From Symptoms to Solution: A Diagnostic Challenge of Whipple's Disease

Abstract

Whipple's disease is caused by the bacterium Tropheryma whipplei. The classic presentation of this disease consists of arthralgias, weight loss, diarrhea, and abdominal pain. However, Whipple's disease can also have other manifestations across multiple organ systems, ranging from lymphadenopathy to pleuropulmonary disease to endocarditis to skin hyperpigmentation and even CNS involvement. We present the case of a 39-year-old male with multiple organ system manifestations of Whipple's disease. He presented with a 50-pound unintentional weight loss, early satiety, arthralgias, chronic cough, pleural effusions, and lymphadenopathy on a CT scan. A transesophageal echocardiogram revealed vegetation on multiple valves, consistent with the diagnosis of endocarditis. Blood cultures showed no growth. Several labs were obtained for a complete work-up for culture-negative endocarditis. The serum polymerase chain reaction (PCR) was reported positive for T. whipplei. Gastric antral biopsy and inguinal lymph node biopsy showed periodic acid-Schiff (PAS)-positive macrophages, confirming the diagnosis of Whipple's disease. The patient was treated with ceftriaxone for a four-week course, followed by Bactrim DS for one year. As was the case with this patient, Whipple's disease can present a wide array of symptoms across multiple organ systems. It is often difficult to diagnose due to its rarity and broad range of non-specific symptoms. Physicians should maintain a high level of suspicion for this disease and include it in their differential diagnosis. A prompt diagnosis and appropriate treatment will yield better outcomes.

Keywords: arthralgias; culture negative infective endocarditis; lymphadenopathy; malabsorption syndrome; tropheryma whipplei; whipple's disease.

Figure 1. Imaging Findings

(A) Bilateral pleural effusion; (B) Axillary lymphadenopathy; (C) Subcarinal-right hilar lymph node measuring 9.25 mm; (D) Prevascular lymph node measuring 5.89 mm; (E) External iliac chain lymph node measuring 10.9 mm; (F) Inguinal lymphadenopathy

Figure 2. Echocardiographic Findings

(A) Mitral valve vegetation; (B) Tricuspid valve vegetation; (C) Aortic valve vegetation; (D) Normal pulmonic valve

Figure 3. Inguinal Lymph Node Biopsy Findings

(A) Sinus hyperplasia (hematoxylin and eosin (H&E) stain); (B) Foamy macrophages (H&E stain); (C) Periodic acid-Schiff with diastase (PAS/D) stain showing Tropheryma whipplei at 40× magnification; (D) PAS/D stain showing T. whipplei at 100× magnification T. whipplei has a plasma membrane enclosed by a three-layered cell wall. The inner layer of the cell wall contains polysaccharides that stain positive with PAS. When the organism is ingested by macrophages, the rod-shaped bacteria become visible within macrophages under PAS staining.

Figure 4. Gastric Antral Biopsy Findings

(A) Hematoxylin and eosin (H&E) stain, low power; (B) H&E stain, high power; (C) Periodic acid-Schiff with diastase (PAS-D) stain, high power, showing PAS-positive macrophages in the antral mucosa Tropheryma whipplei has a plasma membrane enclosed by a three-layered cell wall. The inner layer of the cell wall contains polysaccharides that stain positive with PAS. When the organism is ingested by macrophages, the rod-shaped bacteria become visible within macrophages under PAS staining.