Whipple's Endocarditis Research Articles

An unusual presentation of a rare disease: acute upper limb ischemia as the presenting symptom of Whipple’s Endocarditis, a case report

BackgroundWhipple's disease is known to cause multiple varied systemic symptoms, and is a well-documented cause of culture-negative endocarditis. Endocarditis secondary to Whipple disease, however, has rarely been known to present primarily as a cause of acute limb ischemia. We describe such a case here.Case presentationA previously healthy 40 year old man presented to the emergency department with acute-onset right arm paresthesias. On exam, he was found to be tachycardic with a VI/VI systolic ejection murmur. He was diagnosed with critical limb ischemia and severe aortic regurgitation, and echocardiography showed a large mass on his bicuspid aortic valve. Thrombectomy was performed urgently, with aortic valve repair the following day. As blood cultures and valvular tissue culture remained unrevealing, the patient remained on empiric vancomycin and ceftriaxone for culture-negative endocarditis. 16 s rRNA nucleic acid amplification testing (NAAT) of his formalin-fixed, paraffin-embedded valvular tissue detected T. whipplei, after which the patient was transitioned to ceftriaxone and trimethoprim-sulfamethoxazole for a year of therapy. He continues to do clinically well.ConclusionsWe report an unusual presentation of Whipple endocarditis as an acute upper limb ischemia, absent other classic symptoms of Whipple's disease, and with diagnosis made by 16 s rRNA NAAT of valvular tissue in the setting of culture-negative endocarditis.

Blood Culture-negative Endocarditis Caused by Tropheryma whipplei: Whipple's endocarditis.

A 67-year-old man was admitted with progressive heart failure due to blood culture-negative endocarditis of the aortic valve. Urgent aortic valve replacement was needed. Polymerase chain reaction (PCR) testing of samples of the explanted aortic valve revealed Tropheryma whipplei. The patient received ceftriaxone, followed by long-term co-trimoxazole. Recent arthralgia may have been a diagnostic clue. Whipple's endocarditis should be considered in patients with arthralgia and blood culture-negative endocarditis (BCNIE). Whipple's endocarditis should be considered in patients with symptoms of arthralgia and blood culture-negative endocarditis (BCNIE).Serum polymerase chain reaction is the main diagnostic test.Both physician awareness and multidisciplinary management by regional endocarditis teams are recommended strategies to provide optimal patient care.

710. Non-invasive Diagnosis of Whipple Endocarditis Using Next-Generation Sequencing for Microbial Cell-free DNA in Plasma

Background Tropheryma whipplei is a gram-positive bacillus that causes Whipple’s disease, a protean multisystemic syndrome classically characterized by arthralgias, chronic diarrhea, malabsorption, and weight loss. T. whipplei infection has a wide spectrum of clinical manifestations including pleuropulmonary disease, skin hyperpigmentation and cardiac infection. Endocarditis has been diagnosed in a small number of patients and may represent an atypical presentation of T. whipplei infection. Diagnosis can be challenging and has typically been accomplished with histopathology on resected valvular tissue or GI tract biopsy. Next-generation sequencing (NGS) of microbial cell-free DNA (mcfDNA) in plasma offers a rapid, non-invasive means of diagnosis of this rare cause of culture-negative endocarditis and challenging clinical entity.MethodsMcfDNA analysis was performed in a patient with culture negative endocarditis. McDNA was extracted from plasma and NGS was performed by Karius, Inc. (Redwood City, California). Human sequences were removed and remaining sequences were aligned to a curated database of over 1,400 pathogens. Organisms present above a predefined statistical significance threshold were reported and quantified in DNA molecules per microliter (MPM). Chart review was performed for clinical correlation.ResultsA 64 year-old male with history of valve replacement presented with significant deterioration of the mitral valve. An exhaustive infectious workup including blood cultures was negative. Karius testing detected T. whipplei at 766 MPM within two days of sample receipt. The normal range for T. whipplei is 0 MPM based on a cohort of 684 healthy individuals. Blood PCR for T. whipplei was confirmatory.Table 1: Clinical Parameters of Case ConclusionNGS for mcfDNA in plasma offers a rapid, non-invasive method for identifying T. whipplei and, to our knowledge, the first diagnosis of Whipple disease using NGS of plasma mcfDNA.DisclosuresChristiaan R. de Vries, MD, PhD, Karius (Consultant, Independent Contractor)Stanford University (Employee) Ann Macintyre, DO, Karius (Employee)

