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Difficulty: MediumOrdering Laboratory Tests

A 32-year-old woman comes to the clinic for evaluation of chronic diarrhea and unintentional weight loss over the past eight months. She describes having 3 to 4 loose, foul-smelling bowel movements daily, accompanied by abdominal bloating. She also reports significant fatigue. Her medical history is unremarkable, and she takes no medications. Vital signs are within normal limits. Physical examination reveals mild diffuse abdominal tenderness without guarding or rebound. Laboratory studies obtained last week show a hemoglobin of 10.5 g/dL with a mean corpuscular volume of 74 fL. Which of the following is the most appropriate next step in laboratory evaluation?

  1. Tissue transglutaminase IgA antibody and total serum IgA levelsAnswer
  2. B
    IgG antibodies against deamidated gliadin peptides
  3. C
    Human leukocyte antigen (HLA) DQ2 and DQ8 typing
  4. D
    Fecal calprotectin level
  5. E
    Comprehensive stool microbiology panel including culture

Answer

Tissue transglutaminase IgA antibody and total serum IgA levels
The correct answer involves ordering tissue transglutaminase IgA antibody and total serum IgA levels. This patient presents with classic signs of malabsorption, including chronic diarrhea, bloating, weight loss, and iron deficiency anemia (microcytic anemia). Celiac disease is highly suspected. The most sensitive and specific initial diagnostic laboratory test for celiac disease is the IgA anti-tissue transglutaminase (tTG) antibody. Because selective IgA deficiency is more common in patients with celiac disease than in the general population, a total serum IgA level must be measured simultaneously. If the patient has an IgA deficiency, the IgA anti-tTG will be falsely negative, and IgG-based testing (such as IgG deamidated gliadin peptides) should be utilized instead.

Step-by-Step Solution

1
Analyze the clinical presentation.
The patient has chronic diarrhea, bloating, weight loss, and microcytic anemia.
Identifying the chronicity and specific characteristics of the symptoms helps narrow the differential diagnosis to malabsorptive disorders rather than acute infections.
2
Formulate a leading diagnosis.
Celiac disease is the most likely diagnosis.
The combination of foul-smelling stools (steatorrhea), significant weight loss, and iron deficiency anemia (indicated by low hemoglobin and low MCV) in a young adult strongly suggests celiac disease.
3
Select the appropriate initial laboratory investigation.
Ordering tissue transglutaminase IgA antibody and a total serum IgA level is indicated.
This is the standard, highly sensitive and specific first-line screening protocol for suspected celiac disease.

Key Concept

The initial laboratory evaluation for suspected celiac disease involves testing for tissue transglutaminase (tTG) IgA antibodies alongside a total serum IgA level to avoid false negatives in patients with concurrent selective IgA deficiency.
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Ordering Laboratory Tests

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