CELIAC DISEASE CD

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????? ???????CELIAC DISEASE (CD)

• DR.NIZAR ALHARBAT
• CONSALTANTE OF PEDIATRIC
• ARAB BORD

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????? ???????CELIAC DISEASE (CD)

• ?????? ????? ???? ????? ????? ?? ?????? ???????
  ???????? ????? ????????? ??????? ?? ?????? ?????
  ??? ????? ??????? ???????.
• ???? ??? ???????? ?? ?????? ??? ???? ???? ??
  ????????.

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• ???? ??? CD ????? ????? ??????? ?????? ?? ???
• ????????? ???????
• ????? ?????? ???? HLA
• DQ2 90
• DQ8 8
• ????? ??? ?????? ???? HLA
• 5q31-33 - 2q33
• ?????? ??????
• ????????
• ??????? ??????? ??????
• ??????? ?????????? ???????? Tissue
  Transglutaminase tTG

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????? ????? ??????? Celiac Disease (CD)
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?????? ????????? ??? CD ???? ??? tTG
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• Celiac Disease is a genetically complex,
  multifactorial immune-mediated disease.
• Gluten-derived peptides in susceptible
  individuals cause T-cell activation in the
  intestinal mucosa, which is followed by cytokine
  production and mucosal intestinal damage.

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• ???? ?????? Atypical
• ?? ??? ???? ???? ????? ????????? ???? ?? ?? ????
  ????? ???? ??? ??? ????????.
• ?????? ?? ???????? Silent/ Asymptomatic
• ??? ?????? ???? ???? ?? ???? ?????? ????? ?????
  ????? ????? ??? ??????.
• ????????? Potential
• ???? ????? ??? ??????? ????? ??? ????? ????????.
• ?????? Latent
• ?? ???? ???? ??????? ???? ????? ????? ???? ??????
  ?? ???????? ?????.

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??? ??? ?????? ??? CD
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??? ???? ??? CD
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?????? ????? ??? CDThe Present ( ESPGHAN - 1990 )

• ??? ????? ???????? ?????? ??????? ?? ??? CD
• ???? ????? ???????
• ???? ?????? ????? ??????? ?? ??? CD
• ??????? ?????? ?????? ????? ?????? ??????? ??
  ????????
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• ??????? ??????? ???????? ?????? ???????? ??? CD

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(No Transcript)
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.Wyllie,Hyams,Pediatric gastrointestinal disease,
Saunders, second edition 1999 .

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???????? ??? ???? ?? ??????? ???????? ????? ?
??????? ?? ??????? 40 ? ?????? 60
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.
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Patients older than 2 years IgG IgA

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?????? ??????? ??? CD

• AGA IgG
• ????? ??????? ?????
• ?? ???? ??? ???? ???????? ???? ?????.
• ?? ??????? ???? ?????????.
• EMA IgA
• ???? ??????? ??? ????
• ?????? ?????? ??? ???????lt2 ???.
• ??????? ????????
• ???? ?????? ?????? ?? ????? ???????.
• tTG IgGA
• ????? ?????.
• ????? ????? ?????? ??????? ???????
• ?????? ????? (98.5).
• ????? ?????? (98).
• ?????? ??? ?????.

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???????? ???????? ??? ???? ??? CD
Nelsen DA. Am Fam Physician 2002 662259-2266
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• ???????? ????????? ???????? ?? ??????? ???
  ??????? ???
• ????? ?? ??? ???????.
• ???? ??? ???????? .
• ??? ??????? ??? ????? ? ??? ????? ??? ???????
  .
• ?? ????? ??????? ????? ???? ????? ?????? ????
  ????????
• ( 4 6 ????? ) ??? ????? ?? ????? ???????
  ?????? ??? ???? ?????? ???? ???? ?????? ?? ??????
  ?? ????? ??????? ???? ?? ???? ?????? .

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????? ??????

• 1- ??? ??????? ??????? ???????? ?? ??? ???? ??
  ??? ????? ???? ???? ???????? ( ?????? ????? ) .
• 2- ??? ???? ????? ??????? ( ???????? ???????
  ??????? ? ????? ?????? ) .
• 3- ????? ????? ??????? ?????? ( ????? ??????? ?
  ??????? ) .
• ?? ???? ?????? ???? ??? ????? ??????? ??????? ???
  ???? ??????? ??? ????????? ???? ????? ???
  ??????????? ???? ??????? TEL ? ???? ??????? ? ???
  ?????? ????? ?? ?????? ????? ????? ????? ???????
  ? ???? ??? ??? ??????? ??????? ?? ????? ??????
  ?????? ???? ??????? ??????? .
• ???? ??? ??? ?????? ?????? ?? ???? ???? ???????
  ??????? ?????? ??????? ??? ???????? ???????
  ????????? ???? ????? ?? TEL ? ???????? ???????
  ??????? ??? ???? ??? ??????? ??????? ???? ???????
  ????? .

