What are the gastrointestinal manifestations of Whipple's disease?

Gastrointestinal Manifestations of Whipple's Disease

The primary gastrointestinal manifestations of Whipple's disease include diarrhea, abdominal pain, malabsorption syndrome, weight loss, and steatorrhea, which are caused by bacterial infiltration of the small intestine by Tropheryma whipplei. 1

Clinical Presentation

Common GI Manifestations

• Diarrhea: Often chronic or intermittent, watery in nature
• Abdominal pain: Typically postprandial
• Malabsorption syndrome: Leading to nutritional deficiencies
• Weight loss: Often profound and significant (can be 10% or more of body weight)
• Steatorrhea: Due to fat malabsorption
• Anorexia: Decreased appetite contributing to weight loss

Less Common GI Manifestations

• Abdominal distension: Due to gut stasis and bacterial overgrowth
• Ascites: Can develop in advanced cases
• Gastrointestinal bleeding: Uncommon but reported
• Hepatomegaly: Due to liver involvement

Pathophysiological Mechanisms

The gastrointestinal manifestations of Whipple's disease result from several pathophysiological processes:

1. Small intestinal bacterial overgrowth (SIBO): The combination of gut stasis with reduced propulsion and ineffective migrating motor complex (MMC) allows anaerobic bacteria to proliferate 2

2. Malabsorption: Occurs due to:

   • Bacterial deconjugation of bile salts
   • Degradation of pancreatic enzymes
   • Villous atrophy in the small intestine

3. Nutrient deficiencies: Common deficiencies include:

   • Fat-soluble vitamins (A, D, E, K)
   • Vitamin B12
   • Iron (leading to iron deficiency anemia) 2

4. Gut stasis: Results in:

   • Abdominal distension
   • Potential for large volume vomiting
   • Bacterial overgrowth 2

Histopathological Findings

The diagnosis of Whipple's disease is confirmed by characteristic histopathological findings:

• PAS-positive macrophages: Foamy histiocytes containing PAS-positive inclusions in the lamina propria of the small intestine 1, 3
• Villous atrophy: Variable degrees of atrophy in the small intestine
• Inflammatory infiltrate: In the intestinal mucosa

Diagnostic Approach

1. Endoscopy with small intestinal biopsy: The gold standard for diagnosis

   • Periodic acid-Schiff (PAS) staining showing characteristic macrophage infiltration
   • Histological examination for foamy histiocytes

2. PCR testing: Detection of T. whipplei DNA in:

   • Duodenal tissue samples
   • Peripheral blood
   • Other affected tissues 4, 5

3. Electron microscopy: Can identify bacteria with characteristic trilaminar cell wall ultrastructure 3

Clinical Pearls and Pitfalls

• Early symptom: Arthralgia often precedes gastrointestinal symptoms by months to years, which can delay diagnosis 6, 7
• Diagnostic delay: Due to the wide variability in presentation, diagnosis is often made years or even decades after initial symptoms 3
• Systemic manifestations: GI symptoms may be absent in some cases, with predominant neurological, cardiovascular, or joint manifestations 6
• Relapse risk: Despite treatment, relapses can occur, particularly with CNS involvement 7

Treatment Implications

• Antimicrobial therapy: The cornerstone of treatment

  • Initial therapy: Ceftriaxone or penicillin G intravenously for 2 weeks
  • Followed by: Trimethoprim-sulfamethoxazole orally for 1-2 years 1, 4

• Nutritional support: Often required to address malabsorption and weight loss

• Monitoring: Regular follow-up is essential due to risk of relapse

Whipple's disease, though rare, should be considered in the differential diagnosis of chronic diarrhea and malabsorption, particularly in middle-aged Caucasian men with accompanying arthralgia, as early diagnosis and appropriate treatment significantly improve outcomes.