Whipple’s Disease

Stephen A. Paget

Kristina Belostocki

KEY POINTS

Whipple’s disease (WD) is a rare multisystem syndrome caused by the gram-positive actinomycete Tropheryma whippelii.
The clinical manifestations of WD include insidious onset of fever, arthritis, malabsorption, generalized lymphadenopathy, skin hyperpigmentation, uveitis, or progressive encephalopathy and symmetric, transient, and nondeforming polyarthritis.
Diagnosis is based on recognition of the characteristic clinical picture in addition to typical histologic findings on duodenal or jejunal biopsy and perhaps by polymerase chain reaction (PCR) analysis of tissue or fluid.
Treatment with parenteral antibiotics (penicillin G and streptomycin) followed by oral trimethoprim/sulfamethoxazole is recommended.
Relapses commonly occur months to years after the initial presentation and usually respond to the same antibiotic that initially induced remission.

Whipple’s disease (WD) is a rare multisystem syndrome caused by the gram-positive actinomycete Tropheryma whippelii. It was first described in 1907 when George Whipple reported the case of a 36-year-old physician who died after hospitalization for weakness, fever, cough, abdominal pain, diarrhea, weight loss, arthralgias, hypotension, hyperpigmentation, and anemia. At autopsy, enlarged mesenteric and retroperitoneal lymph nodes with cystic fatty changes were found, and Whipple called the disease intestinal lipodystrophy.

The diverse clinical manifestations of WD reflect the systemic nature of the infection caused by T. whippelii. Nearly every organ system can be involved and WD can march through many different clinical phases, with multiple misdiagnoses and their attendant inappropriate therapies.

ETIOPATHOGENESIS

The bacterium T. whippelii, a member of the actinomycetes group, has been found in a variety of cell types and organs in patients with WD and shown to be the causative organism. It has also been detected in various body fluids including cerebrospinal fluid.
The pathogenesis of WD is not well understood.
- Immune defects involving T cells and macrophages have been described.
- Reduced levels of interleukin-12 and interferon-γ production have been detected in patients with WD. These cytokines may be important because of their ability to contain and clear intracellular bacteria, and could explain the longstanding infection and the presence of the organism in macrophages for years in patients with WD.

PREVALENCE

WD is rare, with the frequency of the disease less than 0.1% in postmortem studies. It is seen primarily in white men (male to female ratio is 10 to 1).

T. whippelii may be an environmental agent present in water, with a possible oral infectious route of the bacillus. It could therefore be present in a larger portion of the population in the absence of clinical WD, possibly as an oral commensal organism. Studies utilizing polymerase chain reaction (PCR) technology have demonstrated the presence of T. whippelii in 5% to 35% of diseasefree individuals.

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