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Difficulty: HardOrdering Laboratory Tests

A 32-year-old woman is evaluated in the outpatient clinic for a 6-month history of fatigue, intermittent abdominal bloating, and large, malodorous bowel movements. Over the same period, she has experienced a 4-kg (8.8-lb) unintentional weight loss. Her past medical history is notable for recurrent sinus infections during childhood, at which time she was diagnosed with selective IgA deficiency. She takes no medications and has no known drug allergies. Vital signs are within normal limits. Physical examination reveals pale conjunctivae and a highly pruritic, grouped vesicular eruption symmetrically distributed on her elbows and knees. Laboratory studies reveal a hemoglobin of 10.2 g/dL and a mean corpuscular volume (MCV) of 74 fL. Which of the following is the most appropriate next step in laboratory evaluation?

  1. A
    Measurement of tissue transglutaminase IgA antibodies
  2. Measurement of deamidated gliadin peptide IgG antibodiesAnswer
  3. C
    Measurement of fecal calprotectin
  4. D
    72-hour quantitative stool fat test
  5. E
    Human leukocyte antigen DQ2 and DQ8 genotyping

Answer

Measurement of deamidated gliadin peptide IgG antibodies
The patient's presentation of malabsorption, iron deficiency anemia, and dermatitis herpetiformis is highly suspicious for celiac disease. While tissue transglutaminase (tTG) IgA is the standard initial screening test, this patient has a documented history of selective IgA deficiency. In such patients, IgA-based assays will be falsely negative. Therefore, testing must rely on IgG-based antibodies, such as deamidated gliadin peptide (DGP) IgG or tTG IgG, to accurately establish the diagnosis.

Step-by-Step Solution

1
Identify the underlying clinical syndrome based on the patient's presentation.
The combination of chronic diarrhea, weight loss, microcytic anemia, and dermatitis herpetiformis strongly indicates celiac disease.
Recognizing the disease is necessary to select the appropriate diagnostic pathway.
2
Determine the standard initial screening test for the suspected condition.
The standard initial serologic test for celiac disease is tissue transglutaminase (tTG) IgA antibody testing.
tTG-IgA is highly sensitive and specific in the general population.
3
Incorporate the patient's specific past medical history into the diagnostic plan.
The patient has a known history of selective IgA deficiency, meaning any IgA-based test will yield a false-negative result.
Comorbid conditions can invalidate standard diagnostic assays.
4
Select the appropriate alternative laboratory test.
An IgG-based assay, such as deamidated gliadin peptide (DGP) IgG or tTG IgG, must be ordered.
IgG-based testing retains high sensitivity and specificity for celiac disease in patients who cannot produce sufficient IgA.

Key Concept

Patients with suspected celiac disease and concurrent selective IgA deficiency must be screened using IgG-based serologic testing (e.g., deamidated gliadin peptide IgG or tTG IgG) rather than standard IgA-based assays to avoid false-negative results.
Estimated Time:1m 30s
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Ordering Laboratory Tests

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