ion syndrome
TRANSCRIPT
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MALABSORPTION SYNDROMEby
DURRIYA RAZA
House officer
Medicine unit IV, CHK
Death sits in the bowels . . . Baddigestion is the root of all evil.
Hippocrates, 400 B.C.
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Case 37-year-old man
32-year history of type 1 diabetes. presented with nausea, vomiting,
abdominal pain, and watery diarrhea forlast 1 week.
His wife and two young children hadsimilar symptoms that had lasted 45 daysand resolved.
Two weeks earlier, he had been treatedwith azithromycin (Zithromax) for sinusitis.
No fevers, chills, hematochezia, andmelana..
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Bowel sounds were present.
soft, flat abdomen with mild diffusetenderness but no rebound orguarding.
Stools for fecal leukocytes, ova andparasites, and c-difficile were allnegative.
He was treated symptomatically withImodium and promethazine withgradual resolution of his symptoms
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Over the subsequent year and a half,the patient had seven similarepisodes.
During these episodes, he wasafebrile but had vomiting and liquid
bowel movements with mucus. The episodes generally lasted for 2
weeks and resolved. Between
episodes, he generally had oneformed bowel movement per day buthad alternating periods ofconstipation and diarrhea.
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Differentials? This patient's history of spouse and young
children with similar symptoms certainly
raises the possibility of viralgastroenteritis and bacterial and parasiticenteric pathogens.
In addition, his previous treatment with abroad-spectrum antibiotic for sinusitisraises the possibility ofpseudomembranous colitis. Appropriatetesting ruled out these possibilities andthe recurrence of symptoms made these
diagnoses less likely. Nausea and vomiting in a patient with
long-standing type 1 diabetes mayrepresent gastroparesis, a manifestation ofdiabetic autonomic neuropathy.
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Medication-induced diarrhea,
enteric pathogens, pseudomembranous colitis,
primary intestinal diseases, such as
inflammatory bowel disease andceliac disease, and pancreaticexocrine insufficiency.
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a s a a sorp on The integrated processes of digestion
and absorption have 3 phases:
Luminal phase
Mucosal phase
Transport phase
Disturbances of these processes lead tomalabsorption
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Mechanism1. Luminal phase (processing defect)
Digestive enzyme deficiency /inactivation
bile salt synthesis; Excretion;loss;bile salt de-conjugation
gastric acid; intrinsic factor (p.anemia)
Bacterial consumption ofnutrients
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Postgastrectomy steatorrhea.
Exocrine Pancreatic insufficiency. Reduced bile salt concentration in
intestine:
I.) Liver Disease
II.) Cholestasis
III.) Bacterial over growth
IV.) Interruption of enterohepatic
circulation of bile salt.
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Mucosal phase
Epithelial transport defectinflammations
infections Brush border hydrolysis defect
congenital/acquireddisacharidase deficiency
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Crohns disease
Coeliac disease Tropical Sprue
Disaccharide Deficiency Lymphoma
TB
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Post-absorptive phase(transport
phase) Enterocyte processing
Abetalipoproteinemia
Lymphocytic obstructionintestinal
lymphangectasia
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gns symp omsCalori Weight loss with normal appetite
Fat Pale,voluminous,greasy offensive diarrhea
Protein Edema, muscle atrophy, amenorrhea
carbohydrate Abdominal bloating, flatus, w. diarrhea
B12 Macrocytic anemiaSubacut combined degeneration of sp.cord
Folic acid Macrocytic anemia
Vit B (general) Cheliosis, glossitis,A.stomatitis, Acrodermatitis
Iron Microcytic anemia
Ca & Vit D Osteomalacea (bone pain,pathologic#), Tetany
Vit A Follicular hyperkeratosis, Night blindness
VIt K Bleeding diathesis, Hematoma
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Malabsorption of fatsDigestive Less time to
mix- gastric
resection,autonomicneuropathy,amyloidosis
Dec micelleformation-
Decreased bile acidsynthesis/secretion-Cirrhosis, Biliaryobstruction, CCKdeficiency, Smallintestinal bacterialovergrowth,
