Long-term morbidity and mortality in Whipple's disease: a single-center experience over 20 years.

Background: Little is known about long-term morbidity and mortality in Whipple's disease (WD). Aim: To describe morbidity and mortality in patients with WD on a long-term follow-up. Materials & methods: Comorbidities, mortality and causes of death were retrospectively registered. Results: A total of 35 patients with WD (9F, 54 ± 11 years) were followed-up for a median of 104 months. Nine patients developed ten complications; three patients died. A total of 31 severe comorbidities apparently unrelated to WD were found in 20 patients: preneoplastic/neoplastic disorders in seven, thromboembolic and cardiovascular events in seven, pneumonia in four, candidiasis in ten patients. Conclusion: WD is frequently complicated by potentially life-threatening infectious, neoplastic and thromboembolic disorders, thus highlighting the need for a life-long multidisciplinary follow-up.

Role of dendritic cells in the pathogenesis of Whipple's disease.

Accumulation of Tropheryma whipplei-stuffed macrophages in the duodenum, impaired T. whipplei-specific Th1 responses, and weak secretion of interleukin-12 (IL-12) are hallmarks of classical Whipple's disease (CWD). This study addresses dendritic cell (DC) functionality during CWD. We documented composition, distribution, and functionality of DC ex vivo or after in vitro maturation by fluorescence-activated cell sorting (FACS) and by immunohistochemistry in situ. A decrease in peripheral DC of untreated CWD patients compared to healthy donors was due to reduced CD11c(high) myeloid DC (M-DC). Decreased maturation markers CD83, CD86, and CCR7, as well as low IL-12 production in response to stimulation, disclosed an immature M-DC phenotype. In vitro-generated monocyte-derived DC from CWD patients showed normal maturation and T cell-stimulatory capacity under proinflammatory conditions but produced less IL-12 and failed to activate T. whipplei-specific Th1 cells. In duodenal and lymphoid tissues, T. whipplei was found within immature DC-SIGN(+) DC. DC and proliferating lymphocytes were reduced in lymph nodes of CWD patients compared to levels in controls. Our results indicate that dysfunctional IL-12 production by DC provides suboptimal conditions for priming of T. whipplei-specific T cells during CWD and that immature DC carrying T. whipplei contribute to the dissemination of the bacterium.

De subitaneis mortibus. XIV. Bacterial arteritis in Whipple's disease.

Although Whipple's disease is clinically recognized for its features of arthritis and diarrhea, pericarditis and cardiac valvular disease are frequently present and a significant number of such patients die suddenly and unexpectedly. This report includes special postmortem cardiovascular examinations in a 55-year-old man who died of Whipple's disease. Pericarditis and valvular disease were extensively present. There was also focal myocardial degeneration, including the sinus node, A-V node and His bundle. Typical Schiff-positive bacilli were found in the tunica media and endothelium most numerously in the small coronary and hepatic arteries, less in splenic and renal arteries, and least in small pulmonary arteries. Large coronary arteries and the aorta were not involved. Three stages of bacterial invasion of the arteries included a noninflammatory phase in which the bacilli were most numerous, a pancreatic phase in which bacilli were distinctly less numerous, and a healed scarring of arteries previously damaged. The combination of pericarditis, valvular disease of the heart, coronary and systemic bacterial arteritis and focal myocardial degeneration and myocarditis is unusual for Whippl'e disease. Studies of other cases are warranted to determine whether bacterial arteriopathy and arteritis have previously been overlooked or if the present case is unique. Evidence that the conduction system of the heart may be involved indicated that careful attention to cardiac rhyth and conduction is merited in future studies of patients with Whipple's disease.