Celiac sprueCeliac sprueUn caso clinico dal web

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Case PresentationCase Presentation

January 1991 J. N. is a 74 year old white female Dx. 12 years ago with irritable bowel syndrome Tx. with Tigan, Lomotil, Donnatal but worsened Up to 8 loose, watery stools/day; abdominal pain;

dec. energy; nausea; and 34 lb. wt. loss in 2 years Work-up - Upper GI showed hiatal hernia

– Pelvic U/S showed small cyst on left ovary

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Case PresentationCase Presentation

vertigo, iron deficiency anemia

Meds: Inderal 20mgMeclizine 25mg

wt. 99lbRectal: no hemorrhoid or

mass, +brown stool with mucous, heme -

A: IBSP: Metamucil, high fiber

diet, Lomotil

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Case PresentationCase Presentation

November 1991 (9 months later) Post hysterectomy, 5-6 stools/day despite 8 tabs.

Lomotil, Wt. 88 lbs., Abd. - benign, Stool - heme+ Colonoscopy - Sessile polyp (benign adenoma)

– Diverticular disease EGD - Hiatal hernia and gastritis

– Flat appearing duodenal mucosa (villous atrophy and chronic inflammation suggestive of celiac disease)

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Case PresentationCase Presentation

Referred to dietitian for gluten-free diet education Dec. 1991 - Strict diet, asymptomatic, Wt. 86 lbs.

– Feels like a “reborn woman” June 1992 - Strict diet, asymptomatic, Wt. 132 lbs. June 1993 - Strict diet, asymptomatic, Wt. 141 lbs. Aug. 1996 - Strict diet, asymptomatic, Wt. 142 lbs

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IntroductionIntroduction

Key Elements

Evidence of malabsorptionPathological damage to the small intestineResponse to a gluten-free diet

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Etiology and PathogenesisEtiology and Pathogenesis

Environmental FactorsCereal grains of wheat, rye, barley, and oats

– Prolamins = alcohol-soluble proteins of gluten12 amino acid segment of the E1b protein

of human adenovirus, serotype 12– 89% of untreated celiac sprue patients– 17% of control subjects

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Major Cereal GrainsMajor Cereal Grains

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Etiology and PathogenesisEtiology and Pathogenesis

Genetic Factors 10% prevalence among first-degree relatives 28-40% concordance rate between HLA identical siblings 70-75% concordance rate between monozygotic twins 90% have HLA-B8, HLA-DR3, or HLA-DQw2 haplotype

– 25-30% of general population have these haplotypes– Only 0.1% of people with these haplotypes develop

celiac sprue

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Etiology and PathogenesisEtiology and Pathogenesis

Immunologic FactorsHumoral and cell-mediated mechanisms

– Antigliadin antibody triggering the complement cascade

– Anti-transglutaminase– Antigliadin antibody causing cytotoxic cell-

mediated mucosal damage– Intraepithelial lymphocytes in the absorptive

cells producing lymphokines

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PathologyPathology

Small intestinal mucosa affected (proximal>distal) Length involved correlates with severity of disease Villous atrophy and crypt hyperplasia decreasing

the villous: crypt ratio Columnar to cuboidal to squamous absorptive cell Microvilli decrease Abnormal tight junctions allow more permeability Increased mitotic activity

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Mucosal ChangesMucosal Changes

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PathologyPathology

Increased numbers of intraepithelial lymphocytes, plasma cells, mast cells, and eosinophils

Continuum of changes (minimal to severe) Injury occurs within hours of ingestion of gluten Recovery takes weeks to months, but many never

demonstrate improvement Pathological changes are not pathognomonic

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Clinical FeaturesClinical Features

Gastrointestinal Symptoms Women 20s - 30s, men - slightly later Diarrhea, abd. distention, flatulence, weakness,

lassitude, and weight loss most common Stools are bulky, loose, pale, float, foul-smelling Diarrhea usually in morning Abd. distention and flatulence usually in evening Abdominal pain is uncommon and may be the first

sign of an underlying malignancy

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Clinical FeaturesClinical Features

Extraintestinal Symptoms Anemia (iron, folate, and rarely B12 deficiency)

– Poor absorption, sloughing cells, microerosions Bleeding (vitamin K deficiency) Osteopenia (bone pain and pathological fractures)

– Decreased Ca++ and vitamin D absorption– Intraluminal binding of calcium

Tetany and secondary hyperparathyriodism

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Clinical FeaturesClinical Features

Extraintestinal Symptoms Neurological deficits (hypokalemia and B12 def.)

