Download Journal Club - Faculty of Medicine, McGill University

Celiac Disease: more than you
ever wanted to know
Internal Medicine
Academic Half Day
Royal Victoria Hospital
Tuesday, March 9, 2010
Clare Bastedo R5, GI
Case 1:
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24F with non-bloody diarrhea (6x/d) x 6
weeks. No PMHx. 5 lbs. wt. loss. Normal
exam.
What else would you like to know on
history and physical exam so you can
come to a diagnosis and treat this patient?
(Remember: Time is limited! )
Acute vs. Chronic Diarrhea
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Acute Diarrhea < 2 weeks
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Persistent > 2 wks
Chronic Diarrhea > 4 weeks
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Decrease in fecal consistency
Chronic Diarrhea
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“Gather my thoughts” – really do this!
“Wash my hands, introduce myself to the
patient”
ABCs
Vital signs including temperature
The Basics – don’t forget them!
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PMHx
Meds, Allergies, Alcohol, Smoking, Drugs
Social History/Employment
Family History
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Esp. IBD, celiac dz, CRC, lactose intolerance
Hx. specific to chronic diarrhea
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Details of the diarrhea
Complications of the diarrhea
Causes of the diarrhea
Details
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OPQRST
Onset, duration, frequency, volume
Bloody, consistency, tenesmus, urgency,
steatorrhea
Changes with meals/foods
Nocturnal symptoms
Associated sx: N/V, pain, jaundice,
constipation, fever, wt. loss
Complications
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Hypovolumia/electrolyte disturbance
Edema (protein-losing enteropathy)
Arthritis - reactive
Screen for nutritional deficiencies
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Anemia, osteoporosis, Vit K and other FSV
Causes – 6 main categories
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Infectious – exposures, travel, HIV, sex, daycare, Abx,
recent hosp adm
Inflammatory – radiation, ischemia RFs, IBD (systemic),
CRC (constitutional)
Osmotic – relation to lactose, antacids, laxatives, gum
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Secretory – drugs, previous surgery, previous bowel
disease, hx. tumors (carcinoid, VIPoma, ZE syndrome)
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Stops while NPO, lower volume, high stool osm gap >125
Continues when NPO, high vol > 1L/d, low stool osm gap <50
Malabsorptive – wheat, ethnicity, other AI d/o, DH, liver
dz screen, bile tract dz, bowel rsxn, pancreatitis
Motility – DM, hyperthyroidism, scleroderma, IBS,
hyperthyroidism, Addison’s
Focused Physical Exam
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Gen: Height, weight, signs of malnutrition
VS: Orthostatic vital signs
H&N: Uveitis, episcleritis, oral ulcers, LNs,
thyroid, pallor
CVS/Resp: volume status, flow murmur
Abdo: pain, distension, HSM, stigmata CLD,
masses, DRE, frank/occult blood
MSSK/Derm: active joints, rash (EN, PG, DH),
bruising, clubbing
Investigations
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CBC, lytes, Cr, glucose, calcium, albumin, liver
profile, INR, Bilirubin, TSH, ESR/CRP
Stool C&S, C. diff, O&P, occult blood, ?fecal
leukocytes
Antiendomysial Ab/Tissue transglutaminase Ab,
EGD + Bx for ?celiac dz
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(NB IgA-based tests so can have false negative in IgA
deficiency … if high suspicion measure IgA level)
Celiac Disease
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An autoimmune disorder that occurs in geneticallypredisposed individuals  result of an immune
response to gluten
One of the most common chronic inflammatory
conditions of the digestive system
Present in approx. 1% of the population (U.S.)
Presentation
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Diarrhea has become less common (<50% of cases)
Typically presents age 10-40
Also iron-deficiency anemia, osteoporosis, dermatitis
herpetiformis, and neurologic disorders, (peripheral
neuropathy and ataxia)
Non-invasive screening (based on serology) shows
that CD is often undiagnosed
Celiac disease
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Characterized by:
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(1) Small intestinal malabsorption
(2) Villous atrophy of the small intestinal
mucosa
(3) Clinical and histologic improvement
following a gluten-free diet
(4) Clinical and histologic relapse when gluten
is reintroduced
Schleisenger
Figure 1. Endoscopic markers of villous atrophy visible in the duodenum
at EGD. (A) Mosaic-patterned mucosa. (B) Deep mucosal grooves. (C)
Scalloping of a duodenal fold. (D) Nodular mucosa. (E) Loss of duodenal
folds. (F) Visible submucosal vessel on a background of fold loss. (G) Multiple
duodenal erosions.
Points to ponder
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How should diagnosis of celiac disease be
made?
Significance of “undiagnosed” celiac
disease?
Known associations and observed M&M
Diagnosis of Celiac Disease
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Small bowel disorder characterized by mucosal
inflammation, villous atrophy, and crypt
hyperplasia
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occurs on exposure to dietary gluten and
demonstrates improvement after withdrawal of dietary
gluten
Wide use of serologic testing for celiac disease
and upper endoscopy complicates the diagnosis
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these tests identify patients who appear to have the
disease but have variable degrees of histopathologic
changes and/or symptoms
Disease spectrum – phenotypes
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Atypical celiac sprue - gluten-sensitive enteropathy
found in atypical manifestations including short stature,
anemia, and infertility
Silent celiac sprue – villous atrophy and no symptoms
Classic or typical celiac sprue - gluten-sensitive
enteropathy found in association with the classic
features of malabsorption
Latent celiac sprue - Abnormal serology + normal
histology + no symptoms; previously abnormal histology
but now normal on GFD
Potential celiac sprue - abnormal serology + normal
histology + no symptoms
Celiac Disease - variation
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Natural history of variant forms of celiac
disease is incompletely understood
Long-term risk of complications in
asymptomatic patients is unclear
Asymptomatic patients may also be least
likely to comply with a gluten free diet,
even if diagnosis of celiac disease is made
Who should be tested?
