Celiac Disease

Snapshot

• A 7-year-old girl is brought in by her parents for poor weight gain and recurrent diarrhea.  They have tried eliminating dairy from her diet with no improvement in symptoms.  She reports 3-5 loose stools per day for the last 6 months. The condition improves when she fasts and is usually worse when she eats fast food like pizza.  On exam, you notice several excoriated areas on the girls arms which she states are very itchy.

Introduction

• Overview
  • chronic autoimmune disorder triggered by an environmental agent (gliadin component of gluten) in genetically predisposed individuals
    • often found in wheat and other grains such as barley and rye
  • often develops in childhood but may develop at any age
• Epidemiology
  • demographics
    • occurs primarily in Caucasians of northern European ancestry
    • > 1:5,000 in North America  
• Pathogenesis
  • upon exposure to gluten, an abnormal immune response leads to the production of several different autoantibodies that affects different organs
    • leads to the formation of an immune complex in the intestinal mucosa (primarily at the small intestine)
  • presence of the immune complex promotes the aggregation of killer lymphocytes, which cause mucosal damage
    • leads to the loss of villi lining (villous atrophy) and proliferation of crypt cells
  • damage of the villi lining leads to dysfunction in nutrient absorption, leading to malabsorption and anemia
• Genetics
  • no single genetic marker exists
  • majority of patients have the variant HLA-DQ2 or HLA-DQ8 allele
    • these predisposing HLA risk alleles are necessary but not sufficient to develop celiac disease
• Associated conditions 
• other autoimmune diseases (e.g., diabetes mellitus type 1)

Presentation

• Symptoms 
  • steatorrhea  
    • can lead to fat soluble vitamin deficiencies 
  • abdominal pain
  • bloating
  • flatulence
  • weight loss/failure to gain weight
  • fatigue
  • some patients are asymptomatic
  • repeated infections (if IgA deficient, common in celiac patients)
    • anaphylaxis if transfused by IgA containing blood products 
• Physical exam
  • abdominal distension
  • pallor
  • mouth ulcers
  • short stature
  • dermatitis herpetiformis  
    • pruritic, red, papulo-vesicular lesion commonly on shoulders, elbows, and knees 
• due to IgA deposits in the upper dermis

Imaging 

• Dual energy X-ray absorptiometry (DEXA)
• to identify risk of fracture and need for bone protection medication

Studies 

• Serum labs
  • serological antibody testing 
    • best initial test
    • anti-tissue transglutaminase (tTg)-IgA antibody 
    • anti-endomysial-IgA antibody 
    • tests for IgA antibodies, will be negative in those with IgA deficiency
      • for patients with IgA deficiency, deamidated gliadin peptide (DGP) IgG testing is available
    • positive serology requires small bowel biopsy for confirmation of diagnosis
  • CBC, iron studies, folic acid, vitamin B12 to evaluate level of malnutrition/malabsorption
  • HLA testing
    • only useful in ruling out celiac disease
• Invasive studies 
  • upper endoscopy with small bowel biopsy  
    • best confirmatory test
    • at least 4 duodenal biopsies are recommended
    • endoscopic features including loss of folds, visible fissures, nodularity, scalloping, and prominent submucosal vascularity 
    • histologic features include 
      • increased intraepithelial lymphocytes and plasma cells 
      • atrophic mucosa with loss of villi 
      • enhanced epithelial apoptosis
• crypt hyperplasia

Differential

• Tropical sprue
  • distinguishing factors 
    • responds to antibiotics and associated with travel to the tropics 
• Inflammatory bowel disease 
  • distinguishing factors
    •  different histological appearance on biopsy
• Irritable bowel syndrome 
  • distinguishing factors
• will have negative biopsy results

Treatment

• Lifestyle modifications
  • gluten-free diet
    • allows healing of the intestinal mucosa and resolution of all symptoms
    • eliminates the heighted risk of osteoporosis and intestinal cancer
  • dietary supplements
• Medical treatment 
  • steroids or immunosuppressant (e.g., azathioprine)
    • consider in patients with refractory disease
  • dapsone 
• treatment of dermatitis herpetiformis 

Complications

• Iron deficiency anemia
• Osteoporosis
• Infertility
• Neurological problems (secondary to malabsorption)
• Intestinal lymphoma
  • develops in 10-15% of patients