DecreasedLipolysis- Chronic
pancreatitis, Cysticfibrosis,Pancreatic/ampullary tumors, Lowluminal pH,Excessive calciumingestion,Lipase/co-lipasedeficiency (rare)
Absorptive Decreased Chylomicron Formation and/or Mucosal
Absorption Celiac Disease, Abetalipoproteinemia (AR),Hypobetalipoproteinemia (incomplete AD), ChylomicronRetention Disease
Postabsorptive
Defective Lymphatic Transport-Primary IntestinalLymphangiectasia,Lymphoma, Whipple Disease, Trauma,Retroperitoneal Fibrosis
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Malabsorption of carbohydrates
Digestive Severe pancreatic insufficiency (amylase
deficiency)
absorptive Primary or Acquired Lactase Deficiency
Post-infectious Lactase Deficiency Celiac Disease Crohn Disease Sucrase-isomaltase deficiency Trehalase deficiency
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Malabsorption of proteinsDigestive Ppartial or total gastrectomy (poor mixing)
Eexocrine pancreatic insufficiency
Ttrypsinogen deficiency
Ccongenital deficiency of intestinal enterokinase
absorptive Celiac Disease and Tropical Sprue
Methionine Malabsorption Syndrome and BlueDiaper Syndrome (tryptophan)
Short Bowel Syndrome
Jejunoileal bypass
Defects in neutral AA transporters (Hartsnup
Disease)
Cystinuria I-III (Cystine and bibasic amino acids)
Oculocerebral Syndrome of Lowe(Lysine/arginine)
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Malabsorption of vitamins
Vitamin B12
(Cobalamin)
Atrophic gastritis (impaired peptin/acid secretion)
Deficiency of gastric intrinsic factor (pernicious anemia /antrectomy )Pancreatic insufficiency/Z-E Syndrome (reduced release ofB12 from R-binding protein)Helminth Infection/SI BOIleal Crohn Disease/Resection
Folic acid Caused by diseases affecting the proximal small bowel
Celiac disease/Whipple/Tropical SprueAlcoholism
Fat SolubleVitamins
(ADEK)
Anything that disrupts fat absorption will result in one/moredeficiency
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Malabsorption of minerals
Calcium #Selective deficiency can occur.
Renal disease/hypoparathyroidism Inborn defect in the vitamin D receptor or 1,25-dihydroxyvitamin D formation#Diseases that reduce intestinal surface area and/or causeformation of insoluble calcium soaps with long-chain fattyacids.
Celiac Disease Bile acid deficiency
Magnesium Usually caused by loss of mucosal surface area and/orluminal binding by malabsorbed fatty acids.
Iron Caused by reduced mucosal surface area, but most often
caused by GI bleeding.
Zinc: Acrodermatitis enteropathica (defect in the Zinc transportprotein hZIP4)
Copper Menkes Disease (kinky hair disease) is caused by an
inherited disorder of cellular copper transport.
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Approach to diagnosis-history
Steatorrhea
Chronic
pancreatitis
Cystic
fibrosis
Surgery
Cholecystect
my, resectio
Bloody
diarrhea Large
volume
Arsenic, drugs,
bowel resection,
crohns,
carcinoid,
gastrinoma
Radiation
IBD,
eosinophilicgastroenteritis,
immunodef
+ pain,
fever
Lactase
def
Osmotic
+ low pH
Chronicdiarrhea
Crohns
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1)anemia,
dermatitis
herpetiformis,edema
ulcerative
colitis
dermatitis
herpetiformis
IBD
2)abdominal
mass or
tenderness
erythemanodosum
Flushing
Carcinoid
celiac
disease
4)mucocutane
ous
manifestations
Edema
ptn losing enteropathy
3)Flatus
undigested CHO
6)amenorrhea
, infertility,
and
impotence
due to malnutrition
Clinical examination
5)Manifestations of
vitamin and mineral
deficiencies
Xeropthalmia, glossitis,
purpura, tetany, peripheral
neuropathy etc
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Investigations:
General: - CBC
- Blood film
- Ca. - B12, folate
- Iron study
- LFT, PT, APTT
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SpecificTests of fat absorption:
Quantitative fecal fat Patient should be on daily diet containing
80-100 grams of fat. Fecal fat estimated on 72 H collection. 6 grams or more of fat/day is abnormal. May be due to: - Pancreatic
- Small intestinal
- Hepatobiliary disease
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Tests for pancreatic function:
1) Bentiromide test: A test ofpancreatic exocrine function in whichorally administered bentiromide is
cleaved by chymotrypsin within thelumen of the small intestine, releasing p-aminobenzoic acid. Diminished urinaryexcretion of p-aminobenzoic acid may
indicate pancreatic insufficiency.
