1 / 40

SYED A. SADIQ, MD Gastroenterology associate of north Texas www.gantgi.com

SYED A. SADIQ, MD Gastroenterology associate of north Texas www.gantgi.com. Celiac Disease . Celiac Disease . Issues for consideration What clinical presentation suggest CD How to screen and diagnose CD How to evaluate someone already on GFD Do we need to screen family members

quade
Download Presentation

SYED A. SADIQ, MD Gastroenterology associate of north Texas www.gantgi.com

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. SYED A. SADIQ, MDGastroenterology associate of north Texaswww.gantgi.com Celiac Disease

  2. Celiac Disease Issues for consideration • What clinical presentation suggest CD • How to screen and diagnose CD • How to evaluate someone already on GFD • Do we need to screen family members • Follow up of patients with CD • What to do with “Non responsive” CD • Managing complications • Potential new therapies

  3. Prevalence of Celiac Disease • Traditionally, highest in western Ireland (1:300), with lower in other European countries (1:1000) and even lower in USA (1:5000) • Higher prevalence (1:100 – 1:300) in genetically susceptible population • In USA less then 10 – 15 % of current cases of CD have been diagnosed as compere to over 50% in some other countries

  4. Susceptibility for Celiac disease Patient with Celiac disease

  5. Susceptibility for Celiac disease • Increased frequency of HLA haplotypes ( DR3-DQ2, DR4-DQ8) • Other Factors involved: • Other genetic influences (GWAS), Gene on chromosome 5, 16 and ? 6… • Environmental factors: Drugs, Infections, Cross reactivity H. P (Cytokines released during infection altering immunity)

  6. Pathophysiology of Celiac Disease IBS CD

  7. Pathophysiology of Celiac Disease • The toxic component of the gluten molecule lies in the “PROLAMIN” portion ( Proline + Glutamine) • Prolamine containing food causing “CD” is present in • Wheat (Gliadin) • Rye (Secalin) • Barley (Hordien) • Prolamine Containing food that DOES NOT causes “CD” • Oat (Avenine) ??? (Wheat cross reactivity) • Rice • Corn

  8. Pathophysiology of Celiac Disease

  9. Pathophysiology of Celiac Disease

  10. Pathophysiology of Celiac Disease

  11. Pathophysiology of Celiac Disease

  12. Clinical Presentation of Celiac disease • Classic “CD” of childhood • Late onset : Non specific symptoms • Dermatitis Herpetiformis • Extra intestinal presentation ( Multiple, e.g undefined iron deficiency Anemia) • Silent / Asymptomatic disease • Latent or Potential “CD”

  13. Clinical Presentation of Celiac diseaseClassical presentation PRESENT IN PEDIATRIC POPULATION • Failure to thrive • Weight loss • Protuberant abdomen • Bloating • Diarrhea- steatorrhea • Abdominal pain • Dramatic response to gluten free diet

  14. Clinical Presentation of Celiac diseasevarying forms • Classical presentation is less common • Average age of diagnosis is 5th decade • Seroprevalance M=F, Diagnosis F > M • Other presentation are more common • Unexplained Iron deficiency Anemia • Osteoporosis • Obstetrical problems • Neuropsychiatric manifestation • Related autoimmune conditions

  15. Clinical Presentation of Celiac diseaseAdults : IBS V/s “CD” • Altered bowel habit ( Diarrhea, constipation, combination) • Bloating • Dyspepsia • Abdominal discomfort • Heartburn

  16. Clinical Presentation of Celiac diseaseDermatitis herpetiformis Pruritic Papulovesicularleions ( IgA deposit at he dermal-Epidermal level) Almost all patient have GI symptoms Topical treatment does not help. GFD resolve all skin lesions

  17. Clinical Presentation of Celiac diseaseObstetric/gynecological • Delayed Menarche • Earlier Menopause • Increased prevalence of early amenorrhea • Infertility • Higher miscarriage rate • Increased IUGR • Lower birth weights • Premature birth

  18. Clinical Presentation of Celiac diseaseNeuropsychiatric & Behavioral Folate and Vit-B12 deficiency • Ataxia • Peripheral neuropathy • Schizophrenia • ADHD • Irritability / cognitive disorder • Depression • Migraine • Cerebral calcifications

  19. Clinical Presentation of Celiac diseaseAssociated conditions • Primary sclerosing cholangitis • Autoimmune cholangitis • Primary biliary cirrhosis • Non specific “Transaminases” (LFT) elevation ( up to x 5) • Progressive systemic sclerosis (Scleroderma) / Sjogren’s syndrome / RA • Hashimoto thyroiditis (Autoimmune thyroid disorder) • Type I Diabetes • Microscopic colitis

  20. Celiac diseasediagnosis

  21. Celiac diseasediagnosis • Intestinal histology “GOLD STANADARD” in diagnosing Celiac Disease (Characteristic histological changes) • Serology • Clinical: some cases histological response to a “GFD” • Rarely necessary to observe clinical and histological response to “Gluten Challenge” • Dermatitis Herpetiformis: a classical skin biopsy is sufficient to make diagnosis

