Celiac disease truths n myths
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Transcript of Celiac disease truths n myths
CHAIRPERSON-
Dr. Ardaman Singh
PRESENTATION-
Dr. Honey Sharma
What is Celiac disease?
Celiac disease Small intestinal malabsorption of nutrients
Seen after the ingestion of wheat gluten or
related proteins from rye and barley
Characterised by villus atrophy of the small
intestinal mucosa and prompt clinical and
histologic improvement following strict
adherence to a gluten-free diet
Clinical and histologic relapse when gluten is
reintroduced.
ATYPICAL CELIAC DISEASE- Fully expressed
gluten-sensitive enteropathy manifest only by
extraintestinal symptoms and signs including short
stature, anemia, osteoporosis, and infertility.
SILENT CELIAC DISEASE- Fully expressed gluten-
sensitive enteropathy usually found after serologic
screening in asymptomatic patients.
CLASSIC/TYPICAL CELIAC DISEASE- Fully
expressed gluten-sensitive enteropathy found in
association with the classic gastrointestinal symptoms of
malabsorption.
LATENT CELIAC DISEASE- Normal villusarchitecture on a gluten-containing diet but, at anothertime, have had or will have gluten-sensitive villus atrophy.
POTENTIAL CELIAC DISEASE- Never had a biopsyconsistent with celiac disease but show immunologicabnormalities characteristic for the disease- positive(Ig)Aantibody to endomysium (or tissue transglutaminase [tTG])or increased intraepithelial lymphocytes (IELs) in the smallintestine.
REFRACTORY/UNCLASSIFIED/INTRACTABLECELIAC SPRUE- Symptomatic, severe small intestinalvillus atrophy that mimics celiac disease but does notrespond to at least six months of a strict gluten-free diet.This is a diagnosis of exclusion that is not accounted for byinadvertent gluten ingestion, other causes of villusatrophy, or overt intestinal lymphoma.
Marked geographic variation
Rare in the predominantly rice-eating area of
southern India, prevalent in Punjab
provinces of northwest India, where wheat
rather than rice, for many generations, has
been staple diet.
Female-to-male ratio of 2 : 1 reported by
some where as some studies report as low as
1.3 : 1 ratio but still suggesting a FEMALE
predominance.
Affects the Mucosa of the small intestine.
Examination of the small intestinal mucosal
surface- a flat mucosal surface with complete
absence of normal intestinal villi.
HISTOLOGIC EXAMINATION- Confirms this loss of
normal villus structure.
Intestinal crypts- Markedly elongated and open
onto a flat absorptive surface.
Total thickness of the mucosa is reduced only
slightly in most cases, because crypt hyperplasia
compensates for the absence or shortening of
the villi.
CENTRAL MECHANISM OF VILLUS SHORTENING
Gliadin-associated toxic effect on maturing enterocytes that results in their premature loss into the intestinal lumen and a compensatory increase in enterocyte replication in the crypts.
Stage 0- Normal preinfiltrative
mucosa, IEL rise
Stage 1-lamina proprialymphocytosis
Stage 2- Crypt hyperplasia
Stage 3-Villous atrophy
Stage 4- total mucosal atrophy
Centre to pathogenesis- Interaction of the water-insoluble protein moiety (gluten) of certain cereal grainswith the mucosa of the small intestine in susceptiblepersons.
ENVIRONMENTAL FACTORS- wheat protein categorizedinto 4 groups.
Prolamins
Glutenins
Globulins
Minor albumins
• Gluten encompasses both the prolamins and the glutenins.
• Prolamins of wheat are referred to as gliadins.
• Prolamins from oats, barley, wheat, and rye haveimmunologic cross-reactivity because of their commonancestry.
• Grains that do not activate disease - rice, corn, sorghum,and millet.
Concordance for celiac disease in first-
degree relatives 8%-18% and 70% in
monozygotic twins.
Celiac disease is associated with specific
HLA-DQ2 haplotypes. The HLA class II
molecule DQ2-more than 90% of persons with
celiac disease. HLA-DQ8 found in remaining.
