Systematic review: Whipple's disease (Tropheryma whipplei infection) and its unmasking by tumour necrosis factor inhibitors

Abstract

Background The classical form of Whipple's disease (WD), clinically characterised by arthropathy, diarrhoea and weight loss, is rare. Recently, other more frequent forms of Tropheryma whipplei infection have been recognised. The clinical spectrum includes an acute, self-limiting disease in children, localised forms affecting cardiac valves or the central nervous system without intestinal symptoms, and asymptomatic carriage of T. whipplei which is found in around 4% of Europeans. Genomic analysis has shown that T. whipplei represents a host-dependent or opportunistic bacterium. It has been reported that the clinical course of T. whipplei infection may be influenced by medical immunosuppression. Aim To identify associations between immunomodulatory treatment and the clinical course of T. whipplei infection. Methods A PubMed literature search was performed and 19 studies reporting on immunosuppression, particularly therapy with tumour necrosis factor inhibitors (TNFI) prior to the diagnosis in 41 patients with Whipple?s disease, were evaluated. Results As arthritis may precede the diagnosis of WD by many years, a relevant percentage (up to 50% in some reports) of patients are treated with immunomodulatory drugs or with TNFI. Many publications report on a complicated Whipple?s disease course or T. whipplei endocarditis following medical immunosuppression, particularly after TNFI. Standard diagnostic tests such as periodic acid-Schiff stain used to diagnose Whipple?s disease often fail in patients who are pre-treated by TNFI. Conclusions In cases of doubt, Whipple?s disease should be excluded before therapy with TNFI. The fact that immunosuppressive therapy contributes to the progression of T. whipplei infection expands our pathogenetic view of this clinical entity.