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.     

Cellular immunity in Q fever: specific lymphocyte unresponsiveness in Q fever endocarditis

Human infection with the rickettsia Coxiella burnetii presents as acute influenza-like primary Q fever, subacute granulomatous hepatitis, or chronic endocarditis with hepatitis. To investigate whether persistent infection is associated with a possible immunologic defect, we tested lymphocyte proliferation specific for Coxiella in vitro in peripheral blood mononuclear cells from patients and controls. All four patients with endocarditis had profound lymphocyte unresponsiveness to Coxiella antigens with normal proliferation to control antigens. Hepatitis and primary Q fever were associated with vigorous responses in vitro to Coxiella antigens. Suppression of lymphocyte unresponsiveness was in part mediated by an antigen-nonspecific, glass-adherent cell. We hypothesize that specific T cell unresponsiveness is an important factor in persistent infection with C. burnetii and offer in vitro lymphocyte stimulation as a more specific diagnostic test to distinguish cases of endocarditis among those with chronic hepatitis due to Q fever.     

Q fever endocarditis on porcine bioprosthetic valves. Clinicopathologic features and microbiologic findings in three patients treated with doxycycline, cotrimoxazole, and valve replacement

Three patients developed Q fever endocarditis on porcine bioprosthetic valves. They had a subacute or chronic course with nonspecific symptoms, enlargement of the liver and spleen, and cardiac failure due to destruction of the cusps, without disruption of the valve ring. High-phase I-specific IgG and IgA antibody titers against Coxiella burnetii were found. C. burnetii was isolated in each patient by inoculating suspensions of valve tissue into a human fetal diploid fibroblast cell line, which was grown as monolayers on slides contained inside rubber-stoppered tube cultures. Patients were treated successfully with doxycycline, cotrimoxazole, and valve replacement and were followed up for periods of 24 to 42 months; no evidence of deterioration was found. The human fetal diploid cell culture may be an expeditious, easy, and safe method to isolate C. burnetii from cardiac valves. Valve replacement seemed necessary to cure prosthetic-valve endocarditis due to C. burnetii infection. Combined therapy with doxycycline and cotrimoxazole may control the disease and prevent reinfection of the homografts replacing the valves.     

Q fever endocarditis in Queensland.

Thirteen patients with proven Q fever endocarditis and three additional patients with probable endocarditis are reviewed. The most helpful diagnostic test is the demonstration of a high complement fixing antibody titre to Phase 1 antigen of Coxiella burneti. The macroscopic pathology of the aortic valve is described and includes aneurysmal pockets in the aortic wall and valve annulus which are demonstrable angiographically. Evidence is presented that the infection may be controlled by prolonged tetracycline therapy and that this is accompanied by a falling antibody titre to Phase 1 antigen. Valve replacement is undertaken only for symptomatic and hemodynamic indications. The combined tetracycline therapy and valve replacement have produced a fall in titres with eradication of infection and palliation of the cardiac disability in all patients followed for long periods.     

Q fever endocarditis: the Mayo Clinic experience

OBJECTIVES: To report the Mayo Clinic experience of Q fever endocarditis. BACKGROUND: Q fever endocarditis is rare in North America with few case reports in the literature. The Centers for Disease Control lists Q fever as a reportable illness but does not differentiate endocarditis as a syndrome in its database. METHODS: A search of the database for elevated Q fever IgG serology at our institution was conducted from December 1980 to December 2005. Patients with elevated serologies were retrospectively identified and their medical records were reviewed to determine which cases met criteria for a diagnosis of endocarditis. RESULTS: Eight patients with elevated serology were identified. One case failed to meet criteria and was therefore excluded. All patients presented with fever and had previously diagnosed valvular disease. Only 3 patients had valvular vegetations on transesophageal echocardiography. All 7 patients were treated with antimicrobial therapy, which was not uniform. Six required surgical intervention on the affected valves, and 2 required multiple valve surgeries. Follow-up ranged from 1 to 17 years. CONCLUSIONS: Q fever endocarditis is a rare disease in the United States, where no reliable reporting exists. Q fever endocarditis involves underlying abnormal native valves or prosthetic valves. Vegetations are small or absent. Relapses are common. Surgeries are common adding to morbidity and cost. The chronicity of the syndrome and its high morbidity mandate an increased awareness of the condition in patients with culture-negative endocarditis or unexplained perivalvular leaks detected by echocardiography. Appropriate diagnosis and tailored treatment are likely to reduce the need for repeat surgeries.     

