Whipple’s disease-associated infective endocarditis: a systematic review

Whipple's disease is an uncommon chronic systemic disease caused by Tropheryma whippelii. The most characteristic findings of late Whipple's disease include diarrhoea, abdominal pain, weight loss, and arthralgias, however, other clinical findings can occur, including lymphadenopathy, fever, neurologic manifestations, myocarditis and endocarditis. The aim of the present study was to systematically review all cases of Whipple's disease-associated infective endocarditis (IE) in the literature. A systematic review of PubMed, Scopus, and Cochrane Library (all published studies up to 28 May 2022) for studies providing data on epidemiology, clinical characteristics as well as data on treatment and outcomes of Whipple's disease-associated IE was performed. A total of 72 studies, containing data for 127 patients, were included. A prosthetic valve was present in 8% of patients. The aortic valve was the most commonly involved intracardiac site followed by the mitral valve. Heart failure, embolic phenomena, and fever were the most common clinical presentations, however, fever occurred in less than 30% of patients. Sepsis was rarely noted. The diagnosis was most commonly performed through pathology through positive PCR or histology in cardiac valves in 88.2% of patients. Trimethoprim with sulfamethoxazole were the most commonly used antimicrobials followed by cephalosporins and tetracyclines. Surgery was performed in 84.3% of patients. Mortality was 9.4%. A multivariate logistic regression analysis model identified presentation with sepsis or development of a paravalvular abscess to be independently associated with increased mortality, while treatment with the combination of trimethoprim with sulfamethoxazole was independently associated with reduced mortality.