Only a minority of persons who express DQ2
actually develop celiac disease. Much of the
genetic predisposition to celiac disease is
conferred by genes other than those
encoding HLA DQ molecules.
Antigliadin antibodies- nonspecific response tothe passage of incompletely digested antigenicgluten proteins across an abnormally permeableintestinal epithelium.
IgA antibodies to endomysium are virtuallypathognomonic for celiac disease .
The target autoantigen contained within theendomysium is the enzyme tTG-2.
Gliadin is a preferred substrate for thisubiquitous calcium-dependent intracellularenzyme, and tTG deamidates key neutralglutamine residues in gliadin and converts theminto negatively charged glutamic acid residues,which are preferred in positions 4, 6, and 7 ofthe nonapeptide antigen-binding groove of theHLA-DQ2 heterodimer thereby facilitatingantigen presentation.
Steatorrhea with or without vomiting
Occ. cramping abdominal pain esp. in 1st and
2nd yr of life
Failure to thrive
Apathetic and Irritable child
Muscle wasting, Hypotonia, and Abdominal
distention
Watery diarrhea or occasionally constipation
Nutritional deficiencies, particularly anemia,
especially in older children.
Overall mean age at presentation- 45 years;approx. 25% of cases diagnosed in patients olderthan 60 years
G.i. symptoms including diarrhea, steatorrhea,flatulence, and weight loss
Diarrhea is episodic rather than continuous.Nocturnal, early morning, and postprandialdiarrhea are common.
Patients with extensive intestinal involvementcan have more than 10 stools per day.
The stools may be light tan or grayish and greasyin appearance, with a tendency to float anddifficult to flush.
Steatorrhea often is absent in patients withdisease limited to the proximal small intestine.
Weight loss
Malaise, lassitude, and fatigue
Occ., severe hypokalemia resulting fromfecal loss of potassium causes severe muscleweakness.
Vague abdominal discomfort and esp.abdominal bloating are extremely common
Severe abdominal pain can occur but isuncharacteristic in uncomplicated celiacdisease
Abdominal distention with excessive amountsof malodorous flatus is a common complaint.
Recurrent severe aphthous stomatitis maybe the sole presenting complaint.
Cutaneous- Ecchymosis, petechiae, edema,dematitis herpatiformis, follicularhyperkeratosis and dermatitis
Endocrinologic- Amenorrhoea, infertility,impotence, sec.hyperparathyroidism
Haematologic- Anaemia, haemorrhage,thrombocytosis
Muscular- Atrophy, tetany, weakness
Neurologic- Peripheral neuropathy, ataxia,demyelinating CNS lesions, seizures
Skeletal- Osteopenia, osteoarthropathy,pathologic fractures
Common manifestation in children and adults
Caused by impaired iron or folate absorption.
In severe disease with ileal involvement, vitamin
B12 absorption also is impaired.
Bleeding into the skin or mucous membranes or
hematuria, epistaxis, or vaginal or
gastrointestinal bleeding caused by a
coagulopathy resulting from impaired intestinal
absorption of fat-soluble vitamin K.
Evidence of hyposplenism with thrombocytosis,
deformed erythrocytes, and splenic atrophy,
occurs in up to 50% of adults with celiac disease
but only rarely is seen in children.
Most common complication
Due to-
impaired calcium absorption
vitamin D deficiency
binding of intraluminal calcium and magnesium tounabsorbed dietary fatty acids (forming insolublesoaps, which are then excreted in the feces).
Present with-
Bone pain, esp. the lower back, rib cage, and pelvis.
Calcium and magnesium depletion can causeparesthesias, muscle cramps, and even frank tetany.With prolonged calcium malabsorption, patients maydevelop secondary hyperparathyroidism.
Caused by lesions of the central or peripheral
nervous system occasionally occur in patients
with celiac disease.
Progressive gait and limb ataxia may be the sole
manifestations of disease in some patients and is
referred to as GLUTEN ATAXIA, result from
immunologic damage to the cerebellum,
posterior columns of the spinal cord, and
peripheral nerves.
The associations of celiac disease and epilepsy,
frequently complex partial seizures, and
bilateral parieto-occipital cerebral calcification
is well recognized. The cause remains unclear.
