> Table of Contents > Celiac Disease
Celiac Disease
Jason E. Domagalski, MD, FAAFP
Matthew W. Short, MD, FAAFP
image BASICS
DESCRIPTION
  • Autoimmune condition characterized by an immunemediated reaction to dietary gluten (found in wheat, barley, rye) primarily affecting the small intestine in genetically predisposed individuals
  • Presentations
    • Typical
      • Diarrheal illness characterized by villous atrophy with symptoms of malabsorption (steatorrhea, weight loss, vitamin deficiencies, anemia). Resolves with a gluten-free diet
      • <50% of adults present with GI symptoms.
    • Atypical
      • Minor GI symptoms, with a myriad of extraintestinal manifestations (e.g., anemia, dental enamel defects, neurologic symptoms, infertility)
    • Asymptomatic (silent) disease
      • Found when screening first-degree relatives
    • Latent
      • Positive laboratory tests and genetics, without signs/symptoms
  • System(s) affected: gastrointestinal
  • Synonym(s): celiac sprue; gluten enteropathy
EPIDEMIOLOGY
Incidence
  • 1 to 13 per 100,000 worldwide (1)
  • 6.5 per 100,000 in United States (2)
  • Primarily impacts individuals of Northern European ancestry
  • Predominant sex: female > male (3:2)
Prevalence
  • 0.7% in United States; an estimated 3 million Americans have celiac disease (3).
  • Prevalence is 8 to 204 per 100,000 worldwide and increasing (1).
ETIOLOGY AND PATHOPHYSIOLOGY
Sensitivity to gluten, specifically gliadin fraction. Tissue transglutaminase (tTG) modification of protein leads to immunologic cross-reactivity, inflammation, and tissue damage (villous atrophy) with subsequent malabsorption.
Genetics
Homogenicity for HLA-DQ2 increases the risk of celiac disease and enteropathy-associated T-cell lymphoma.
RISK FACTORS
  • First-degree relatives: 5-10% incidence (4)
  • Monozygotic twins: 70% incidence
  • 25% risk in family members with an autoimmune disease
Pediatric Considerations
No associations found with breastfeeding duration, age, concurrent infection, or gastroenteritis at time of gluten introduction.
GENERAL PREVENTION
Avoid gluten-containing products (wheat, barley, rye, and possibly oat products).
COMMONLY ASSOCIATED CONDITIONS
  • Dermatitis herpetiformis: 85% of patients have celiac disease. All patients should follow gluten-free diet (4).
  • Secondary lactase deficiency
  • Osteopenia
  • Thyroid disease: Hashimoto thyroiditis
  • 3-10% of patients with type 1 diabetes also have celiac disease.
  • Symptomatic iron deficiency, 10-15% have celiac disease
  • Elevated AST and ALT (with no direct cause)
  • Hyposplenism
  • Irritable bowel syndrome (IBS)
  • Restless leg syndrome
  • Celiac disease is associated with increased risk for adenocarcinoma and lymphoma of the small bowel.
    • The risk of lymphoproliferative malignancies depends on small intestinal histopathology.
    • Little to no increased risk in latent celiac disease (seropositive but normal biopsy) (5)[A].
  • Other autoimmune disorders
Pregnancy Considerations
  • Prevalence of celiac disease: 2.5 to 3.5 times higher in women with unexplained infertility
  • Up to 19% of men with celiac disease have androgen resistance. Semen quality and likelihood of pregnancy increase with gluten-free diet.
  • Higher rates of low birth weight, spontaneous abortions, and stillbirths
Pediatric Considerations
Failure to thrive and delayed growth may be early manifestations. Some children may outgrow wheat intolerance after prolonged gluten-free diets but should watch for recurrence in middle age.
image DIAGNOSIS
PHYSICAL EXAM
Often normal but look for
  • Oropharynx: aphthous stomatitis
  • Skin: dermatitis herpetiformis (symmetric erythematous papules and blisters on elbows, knees, buttocks, and back)
  • Abdomen: distention
DIFFERENTIAL DIAGNOSIS
  • Short bowel syndrome
  • Dyspepsia, gastroesophageal reflux disease (GERD)
  • Pancreatic insufficiency
  • Crohn disease; Whipple disease; tropical sprue
  • Hypogammaglobulinemia
  • Intestinal lymphoma
  • HIV enteropathy
  • Acute enteritis; radiation enteritis, eosinophilic gastroenteritis
  • Giardiasis
  • Pancreatic disease
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Do not base diagnosis on serology alone. Patients with symptoms highly suggestive of celiac disease or those with positive serologies should undergo endoscopy for biopsy. Tissue biopsy is the gold standard for diagnosis.