– Paresthesias, sensory deficits, ataxia, peripheral neuropathy

Night blindness (vitamin A deficiency) Depression and anxiety Menstrual irregularities and infertility

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Physical FindingsPhysical Findings

Correlates with severity of intestinal involvement Pallor Wt. loss, wasting, loose skin folds, hypotension Cheilosis, glossitis, aphthous ulcers Doughy, protuberant, tympanic abdomen Ascites and peripheral edema Ecchymoses Hyperkeratosis follicularis Dec. DTRs or sensation, +Chvostek / Trousseau

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Diagnostic StudiesDiagnostic Studies

Malabsorption Studies Previously the main diagnostic test Very nonspecific Unhelpful in asymptomatic patients D-xylose test (decrease in serum or urine levels)

– Sensitivity = 95% Lactose intolerance test (inapprop. low glucose) Breath hydrogen test (inapprop. high expired air

hydrogen)

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Diagnostic StudiesDiagnostic Studies

Radiologic Studies Upper GI barium study

– Dilatation of small bowel loops– Coarsening and obliteration of mucosal folds

Nonspecific, thus little use in initial work-up Irregularly narrowed segments c/w lymphoma Rigidity c/w collagenous sprue Osteopenia or pathological fractures on plain films

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Celiac SprueCeliac Sprue

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Diagnostic StudiesDiagnostic Studies

Serologic Studies Combination of tests may be adequate for

screening high risk individuals 2% incidence of IgA deficiency Benefit from treating asymptomatic patients with

positive antibody test and characteristic biopsy Following levels helpful in assessing dietary

compliance and disease progression/complications

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Diagnostic StudiesDiagnostic Studies

Histopathologic Studies Endoscopic duodenal biopsy is the gold standard Classical histology is not pathognomonic Second biopsy demonstrating improvement on

diet may be replaced by serologic markers Biopsy (third) after gluten challenge not

recommended unless patient is currently on gluten-free diet and initial biopsy not obtained

EGD may show flattening of duodenal folds

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Associated DisordersAssociated Disorders

Dermatitis Herpetiformis 5% of celiac sprue patients have DH Nearly 100% of DH patients have celiac sprue Vesicles / excoriations which are pruritic / burning Associated with HLA-B8 and HLA-Dw3 Biopsy shows IgA deposits at dermal / epidermal

junction Treatment with gluten-free diet (slow) or dapsone

(faster)

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Dermatitis HerpetiformisDermatitis Herpetiformis

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Dermatitis HerpetiformisDermatitis Herpetiformis

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Associated DisordersAssociated Disorders

Other Disorders IgA deficiency - 10 times more frequent Insulin dependent diabetes mellitus-4.1% have CS Autoimmune thyroid disease - 4.8% have CS Sjogren’s syndrome, SLE, vasculitis, RA IgA mesangial nephropathy Primary biliary cirrhosis, primary sclerosing

cholangitis, inflammatory bowel disease

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Treatment and PrognosisTreatment 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

noncompliance (dietary education is necessary)

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Treatment and PrognosisTreatment 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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ComplicationsComplications

Malignancy Twofold increase in developing malignancy -

lymphoma (50%), carcinoma of esophagus, mouth, pharynx, larynx, and small intestine

Relative risk of lymphoma is 25-120x, greatest in men, older patients, and those untreated >10 years

Suspect when previous diet-responsive patient develops weight loss, abdominal pain, weakness malabsorption, pyrexia, lymphadenopathy

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ComplicationsComplications

Malignancy Prognosis poor with surgical resection, XRT, and

chemotherapy (9 month life expectancy) Reason for increased incidence ?

– Increased mitotic activity, increased mutations– Increased permeability to carcinogens– Damaged mucosa’s contact with oncoviruses

Strict gluten-free diet reduces risk to 1.2x normal

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ComplicationsComplications

Ulcerative Jejunoileitis - 75% mortality– Ulceration and stricture formation - resection– Obstruction, perforation, bleeding, peritonitis

Collagenous Sprue– Subepithelial deposition of collagen– Tend to be refractory - corticosteroid trial

Neurological and Psychological– Sensory ataxia, numbness, tingling, pain,

weakness, unsteady gait, depression

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Collagenous SprueCollagenous Sprue

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SummarySummary

Sm. bowel malabsorptive disease (children/adults) Intolerance to gluten (wheat, rye, barley, oats) Abd. discomfort, diarrhea, wt. loss, extraintestinal Sm. bowel bx (villous atrophy / crypt hyperplasia) Response to a gluten-free diet (dec. complications) Serologies aid in screening / following compliance Prognosis is good as disorder is potentially curable Potentially fatal disease if overlooked