Common in women with untreated celiacdisease.
Amenorrhea occurs in one third of women ofchildbearing age and menarche is delayed,typically by one year, in untreated subjects.
A high prevalence of silent celiac disease hasbeen reported in women with recurrentspontaneous abortions, intrauterine fetalgrowth retardation.
Infertility secondary to impotence or anabnormally low sperm count can occur inmen with untreated celiac disease.
On average, Three inches shorter than their peers.
Evidence of weight loss- loose skin folds and muscle wasting
Clubbing and koilonychia
Pitting edema of the lower extremities secondary to hypoproteinemia.
Hypotension related to fluid and electrolyte depletion
The skin is dry with poor turgor, if dehydrated.
Increased skin pigmentation.
Aphthous stomatitis, angular cheilosis, and glossitis with decreased papillation of the tongue and Dental enamel defects.
Serum IgA EMA or tTG antibody and small intestinal biopsy are the most
reliable diagnostic tests.
SEROLOGY-IgA EMA and IgA tTG are based on the target antigen tTG, and IgA
and IgG AGAs are based on the target antigen gliadin.
IgA EMA sensitivity 90%, specificity 99%, and reproducibility 93% and currently
remains the gold standard.
GENETIC TESTING
Almost all patients with
celiac disease are positive
for HLA DQ2 or DQ8.
HLA testing may be helpful
in excluding celiac disease
in specific clinical
situations, mainly before
embarking on a gluten
challenge or evaluating a
patient who has a celiac-
like enteropathy but
negative IgA tTG, EMA, and
DGP serologies.
Biopsy of the small intestine- The standardtest to establish the diagnosis.
Multiple biopsies should be obtained (e.g., atotal of six to eight biopsies from the secondand third parts of the duodenum).
Increased IEL’s, flat villi, hyperplastic cryptsand inc. lymphocytes in lamina propria.
Scalloping or absence of duodenal foldsnoted.
Other endoscopic features include multiplefissures or a mosaic-like appearance wherethe fissures circumscribe areas of mucosalnodularity in a manner similar to thegrouting around a mosaic tile.
Pancreatic insufficiency
Cholestatic liver disease
Terminal ileal disease or resection
Small intestinal bacterial overgrowth
Whipple's disease
Infiltration of the mucosa with Mycobacterium avium complex.
Parasitic infections- strongyloidiasis, coccidiosis, hookworm disease
Hypogammaglobulinemia
An acute viral gastroenteritis
Cow's milk or soy protein intolerance
Collagenous sprue
Definite
•Bird-fancier’s lung
•Dermatitis hepatiformis
•DM Type1
•Down’s syndrome
•Epilepsy with cerebral calcification
•Fibrosing alveolitis
•Hypo/hyperthyroidism
•Idiopathic pulmonary hemosiderosis
•IG A deficiency
•IGA mesangial nephropathy
•IBD
•Microscopic colitis
•Recurrent pericarditis
•RA
•Sarcoidosis
Possible
•Addison’s disease
•AIHA
•Autoimmune liver disease
•Cavitory lung disease
•CHD
•Cystic fibrosis
•Immune thrombocytopenic purpura
•Iridiocyclitis/choroiditis
•Macroamylasemia
•Myasthenia gravis
•Polymyositis
•Schizophrenia
•Sjogren syndrome
•Systemic and cutaneous vasculitides
•SLE
Avoid foods with wheat, rye, barley gluten.
Avoid all oats initially.
Avoid malt unless clearly labelled derived fromcorn.
Use only rice, corn, maize, millet, amaranth,sorghum, potato or potato starch, soyabean, andnut flours.
Wheat starch only used if it contains < 20ppmgluten and marked as gluten free.
Read labels and ingredients of processed foods.
Avoid beer unless labelled gluten free.
Wine, whiskey and brandy are allowed.
