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Difficulty: HardGastroenterology and Hepatology

A 38-year-old man seeks evaluation at an outpatient clinic for a four-month history of unremitting, voluminous watery diarrhea accompanied by a 12 kg12 \text{ kg} weight loss, intermittent low-grade fevers, and diffuse abdominal cramping. He has a history of advanced human immunodeficiency virus (HIV) infection but discontinued his antiretroviral therapy two years ago due to medication fatigue. His last known CD4+ T-lymphocyte count was 35/mm335/\text{mm}^3. Vital signs show a temperature of 37.9∘C37.9^\circ\text{C}, blood pressure of 105/65 mm Hg105/65 \text{ mm Hg}, and heart rate of 98/min98/\text{min}. Physical examination is notable for temporal wasting and mild, diffuse abdominal tenderness without rebound or guarding. Laboratory studies reveal a mild normocytic anemia and an elevated serum alkaline phosphatase level. Stool studies are negative for ova, parasites, and *Clostridioides difficile* toxin. An esophagogastroduodenoscopy (EGD) is performed. Biopsy of the descending duodenum reveals blunted villi and a dense infiltration of the lamina propria with enlarged, foamy macrophages. These macrophages stain strongly positive with periodic acid-Schiff (PAS). An acid-fast bacillus (AFB) stain of the tissue is subsequently performed and is positive. Based on these findings, which of the following is the most appropriate targeted pharmacotherapy for this patient's gastrointestinal condition?

  1. Clarithromycin and ethambutolAnswer
  2. B
    Intravenous ceftriaxone followed by oral trimethoprim-sulfamethoxazole
  3. C
    Intravenous ganciclovir
  4. D
    Strict lifelong adherence to a gluten-free diet
  5. E
    Oral vancomycin

Answer

The most appropriate therapy is the combination of clarithromycin and ethambutol.
The patient's clinical presentation, profoundly low CD4 count, and duodenal biopsy findings of PAS-positive, AFB-positive foamy macrophages confirm a diagnosis of gastrointestinal Mycobacterium avium complex (MAC) infection. The standard treatment for MAC enteritis (and disseminated MAC) requires a multi-drug antimicrobial regimen containing a macrolide (such as clarithromycin or azithromycin) and ethambutol to clear the infection and prevent the emergence of resistance.

Step-by-Step Solution

1
Analyze the patient's immune status and clinical presentation.
The patient has advanced HIV with a CD4 count < 50/mm³, chronic diarrhea, significant weight loss, and fever.
Identifies the patient as highly susceptible to severe opportunistic intestinal infections.
2
Interpret the duodenal biopsy findings.
The biopsy shows PAS-positive foamy macrophages in the lamina propria.
PAS-positive macrophages narrow the differential diagnosis primarily to Whipple disease (Tropheryma whipplei) and Mycobacterium avium complex (MAC) enteritis.
3
Differentiate between the top two diagnoses using special stains.
The tissue is positive for acid-fast bacilli (AFB).
MAC is an acid-fast organism, whereas Tropheryma whipplei is non-acid-fast, confirming a diagnosis of MAC enteritis.
4
Select the appropriate pharmacotherapy for the confirmed diagnosis.
MAC infection requires a multi-drug regimen, typically a macrolide combined with ethambutol.
Ensures effective eradication and prevents resistance in disseminated or localized gastrointestinal MAC.

Key Concept

Differentiating Whipple disease from MAC enteritis based on AFB staining, and selecting appropriate MAC-targeted antibiotic therapy.
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Topics

Gastroenterology and Hepatology

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