, DDW 2007
12
Classical presentation of celiac
disease 1960-ies, Helsinki, Finland
  • Number
    53
  • Age at initial symptoms (months)
    7.7
  • Duration of gluten ingestion (months)
    4.3
  • Age at admission (months)
    10.2
  • Diarrhea
    87
  • Vomiting
    74
  • Growth retardation
    98
  • Weight below 2.5 percentile
    70
  • Distended abdomen
    64

Acta Ped Scand 1967
13
Celiac Disease in Adults
  • 20 over age 60
  • Often mistaken for Irritable Bowel Syndrome
  • 50 do not have diarrhea
  • Iron deficiency anemia most common presentation
  • Unmasking by gastric surgery
  • May present as recurrent canker sores
  • Significant fatty stools uncommon
  • Abdominal pain uncommon

14
Atypical Presentations (1)
  • Nonspecific Weight loss, lethargy,
    fatigue
  • Hematological bruising (Vitamin K), anemia
  • (iron,folate
    ,B12)
  • hyposplenism
    (thrombocytosis)
  • Neurological cerebellar ataxia,
    peripheral

  • neuropathy,post/lateral column

  • abnormalities, neuromyopathies,
  • epilepsy
    (/-cerebral calcifications)
  • demyelinating CNS
    lesions

15
Atypical Presentations (2)
  • Musculoskeletal Osteoporosis, osteomalacia, s

  • osteoarthropathy,tetany,weakness
  • dental enamel
    hypoplasia,
  • Gynecologic primary or secondary
    amenorrhea
  • infertility,
    recurrent abortions
  • Dermatologic alopecia, follicular
    keratosis
  • Psychiatric depression, psychosis,
  • schizophrenia

16
Atypical Presentations (3)
  • Endocrine pubertal delay, short
    stature,
  • 2nd
    hyperparathyroidism, infertility,
  • impotence,
    amenorrhea

17
Dietary Response -? Diagnostic
  • Placebo response in IBS up to 70
  • Gluten (increased prolamines) is hard to digest
  • GFD often eliminates other dietary factors
  • Symptomatic response to GFD, especially a
    transient response, does not imply the diagnosis
    of celiac disease

18
Laboratory tests
  • Protein Albumin, globulins, Liver tests
  • Carbs glucose, Lactose-H breath test,
    (D-Xylose)
  • Fats (stool for fat), lipid profile,
    carotene
  • Minerals Ca, Mg, P, Fe, ferritin,zinc
  • Vitamins RBC folate, B12, Vit A, 25-OH
    Vitamin D, PT

19
Serologic Tests for Celiac Disease
  • Serologic Test Sensitivity
    Specificity PPV NPV

  • percent
  • Anti-EMA (IgA) 85-98
    97-100 99 93
  • IgA antigliadin 75-90
    82-95 28-100 65-100
  • IgG antigliadin 69-85
    73-90 20-95 41- 88
  • tTg (IgA) 92-98
    95-98

20
Epidemiology of Celiac Disease the sprue iceberg
Clinical CD
Abnormal mucosa
Silent CD
EMA present
EMA present Asymptomatic
Latent CD
Normal mucosa
Healthy individuals
21
The asymptomatic patient
  • Advantages of screening
  • Reduction in risk of enteropathic T-cell
    lymphoma
  • Reversal of unrecognized nutritional
    deficiences
  • Resolution of mild or unrecognized symptoms
  • Avoidance of other autoimmune disorders
  • Improvement of general well-being
  • Disadvantages of screening
  • Lack of motivation to adhere to GFD
  • Adverse psychological effects
  • Mass screening currently not advocated

22
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23
Pathology of celiac disease
  • Length of SB involvement correlates with clinical
    severity
  • GFD results in marked improvement beginning
    distally
  • Histology is not specific