A RARE CASE OF CULTURE NEGATIVE WHIPPLE’S ENDOCARDITIS

SESSION TITLE: Cardiovascular Cases SESSION TYPE: Med Student/Res Case Report PRESENTED ON: 10/22/2019 3:45 PM - 4:45 PM INTRODUCTION: Whipple’s disease is a rare opportunistic infection (1 out of 1,000,000). The classical presentation of Whipple’s disease involves joint arthropathy (migratory oligoarticular or polyarticular) and digestive disorders (diarrhea and weight loss). Cardiovascular disease involvement is noted about one third of the time (pericarditis, congestive heart failure [CHF], or rarely culture-negative endocarditis). This case highlights the importance of a high clinical index of suspicion for Tropheryma whipplei culture-negative endocarditis, in the setting of rheumatologic disease and abrupt worsening of cardiac function, without overt gastrointestinal symptoms. CASE PRESENTATION: An 84-year-old man with past medical history of prostate cancer, polymyalgia rheumatica (PMR), cryptogenic stroke, and mild mitral valve prolapse of posterior mitral valve leaflet was admitted for severe mitral insufficiency with recent acute CHF symptoms. Documented diagnosis of PMR occurred 18 months prior to acute CHF symptoms, for which the patient was treated with continuous, extensive prednisone taper, starting at 15 mg daily. Clinical presentation of acute CHF and transthoracic echocardiography showing myxomatous degeneration of posterior mitral leaflet, partially flail, with severe mitral regurgitation, prompted evaluation by cardiothoracic surgery. Patient underwent mitral valve repair and pathology was suggestive of nonbacterial thrombotic endocarditis with vegetative studding of mitral valve anterior leaflet. Serum polymerase chain reaction for T. whipplei was negative and the patient was initially treated with intravenous vancomycin and cefepime. Antibiotic regimen transitioned to intravenous ceftriaxone 2gm daily and ampicillin-sulbactam 3 gm every 6 hours for 6 weeks for seronegative endocarditis of unknown etiology. Genome sequencing of valvular tissue detected T. whipplei deoxyribonucleic acid (DNA) with 16s ribosomal ribonucleic acid (rRNA) gene primer set and Periodic acid-Schiff (PAS) staining was positive. This case of Whipple’s endocarditis is currently being treated with trimethoprim-sulfamethoxazole for an anticipated 12 months. DISCUSSION: This case illustrates the importance of considering T. whipplei as a causal agent of culture-negative endocarditis, especially in the presence of rheumatologic disease and absence of overt gastrointestinal symptoms. Furthermore, in cases of recently diagnosed rheumatologic disease with iatrogenic immunosuppression, risk factors for T. whipplei exposure should be evaluated. The limitations of serum polymerase chain reaction assay as a diagnostic tool for T. whipplei further supports a high suspicion should be maintained in culture-negative endocarditis. CONCLUSIONS: A history of culture-negative endocarditis, in the presence of recently diagnosed and treated rheumatologic disease, without gastrointestinal symptoms should raise suspicion for Whipple's Endocarditis. Reference #1: Fenollar, Florence, et al. “Whipples Disease.” New England Journal of Medicine, vol. 356, no. 1, 2007, pp. 55–66., https://doi.org/10.1056/nejmra062477. Reference #2: Alozie, Anthony, et al. “Arthralgia and Blood Culture-Negative Endocarditis in Middle Age Men Suggest Tropheryma Whipplei Infection: Report of Two Cases and Review of the Literature.” BMC Infectious Diseases, vol. 15, no. 1, 2015, https://doi.org/10.1186/s12879-015-1078-6. Reference #3: Gabus, Vincent, et al. “Tropheryma Whipplei Tricuspid Endocarditis: a Case Report and Review of the Literature.” Journal of Medical Case Reports, vol. 4, no. 1, 2010, https://doi.org/10.1186/1752-1947-4-245. DISCLOSURES: No relevant relationships by SIJAN BASNET, source=Web Response no disclosure on file for Ronald Herb; No relevant relationships by Abigayle Sullivan, source=Web Response No relevant relationships by Emily Zagorski, source=Web Response

Whipple's disease and Tropheryma whipplei infections: when to suspect them and how to diagnose and treat them.

