Description

• A non–IgE-mediated immune enteropathic reaction to gliadin, a protein component of dietary gluten (found in wheat, barley, rye, and other grains) 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, dermatitis herpetiformis (DH) rash); resolves with a gluten-free diet (GFD)
    • <50% of adults present with gastrointestinal (GI) symptoms.
  • Atypical
    • Minor GI symptoms, with a myriad of extraintestinal manifestations (e.g., anemia, elevated LFTs, dental enamel defects, neurologic symptoms, infertility)
  • Asymptomatic (silent) disease
    • Found when screening first-degree relatives
    • Positive laboratory tests and genetics, without signs/symptoms; normal histology on biopsy
• System(s) affected: GI
• Synonym(s): celiac sprue; gluten-sensitive enteropathy; nontropical sprue

Epidemiology

Celiac disease (CD) is now recognized globally and incidence is increasing (1).

Etiology and Pathophysiology

Sensitivity to gluten, specifically gliadin protein fraction; tissue transglutaminase (tTG) modification of the gliadin protein leads to immunologic cross-reactivity, inflammation, and tissue damage (villous atrophy) with subsequent GI symptoms and malabsorption.

Risk Factors

First-degree relativesPediatric Considerations
No other risk factors (e.g., grain processing, genetically modified organisms, hygiene and illness during childhood, breastfeeding, time of introduction of solid foods, pollution, tobacco use, and medication) definitively explain why some susceptible individuals develop celiac, whereas others do not.

• If a first-degree relative has confirmed CD, then testing of the patient is warranted (3).
• Patients with type 1 diabetes should be tested for CD if there are any signs or symptoms (3).

Commonly Associated Conditions

• DH: 85% of patients with DH have CD. All patients with DH should follow a GFD.
• Secondary lactase deficiency
• Osteopenia and osteoporosis
• Infertility
• Thyroid disease: Hashimoto thyroiditis
• Type 1 diabetes
• Symptomatic iron deficiency: 10–15% have CD.
• Elevated AST and ALT (with no direct cause)
• Hyposplenism
• Oral aphthous ulcers
• Irritable bowel syndrome (IBS)
• Restless leg syndrome
• CD is associated with an 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 CD (seropositive but normal biopsy)
• Associated autoimmune conditions (type 1 diabetes, autoimmune thyroiditis, primary biliary cirrhosis, autoimmune hepatitis, psoriasis, Sjögren disease)
• Associated genetic conditions (Down syndrome, IgA deficiency, Turner syndrome, Williams syndrome)

Pregnancy Considerations

• Prevalence of CD: 2.5 to 3.5 times higher in women with unexplained infertility
• Up to 19% of men with CD have androgen resistance. Semen quality and the likelihood of pregnancy increase with GFD.
• Higher rates of low birth weight, prematurity, spontaneous abortions, intrauterine growth restriction, and stillbirths

Pediatric ConsiderationsChildren with type 1 diabetes, Down syndrome, Turner syndrome, Williams syndrome, IgA deficiency, and autoimmune thyroid disease are at risk for CD (3)[C].