24
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28
Causes of villous atrophy
  • Cows milk protein intolerance (children)
  • Post-gastroenteritis
  • Giardiasis
  • Peptic duodenitis (including ZES)
  • Crohns disease
  • Small intestinal bacterial overgrowth
  • Eosinophilic enteritis
  • Radiation or cytotoxic therapy
  • Tropical sprue
  • Severe malnutrition
  • Diffuse small intestinal lymphoma
  • Graft versus host disease
  • Hypogammaglobulinemia
  • Alpha chain disease

29
Prevalence of autoimmune disease in celiac disease
30
Celiac disease and associated disorders Definite
Association
  • Dermatitis herpetiformis
  • Insulin-dependent Diabetes
  • Thyroid disease
  • IgA deficiency
  • Epilepsy with cerebral calcifications
  • Inflammatory bowel disease
  • Microscopic colitides
  • IgA mesangial nephropathy
  • Chronic autoimmune hepatitis
  • Sclerosing cholangitis
  • Primary biliary cirrhosis
  • Down syndrome (3-12)
  • Turner syndrome
  • Rheumatoid arthritis
  • Sarcoidosis
  • Bird fanciers lung
  • Fibrosing alveolitis
  • Recurrent pericarditis
  • Idiopathic pulmonary hemosiderosis

31
Dermatitis herpetiformis
  • Papulovesicular lesions of extensor surfaces,
    buttocks, trunk, neck and scalp
  • Intensely pruritic
  • Early or middle adult life M F
  • 2/3 have patchy enteropathy tends to be less
    severe
  • Less than 10 have intestinal symptoms
  • 10 40 fold increased risk of lymphoma

32
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33
Dermatitis herpetiformis
  • Frequency of Abs to tTG only about 75
  • More than 80 of pts with DH have sprue
  • 10 of celiacs have DH
  • Tx Dapsone 1 2 mg/kg (does not improve SB)
  • GFD allows most patients to reduce/stop Dapsone

34
Celiac disease and type 1 DM
  • Patients (n)
    Pos ()
  • Finland children
    (776) 2.4
  • Finland adults (195)
    4.1
  • Italy children
    (498) 3.2
  • Italy adults
    (383) 2.6
  • Italy adults
    (639) 7.8
  • Sweden children (436)
    4.6
  • Ireland adults (101)
    4.9
  • UK adults
    (767) 2.0
  • Germ/Switz children (1032)
    1.2
  • Australia children
    (273) 1.8
  • USA children
    (211) 1.4

35
Celiac disease and Osteoporosis
  • Prevalence of CD is increased in osteoporosis
    (1.5-3) Especially in premature
    osteoporosis/osteomalacia
  • Newly diagnosed CD spine 28 hip 15
  • Patients with asymptomatic CD have increased risk
  • Postmenopausal females are at greatest risk

36
Celiac disease and Osteoporosis
  • Vitamin D deficiency is common in CD
  • Bone mineral density increases with GFD,
    especially in the first year of treatment
  • Axial bone mass increases more then appendicular
    BMD

37
Celiac disease and Osteoporosis
  • Adequate calcium and vitamin D intake
  • Regular weight bearing exercises
  • Smoking cessation avoid alcohol
  • Correction of hypogonadism

38
Celiac Disease and Osteoporosis
39
Celiac disease and associated conditions Possible
association
  • Congenital heart disease
  • Lung cavities
  • Sjogrens syndrome
  • Systemic and cutaneous vasculitis
  • SLE
  • Polymyositis
  • Schizophrenia
  • Myasthenia gravis
  • Iridocyclitis or choroiditis
  • Cystic fibrosis
  • Macroamylasemia
  • Addisons disease
  • Autoimmune thrombocytopenic purpura
  • Autoimmune hemolytic anemia

40
Celiac Disease and Malignancies
  • 44/105 deaths during 13.5 years in 653
    (untreated) patients from Edinburgh, Scotland

  • Risk
  • All malignancies 3 x
  • Lymphoma 30 x
  • Intestinal carcinoma 3 x
  • Esophageal carcinoma 8 x

