A 55-year-old man presents to his primary care physician with 8 months of diarrhea, weight loss, and fatigue. He reports having 5–6 loose bowel movements daily and has unintentionally lost 20 pounds. Over the past year, he has also experienced migratory pain and stiffness involving his knees, wrists, and ankles. He was previously evaluated by a rheumatologist and treated with nonsteroidal anti-inflammatory drugs without improvement. His medical history is otherwise unremarkable. Temperature is 37.0°C (98.6°F), blood pressure is 118/72 mm Hg, pulse is 84/min, and respiratory rate is 14/min. Physical examination reveals a thin man with mild diffuse abdominal tenderness. Laboratory studies demonstrate the following:
Upper endoscopy with small bowel biopsy demonstrates foamy macrophages within the lamina propria that stain positive with periodic acid-Schiff (PAS).
Which of the following is the most likely diagnosis?
The correct answer is:
E) Whipple disease
This patient has Whipple disease, a rare systemic infection caused by Tropheryma whipplei. The diagnosis is suggested by the combination of chronic diarrhea, weight loss, malabsorption, iron deficiency anemia, hypoalbuminemia, migratory arthralgias, and PAS-positive foamy macrophages on small bowel biopsy.
Whipple disease is one of the classic board-style causes of malabsorption. The organism infiltrates the small intestinal mucosa and impairs nutrient absorption, leading to chronic diarrhea, weight loss, vitamin deficiencies, and protein-calorie malnutrition. However, the most distinctive clue is often the presence of extraintestinal manifestations that precede gastrointestinal symptoms by years. Migratory arthralgias are particularly common and frequently lead patients to seek rheumatologic evaluation before the diagnosis becomes apparent.
Small bowel biopsy is the diagnostic test most commonly tested on Step 2. Histology demonstrates PAS-positive macrophages within the lamina propria due to accumulation of bacterial glycoproteins. Polymerase chain reaction (PCR) testing can also support the diagnosis.
Because T. whipplei can disseminate to the central nervous system, heart, and other organs, prolonged antibiotic therapy is required. Untreated disease can be fatal.
A high-yield Step 2 distinction is that celiac disease causes malabsorption but does not produce PAS-positive macrophages or characteristic migratory arthralgias.
Answer choice A: Celiac disease, is incorrect.
Celiac disease can cause diarrhea, weight loss, iron deficiency anemia, and hypoalbuminemia. However, biopsy typically demonstrates villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis rather than PAS-positive macrophages. Migratory arthralgias may occur but are much less characteristic.
Answer choice B: Crohn disease, is incorrect.
Crohn disease can produce weight loss, diarrhea, anemia, and extraintestinal manifestations such as arthritis. However, biopsy findings would demonstrate transmural inflammation and granulomas rather than PAS-positive macrophages.
Answer choice C: Giardiasis, is incorrect.
Giardiasis causes malabsorptive diarrhea, bloating, and weight loss but is not associated with migratory arthralgias or the characteristic biopsy findings seen here.
Answer choice D: Tropical sprue, is incorrect.
Tropical sprue is a malabsorptive disorder associated with residence in tropical regions. It can cause nutritional deficiencies and diarrhea but does not produce PAS-positive macrophages or systemic manifestations such as migratory arthritis.
Key Learning Point
Whipple disease is caused by Tropheryma whipplei and classically presents with malabsorption, weight loss, chronic diarrhea, and migratory arthralgias. Small bowel biopsy demonstrates PAS-positive foamy macrophages within the lamina propria.