2) Schilling test
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The Schilling Test-
determine the cause for cobalamin
malabsorption. Since cobalamin absorption requires
multiple steps, including gastric, pancreatic,and ileal processes, the Schilling test can
also be used to assess the integrity of theseother organs
Achlorhydria, Bacterial overgrowthsyndromes
administering 58Co-labeled cobalamin orallyand collecting urine for 24 h. Urinaryexcretion of cobalamin will reflect
cobalamin absorption
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3) Pancreatic stimulation test
Secretin stimulation
4) Radiographic techniques:
- Plain abdominal X-ray- U/S abdomen
- ERCP
- CT abdomen
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Carbohydrate absorption test
1) Hydrogen breath test
the patient takes a base reading of hydrogenlevels in his/her breath. The patient is thengiven a small amount of fructose, and thenrequired to take readings every 15, 30 or 60minutes for two to three hours. If the level ofhydrogen rises above 20 ppm (parts permillion) over the lowest preceding valuewithin the test period, the patient is typicallydiagnosed as a fructose malabsorber.
Hydrogen excretion in bacterialovergrowth
small intestinal malabsorption
http://en.wikipedia.org/wiki/Fructosehttp://en.wikipedia.org/wiki/Fructose -
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2) D-xylose test
5-carbon sugar excreted unchanged in urine 25 grams given Urine collected for 5 hours Normally 25% is excreted In patients with fat malabsorption, this test
differentiates pancreatic from small intestinalmalabsorpton.
D-xylose is normal in pancreatic disease Serum level of D-xylose at 1-2 hours after
ingestion can be measured.
An abnormal test (
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1) Radiography of small intestine:
Barium swallow and follow-through to see
- Blind loop
- Stricture- J. diverticular
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2) Intestinal mucosal biopsy:
- using crossby capsule- endoscopy
Coeliac disease:- Villous atrophy
Tropical spure:
- short villi and increased lymphocyte
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Coeliac Disease(gluten-free diet results in eventual restoration)
Normal mucosa
Villi( V) ,
Small crypts (C)
Coeliac diseaseInflammatory cells (L)Loss of villiElongated crypts (C)
Coeliac disease (dissecting microscope)
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Coeliac disease (dissecting microscope)
Normal jejunal mucosa
series of ridges and
finger-like projections
Coeliac diseasesurface becomesfiattened, developinga mosaic-like pattem
Selection of tests in evaluation malabsorption
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Selection of tests in evaluation malabsorption
Quantitaive fecal fat
Normal Abnormal
D-xylose test
Normal Abnormal
Abd. Radiograph14 C-D-xylose test
Bentiromide test
CT-abd. Normal
Small intestinalBx
Abnormal
Jej culture
Tetracyclin
Then repeat breath test
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Endoscopy Gross morphology gives diagnostic clue
Cobblestone appearance crohn's D.
Reduced duodenal folds and scalloping
of duodenal mucosa celiac disease Use of vital dyes to identify villous atrophy
Biopsy to establish Dx For pts with documented steatorrhea
or ch. Diarrhea
Lesions seen classifid in to three Diffuse,specific e.g. whippls Disease
Patchy, specificcrohns D., lymphomainfectious causes
Diffuse,non-specific celiac sprue, Tropical sprueautoimmune enteropathy
Suspected distal pathology - push enteroscopywireless capsule
endoscopy
opsy o ma - n es na ucosa
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opsy o ma n es na ucosaDiffuse, specific
Whipples disease Macrophages containing PAS+ material
Agammaglobulinemia No plasma cells, no villi
Patchy, specific
Intestinal lymphoma Malignant cells in lamina propria
Intestinal lymphangiectasia Dilated lymphatics
Eosinophilic gastroenteritis Eosinophil infiltration
Amyloidosis Amyloid deposits
Crohns disease Noncaseating granulomas
Mastocytosis Mast cell infiltration
Diffuse, nonspecific
Celiac and tropical sprue Short or absent villi; mononuclear infiltrate;
Bacterial overgrowth Patchy damage to villi;
Folate, B12 deficiency, Radiation Short villi
Zollinger-Ellison syndrome Mucosal ulceration
Protein-calorie malnutrition Villous atrophy
RESULTS OF DIAGNOSTIC STUDIES IN
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RESULTS OF DIAGNOSTIC STUDIES IN
DIFFERENT CAUSES OF
STEATORRHEA
Second line tests
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Second line tests
Sigmoidoscopy, colonoscopy, ERCP
Esophagogastroduodenoscopy with smallintestinal biopsies
Abdominal ultrasound
Capsule endoscopy
immunoglobulins, human immunodeficiencyvirus antibodies, antinuclear antibodies,ferritin, food allergen-specific IgE,adrenocorticotropic hormone, cortisol,chromogranin A, gastrin, urinary 5-HIAA
Quantitative fecal fat
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Third line tests MRI Abdominal angiogram
PET Somatostatin (octreotide) scan Endoscopic ultrasound
Enteroscopy, including biopsies Spiral CT of the pancreas for tumor Tests for bile acid malabsorption Glucagon, somatostatin in
serum/plasma
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Back to our case CBC, electrolytes, blood urine nitrogen,
creatinine, liver function studies, and
thyroid-stimulating hormone were allwithin normal limits. Treatment with metaclopramide (Reglan)
and domperidone did not prevent theepisodes, nor did treatment withtetracycline 250 mg 3 times per day for 14days.
