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Difficulty: HardOrdering Laboratory Tests

A 31-year-old man presents to the outpatient clinic reporting a 4-month history of frequent, bulky, foul-smelling bowel movements, significant flatulence, and a 4-kg (8.8-lb) weight loss. He notes that the diarrhea does not resolve with fasting. He also complains of an intensely pruritic, blistering rash on his forearms and knees that has worsened over the past few weeks. His medical history is notable for recurrent sinusitis since childhood. Vital signs are within normal limits. Physical examination reveals conjunctival pallor and excoriated papules with occasional intact vesicles on the extensor surfaces of the upper and lower extremities.

Laboratory testing reveals:

Laboratory parameterResultReference range
Hemoglobin10.5 g/dL13.5–17.5 g/dL
Mean corpuscular volume76 fL80–100 fL
Total serum IgA4 mg/dL70–400 mg/dL
IgA anti-tissue transglutaminase2 U/mL<4< 4 U/mL (Negative)

Which of the following is the most appropriate next step in laboratory evaluation for this patient's underlying condition?

  1. IgG deamidated gliadin peptide antibody testingAnswer
  2. B
    IgA anti-endomysial antibody testing
  3. C
    HLA-DQ2 and HLA-DQ8 genotyping
  4. D
    Fecal calprotectin level
  5. E
    24-hour urine 5-hydroxyindoleacetic acid measurement

Answer

IgG deamidated gliadin peptide antibody testing
The correct answer is IgG deamidated gliadin peptide antibody testing. This patient presents with classic signs of celiac disease, including chronic malabsorptive diarrhea and dermatitis herpetiformis. Celiac disease is strongly associated with selective IgA deficiency (seen in 2-3% of patients with celiac disease). The initial laboratory workup shows a profoundly low total serum IgA level. The standard screening test for celiac disease is the IgA anti-tissue transglutaminase (anti-tTG) antibody. However, in the setting of selective IgA deficiency, the IgA anti-tTG will predictably yield a false-negative result, as seen in this patient. Therefore, the most appropriate next step in laboratory evaluation is to order an IgG-based serologic test, such as IgG deamidated gliadin peptide (DGP) antibody or IgG anti-tTG antibody, which accurately detects the immune response in these patients.

Step-by-Step Solution

1
Analyze the patient's clinical presentation.
The combination of malabsorptive diarrhea, weight loss, microcytic anemia, and dermatitis herpetiformis (pruritic vesicles on extensor surfaces) is highly characteristic of celiac disease.
Establishing the most likely clinical diagnosis guides the interpretation of the laboratory workup.
2
Interpret the initial laboratory results.
The total serum IgA is profoundly low (44 mg/dL), confirming selective IgA deficiency. The IgA anti-tissue transglutaminase (anti-tTG) is negative.
Identifying the total IgA level is critical to determining the validity of the specific IgA anti-tTG test.
3
Determine the limitation of the initial test.
In patients with selective IgA deficiency, all IgA-based serologic assays for celiac disease will be falsely negative.
Patients with IgA deficiency cannot produce the IgA autoantibodies typically measured in standard celiac screening.
4
Select the appropriate alternative diagnostic test.
An IgG-based celiac serology, such as the IgG deamidated gliadin peptide (DGP) antibody or IgG anti-tTG antibody, must be ordered.
IgG-based assays bypass the patient's inability to mount an IgA response, providing an accurate assessment for celiac disease.

Key Concept

Diagnostic evaluation of celiac disease in patients with concurrent selective IgA deficiency requires the use of IgG-based serologic testing.
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Ordering Laboratory Tests

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