Pathogenesis of Whipple's disease

Whipple´s disease is caused by chronic infection with the bacterium Tropheryma whipplei. T whipplei appears intra- as well as extracellulary and can be detected by a PAS-staining of intestinal biopsies within infected macrophages, indicated by a deep red colour representing the bacteria or parts of their cell walls.

Despite the identification of the bacterium, details about the pathogenesis of Whipple´s disease is still far from clear, but there are several hints for a genetic or acquired immunological predisposition. Although the presence of T whipplei is presumed to be ubiquitous, Whipple's disease occurs mainly in middle aged individuals (mean age at diagnosis about 50 years). Specific environmental factors or habits have not yet been associated with the disorder. The disease sometimes has, even after extensive antibiotic therapy, a chronic relapsing course and T whipplei can persist for a long time within the affected tissues.

Some familial cases have been reported, and a genetic susceptibility might be suggested since about 26% of patients (three to four times more than expected) are positive for HLA B27. Taken together, these observations suggest that a host factor, putatively of an immunological nature, plays an important role in the occurrence of the disease.

The most probable theory is that a defect in cellular immune responses predisposes patients for an infection with T whipplei. This presumed immunological defect is likely to be quite specific for T whipplei, since patients are not generally affected by infection with other organisms. Figure 1 summarizes the defective immune responses seen in patients infected with T whipplei. It still remains unclear whether the primary defect localizes within the T-cells or the macrophages.