A hydrogen breath test was negative. Colonoscopy was normal.
Upper GI endoscopy revealed a normalesophagus, stomach, pylorus, andduodenum.
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Multiple biopsy specimens wereobtained from the post-bulbar
duodenum and sweep. Biopsies from the small intestine
revealed blunting of the villaeconsistent with celiac disease.
In addition, IgA anti-endomysialantibodies were performed. Thesewere positive in a titer of 1 to 640.
The patient began a gluten-free dietwith complete resolution of hissymptoms and a 10-lb weight gainwithin 2 months.
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Celiac disease and type 1 diabetes areautoimmune diseases with a common
genetic predisposition. Both celiac diseaseand type 1 diabetes are associated with ahigh frequency of HLA-DR3 genotypes. Asa result, celiac disease is more frequent in
type 1 diabetes than in type 2 diabetes orin the general population. Studies thathave screened patients with type 1diabetes for celiac disease have found
rates of celiac disease between 1% and8%. These rates are 411 times higher thanrates of celiac disease in the generalpopulation.
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CELIAC
DISEASE
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Celiac disease (CD) is an immune-mediated disorder that develops in
genetically susceptible persons whengluten, a major protein found in wheat,barley, and rye is ingested in the diet.Also called nontropical sprue, celiac
sprue, or gluten-sensitive enteropathy,CD is primarily an enteropathycharacterized by inflammation of the
small bowel mucosa and atrophy of thevilli, resulting in nutrient malabsorption,wasting, and diarrhea.
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Any organ system may be involved inCD, and patients can developextraintestinal manifestationsalsocalled atypical manifestationssuch as
anemia, bone disease, infertility,unfavorable outcomes of pregnancy,lymphoma, and liver disease.
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Prevalence and epidemiology
Women are affected more commonly
than men, but there is no agepredilection.
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Patients Who Are at Risk for CeliacDisease and Should Be Tested Patients with gastrointestinal and
classic symptoms: diarrhea, weightloss, abdominal distention, failure tothrive
Patients with autoimmune diseases,type 1 diabetes, thyroid disorders,Sjgren's syndrome, microscopiccolitis, inflammatory bowel disease
First-degree relatives
Patients with elevated liver enzymes
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Patients with Down syndrome
Patients with iron deficiency anemia Patients with osteoporosis
Patients with delayed puberty
Infertile patients Patients with irritable bowel
syndrome
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Pathophysiology Celiac disease is a multifactorial and
a multisystem disorder involving agenetic predisposition,environmental exposure of the small
bowel mucosa to gluten, and animmunologic response to gluten.
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Genetic susceptibility definespersons who possess the gene pairencoding the majorhistocompatibility complex class IIHLA DQ2 or DQ8. These genes are
virtually required for CD to occur, andlack of these genes makes CD veryunlikely.
The majority ( 90%) of persons with CD
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The majority (>90%) of persons with CDpossess the HLA DQ2 haplotype, and 5% to10% possess the DQ8 haplotype, conferring a
negative predictive value greater than 98%.These haplotypes are encoded within the HLAclass II region of the major histocompatibilitycomplex on chromosome 6p.
However, about 40% of the general population
carry these haplotypes without having thedisease, which makes their presencenecessary but not sufficient for itsdevelopment.
Intestinal antigen-presenting cells in peopleexpressing HLA-DQ2, or HLA-DQ8, bind withdietary gluten peptides in their antigen-binding grooves activate specific mucosalT lymphocytes cytokines mucosaldamage.