  • IgA antitissue transglutaminase (IgA-anti-tTG) is the preferred single serologic test in patients >2 (4)[C].
  • Total serum IgA
  • IgA-deficient patients have false-negative IgA anti-tTG antibodies.
  • IgA deficiency is 10 to 15 times more prevalent in patients with celiac disease.
  • The tTG antibody test is the preferred test (over the deamidated gliadin peptide [DGP] antibody) (6,7,8)[A].
Follow-Up Tests & Special Considerations
  • If patient is IgA deficient OR if IgA anti-tTG are negative, follow up blood tests.
    • Anti-DGP IgA and IgG
      • Sensitivity, 94%; specificity, 99% (˜anti-TTG)
  • Do not use HLA DQ serotyping for initial diagnosis. Consider if discrepant serology-histology results in patients unable to test on gluten-free diet and children with Down syndrome (4)[C].
  • Consider bone mineral density testing at diagnosis and after 1 year if osteopenia/osteoporosis on initial testing or 2 years if normal initially and patient still symptomatic or noncompliant.
Pediatric Considerations
  • Antigliadin antibody (AgA-IgG and IgA) may be used for children age <2 years because tTG and endomysial (EMA) antibodies may be absent.
  • Anti-DGP test is sensitive in children.
  • IgA tTG >10 times normal with positive EMA testing and HLA-DQ2 has PPV of 97.4% and may not need confirmatory intestinal biopsies for diagnosis (4)[C].
Diagnostic Procedures/Other
  • Endoscopy with a minimum of four biopsies of the distal duodenum and two of the duodenal bulb at time of initial evaluation correctly diagnosed 95% of children (4)[C].
  • P.169

  • Video capsule endoscopy is a promising alternative with a sensitivity and specificity of 80% and 95%. Particularly helpful if antibody screening and clinical picture are consistent with celiac disease despite nondiagnostic duodenal biopsies (9)[A].
Test Interpretation
Small bowel biopsy
  • Villous atrophy, hyperplasia and lengthening of crypts, infiltration of plasma cells, and intraepithelial lymphocytosis in lamina propria
  • Villous atrophy also caused by Crohn disease, radiation enteritis, giardia and other food intolerances
image TREATMENT
GENERAL MEASURES
  • Remove gluten from the diet.
    • Rice, corn, and soybean flour are safe and palatable substitutes (4)[C].
  • Levels of IgA antigliadin normalize with gluten abstinence.
  • LIFELONG abstinence is required; immune response to gluten will recur with resumption of gluten consumption.
MEDICATION
First Line
Usually no medications: Gluten-free diet is the treatment.
Second Line
  • In refractory disease, consider
    • Steroids (prednisone, 40 to 60 mg/day PO in cases of refractory sprue)
    • Azathioprine (used with caution; use may lead to lymphoma)
    • Cyclosporine
    • Infliximab
    • Cladribine
  • Patients may develop nutritional deficiencies depending on the severity of the disease.
Third Line
There are numerous clinical trials testing the efficacy of intraluminally acting agents such as Lactobacilli to gluten endopeptidases, inhibitors of transepithelial gliadin uptake, immunomodulation, and even vaccination (10). Findings are largely awaiting further validation.
ISSUES FOR REFERRAL
  • Additional nutritional support
  • Refractory disease
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
  • Consultation with registered dietitian
  • Screen for osteoporosis and treat accordingly.
Patient Monitoring
  • Repeat EGD if no clinical response to gluten-free diet or relapse in symptoms (4)[C].
  • Follow anti-tTG IgA or deaminated antigliadin antibodies as a measure of response/compliance with diet (vs. antigliadin IgA or IgG).
DIET
  • Remove gluten: wheat, rye, barley, and products with gluten additives.
  • Dietary change is challenging (especially learning sources of “hidden” gluten) and should be coordinated with a skilled registered dietitian.