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Marsh stage 1
Intraepithelial lymphocytosis (infiltrative
lesion, intraepithelial lymphocytes gt40 per 100
enterocytes)
Marsh stage 2
Lymphocytic enteritis with crypt hyperplasia
(hyperplastic lesion, villous abnormality
epithelial lymphocytosis)
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Marsh stage 3
Marsh IIIA, partial villous atrophy.
Marsh IIIB, subtotal villous atrophy
Marsh IIIC, total villous atrophy.
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• ? ??? ??? ?????? ??????? ?? ??? ???????? ????? ??
  ???? ???????? ????? ?????? ?????? ?? ???????
  ????? ????? ??????? ? ???? ?????? ??????? ????? ?
  ???? ?? ????? ?????? ?????? ?????? ??????????
  ?????? ????? ??????? ??? ???? ??? ?? ???
  ????????? ??????? ????? ????? ? ???? ?????
  ???????? ??????? .
• ???? ???? ??? ?? ?????? ?????? ?????? ????? ????
  ?????? ???????????? ?????? ??????? ??????????
  TTG ???????? ?? ???? ??????? ? ????? ??????? ?
  ?????? ??? ???? ??????? ? ???????? ??????? ??
  ??????? .
• ? ?????? ??? ?? ?? ???????? ?????? ???????
  ??????? ??? ????? ???? ?? HLA ??? ????? ??? HLA
  ???? ?? ????? ???? ?????? ????? ????? ???????
  ?????? ??????? ??? ???? ???????? ??? ?? ???
  ?????? ????? ???? ??????? ?????? .
• ????? HLA ?? ?????? ?? ??????? ?????? ?????
  ??????? ???? ???? ? ??? ????? ??? ???? .

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• ???? ?? ?????? ???? ?? ???? ?????? ??????
  ??????? ????? ??????? ? ? ???? ?? ???? ??????
  ?????? ?? ?????? ???????? ? ?? ???? ?? ??? ????
  ???? ???? ????? ??? ????? ?? ?????????? ???????
  ???????? .

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Avoid for life
??????

• ?????? ???????? ???? ???????? ?? ????? ? ?????? ?
  ?????? ? ?? ??????? ??????? ??? ????? .
• ???????? ???? ??????? ????? ??? ??? ??????? ?
  ???????? ???? ???????. ? ?? ???? ????? ?????? ??
  ?? ??? ?? ??????? .

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Medical Care

• In the early phase of treatment, most patients
  may be lactose intolerant because of the
  reduction of available absorptive area.
• Thus, a lactose-free (not milk-free) diet can be
  used, but only for the first few weeks because
  this condition is transient.
• In some patients who present with obvious
  malabsorption, specific nutritional deficiencies
  must be sought and, if present, treated
  adequately with supplements. These most commonly
  include Fe, folate, and vitamin B-12.
• It now appears that oats are safe, but long-term
  studies still are lacking

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Treatment and Prognosis

• Therapy of choice is lifelong gluten-free diet.
• Major lifestyle change as common foods have to be
  substituted / avoided compromising taste.
• Symptoms improve within days to weeks.
• Pathological changes take months or longer.
• Foods may be added back in small amounts
  (trial)!!!????????
• Most common cause of failed therapy is dietary
  non-compliance (dietary education is necessary)

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Treatment and Prognosis

• Those not responding to diet are termed
  refractory sprue may respond to
• Corticosteroids
• Cyclosporine and azathioprine (not proven.)
• Many develop secondary lactase deficiency
• Avoid milk products until stable.
• Replace vitamin and electrolyte deficiencies.

• Prognosis is excellent for those who respond to a
  gluten-free diet (majority).

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CD and Malignancy
UpToDate, 2006
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FUTURE TREATMENT ????

• Genetically engineered grains.
• Enzymatic digestion of toxic gliadin peptides.
• Inhibition of the zonulin pathway.
• Blocking TTG enzymatic activity.
• Blocking of gliadin peptide binding on HLA DQ2/8
  on APC.
• Inhibition of antigen presentation by APC to T
  lymphocytes.
• Inhibition of cytokine production and/or
  function.
• Inhibition of activation of T killer lymphocytes.

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RECOVERY

• Dietary compliance can be the most difficult
  aspect of treatment.
• BUT
  REWARDING.
• The recovery in children seemed to progress
  faster and more completely than in adults.
• Considered regression of mucosal abnormalities,
  with normalization of villi to Marsh 0, I, or II,
  as histological remission and, thus, the end
  point of the follow-up study.
• The working group on celiac disease of the
  European Society for Paediatric Gastroenterology
  and Nutrition does not specifically define
  histological remission.

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