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Difficulty: HardOrdering Laboratory Tests

A 2828-year-old woman is evaluated in the clinic for a 66-month history of extreme fatigue, abdominal bloating, and frequent, bulky, foul-smelling bowel movements. She has unintentionally lost 4.54.5 kg (1010 lb) during this period. Her medical history is significant for three distinct episodes of acute bacterial sinusitis over the past year. She takes no medications and has no known drug allergies. Vital signs are within normal limits. Physical examination reveals mild conjunctival pallor and a mildly distended abdomen with hyperactive bowel sounds. Initial laboratory testing shows:

Hemoglobin: 10.110.1 g/dL
Mean corpuscular volume: 7474 fL
Ferritin: 88 ng/mL (normal: 1515-200200 ng/mL)
Tissue transglutaminase (tTG) IgA antibody: Negative
Total serum IgA: 44 mg/dL (normal: 7070-400400 mg/dL)

Which of the following is the most appropriate next step in laboratory evaluation?

  1. Serum deamidated gliadin peptide (DGP) IgG and tissue transglutaminase (tTG) IgG antibodiesAnswer
  2. B
    HLA-DQ2 and HLA-DQ8 genetic testing
  3. C
    Quantitative serum immunoglobulin G (IgG) and immunoglobulin M (IgM) levels
  4. D
    Fecal elastase concentration
  5. E
    Fecal calprotectin level

Answer

Serum deamidated gliadin peptide (DGP) IgG and tissue transglutaminase (tTG) IgG antibodies
The correct answer is serum deamidated gliadin peptide (DGP) IgG and tissue transglutaminase (tTG) IgG antibodies. This patient presents with classic signs of malabsorption (steatorrhea, weight loss) and iron deficiency anemia, which are highly suggestive of celiac disease. Her initial screening test, tTG IgA, is negative. However, the laboratory results also show concurrent selective IgA deficiency (total IgA <5< 5 mg/dL). Selective IgA deficiency is up to 1010 to 1515 times more common in patients with celiac disease than in the general population, and it classically presents with recurrent sinopulmonary infections, as seen in this patient's history. Because she lacks sufficient IgA, any IgA-based serology will be falsely negative. The most appropriate next step in laboratory evaluation is to order IgG-based celiac serologies, such as DGP IgG and tTG IgG, to accurately assess for the disease before proceeding to confirmatory endoscopy.

Step-by-Step Solution

1
Analyze the clinical presentation and initial laboratory findings.
The patient has chronic malabsorptive diarrhea, weight loss, and iron deficiency anemia, which is highly suspicious for celiac disease.
Establishing the pre-test probability is essential for interpreting the subsequent serologic tests.
2
Interpret the specific serologic panel provided in the stem.
The tissue transglutaminase (tTG) IgA is negative, but the total serum IgA is profoundly low (44 mg/dL), indicating selective IgA deficiency.
Selective IgA deficiency is more common in patients with celiac disease. Its presence invalidates the negative predictive value of any IgA-based screening test.
3
Determine the next branch of the diagnostic algorithm.
Order IgG-based celiac serologies (DGP IgG and tTG IgG).
When a patient lacks sufficient endogenous IgA, IgG-based antibodies must be measured to accurately screen for celiac disease prior to considering endoscopy.

Key Concept

In patients suspected of having celiac disease who have concurrent selective IgA deficiency, standard IgA-based serologic tests (like tTG IgA) will be falsely negative; therefore, IgG-based serologies (such as DGP IgG and tTG IgG) must be ordered.
Estimated Time:1m 15s
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Ordering Laboratory Tests

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