Q fever: a rare cause of endocarditis

Coxiella Burnetii endocarditis is very rare. It is the main complication of the chronic form of Q fever. Blood cultures are negative and clinical presentation very variable and diagnosis is essentially based on indirect immunofluorescence serum analysis. The authors report the case of a 19 year old patient with a history of rheumatic aortic regurgitation admitted for an episode of left ventricular failure in a context of long-term pyrexia without valvular vegetations or mutilation. The antiphase I Ig G antibody levels were significant. Treatment with doxycycline and fluoroquinolone was initiated. The clinical improvement was spectacular. Three months later, the patient underwent aortic valve replacement and histological examination of the valve showed subacute endocarditis on chronically fibrotic valvular disease. This is an interesting case by its rarity and its diagnostic and therapeutic problems.     

Whipple's endocarditis: review of the literature and comparisons with Q fever, Bartonella infection, and blood culture-positive endocarditis.

Whipple's disease is a systemic infection sometimes associated with cardiac manifestations. Recently, there has been an increase in the number of reported cases of Whipple's endocarditis. The purpose of our study was to describe this entity. Data from 35 well-described cases of Whipple's endocarditis were collected and compared with those of blood culture-positive endocarditis, Q fever endocarditis, and Bartonella endocarditis. Some patients with generalized Whipple's disease presented with cardiac involvement, among other symptoms. Others presented with a nonspecific, blood culture-negative endocarditis with no associated symptoms. In comparison with cases of endocarditis due to other causes, congestive heart failure, fever, and previous valvular disease were less frequently observed in the cases of Whipple's endocarditis. Without examination of the excised valves, the diagnosis of infective endocarditis could not have been confirmed in most cases. Treatment is not well established. Whipple's endocarditis is a specific entity involving minor inflammatory reactions and negative blood cultures, and its incidence is probably underestimated.     

Q fever endocarditis in the United States.

A patient with Q fever endocarditis, which is almost unknown in the United States, was followed for a total of 32 months; the study was begun 3 1/2 months before aortic valve replacement. Diagnosis was confirmed by serology, visualization of Coxiella burnetii in excised aortic valve tissue by direct and immunofluorescence staining, and isolation of C. burnetii from aortic valve tissue. Serum antibodies against phase I and phase II antigens of C. burnetii were identified. Almost all phase I and phase II antibodies were IgG. These findings are compared with those in an uncomplicated case of acute Q fever. New findings on the immune response to chronic Q fever are presented.     

Risks factors and prevention of Q fever endocarditis.

Coxiella burnetii causes acute and chronic Q fever. To evaluate the risk factors of development of chronic endocarditis following Q fever and to assess the best preventive therapy, a retrospective study of patients diagnosed as having Q fever during 1985-2000 was conducted. Twelve patients with acute Q fever who developed endocarditis and 102 patients with Q fever endocarditis were included in the study. When compared to 200 control patients with acute Q fever, preexisting valvular disease (P<10(-7)), especially a prosthetic valve (P=.01), were encountered more often among patients with endocarditis. Among patients with valvular defects, we estimate the risk of developing endocarditis to be 39%. A combination of doxycycline plus hydroxychloroquine was better at preventing the development of endocarditis than doxycycline alone (P=.009). Our results should encourage physicians to detect valvular lesions in patients with acute Q fever and to search for acute Q fever in patients with a valvulopathy and unexplained fever. A proper treatment for such patients and a scheduled follow-up should reduce the risk of developing endocarditis.     

