First impressions may be misleading: syphilitic aortitis presenting as severe acute aortic regurgitation

Acute severe aortic regurgitation is a life-threatening condition with high morbidity and mortality, and patients often present with cardiogenic shock.^[1,2] Infective endocarditis is a frequent cause^[3,4] and is commonly presumed in emergency department presentations. However, several conditions may mimic endocarditis, including inflammatory and infectious aortitis with valvular destruction.^[5,6]

Cardiovascular syphilis is a late manifestation of untreated Treponema pallidum infection, leading to aortitis, aneurysm formation and aortic valve regurgitation. Although rare in the antibiotic era, syphilitic aortitis remains clinically relevant because of the increasing incidence of syphilis worldwide.^[7]We report a case of syphilitic aortitis presenting as presumed infective endocarditis with acute severe aortic regurgitation, highlighting the diagnostic challenges encountered.

A 53-year-old Caucasian male with a history of hypertension and psoriasis presented to the emergency department with altered mental status, dyspnea, cyanosis, mild chest pain, and severe limb edema. He reported fatigue and progressive shortness of breath during the preceding week.

Physical examination showed blood pressure 164/60 mmHg (1 mmHg=0.133 kPa), diffuse lung crackles, severe peripheral edema and compromised distal perfusion. Neurological examination was normal. Arterial blood gas revealed severe metabolic acidosis (pH 7.23, bicarbonate 7 mEq/L), elevated lactate level (14 mmol/L), and a PaO₂/FiO₂ ratio of 131. Laboratory tests showed hemoglobin concentration within the normal range, creatinine 1.8 mg/dL (reference: 0.7-1.2 mg/dL), signs of hepatocellular injury (aspartate aminotransferase [AST] 334 U/L [reference: 10-40 U/L]; alanine aminotransferase [ALT] 372 U/L [reference: 7-56 U/L], gamma-glutamyl transferase [GGT] 249 U/L [reference: 9-48 U/L], alkaline phosphatase [ALP] 258 U/L [reference: 44-147 U/L]), elevated C-reactive protein [CRP] 11 mg/dL [reference: <0.5 mg/dL] and N-terminal pro-B-type natriuretic peptide [NT-proBNP] 15,959 pg/mL [reference: <125 pg/mL]).

Transthoracic echocardiography (TTE) revealed a dilated left ventricle with moderately reduced ejection fraction (42%) and severe aortic regurgitation (pressure half-time [PHT] 117 ms, vena contracta 7 mm, and holodiastolic aortic flow reversal). Possible vegetation was suspected (Figure 1A, C and D). Head computed tomography (CT) revealed no abnormalities, and thoraco-abdomino-pelvic CT revealed bilateral pulmonary consolidations.

Figure 1. TTE and TOE images. A: color Doppler showing severe aortic regurgitation; B: aortic root aneurism (50 mm); C: PW Doppler showing severe aortic regurgitation (PHT 117 ms); D: possible vegetation seen on TTE; E: TOE images showing valvular destruction but no vegetation; F: TOE 3D image of the aortic valve showing no vegetation. TTE: transthoracic echocardiography; TOE: transesophageal echocardiography; PW Doppler: pulsed-wave Doppler; PHT: pressure half-time.

A diagnosis of presumed infective endocarditis (with concomitant pneumonia) was presumed. Empirical antibiotic therapy was initiated with ampicillin (12 g/d), flucloxacillin (12 g/d), ceftriaxone (4 g/d), and gentamicin (180 mg/d).

Transesophageal echocardiography (TOE) performed subsequently revealed extensive aortic valve destruction and severe regurgitation but no vegetation. An aortic root aneurysm measuring 50 mm was identified (Figure 1 B, E and F). Coronary angiography showed a 50% ostial right coronary lesion in the context of suspected aortitis.

Extensive etiological investigation showed more than 10 negative blood cultures, including tests for slow-growing organisms. Serologies for Brucella, Coxiella burnetii, and Bartonella were negative. Tropheryma whipplei polymerase chain reaction (PCR) and human immunodeficiency virus (HIV) test results were negative. Urinary antigens for Pneumococcus and Legionella were also negative.

However, serum syphilis serology was positive, with a venereal disease research laboratory (VDRL) titer of 1:256 and Treponema pallidum hemagglutination assay (TPHA) positive.

Cerebrospinal fluid (CSF) analysis revealed clear, colorless fluid with leucocytes 10 cells/µL (reference <5 cells/µL; predominance of polymorphonuclear cells), protein 57 mg/dL (reference 15-45 mg/dL), glucose 48 mg/dL (reference 60%-80% of serum glycemia) and TPHA positive, confirming neurosyphilis.

Surgical aortic valve replacement was performed with a mechanical St. Jude Regent™ 23 mm prosthesis (Abbott, USA). The ascending aorta and arch were replaced with a vascular conduit. Intraoperative findings revealed an aneurysmal proximal ascending aorta and arch with a calcified wall and a tricuspid aortic valve with retracted leaflets (geometric height <10 mm), with no vegetation; the aortic wall appeared thickened with an inflammatory appearance. Histopathological examination of the resected aortic tissue demonstrated an elastic artery with American Heart Association (AHA) type IV and V atherosclerotic lesions compressing the tunica media, with dissociation of elastic fibers by mild intralamellar accumulation of mucoid extracellular matrix and confirmed aortic aneurysm.

The final diagnosis was syphilitic aortitis with contiguous involvement of the aortic valve causing severe regurgitation. The patient received intravenous penicillin G (24 million units/d) for 14 d and had an uneventful recovery. He was discharged in New York Heart Association (NYHA) functional class I and was enrolled in cardiac rehabilitation.

This case illustrates the diagnostic challenge of differentiating infective endocarditis from non-endocarditic infectious and non-infectious causes of severe aortic regurgitation and emphasizes the importance of maintaining a broad differential diagnosis when evaluating acute severe valvular dysfunction.

Although infective endocarditis (IE) was initially suspected, the patient did not fulfill the modified Duke criteria and had only one dubious major and one minor criterion. Blood culture-negative endocarditis is most strongly associated with prior antibiotic exposure or fastidious organisms.^[1] However, structural valve destruction with concomitant aortic aneurysm should raise suspicion for alternative etiologies, including inflammatory or infectious aortitis. The absence of vegetation and retracted leaflets on surgical inspection supported the ruling out of infective endocarditis and is consistent with aortitis-driven valvular destruction. Other causes of culture-negative endocarditis include autoimmune aortitis (Takayasu arteritis, giant cell arteritis), connective tissue diseases, and fastidious organisms. Takayasu and giant cell arteritis are typically present in younger women and older adults, respectively, with systemic inflammatory features, and rarely cause rapid valvular destruction. Syphilitic aortitis, in contrast, results from obliterative endarteritis of the vasa vasorum by T. pallidum, leading to medial necrosis, aneurysm formation, and aortic root dilatation with valve regurgitation. This pathogenesis distinguishes it from non-infectious aortitis and explains the combination of aortic aneurysm and severe valvular destruction seen here.

In summary, syphilitic aortitis is a rare but important cause of severe aortic regurgitation. When suspected infective endocarditis is not supported by microbiological evidence and imaging reveals aortic aneurysm or root involvement, alternative diagnoses must be considered. Early multidisciplinary management is essential to provide the right treatment and optimize outcomes.

Funding: None.

Ethical approval: Informed consent was obtained from the patient for publication of this case report.

Conflicts of interest: The authors declare that they have no conflicts of interest.

Contributors: All authors had substantial contributions to the acquisition, analysis, or interpretation of data for the work, and final approval of the version to be published.