Clinical Features of Whipple Disease
Whipple disease is characterized by a diverse array of clinical manifestations, including joint inflammation, gastrointestinal symptoms, weight loss, and neurological abnormalities, with arthralgia often being an early symptom that can precede other manifestations by years. 1
Key Clinical Manifestations
Gastrointestinal Features
- Weight loss (common and often significant)
- Chronic diarrhea
- Abdominal pain
- Malabsorption leading to:
- Fat-soluble vitamin deficiencies (A, D, E, K)
- Vitamin B12 deficiency
- Iron deficiency anemia 1
- Abdominal distension
- Potential for large volume vomiting 1
Systemic Features
Musculoskeletal Features
- Arthralgia/arthritis (often seronegative)
Neurological Features
- Present in 10-20% of patients but may occur in all cases 2
- Can be the initial presentation without concurrent intestinal manifestations 5
- Common neurological manifestations include:
Ocular Manifestations
- Uveitis
- Retinitis
- Optic neuritis
- Papilledema 5
Disease Course and Diagnosis
Diagnostic Challenges
- Average time to diagnosis is approximately 6 years 4
- Often misdiagnosed as rheumatoid arthritis or sarcoidosis 5
- Absence of digestive symptoms can lead to delayed diagnosis 4
Disease Progression
- Without treatment, the disease is lethal 2
- CNS is the most common site of disease relapse 2
- Neurological involvement represents the greatest risk for long-term disability 5
Special Considerations
Patient Demographics
- Predominantly affects middle-aged men 6
- Worldwide prevalence of approximately 30 affected individuals per million population 7
Clinical Patterns
- Classic presentation: weight loss, chronic diarrhea, arthralgias, and low-grade fever 6
- Atypical presentations are increasingly recognized 6
- Neurological symptoms may occur without gastrointestinal involvement 5
Diagnostic Approach
- Gold standard: endoscopy with small intestinal biopsy showing PAS-positive macrophage infiltration 1
- PCR testing for T. whipplei DNA in duodenal tissue, peripheral blood, and other affected tissues 1
- Brain imaging (CT/MRI) may show cortical/subcortical atrophy, hydrocephalus, or focal lesions, but is often normal 2, 5
Whipple disease should be considered in patients with unexplained weight loss, joint symptoms, and gastrointestinal complaints, particularly when these symptoms persist over years. Due to its multisystem nature and variable presentation, a high index of suspicion is needed, especially in cases with predominant neurological or rheumatological manifestations without obvious gastrointestinal symptoms.