The delay between first clinical signs and diagnosis of Whipple's disease and Tropheryma whipplei infections is more than 6 years, and relapses are frequently observed, resulting in a need for clinicians to be aware of this infection. 18 FDG-PET is useful in the diagnosis and the follow-up of patients (particularly in case of neurological involvement). Histological involvement remains the goldstandard for classic Whipple's disease diagnosis. PCR performed on biopsies of fluid is the main tool for the diagnosis of localized chronic infections. PCR performed on urine samples should become an important role of noninvasive diagnostic strategies, while T. whipplei PCR performed on saliva and stool lack specificity. Because of lifetime susceptibility to T. whipplei and in-vitro susceptibility data, a 1-year course of doxycycline and hydroxychloroquine followed by a lifelong treatment by doxycycline is recommended for Whipple's disease, localized endocarditis and encephalitis. Clinical involvement of the different T. whipplei infections is well described, as well as the treatment of Whipple's disease, endocarditis and encephalitis. The place of PCR performed on urine remains to be clarified for diagnosis of localized T. whipplei infections and acute infections as well as the optimal treatment for arthritis and acute infections.

Whipple's Endocarditis Presenting as Heart Failure and Literature Review of Cardiac Manifestations of Whipple's Disease

Whipple's Endocarditis Presenting as Heart Failure and Literature Review of Cardiac Manifestations of Whipple's Disease

Cardiotoxicité précoce de l’hydroxychloroquine

IntroductionHydroxychloroquine (HCQ) is most frequently used in the treatment of systemic inflammatory diseases. Cardiac complications of anti-malarial drugs are uncommon, and most of the time are the result of a long-term exposition. In this case, cardiotoxicity is the consequence of the lysosomal dysfunction and the result of intracytoplasmic granular material inclusions. Case reportWe report a 77-year-old woman who presented a very early and reversible cardiotoxicity, probably related to the quinidine like effect of the HCQ, 10days after initiation of therapy for Whipple endocarditis. ConclusionWe discuss the different mechanisms of cardiotoxicity of anti-malarial drugs and their clinical manifestations.

Tropheryma whipplei Endocarditis: A Two-patient Case Series

BackgroundWhipple endocarditis is caused by Tropheryma whipplei and is a well-described complication of Whipple's disease. Limited and small case series have been published regarding the presentation, diagnosis, and clinical course of this disease. Methods/ResultsWe describe 2 cases of patients with T. whipplei endocarditis, one of which underwent a successful heart transplant. ConclusionIn both cases of Whipple's endocarditis, there was a subacute prodromal phase followed by an acute rapid decompensation with severe destruction of the aortic valve, heart failure, and embolism. Because the diagnosis of T. whipplei endocarditis is typically not made until pathological examination of tissue, clinicians must have a high suspicion for it in the absence of other offending organisms, especially among middle-aged white males with sub-acute symptoms and embolic complications.

Tropheryma whipplei aortic valve endocarditis without systemic Whipple's disease

Culture-negative endocarditis is most often the result of prior antimicrobial therapy. Tropheryma whipplei is the etiologic agent of Whipple's disease, which is typically characterized by diarrhea, weight loss, and intra-abdominal lymphadenopathy. We present the case of a 48-year-old male with Whipple's endocarditis of the aortic valve who did not develop signs of systemic Whipple's disease. Our patient was treated with a regimen that included ceftriaxone for 6 weeks prior to his cardiac surgery, yet valve pathology demonstrated abundant T. whipplei, suggesting that a prolonged antibiotic course is necessary for the treatment of Whipple's endocarditis.

