Arthralgia and blood culture-negative endocarditis in middle Age Men suggest tropheryma whipplei infection: report of two cases and review of the literature

Abstract

BackgroundWhipple’s disease is a rare, often multisystemic chronic infectious disease caused by the rod-shaped bacterium Tropheryma whipplei. Very rarely the heart is involved in the process of the disease, leading to culture-negative infective endocarditis. Up to 20 % of all infective endocarditis are blood culture-negative and therefore a diagnostic challenge. We present two unusual cases of culture-negative infective endocarditis encountered in two different patients with prior history of arthralgia. A history of rheumatic arthritis or even a transient arthralgia should put Tropheryma whipplei on the top of differentials in patients of this age group presenting with culture-negative infective endocarditis, especially in cases of therapy resistance to antirheumatic agents.Case presentationThe first patient was a 55 year-old Caucasian male with culture-negative Whipple-related adhesive pericarditis and endocarditis of the aortic valve. Importantly, the patient reported a 15-year history of therapy resistant sero-negative migratory polyarthritis. Aortic valve endocarditis developed during treatment with tocilizumab. The second patient was a 65-year-old male patient with no prior history of the classic Whipple’s disease who presented with a culture-negative aortic valve endocarditis. His past medical history revealed episodes of transient arthralgia, which he was not treated for however, due to the self-limiting nature of the symptoms. Both patients underwent aortic valve replacement surgery. During surgery, pericardectomy was necessary in the first patient due to adhesive pericarditis. Post surgery both patients were started on long-term treatment with trimetoprim-sulfamethoxazol. At 1-year follow-up of both patients, echocardiographic and clinical assessment revealed no signs of persistent infection. Both men reported negative history of arthralgia during the one year period post surgery.ConclusionTropheryma whipplei culture negative-infective endocarditis is an emerging clinical entity, predominantly found in middle-aged and older men with a history of arthralgia. These data highlight the need for ruling out Whipple’s disease in patients with a history of arthralgia prior to initiation of biological agents in treatment of rheumatoid arthritis. There is also a need to assess for Tropheryma whipplei in all patients with culture- negative infective endocarditis.

A rare case of Whipple’s disease with endocarditis in a patient with dextrocardia

“…5 It typically presents with arthropathy, diarrhea, and usually has systemic signs and symptoms of weight loss, intermittent fever, night sweats, and lymphadenopathy. 4,6 Isolated valvular disease caused by T. whipplei , however, is not uncommon and can present in 20%–55% of patients with Whipple’ disease without gastrointestinal involvement. 6,7 A recent study has in fact identified this pathogen as the most common cause of culture-negative endocarditis, followed by Bartonella quintana and Coxiella burnetii .…”

“…2,3 The classical presentation of Whipple’s disease involves joint arthropathy (migratory oligoarticular or polyarticular) and digestive disorders (diarrhea, malabsorption, and weight loss). 4 Cardiac involvement has been reported in 17%–55% of patients with classic Whipple’s disease, including pericarditis, myocarditis, heart failure, or rarely culture-negative endocarditis. 2 This case highlights the importance of a high clinical index of suspicion T. whipplei culture-negative endocarditis, in the setting of arthralgia and abrupt worsening of cardiac function, without overt gastrointestinal symptoms.…”

Thrombocytopenia and endocarditis in a patient with Whipple’s disease: case report

“…Prior to the ability to culture Tropheryma Whipplei, successful treatment was also determined using clinical judgment and disappearance of previously positive tests such as PCR. Many cases were treated with induction therapy of different antibiotics, such as benzylpenicillin 1.2 million units and streptomycin 1GM daily for 2 weeks, with a seemingly agreed upon maintenance therapy of trimethoprim-sulfamethoxazole for at least 1 year [10]. However, recent publications have noted several cases of relapse on this regimen and note the preferred therapy to be a combination of doxycycline and hydroxychloroquine [11,12].…”

Culture Negative Endocarditis: Advances in Diagnosis and Treatment

“…T. whipplei is a known cause of CNE, and its true prevalence may be underestimated. When associated with arthralgia in middle-age men, it is almost pathognomonic for T. whipplei as the etiologic agent [49,50]. While the organism can be cultured in fibroblasts [48], diagnosis of CNE typically requires PCR analysis of valvular tissue [51].…”