Gastroenterology · Malabsorption Syndromes
The facts most likely to be tested
The initial screening test of choice is serum IgA tissue transglutaminase (tTG) antibody.
Patients with suspected celiac disease must be on a gluten-containing diet at the time of serologic testing to avoid false-negative results.
Individuals with selective IgA deficiency will have a false-negative IgA tTG, necessitating testing for IgG-based antibodies or total serum IgA levels.
The gold standard for definitive diagnosis is an endoscopic small bowel biopsy showing villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis.
Dermatologic manifestations include dermatitis herpetiformis, a pruritic, vesicular rash on the extensor surfaces associated with granular IgA deposits in the dermis.
Long-term complications include an increased risk of refractory sprue and enteropathy-associated T-cell lymphoma (EATL).
Treatment requires a strict, lifelong gluten-free diet to resolve symptoms and prevent malabsorption and nutritional deficiencies.
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A 34-year-old woman presents with a 6-month history of chronic diarrhea, bloating, and weight loss. She also reports a pruritic, blistering rash on her elbows and knees. Physical examination reveals pallor and atrophic glossitis. Laboratory studies demonstrate a microcytic anemia with a hemoglobin of 10.2 g/dL. Her serum IgA tTG antibody is significantly elevated.
What is the most likely diagnosis and the underlying pathophysiology of her skin findings?
Celiac disease with dermatitis herpetiformis caused by IgA immune complex deposition.
The patient's presentation of malabsorption and iron deficiency anemia is classic for celiac disease, and the rash is pathognomonic for dermatitis herpetiformis, which is an extraintestinal manifestation of the condition.
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High yield triage
Etiology / Epidemiology
Autoimmune reaction to gluten (gliadin) in genetically susceptible individuals (HLA-DQ2/DQ8).
Clinical Manifestations
Malabsorption, steatorrhea, and dermatitis herpetiformis (pruritic papulovesicles).
Diagnosis
IgA tissue transglutaminase (tTG) antibody is the initial screening test of choice.
Treatment
Strict gluten-free diet (lifelong) is the only effective management.
Prognosis
Increased risk of Enteropathy-associated T-cell lymphoma (EATL) if non-compliant.
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Epidemiology & Etiology
Strong genetic association with HLA-DQ2 and HLA-DQ8 alleles. Often presents in childhood or the 4th-5th decade of life. Associated with other autoimmune conditions like Type 1 Diabetes and Hashimoto thyroiditis.
Pertinent Anatomy
Primary damage occurs in the proximal small intestine (duodenum and jejunum). This location explains the malabsorption of iron, folate, and fat-soluble vitamins.
Pathophysiology
Ingestion of gluten triggers an immune response causing villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. This leads to a loss of absorptive surface area. Malabsorption results in osmotic diarrhea and nutrient deficiencies.
Clinical Manifestations
Classic symptoms include chronic diarrhea, weight loss, and bloating. Look for dermatitis herpetiformis (pathognomonic pruritic vesicles on extensor surfaces). Red flags include iron deficiency anemia, failure to thrive in children, and osteomalacia due to calcium/vitamin D malabsorption.
Diagnosis
Order IgA tissue transglutaminase (tTG) antibody first; ensure patient is on a gluten-containing diet to avoid false negatives. If IgA deficient, order IgG-based testing. The gold standard for definitive diagnosis is small bowel biopsy showing villous atrophy.
Treatment
Lifelong gluten-free diet is the cornerstone of therapy. Patients must avoid wheat, rye, and barley. Avoid oats unless certified gluten-free due to cross-contamination. Supplement iron, folate, and B12 if deficiencies are present.
Prognosis
Most patients achieve clinical remission with diet. Failure to improve suggests refractory disease or Enteropathy-associated T-cell lymphoma (EATL). Annual monitoring of antibody titers and bone density is recommended.
Differential Diagnosis
Tropical sprue: history of travel to endemic areas
Whipple disease: systemic symptoms like arthralgias and lymphadenopathy
Irritable bowel syndrome: normal labs and no malabsorption
Small intestinal bacterial overgrowth: positive breath test
Giardiasis: history of contaminated water exposure