Immunofluorescence studies of cardiac valves in infective endocarditis

Mitral and aortic valves removed at emergency cardiac surgery from a patient with infective endocarditis caused by Streptococcus viridans were studied by immunofluorescence to ascertain the extent and pattern of various immune reactants within the large valvular vegetations. Heavy intravalvular deposits of IgG as well as bacterial antigen were present. Much more focal interstitial IgM and C3 deposits were noted within vegetations and valve substance. Diffuse endocardial and subendocardial deposition of C5b-C9 and C9 complement neoantigens was present. Direct staining of valvular tissues and vegetations for rheumatoid factor showed extensive interstitial tissue deposition. These findings emphasize the large amounts of immune reactants and constituents of immune complexes present in valves and vegetations of patients with infective endocarditis.     

Q fever endocarditis: a case report and review of the literature

The case of a 31-year-old man from Alberta diagnosed with Q fever endocarditis is presented. To the authors' knowledge, this is the first case of Q fever endocarditis diagnosed in the province of Alberta. The patient had undergone open valvulotomy for congenital aortic stenosis as an infant. He presented with congestive heart failure secondary to severe aortic regurgitation and underwent mechanical aortic valve replacement. Early failure of the mechanical prosthesis and numerous laboratory abnormalities prompted an investigation for endocarditis, which was initially negative. Markedly positive serology eventually established the diagnosis of chronic Q fever. The patient subsequently underwent a second aortic valve replacement following initiation of appropriate antimicrobials directed against Coxiella burnetii. The present report reviews the clinical presentation and diagnosis of Q fever endocarditis. It highlights the insidious and nonspecific nature of the presenting symptoms, and emphasizes the use of serology for diagnosis. Increased awareness and earlier diagnosis can significantly decrease the morbidity and mortality associated with this disease.     

Sequential analysis of 43 patients with non-Hodgkin's lymphoma: clinical correlations with cytogenetic, histologic, immunophenotyping, and molecular studies

Few reports correlating specific cytogenetic abnormalities with distinct subtypes of lymphoma have performed serial studies at diagnosis and at tumor recurrence or progression. In our file of 325 cytogenetically analyzed non-Hodgkin's lymphoma (NHL) patients studied over the past decade, 43 had serial biopsies, 39 of whom had at least two successful preparations; of the 43, nine had one and 32 had two or more cytogenetically abnormal specimens. In this study, we correlated cytogenetic, histopathologic, molecular, and clinical parameters. Patients with low-grade lymphomas were as likely as patients with intermediate- or high-grade lymphomas to acquire new chromosomal abnormalities with time (16 of 23 patients as compared with 7 of 16; P2 = .11, chi 2 test). In four patients, originally diagnosed indolent disease progressed to aggressive disease; all had t(14;18), all gained additional chromosomal abnormalities with disease progression, and three of the four expressed abnormalities associated with disease progression and/or short survival: der(18), +7, and/or +12. Cytogenetic results from early disease were compared with those obtained later in disease: in the t(14;18) group, the most common abnormalities were +7 (eight patients) and der(18) (five patients), both seen later in disease. The most common abnormalities in patients without t(14;18) were 6q deletions; they were seen in both early and late disease and were associated with significantly shorter survivals (P2 = .0014) compared with all patients without 6q deletions. Secondary chromosomal abnormalities, observed after at least one previous abnormal study, were seen in 19 of 22 t(14;18) patients and in 11 of 21 patients without t(14;18) and were associated with a poor survival (P2 = .13) compared with patients without any secondary chromosomal abnormalities. Chromosome 1 abnormalities were seen in almost half of the patients and were observed in initial specimens and early in disease as well as late in disease and as secondary abnormalities; 1q involvement was more frequent than 1p (15 versus eight patients) and was significantly associated with poor survival only in patients with intermediate-/high- grade disease; the most common breakpoints were 1q21-q22 (nine patients) and 1p36 (six patients). Breakpoints at 2q21 and 3q27-q29 were limited to patients with t(14;18) and were almost exclusively secondary in nature. Molecular studies in 24 of our patients showed discrepancies with the cytogenetic results in only three patients: two had t(14;18) but no molecular rearrangements while two patients had no visible t(14;18) but were positive for major breakpoint region (MBR) rearrangement. The presence of MBR or minor breakpoint cluster (MCR) rearrangement had no apparent effect on survival.(ABSTRACT TRUNCATED AT 400 WORDS)