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Clinical manifestations Celiac disease exhibits a spectrum of
clinical and pathologic manifestations. Symptoms can manifest in infancy and as
early as cereals are introduced in the diet. Crampy abdominal pain, steatorrhea,
failure to thrive, apathy and irritability,muscle wasting, and hypotonia aredescribed.
Any of these symptoms should trigger adiagnostic workup.
Catch-up growth is well documented oncea gluten free-diet is introduced.
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In adults, the clinical symptoms arevariable and not specific.
The classic symptoms of malabsorptionare less encountered.
On the other hand, atypical presentationsare increasingly recognized and becomingmore common.
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Patients with CD can exhibit weakness,fatigue, and dyspnea as a result ofvitamin B12, folate, and iron deficiency;
bone fractures, muscular atrophy, andtetany as a result of osteoporosis andosteopenia due to vitamin D and calciumdeficiencies;
peripheral neuropathy and ataxia as aresult of cerebellar and posterior columninflammatory damage;
and secondary hyperparathyroidism,edema, petechiae, and dermatitis
herpetiformis. Infertility is observed inmen and women. Amenorrhea,intrauterine growth retardation, andunfavorable outcomes of pregnancy have
been reported.
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Essentials of diagnosis Weight loss
Distention, flatulence, greasy stools Increased fecal fat (>7g/24h)
Abnormal small bowel biopsy
Clinical improvement on gluten-freediet
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Diagnosis Once the clinical suspicion in patients at risk
factors is raised, the initial step toward a
diagnosis is to obtain celiac serology antibodytesting. This should be followed by a small bowelbiopsy. The patient should be tested whilefollowing a gluten-containing diet.
The most sensitive and specific serologic tests
are endomysial antibody IgA EMA and tissuetransglutaminase antibody IgA tTG. Sensitivitiesand specificities are higher than 85% and 97%,respectively, for EMA and 90% and 97%,respectively, for tTG. Gliadin antibodies have
lower sensitivities and specificities and are notrecommended for screening; however, gliadinantibodies may have a role in monitoringadherence to a gluten-free diet.
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Pathologic changes on small-bowel biopsyare characterized by a spectrum of
abnormalities described by Marsh andknown as the Marsh criteria. The hallmarkof CD is Marsh 3 or villous atrophy;however, this may be patchy or present inother disorders as inhypogammaglobulinemia, acute infectiousgastroenteritis, or milk intolerance.
Additionally, there is growing evidencethat CD may be diagnosed when changesof earlier phase on biopsy such as Marsh 1or Marsh 2 are seen.
Establishing Diagnosis in the
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Absence of Typical Symptoms The wide range of clinical
manifestations of the diseasecoupled with less than Marsh 3 onbiopsy makes the diagnosis of CD
challenging for the clinician. Inthese situations, genetic testing orgluten challenge may be necessary
for a definite diagnosis. A fewscenarios may be encountered in aclinical setting and their proposeddiagnostic workups include:
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Positive serology and villousatrophy: Diagnosis established.Patient should be treated.
Positive serology and normal smallbowel mucosa biopsy: Disease isconsidered latent and biopsy shouldbe repeated after a gluten challengeor a few months later on a normal
diet.
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Positive serology and increasedintraepithelial lymphocytes: Potential
celiac disease; repeat biopsy after a glutenchallenge or in a few months on a normaldiet, or obtain HLA typing. If any ispositive, start a gluten-free diet.
Normal serology and normal biopsy: Lookfor other causes of the patient'ssymptoms.
Normal serology and villous atrophy:Exclude other causes of villous atrophy,immunodeficiency, IgA deficiency.
TREATMENT
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Treatment consists of withdrawinggluten from the diet for life. It entailseliminating wheat, barley, and rye.This allows healing of the smallbowel mucosa and restitution of
nutritional status.
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Deficiencies of vitamins D and B12,folic acid, calcium, and iron andnutritional deficiencies should bereplaced as necessary.
Prevention of bone loss andpneumococcal vaccination due tohyposplenism are necessary.
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Response to the gluten-free diet isassessed by clinical and serologicimprovement. There is no clearconsensus on whether a repeat smallbowel biopsy is necessary. However,
repeat biopsy may be indicated incases where adherence to diet isproved but response to diet is
equivocal or lacking.
Foods That Are Safe in Celiac
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Disease
Plain meat (no bread or bread
crumbs)
Poultry
Fish
Shellfish Milk
Vegetables
Fruit Fats and oils
Butter
References
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Harrisons internal medicine
Current diagnosis and treatment ingastroenterology
Pubmed.com
Emedicine.com
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THANK YOU