Beware of gluten in medications
Beers, Herbal tea
Soups, Gravy and soy sauses
Candy, Wafers
Lipstick and lip balms
Meat and sea food
Nutritional supplements
Salad dressings
Toothpaste
Key element
AVOIDWHEAT
Consult a skilled dietician
Education about disease
Life long adherence to gluten free diet
Identify and treat nutritional deficiencies
Access to advocacy group
Continuous long term follow up
Considerable variation among patients with
celiac disease in their ability to tolerate
gluten.
Some patients are exquisitely sensitive to
ingestion of even minute amounts of gluten
and can develop massive watery diarrhea
within hours of eating very small amounts of
gluten.
Occasionally, the diarrhea is so severe that it
can induce acute dehydration, termed
gliadin shock or celiac crisis.
Appropriate supplemental therapy tocorrect nutritional deficiencies.
The risks of osteopenia and osteoporosisshould be explained and general adviceshould be given about weight-bearingexercises, dietary calcium and vitamin Dintake.
Glucocorticoids are not indicated in theroutine management of celiac disease butare reserved for severely ill patients whopresent with acute celiac crisis manifestedby severe diarrhea, dehydration, weight loss,acidosis, hypocalcemia, andhypoproteinemia.
The persistence of symptoms, signs, orlaboratory abnormalities typical of celiac diseasedespite adherence to a gluten-free diet for atleast six months.
Primary NRCD- Nonresponsive immediately afterthe initial diagnosis
Secondary NRCD- Nonresponsive following aperiod of response to the gluten-free diet
The single most common cause for NRCD-continued gluten ingestion, which is ofteninadvertent and occult.
A persisting elevation of anti-tTG is stronglyassociated with ongoing gluten exposure.
Intolerance to disaccharides (e.g., lactose,fructose) also is common, especially in primaryNRCD.
Unclassified or intractable celiac disease-
defined as symptomatic, severe small
intestinal villus atrophy that mimics celiac
disease but does not respond to at least six
months of a strict gluten-free diet and is not
accounted for by other causes of villus
atrophy or overt intestinal lymphoma.
Uncommon in adults, extremely rare in
children, and largely a diagnosis of exclusion
Complications- Ulcerative jejunoileitis,
Cryptic intestinal T- cell lymphoma
Glucocorticoids
Immunosuppressive therapy- Azathioprine or 6-mercaptopurine used as a glucocorticoid-sparingagent if a dose of 10 mg of prednisolone or more/dayis required to keep the condition under control.
Other drugs- cyclosporine, infiximab
Oral budesonide is fast becoming a drug of firstchoice for treatment of refractory celiac disease.
Trial of immunosuppressive therapy is worthconsidering in all patients with refractory celiacdisease, caution must be used, because thesepatients often are malnourished and hyposplenic;hence prone to opportunistic infections.
Small intestinal lymphoma- often multifocal anddiffuse, accounts for one half to two thirds ofthe malignancies complicating celiac disease andtypically occurs after 20 to 40 years of disease.
Typically of T-cell origin
In patients whose disease was previouslycontrolled on a gluten-free diet, recurrence ofgastrointestinal symptoms (e.g., abdominal pain,weight loss, diarrhea) should raise the clinicalsuspicion of lymphoma.
Carcinoma, particularly of the oropharynx,esophagus, and small intestine, account for onethird of the remaining malignancies complicatingceliac disease. The average patient affected-older than 50 years.
Excellent prognosis- if it is diagnosed early
and the patient adheres to a lifelong gluten-
free diet.
Conversely, if not recognized, patients can
develop marked malnutrition and debilitation
and can die of complications such as
intercurrent infection, hemorrhage, or
malignancy.
Past studies- mortality increased 1.9-3.4 fold
if nonadherence to gluten free diet.
Oral glutenases
Larazotide acetate- an octapeptide inhibitorof paracellular permeability derived from aprotein (zonula occludens toxin) secreted byVibrio cholerae
Genetic modification of wheat to deletetoxic peptides
tTG inhibitors are also being evaluated for their ability to reduce gluten toxicity.
Blockade of signals derived from IL-15- an attractive possibility in refractory celiac disease
MESSAGE
KEEP HIGH CLINICAL
SUSPICION
PATIENT
COUNSELLING IS
EQUALLY IMPORTANT
AS DIETARY
TREATMENT