Celiac Disease

From: 5 minutes clinical consult

Description
Classically, a chronic diarrheal disease characterized by intestinal malabsorption of virtually all nutrients and precipitated by eating gluten-containing foods. Multiple forms exist.
Nondiarrheal form may actually be most common (intestinal villous atrophy produces vitamin and mineral malabsorption).
System(s) affected: GI
Synonym(s): Sprue; Gluten enteropathy; Celiac sprue

Epidemiology
Incidence
Disease primarily of individuals of Northern European ancestry.
Predominant sex: Female > Male (3:2)
Prevalence
~1 in 133 persons in US
Risk Factors
1st-degree relatives: 10% incidence
71% in monozygotic twins

Genetics
HLA-DQ2 and/or DQ8 closely associated (testing may be indicated if indeterminate small bowel pathology)

General Prevention
Avoid all gluten-containing products (wheat, barley, rye, and possibly oat products).


Etiology
Sensitivity to gluten, specifically gliadin fraction

Commonly Associated Conditions
May have secondary lactase deficiency
Extraintestinal manifestation may include marked decrease in bone density
Dermatitis herpetiformis common
Autoimmune thyroiditis
Diabetes, type 1 (prevalence of celiac disease in type 1 diabetes is 3–8%)
Elevated AST and ALT
Recurrent fetal loss or infertility

ALERT
Pregnancy Considerations
Celiac disease may be an underappreciated cause of male and female infertility. Consider celiac disease in pregnant women with severe anemia.

Signs and Symptoms
History
Diarrhea
Steatorrhea
Muscle cramps
Iron-deficiency anemia
Nervousness
Weight loss
Failure to thrive (slowing velocity of weight gain)
Weakness
Lassitude
Fatigue
Large appetite
Explosive flatulence
Abdominal pain, nausea, vomiting rare
Recurrent aphthous stomatitis
Abdominal distention

ALERT
Pediatric Considerations
Failure to thrive and delayed growth with short stature may be early manifestations. A few children may outgrow intolerance to wheat after prolonged glutenfree diets, but should be cautioned to watch for signs of recurrence in middle age.

Diagnostic Tests and Interpretation

Lab
Initial Labs
Positive IgA antiendomysial antibodies and IgA tissue transglutaminase (sensitivity 90–98%, specificity 98%) when on normal (non–glutenfree) diet.

Follow-Up and Special Considerations
IgA-deficient patients have false-negative IgA antiendomysial and IgA antitransglutaminase antibodies.
72-hour fecal fat showing >7% fat malabsorption
Elevated liver function tests
-Xylose test showing malabsorption
Decreased calcium
Increased PT
Decreased neutral fats
Decreased cholesterol
Decreased vitamin A
Decreased vitamin B12 (rare)
Decreased vitamin D
Decreased vitamin C
Decreased folic acid
Decreased iron (common)
Decreased total protein
Decreased hemoglobin (common)

Imaging
Initial Imaging Approach
Upper GI series showing flocculation of barium, edema, and flattening of mucosal folds

Follow-Up and Special Considerations
Evaluate for osteoporosis

Diagnostic Procedures/Other
Endoscopy with diagnostic biopsy of the duodenal mucosa with repeat endoscopy and normal biopsy on a glutenfree diet is necessary before a firm diagnosis can be made.
In general, diagnosis should not be made based on serology alone.

Pathological Findings
Small bowel biopsy:
Flattened villi, hyperplasia and lengthening of crypts, infiltration of plasma cells and lymphocytes in lamina propria

Differential Diagnosis
Short bowel syndrome
Pancreatic insufficiency
Crohn disease
Whipple disease
Hypogammaglobulinemia
Tropical sprue
Lymphoma
AIDS
Acute enteritis
Giardiasis
Eosinophilic gastroenteritis
Pancreatic disease

Medication (Drugs)
First Line
Usually none: Diet is treatment

Second Line
In refractory disease, consider:
Steroids (prednisone, 40–60 mg/d PO in cases of refractory sprue)
Azathioprine (Immunosuppressants should be used with caution; use may lead to lymphoma in celiac disease).
Cyclosporine
Infliximab
Cladribine
Patients may require supplemental calcium, calcium carbonate, 500 mg PO b.i.d., and vitamin D (ergocalciferol) 10–100 g/d; in severe malabsorption, up to 2.5 mg/d may be required.

Additional Treatment
General Measures
Removal of gluten from the diet. Rice, corn, and soybean flour are safe, palatable substitutes.
Levels of IgA antigliadin normalize with gluten abstinence

Issue for Referral
Additional nutritional support
Refractory disease

Follow-Up Recommendations
Consultation with dietician
Screening for osteoporosis

Patient Monitoring
Repeat endoscopy after 6–8 weeks on a glutenfree diet (in selected cases).
IgA antigliadin assay may be used to monitor response to gluten-free diet.

Diet
Removal of gluten: Wheat, rye, barley, and those with gluten additives. This is a difficult diet, and should be coordinated with a skilled dietician.

Patient Education
Discuss importance of recognizing gluten in various products
Highlight potential complications and outcomes of failing to follow a gluten-free diet

Prognosis
Good with correct diagnosis and adherence to gluten-free diet
Patient should feel better in 7 days.
All symptoms usually disappear in 4–6 weeks.
It is unknown whether strict dietary adherence decreases cancer risk.

Complications
Malignancy: <10% of patients (50% of whom have small bowel lymphoma)
Refractory sprue:
May respond to prednisone 40–60 mg/d PO
Refractory sprue unresponsive to corticosteroid therapy raises the specter of adult-onset autoimmune enteropathy or cryptic T-cell lymphoma. In this circumstance, screening for antienterocyte autoantibodies and careful scrutiny of the small intestine, including retroperitoneal lymph node biopsy with full-thickness small bowel biopsy, may be needed.
Chronic ulcerative jejunoileitis:
Associated with multiple ulcers, intestinal bleeding, strictures, perforation, obstruction, and peritonitis
7% mortality
Osteoporosis secondary to decreased vitamin D and calcium absorption
Dehydration
Electrolyte depletion
Refractory cases may need total parenteral nutrition.

[General]
AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease. Gastroenterology 2006;131:1977–1980.
Carroccio A, et al. Screening for celiac disease in patients with chronic liver disease. Gastroenterology 2003;125:1289.
Celiac Disease: A Hidden Epidemic by Peter Green.
Celiac Sprue Association (CSA) http://www.csaceliacs.org
Green PH, et al. Celiac disease. N Engl J Med 2007;357:1731–1743.
Guidelines for a Gluten-free Lifestyle, 3rd. ed. Celiac Disease Foundation. http://www.celiac.org
Hutchinson JM, et al. Advances in celiac disease. Curr Opin Gastroenterol 2008;24:129–134.
Niewinski MM. Advances in celiac disease and gluten-free diet. J Am Diet Assoc 2008;108:661–672.
Quick Start Diet Guide: Celiac Disease Foundation (CDF) & Gluten Intolerance Group (GIG). http://www.celiac.org,http://www.gluten.net

Other
See Also (Topic, Algorithm, Electronic Media Element)
Algorithm(s): Diarrhea, Chronic; Malabsorption Syndrome

ICD-9 579.0 Celiac disease
SNOMED 396331005 celiac disease (disorder)

CLINICAL PEARLS
Common condition (1 in 133)
Characterized by mucosal inflammation and villous atrophy
Associated with malabsorption of nutrients
Treatment is glutenfree diet

AUTHOR
Brandi Kelly, PharmD
Gary McWilliams, MD