Transcript Celiac sprue

Celiac sprue
Un caso clinico dal web
Case 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
2
Case Presentation
vertigo, iron deficiency
anemia
Meds: Inderal 20mg
Meclizine 25mg
wt. 99lb
Rectal: no hemorrhoid or
mass, +brown stool
with mucous, heme A: IBS
P: Metamucil, high fiber
diet, Lomotil
3
Case 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)
4
Case 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
5
Introduction
Key Elements
Evidence of malabsorption
 Pathological damage to the small intestine
 Response to a gluten-free diet

6
Etiology and Pathogenesis
Environmental Factors

Cereal grains of wheat, rye, barley, and oats
–

Prolamins = alcohol-soluble proteins of gluten
12 amino acid segment of the E1b protein of
human adenovirus, serotype 12
–
–
89% of untreated celiac sprue patients
17% of control subjects
7
Major Cereal Grains
8
Etiology 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
9
Etiology and Pathogenesis
Immunologic Factors

Humoral and cell-mediated mechanisms
–
–
–
–
Antigliadin antibody triggering the complement
cascade
Anti-transglutaminase
Antigliadin antibody causing cytotoxic cellmediated mucosal damage
Intraepithelial lymphocytes in the absorptive
cells producing lymphokines
10
Pathology







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
11
Mucosal Changes
12
Pathology





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
13
Clinical 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
14
Clinical 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)
++ and vitamin D absorption
– Decreased Ca
– Intraluminal binding of calcium
Tetany and secondary hyperparathyriodism
15
Clinical 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
16
Physical 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
17
Diagnostic 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)
18
Diagnostic 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
19
Celiac Sprue
20
Diagnostic 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
21
Diagnostic 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
22
Associated 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)
23
Dermatitis Herpetiformis
24
Dermatitis Herpetiformis
25
Associated 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
26
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
noncompliance (dietary education is necessary)
27
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)
28
Complications
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
29
Complications
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
30
Complications



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
31
Collagenous Sprue
32
Summary








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
33