Endocardite infectieuse isolée : une présentation atypique de la maladie de Whipple

Diagnosis of Whipple's disease is difficult, and thus its frequency is probably underestimated, particularly in culture-negative infective endocarditis. However, it must be systematically searched for in such a situation, first because it is associated with a poor natural outcome, and second because Tropheryma whipplei is not covered by the conventional empirical therapy recommended for culture-negative infective endocarditis. Whipple's disease endocarditis is usually associated with weight loss, intestinal and joint involvement. Nevertheless, it is sometimes the only manifestation of the disease, which makes the diagnosis much more difficult. We report the case of a 66-year-old patient with Barlow's disease, who underwent mitral valve replacement for severe mitral regurgitation. Vegetations were observed on the resected valve, both macroscopically and histologically. No microorganism was found at first. The diagnosis of Whipple's disease endocarditis was finally obtained by Polymerase Chain Reaction on valve tissue, and later confirmed by Periodic Acid Schiff staining. The outcome was favorable after a prolonged antibiotic therapy including doxycycline and hydroxychloroquine.

Should We Systematically Perform Central Nervous System Imaging in Patients with Whipple's Endocarditis?

Background Whipple's endocarditis is an uncommon disease, with approximately 100 cases reported to date. Case series suggest that Whipple's endocarditis usually presents without extracardiac manifestations of Whipple's disease. Methods We report 4 consecutive cases of Whipple's endocarditis associated with brain lesions. All patients fulfilled Duke Criteria for definite endocarditis. Whipple's disease was diagnosed through 16S rRNA polymerase chain reaction assays on valves excised from patients with culture-negative endocarditis (n = 3) or through polymerase chain reaction and periodic acid staining-positive foamy macrophages on duodenal biopsy (n = 1). Results All patients were male, aged 56 to 72 years. They presented with mitral (n = 1), aortic (n = 1), mitral and aortic (n = 1), and tricuspid (n = 1) endocarditis. Brain magnetic resonance imaging was performed because of mild-to-moderate cognitive disorders (n = 3) or ataxia (n = 1) and revealed multiple (n = 3) or solitary (n = 1) contrast-enhancing lesions. Cerebrospinal fluid studies revealed meningitis in 1 case. Polymerase chain reaction assays on cerebrospinal fluid were negative for all patients. All patients received intravenous ceftriaxone (2-4 weeks) associated with gentamicin (2 weeks), followed by 1 year of oral trimethoprim-sulfamethoxazole, with favorable outcomes. Conclusion Whipple's associated central nervous system disease may be common but frequently undiagnosed, in patients with Whipple's endocarditis. Because treatment is different when neurologic disease is present (ie, trimethoprim-sulfamethoxazole vs doxycycline/hydroxychloroquine), clinicians should consider brain imaging in patients diagnosed with Whipple's endocarditis.

Whipple's endocarditis as a complication of tumour necrosis factor- antagonist treatment in a man with ankylosing spondylitis

Whipple's endocarditis as a complication of tumour necrosis factor- antagonist treatment in a man with ankylosing spondylitis

Cardiac valves in patients with Whipple endocarditis: microbiological, molecular, quantitative histologic, and immunohistochemical studies of 5 patients.

The pathological features of Whipple endocarditis, which is caused by Tropheryma whipplei, were histologically evaluated in cardiac valves from 5 patients. We used quantitative image analysis to compare the valvular fibrosis, calcifications, vegetations, inflammation, and vascularization due to Whipple endocarditis with those due to non-Whipple endocarditis and degenerative valves. We also studied the presence of T. whipplei in valves by immunohistochemical analysis, culture, and polymerase chain reaction (PCR). In histologic analysis, Whipple endocarditis was characterized by significant fibrosis, a lack of calcifications, slight inflammation and vascularization, and vegetations of intermediate size. Inflammatory infiltrates consisted mainly of foamy macrophages and lymphocytes. We found that the detection of T. whipplei in cardiac valves, by immunohistochemical analysis, was correlated with the detection of the bacterium by culture and PCR. We report, for the first time, the immunodetection of T. whipplei in a surgically removed arterial embolus. Pathological and immunohistologic analyses may contribute to the diagnosis of Whipple endocarditis.

