Tropheryma whipplei infection (Whipple's disease) in a patient after liver transplantation.

Whipple's disease (WD) is a rare infection caused by the bacterium Tropheryma whipplei that can affect multiple organs and most commonly occurs in the immunocompetent host. Only 3 cases of WD have been reported in the setting of immunosuppression for organ transplantation. Here, we report the first case of WD, to our knowledge, in a patient after liver transplantation with comorbid graft-versus-host-disease. We discuss the diagnostic challenges in this setting and the value of electron microscopy and in situ hybridization methods for confirming the infection. WD may be under-diagnosed in immunosuppressed transplant patients because the disease can present with atypical clinical and histological features that suggest other conditions.

Tropheryma whipplei, the Whipple's disease bacillus, induces macrophage apoptosis through the extrinsic pathway.

Tropheryma whipplei, the etiological agent of Whipple's disease, is an intracellular bacterium that infects macrophages. We previously showed that infection of macrophages results in M2 polarization associated with induction of apoptosis and interleukin (IL)-16 secretion. In patients with Whipple's disease, circulating levels of apoptotic markers and IL-16 are increased and correlate with the activity of the disease. To gain insight into the understanding of the pathophysiology of this rare disease, we examined the molecular pathways involved in T. whipplei-induced apoptosis of human macrophages. Our data showed that apoptosis induction depended on bacterial viability and inhibition of bacterial protein synthesis reduced the apoptotic program elicited by T. whipplei. Induction of apoptosis was also associated with a massive degradation of both pro- and anti-apoptotic mediators. Caspase-specific inhibition experiments revealed that initiator caspases 8 and 10 were required for apoptosis, in contrast to caspases 2 and 9, in spite of cytochrome-c release from mitochondria. Finally, the effector caspases 3 and 6 were mandatory for apoptosis induction. Collectively, these data suggest that T. whipplei induces apoptosis through the extrinsic pathway and that, beside M2 polarization of macrophages, apoptosis induction contributes to bacterial replication and represents a virulence trait of this intracellular pathogen.

New insights into Whipple's disease - a rare intestinal inflammatory disorder.

Whipple's disease (WD) is a rare systemic infectious disorder caused by the actinomycete Tropheryma whipplei. This chronic disease, first described by Whipple as 'intestinal lipodystrophy', affects preferentially middle-aged white men who may present with weight loss, diarrhea, abdominal pain and arthralgia. Thus, it represents an important differential diagnosis of chronic diarrhea. A variety of other clinical patterns, such as involvement of the heart, lung, or central nervous system (CNS), are frequent. In addition, individuals with isolated heart valve involvement or asymptomatic carriers may be observed. The diagnosis often is established by small bowel biopsy, which is characterized by periodic acid-Schiff-positive inclusions representing the causative bacteria. T. whipplei can be detected by specific polymerase chain reaction, immunohistochemistry or electron microscopy and was cultured a few years ago. Several studies show that subtle defects of the cell-mediated immunity exist in active and inactive WD which may predispose individuals with a certain HLA type to a clinical manifestation of T. whipplei infection. As confirmed in a recent controlled trial, most patients respond well to a prolonged antibiotic treatment, but some patients with relapsing disease or CNS manifestation may have a poor prognosis. In the presentation, the relevance of WD in the differential diagnosis of chronic diarrhea and the new findings of this enigmatic rare disorder will be discussed.