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NIH guidelines (2004)
GI symptoms – diarrhea, weight loss, bloating,
even if c/w IBS or lactose intol
Without other explanation for:
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iron deficiency anemia, folate or vitamin B12 deficiency, persistent
elevation in LFTs, short stature, delayed puberty, recurrent fetal loss,
low birthweight infants, reduced fertility, persistent apthous
stomatitis, dental enamel hypoplasia, idiopathic peripheral
neuropathy, nonhereditary cerebellar ataxia, or recurrent migraines
Symptomatic patients at high-risk
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type 1 DM or other AI disorders, 1st- and 2nd-degree
relatives of individuals with celiac disease, patients
with Turner, Down, or Williams syndromes
Screening of asymptomatic pts?
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General population – not recommended
Osteoporosis? – not officially
recommended, but study group with
osteoporosis had significantly higher
incidence of abn biopsies than controls
(3.2 vs. 0.2%) Arch Intern Med 2005 Feb 28;165(4):393-9.
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Most had other symptoms/signs
Check if other clinical symptom/lab abn.
CD - diagnosis
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No single test can confidently establish the
diagnosis of celiac disease in every individual
Most important initial step  recognition of the
many clinical features that can be associated
Test on a gluten-rich diet (bx/serology)
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2-12 weeks
Gold-standard = small bowel biopsy abnormal on
gluten challenge
SB biopsy
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At least four biopsies in 2nd/3rd stage of
duodenum
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All who have anti-TTG or EMA positive unless
DH and positive biopsy
Atrophic with loss of folds, visible fissures,
nodular appearance or scalloped folds
Diagnosis presumed with serology and
biopsy, but confirmed with resolution on
gluten-free diet
Dermatitis Herpetiformis:
Serology
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IgA anti-TTG and IgA endomysial Ab have
equivalent diagnostic accuracy – based on
target Ag tTG
Antigliadin Ab tests - no longer used routinely
because of lower sens and spec
IgA EMA – + or - ; sens 90%, spec 99%,
reproducibility 93%  gold standard
IgA anti-tTG is slightly less reliable; sens 93%,
spec 95%, reproducibility 83%)
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98% of ppl with celiac dz vs. 5% ppl without
Sens and spec  depend on the prevalence of
the disease in the tested population
EMA, anti-TTG
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Negative result for either test has a high
negative predictive value  may eliminate
need for small bowel biopsy
Positive predictive values are high even in
low-risk populations
UTD: recommends performing both IgA
endomysial (or TTG) and small bowel
biopsy prior to dietary treatment
Screening – general population?
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Screening studies suggest incidence of celiac
disease in whites of N. European ancestry may
be as high as 1:100 to 1:250
Benefit of screening (EMA or anti-TTG) not yet
demonstrated
Theoretical benefits:
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reduction in risk for enteropathy-associated T-cell
lymphoma
reversal of unrecognized nutritional deficiency states
resolution of mild or ignored intestinal symptoms
avoidance of other auto-immune disorders
improvement in general well-being
Screening?
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Screening study of 4615 adults from N. Italy 
IgA EMA had PPV of 100% Acta Paediatr Suppl 1996 May;412:42-5.
17,201 children (6 - 15) from Italy were
screened with a prevalence of CD of 1:184
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The ratio of undiagnosed to diagnosed celiac disease
was a 7:1
Most children had minor but significant nonspecific
symptoms Acta Paediatr Suppl 1996 May;412:25-8
In the U.S. prevalence of CD was 1:22 in 1stdegree relatives, 1:39 in 2nd-degree relatives,
1:56 in symptomatic pts, and 1:133 in low-risk
group Arch Intern Med 2003 Feb 10;163(3):286-92.
Risk of malignancy
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Several studies have suggested increased
overall mortality (mostly from GI malignancies)
in patients with celiac disease compared to the
general population Lancet 2001 Aug 4;358(9279):356-61., Gastroenterology 2002
Nov;123(5):1428-35.
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Malignant lymphomas, small-intestinal, oropharyngeal,
esophageal, large intestinal, hepatobiliary, and pancreatic
carcinomas (1.3 –2.0 x risk)
Prospective cohort study with up to 24-years of follow-up (5684
person years) identified 31 malignancies compared with 30 that
would have been expected in the general population (more NHL
in CD population). Aliment Pharmacol Ther 2004 Oct 1;20(7):769-75.
Logistics
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Patients who have a positive screen would
have to comply with strict (expensive?)
diet though they feel well
Psychological harm?
Widely accepted to test for celiac disease
if subtle manifestation
Increase in Prevalence?
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Number of cases detected may be
increased due to improvements in
serological markers and increased
clinical suspicion
Recent Finnish report has observed an
increasing prevalence (x2) in celiac
disease over a 20-year period Lohi S, Mustalahti K,
British Medical Bulletin 2008 88(1):157-170
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Kaukinen K, et al. Increasing prevalence of coeliac disease over time. Aliment Pharmacol Ther
(2007) 26:1217–1225.