  22. Celiac diseasediagnosis Marsh Classification

  23. Celiac diseasediagnosis NORMAL Celiac disease

  24. Celiac diseaseSerology diagnosis Important to check serum total IgA level in all patients

  25. Celiac diseasediagnosis What are the best serological test for screening: • Overall, tTGIgA remain the best recommended test • EMA IgA is helpful if positive • Anti GlidanAb, no longer used as first line. • Always check total IgA, to avoid false negative results

  26. Celiac disease diagnosis genetics • HLA DQ screening test: PCR of RNA extracted from cells. • DR3-DQ2 or DR5/7-DQ2---90-95 % • DR4-DQ8 – 5-10 % • Only HLA DQ2 or DQ8 are at risk for CD

  27. Celiac disease diagnosis genetics WHO TO TEST: • Close relative of patients with confirmed CD (Wishing to know if they are at risk) • Patient on Gluten free diet who are candidate to undergo a gluten challenge to confirm CD • Equivocal histology and serology, Suspect CD How often to test: Once in life time

  28. Celiac disease proposed new criteria for diagnosis Four out of Five are sufficient to diagnose CD: • Typical symptoms of CD • High titers of serum CD IgA class autoantibodies ( tTG > 10 X UL, option to diagnose without biopsy) • HLA DQ2/DQ8 genotype • Celiac enteropathy by small bowel biopsy (GOLD STANDARD) • Response to CFD

  29. Celiac diseasediagnosis algorithm

  30. Celiac disease management • Goal: Return of normal health and prevent complications • Life long GFD • Low lactose diet • Nutritional supplement (Calcium, Vit-D, Iron, Folate and other micronutrients) • Utilize registered dietician • Encourage patient to gain self knowledge, by joining local chapter of various Celiac organization

  31. Celiac disease management TREATMENT = GLUTEN FREE DIET • Non compliance is the biggest issue • Eating out of home • Peer pressure in children • Less acceptable taste • Accidental ingestion of Gluten • Cost 1-3 times higher • GFD ameliorate complication of CD • Unclear how much if any is safe ( New FDA guideline 20 PPM (up to 10 mg/day is safe) • Labeling in USA for wheat since 2008 (Gluten free product since 2008)

  32. Celiac disease untreated • Manifestation of malabsorption ( Anemia , Osteoporosis, neurological symptoms) • Decrease QOL • Infertility, Miscarriage, IUGR • Malignancy ( ~ 4 times general population) • Slight increase in mortality • May progress to refractory disease

  33. Celiac disease Response to treatment • Clinical improvement in 2 weeks in 70 %, and by 6 weeks > 90 % • Serologic improvement by 4-6 weeks • Weight restoration • Constipation is quite common ( Diarrhea in disease state) • Histological improvement is last ( May take up to 2 years or more)

  34. Celiac disease Follow-up • Correct nutritional deficiencies • Follow tTG IgA initially until normalize, Then Check tTG IgA every year or two thereafter • Repeat DEXA scan ever 2 year if abnormal • In persistent symptoms for over a year or so check radiological studies and +/- repeat EGD ( For lymphoma surveillance) • Promote general good health ( Exercise, maintain BMI and adhere to screening)

  35. Celiac disease Non Responder • Celiac disease and Microscopic colitis: • 4-5 % have coexisting MC • Older group of patient • More severe CD ( Severe mucosal atrophy) • High morbidity • Coincident disorder: • Lactose deficiency • Pancreatic insufficiency • Small intestinal bacterial overgrowth (SIBO) • IBS

  36. Celiac disease Refractory celiac disease • Despite strict GFD for 6-12 months: Severe villous atrophy with persistent malabsorption • Rare with low prevalence • Primary form – No initial response to GFD • Secondary form ( More common): After initial response to GFD • tTG IgA remain normal if patient is on GFD • Risk for RCD: old age, Two DQ2 alleles • Poor prognosis: 40-50 % mortality rate ( 50 % patient dies within 3-5 years of diagnosis) • Higher incidences of intestinal lymphomas

  37. Celiac disease Refractory celiac disease

  38. Celiac disease Refractory celiac disease Treatment options: • Anti-Inflammatory agents: Mesalamine • Immune modulating therapies: e.g. Corticosteroid therapy, Anti TNF • Nutritional support: TPN, Hypoallergenic-elemental formula • Hematopoietic Stem cell transplantation • Anti IL-15

  39. Celiac disease prevention and future • Prevention: • Affective screening • Different times of introduction of “Gluten” in to the infant diet • Modify Gluten molecules: • Endopepetidases: “KUMAMOLISIN-AS” ( KUMA-MAX) break the gluten molecule, so it is no longer immunogenic • Immunotherapy: • Block: tTG expression, HLA or T cell response

  40. Celiac disease take home message • CD is not rare ( 1 in 100-300) • It present in many different ways and is associated with various autoimmune diseases • Increase reporting of Gluten sensitivity or Gluten Intolerance • Diagnostic test perform well but have some limitations • Gluten free diet remain the main stay of successful treatment • Potential new therapies are being investigated • Multiple causes of nonresponsive celiac disease

More Related