Logan et al, Gastroenterology 1989
41
Cancer and Celiac Disease
  • 12, 000 celiac patients in Sweden over 30 years
  • 6-fold increased risk of lymphoma (18 of all Ca)
  • Oropharyngeal Ca (SCC)
  • Esophageal Ca (SCC)
  • Small bowel Ca
  • Colon Ca - confined to subjects older than 60
  • Primary liver Ca
  • Reduced occurrence of breast Ca

  • Askling et al. Gastro 2002

42
Celiac Disease and cancer
  • Strict adherence to a GFD probably reduces
    the risk of enteropathy-associated T cell
    lymphoma as well as the other malignancies

43
Treatment of Celiac Disease
  • Dietary counseling and strict avoidance of gluten
  • Initial avoidance of dairy products
  • Replacements of micronutrients in case of
    deficiencies
  • Corticosteroids/azathioprine for celiac crisis or
    refractory sprue

44
Treatment of Celiac Disease
  • Non-compliance is an issue - eating out of home

  • - peer pressure for children

  • - less acceptable taste

  • - accidental ingestion of G.

  • - cost, availability, labelling
  • Use of oats, wheat starch controversial
  • GFD reduces risk of malignancy
  • Unclear how much gluten if any is safe
  • - new FDA guidelines up to 10 mg/day safe ?

  • S. Crowe, DDW
    2007

45
Response to Treatment
  • Clinical improvement in 2 weeks in 70 , by 6
    weeks in most
  • Serological improvement by 4 6 weeks
  • Histological improvement in up to 2 years
  • Gaining weight above ideal BMI
  • Constipation
  • Falling off the diet and getting ill again

  • S. Crowe, DDW 2007

46
Patient on GFD no Biopsy!
  • Celiac disease is
    possible and patient
  • willing to undergo
    a gluten challenge
  • YES, ideally get NO, but wants
    no further testing if
  • genetic testing genetic
    testing wants to stay on GFD

  • regardless of
    testing
  • Challenge if DQ2 or DQ8
  • Positive check Abs q 2 m
  • EGD Bx, if Ab ve, ve, increases
    -ve not celiac dis.
  • Symptoms develop or likelyhood of CD
    ? Use GFD for
  • By 6 months suggest G
    challenge symptom control only

S.Crowe, DDW 2007
47
Gluten Challenge
  • Gradual increase of gluten in diet up to target
    (typically 4 slices of bread/day)
  • Check tTG at 4-6 weeks and at intervals
    thereafter until positive
  • Biopsy if diarrhea develops and/or become
    seropositive
  • Management if sero-negative at 3-6 months needs
    to be individualized

S.Crowe, DDW 2007
48
Treatment of celiac disease
  • Histology may not recover completely despite
    clinical normalization
  • Negativation of IgA anti-TTG after 4 6 months
    of a strictly gluten-free diet (GFD)
  • Diagnosis to be reconsidered when no clinical
    improvement is reached after 6 9 months of a
    GFD
  • Risk of malignancy approaches baseline after 5
    years of a GFD

49
Why a Gluten Free Diet ?
  • Benefits overall cancer risk
  • Improves unexplained infertility
  • Improves osteoporosis
  • Corrects iron deficiency
  • Improved QOL even for those detected by screening
  • GFD is beneficial for preventing, reversing
    and/or treating some complications

50
Summary
  • Celiac disease is not rare (1 in 100-300)
  • It can present in many ways
  • iron deficiency anemia, depression,
    osteoporosis, abnormal liver tests, non-specific
    or IBS-like symptoms, dyspepsia, DH, recurrent
    miscarriages, microscopic colitis
  • Associated with autoimmune diseases
  • Screening with tTG IgA is best
  • Confirm diagnosis with duodenal biopsy
  • Cornerstone of treatment is avoidance of gluten

51
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