PATIENT EDUCATION
  • Discuss how to recognize gluten in various products.
  • Highlight potential complications and outcomes of failing to follow a gluten-free diet.
PROGNOSIS
  • Good prognosis if adherent to gluten-free diet
  • Patients should feel better within 7 days of dietary modification.
  • Symptoms usually disappear in 4 to 6 weeks.
  • It is unknown whether strict dietary adherence decreases cancer risk.
REFERENCES
1. Kang JY, Kang AH, Green A, et al. Systematic review: worldwide variation in the frequency of coeliac disease and changes over time. Aliment Pharmacol Ther. 2013;38(3):226-245.
2. Riddle MS, Murray JA, Porter CK. The incidence and risk of celiac disease in a healthy US adult population. Am J Gastroenterol. 2012;107(8): 1248-1255.
3. Rubio-Tapia A, Ludvigsson JF, Brantner TL, et al. The prevalence of celiac disease in the United States. Am J Gastroenterol. 2012;107(10):1538-1544.
4. Rubio-Tapia A, Hill ID, Kelly CP, et al. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108(5): 656-676.
5. Elfström P, Granath F, Ekström Smedby K, et al. Risk of lymphoproliferative malignancy in relation to small intestinal histopathology among patients with celiac disease. J Natl Cancer Inst. 2011;103(5):436-444.
6. Lewis NR, Scott BB. Meta-analysis: deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac disease. Aliment Pharmacol Ther. 2010;31(1):73-81.
7. Van der Windt DA, Jellema P, Mulder CJ, et al. Diagnostic testing for celiac disease among patients with abdominal symptoms: a systematic review. JAMA. 2010;303(17):1738-1746.
8. Sugai E, Vázquez H, Nachman F, et al. Accuracy of testing for antibodies to synthetic gliadin-related peptides in celiac disease. Clin Gastroenterol Hepatol. 2006;4(9):1112-1117.
9. Rokkas T, Niv Y. The role of video capsule endoscopy in the diagnosis of celiac disease: a metaanalysis. Eur J Gastroenterol Hepatol. 2012; 84(3):303-308.
10. Crowe S. Management of celiac disease: beyond the gluten-free diet. Gastroenterology. 2014; 146(7):1594-1596.
Additional Reading
  • Bolotin D, Petronic-Rosic V. Dermatitis herpetiformis. Part II. Diagnosis, management, and prognosis. J Am Acad Dermatol. 2011;64(6):1027-1033.
  • Celiac Disease Foundation: https://celiac.org/
  • Celiac Disease Foundation. Quick start gluten-free diet guide for celiac disease and non-celiac gluten sensitivity. http://celiac.org/wp-content/uploads/2013/12/quick-start-guide.pdf
  • Celiac Sprue Association (CSA): http://www.csa.celiacs.org
  • Giersiepen K, Lelgemann M, Stuhldreher N, et al. Accuracy of diagnostic antibody tests for coeliac disease in children: summary of an evidence report. J Pediatr Gastroenterol Nutr. 2012;54(2):229-241.
  • Gluten Intolerance Group (GIG). https://www.gluten.org/
  • Kagnoff MF. AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease. Gastroenterology. 2006;131(6):1977-1980.
  • Rozenberg O, Lerner A, Pacht A, et al. A novel algorithm for the diagnosis of celiac disease and a comprehensive review of celiac disease diagnostics. Clin Rev Allergy Immunol. 2012;42(3):331-341.
  • Welander A, Tjernberg AR, Montgomery SM, et al. Infectious disease and risk of later celiac disease in childhood. Pediatrics. 2010;125(3):e530-e536.
See Also
Algorithms: Diarrhea, Chronic; Malabsorption Syndrome
Codes
ICD10
K90.0 Celiac disease
Clinical Pearls
  • Test for celiac disease in patients with presumed IBS, dermatitis herpetiformis, or unexplained transaminitis.
  • Test total IgA levels along with IgA anti-tTG antibodies in patients >2 years of age.
  • Positive serology is not definitive; endoscopic biopsy is the gold standard for diagnosis.
  • Standard of treatment is a gluten-free diet. Patient symptoms should improve within 7 days if fully compliant.