Whipple Disease Differential Diagnoses

Updated: Oct 24, 2019
  • Author: Ingram M Roberts, MD, MBA; Chief Editor: Burt Cagir, MD, FACS  more...
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Diagnostic Considerations

Maintain a high clinical suspicion for Whipple disease in patients diagnosed with chronic inflammatory rheumatism that is partially or not controlled by treatment with anti-tumor necrosis factor-alpha (anti-TNF-a) agents, and whose condition worsens after such therapy. [28]

A recent, single-center retrospective study reviewed seven patients with suspected seronegative rheumatoid arthritis who had inappropriate treatment response and were ultimately diagnosed with Whipple disease. [36] All patients had no gastrointestinal symptoms, increased levels of C-reactive protein, while absent rheumatoid factor and anti-CCP-antibodies. These patients were unresponsive to treatment with steroids, methotrexate and biologic agents. T whipplei was identified in synovial fluid and all patients responded positively with antibiotic therapy. [36]

The following conditions should also be considered in the differential diagnosis of patients with suspected Whipple disease:

  • Acquired immunodeficiency (AIDS)–related complex

  • Endocarditis, bacterial and nonbacterial

  • Human immunodeficiency virus (HIV) enteropathy

  • Macroglobulinemia

  • Mycobacterium avium intracellulare infection

  • Abetalipoproteinemia and hypobetalipoproteinemia

Differential Diagnoses