Cloning and Sequencing of a Part of the Heat Shock Protein 65 Gene ( hsp65 ) of “ Tropheryma whippelii ” and Its Use for Detection of “ T. whippelii ” in Clinical Specimens by PCR

Using broad-spectrum primers, we have amplified, cloned, and sequenced a 620-bp fragment of the "Tropheryma whippelii" heat shock protein 65 gene (hsp65) from the heart valve of a patient with Whipple's endocarditis. The deduced amino acid sequence shows high similarity to those from actinobacteria, confirming that "T. whippelii" is indeed a member of this phylum. Based on the nucleotide sequence, we have developed a "T. whippelii"-specific seminested PCR. Seventeen patients shown to be positive by 16S ribosomal DNA (rDNA) PCR and/or internal transcribed spacer (ITS) PCR were also positive by hsp65 PCR. All 33 control specimens from patients without Whipple's disease and negative for "T. whippelii" by both seminested 16S rDNA and ITS PCR remained negative. All amplicons digested with XhoI revealed an identical restriction pattern. Eight of the 17 hsp65 amplicons representing all three previously described ITS types were sequenced. Three of the amplicons showed slight differences, but none of the mutations detected affected the amino acid sequence of the corresponding protein. We conclude that the hsp65 gene is a suitable target for the specific detection of "T. whippelii." Its product represents a putative antigen for a future serodiagnostic assay.

Cloning and sequencing of a part of the heat shock protein 65 gene (hsp65) of "Tropheryma whippelii" and its use for detection of "T. whippelii" in clinical specimens by PCR.

Using broad-spectrum primers, we have amplified, cloned, and sequenced a 620-bp fragment of the "Tropheryma whippelii" heat shock protein 65 gene (hsp65) from the heart valve of a patient with Whipple's endocarditis. The deduced amino acid sequence shows high similarity to those from actinobacteria, confirming that "T. whippelii" is indeed a member of this phylum. Based on the nucleotide sequence, we have developed a "T. whippelii"-specific seminested PCR. Seventeen patients shown to be positive by 16S ribosomal DNA (rDNA) PCR and/or internal transcribed spacer (ITS) PCR were also positive by hsp65 PCR. All 33 control specimens from patients without Whipple's disease and negative for "T. whippelii" by both seminested 16S rDNA and ITS PCR remained negative. All amplicons digested with XhoI revealed an identical restriction pattern. Eight of the 17 hsp65 amplicons representing all three previously described ITS types were sequenced. Three of the amplicons showed slight differences, but none of the mutations detected affected the amino acid sequence of the corresponding protein. We conclude that the hsp65 gene is a suitable target for the specific detection of "T. whippelii." Its product represents a putative antigen for a future serodiagnostic assay.

PCR in routine clinical diagnosis

With the advent of molecular diagnostics culture-negative endocarditis caused by the organism Tropheryma whippelii is an increasingly described entity. We describe two patients with afebrile, culture-negative endocarditis caused by T. whippelii who had neither the gastrointestinal nor arthritic manifestations of Whipple's disease.Whipple's disease is a systemic illness caused by the organism Tropheryma whippelii and is typically characterized by diarrhea, weight loss, and arthropathy [Clin. Microbiol. Rev. 2001;14:561–583; Medicine (Baltimore) 1997;76:170–184]. Whipple's endocarditis is relatively common in autopsy studies [Can. J. Cardiol. 1996;12:831–834] but has rarely been diagnosed before death. With the advent of molecular diagnostic tools such as the polymerase chain reaction (PCR), Tropheryma whippelii as a cause of culture-negative endocarditis has become increasingly recognized [Clin. Infect. Dis. 2001;33:1309–1316; Ann. Intern. Med. 1999;131:112–116; Infection 2001;29:44–47; Ann. Intern. Med. 2000;132:595]. With this increased recognition has come the realization that Whipple's endocarditis can occur without other common manifestations of Whipple's disease [Ann. Intern. Med. 1999;131:112–116; Infection 2001;29:44–47; Ann. Intern. Med. 2000;132:595]. We report here two cases of Whipple's endocarditis without discrete febrile illness, gastrointestinal manifestations, or arthritic manifestations, diagnosed by PCR of resected valvular material.