**3. Clinical features**

Comorbidities or other predisposing risk factors have been not uniformly reported in the literature [118]. Previous valvular affectation has been documented in 21% of the diagnosed cases, while prosthetic valve replacement previously to the event seems not an important condition (<5% of the available series). Alcohol abuse has been reported in very few cases, however alcohol intake (>60 g/d) was referred by the 23.5% of the patients in the Spanish series [70]. Previous cardiac condition or a cardiac event (i.e., coronary heart disease) has been observed in 50% of cases [66]. Data of historical immunosuppression forms (autoimmune disease or immunosuppressive therapies such as steroids or tumor necrosis factor inhibitors) have been reported in 21 cases (12%).

Classical Whipple's disease has been reported as concomitant with the diagnose of endocarditis in few cases (6%) [66, 70]. However, in lot of cases this data is not available and in some of them although, classical Whipple's Disease has not been diagnosed, it cannot be excluded.

The signs and symptoms *T. whipplei* endocarditis are not the typical ones. Fever has been only reported in 21% of the cases. Cardiac failure and arthralgia have been shown as the main presenting symptoms and have been described in 43% and 52% of patients, respectively. Cardiac failure is of special interest because it is the first manifestation in a high percentage of patients. Long lasting arthralgias presence as a prominent symptom varies depending on the series. While in the French series arthralgias were present in 75% of patients [39], in the Spanish one this condition was present in 53% [70]. These variations could be due to this symptom is sometimes weak and only detected after an exhaustive clinical research. Some authors suggest that, in those patients with sub-acute endocarditis and low-grade fever or not fever, if arthralgias are present, *T. whipplei* as causative agent should be suspected [39, 103]. Asthenia and malaise lasting more than six months were notified by the 41.2% of the patients in one series [70]. Other signs such as weight loss or gastrointestinal symptoms have been observed in 25% and 21% of the reported patients [118]. In addition, central nervous system manifestations (i.e., emboli) have been detected in 16% of patients.

The valve involved in patients with *T. whipplei* endocarditis has been predominantly the aortic (63%). Involvement of multiple valves (mainly aortic valve in combination with the mitral or tricuspid valve, and mitral-tricuspid affection) has been noticed in 23% of patients. Only mitral valve affectation has been observed in 20% of patients and tricuspid valve just in six of 174 patients (3%). Native valve was affected in the vast majority of cases.

#### **Figure 1.**

*Valve vegetation specimen obtained after surgery from a patient with T whipplei endocarditis.*


**Table 1.**

*Main clinical epidemiological, clinical and outcome characteristics of patients with* T. whipplei *endocarditis reported in the literature. Updated from McGee et al. [118].*

**75**

Tropheryma whipplei *Endocarditis*

*DOI: http://dx.doi.org/10.5772/intechopen.95378*

2536 ng/L has been also reported [118].

**4. Diagnosis**

underestimated [119].

Main characteristics of patients are shown in **Table 1**.

tories, moreover if culture of the bacteria is intended to carry out.

clinical evidence of disease [42, 121, 122].

Echocardiography features are one of the most valuable tools for suspecting infectious endocarditis. According to the literature, when these data were recorded, presence of vegetations was observed in more than the half of patients [66]. In our series, echocardiography was performed in all patients (both transthoracic and transesophageal in more than 80%) and allowed the diagnosis of infectious endocarditis in 70% of patients through the visualization of vegetations in the vast majority, or by indirect signs in a few [70]. Valve vegetation from a patient after cardiac valve surgery is shown in **Figure 1**. In the French series, echocardiography showed vegetations in 78% of the patients, but these data are not recorded in the German one [39, 65]. Data of vegetation appearance or size is rarely reported. Data of size vegetations when available, shown a minimum size of 5 mm and a maximum of 33 mm [118]. The main laboratory recording abnormalities at the time of the diagnosis have been anemia, which was detected in 40% of patients but this date can reach 88.2% in some series, and increasing of C-reactive protein in range from 2.3 to 137 mg/L [70]. In patients who had heart failure, B-type natriuretic peptide (BNPs) of up to

The suspicion and diagnosis of *T. whipplei* endocarditis is complicated. To date, 174 cases have been reported but, due to the difficulties for the identification of *T. whipplei*, the prevalence of the endocarditis it causes could be

Diagnosis of *T. whipplei* endocarditis remains a challenge for several reasons. One of them is because this endocarditis does not exhibit the typical sings (no fever nor peripheral stigmata and low inflammatory response) and blood cultures used to be negative; therefore, modified Duke's criteria are ineffective for diagnosis before heart valve analysis [39]. In this sense, some series have shown that only 3.6% patients met criteria for endocarditis according to the modified Duke criteria and 60.7% met for possible endocarditis [39]. It is very difficult to perform a microbiological or histological diagnose without analyzing the surgical remove valve. Routine blood and tissue culture are not often useful for the diagnosis. Thus, the diagnosis is often made post-surgery and valve analysis requires specialized labora-

Different targets have been used for molecular analyses. PCR based on the 16S rRNA amplification and subsequent sequencing has been widely used and has been the first-line screening in our series. However, some authors alert that this broadspectrum PCR could have a limited sensitivity (value sensitivity 60%, specificity 100%) [120], while specific qPCR for *T. whipplei* have showed higher sensitivities [48, 60]. So, if 16S rRNA PCR has been negative, specific targets should be used in highly suspected cases of *T. whipplei*. At least 2 of the PCRs must be positive and their sequences have to show higher identity with the bacterium studied. PCR yield in other specimen different from valves varies depending on the specimen type and should be interpreted with caution according to the clinical context [66, 118]. A positive PCR result from a non-sterile site such as stool or saliva samples has been used to diagnose classical Whipple's disease and to detect asymptomatic carriers, but is nor sensible nor specific for the diagnosis of *T. whipplei* endocarditis without

The role of serological tests in the diagnosis of Whipple's disease is unclear because healthy carrier patients may paradoxically have a higher immune response Tropheryma whipplei *Endocarditis DOI: http://dx.doi.org/10.5772/intechopen.95378*

Echocardiography features are one of the most valuable tools for suspecting infectious endocarditis. According to the literature, when these data were recorded, presence of vegetations was observed in more than the half of patients [66]. In our series, echocardiography was performed in all patients (both transthoracic and transesophageal in more than 80%) and allowed the diagnosis of infectious endocarditis in 70% of patients through the visualization of vegetations in the vast majority, or by indirect signs in a few [70]. Valve vegetation from a patient after cardiac valve surgery is shown in **Figure 1**. In the French series, echocardiography showed vegetations in 78% of the patients, but these data are not recorded in the German one [39, 65]. Data of vegetation appearance or size is rarely reported. Data of size vegetations when available, shown a minimum size of 5 mm and a maximum of 33 mm [118].

The main laboratory recording abnormalities at the time of the diagnosis have been anemia, which was detected in 40% of patients but this date can reach 88.2% in some series, and increasing of C-reactive protein in range from 2.3 to 137 mg/L [70]. In patients who had heart failure, B-type natriuretic peptide (BNPs) of up to 2536 ng/L has been also reported [118].

Main characteristics of patients are shown in **Table 1**.
