Syphilitic Aortitis

Syphilitic aortitis is a manifestation of tertiary cardiovascular syphilis, caused by Treponema pallidum. It affects the ascending aorta and arch, and appears 10 to 30 years after untreated primary infection.

It develops in about 10% of untreated patients. It has become uncommon with penicillin, but cases are rising with the resurgence of syphilis and HIV infection.

Complications are saccular or fusiform aneurysm of the ascending aorta and arch, aortic regurgitation (20 to 30%), and coronary ostial stenosis (about 20 to 25%). Rupture and compression of neighbouring structures can follow.

Neurosyphilis may coexist, as tabes dorsalis, general paresis, Argyll Robertson pupils or meningovascular disease. Syphilis remains common in sub-Saharan Africa, and screening in HIV care and antenatal care identifies cases.

Pathophysiology. Treponemes reach the aortic wall through the vasa vasorum. Obliterative endarteritis of the vasa vasorum causes ischaemic necrosis of the media, elastic fibre loss and scarring (tree bark appearance), then aneurysm.

Dilatation of the root and commissural separation cause regurgitation. Fibrosis at the coronary ostia causes stenosis.

• Often asymptomatic, found on chest X-ray (linear calcification of the ascending aorta) or imaging.
• Chest pain, dyspnoea and heart failure from aortic regurgitation, with a wide pulse pressure and a diastolic murmur.
• Angina from coronary ostial stenosis.
• Compression: hoarseness, dysphagia, cough, stridor, superior vena cava obstruction, and erosion of the sternum or ribs by a pulsatile mass.
• Rupture or dissection. History of earlier syphilis, genital ulcer, rash, or untreated infection. Neurological or ocular findings.

Red flags.

• Visual, hearing or neurological symptoms (neurosyphilis, otosyphilis, ocular syphilis)
• Sudden severe chest pain or hypotension (rupture or dissection)
• Angina or ischaemia from ostial stenosis
• Pregnancy
• HIV infection or a penicillin allergy

• Serology. Treponemal test (enzyme immunoassay, chemiluminescence, TPPA or TPHA), confirmed by a second treponemal test, and a non-treponemal test (RPR or VDRL) with titre. The non-treponemal titre is low in late disease and negative in a minority. A reactive treponemal test with a compatible lesion is enough.
• Cerebrospinal fluid. Lumbar puncture when there are neurological, ocular or auditory signs, in HIV infection, or before treatment failure is assumed. Neurosyphilis is suggested by more than 5 white cells/microlitre, protein over 0.45 g/L, or a reactive CSF-VDRL.
• HIV test, hepatitis serology and screening for other infections.
• Imaging. Chest X-ray, echocardiography for root, valve and regurgitation, CT or MR angiography for aneurysm, wall thickening and calcification, and coronary CT or angiography for ostial stenosis.
• Ophthalmology and audiology when symptoms are present.

Differential diagnosis.

• Tuberculous and bacterial aortitis
• Atherosclerotic and degenerative aneurysm
• Marfan and Loeys-Dietz syndromes and bicuspid aortopathy
• Takayasu arteritis, giant cell arteritis and ankylosing spondylitis
• Rheumatic aortic regurgitation and endocarditis
• Mycotic aneurysm

Penicillin.

• Benzathine benzylpenicillin 2.4 million units intramuscularly once weekly for 3 weeks, after CSF examination excludes neurosyphilis.
• Neurosyphilis or ocular and otic syphilis: aqueous benzylpenicillin 18 to 24 million units daily intravenously as 3 to 4 million units every 4 hours, or by continuous infusion, for 10 to 14 days. Alternative: procaine benzylpenicillin 2.4 million units intramuscularly once daily with probenecid 500 mg orally four times daily for 10 to 14 days.
• Penicillin allergy: doxycycline 100 mg orally twice daily for 28 days (avoid in pregnancy), or desensitisation. In pregnancy, desensitise and give penicillin.
• A Jarisch-Herxheimer reaction (fever, myalgia, hypotension in the first 24 hours) can occur. Prednisolone 20 to 40 mg orally once daily for 3 days, started the day before treatment, is used in some centres, with benefit unproven.
• Penicillin does not reverse the scarring or aneurysm, so surgical decisions follow vascular criteria.

Cardiovascular treatment.

• Aneurysm: surgery at 50 mm or more or with symptoms, with replacement of the ascending aorta or root. Replace the aortic valve for severe regurgitation. Bypass grafting or ostial reconstruction for coronary ostial stenosis. Do not delay urgent surgery for antibiotics, but give penicillin before elective surgery. Operative risk is higher than for degenerative aneurysm.
• Blood pressure under 130/80 mm Hg. Bisoprolol 2.5 mg orally once daily, increased to 5 to 10 mg once daily, maximum 20 mg daily (do not exceed 10 mg daily at creatinine clearance under 20 mL/min or in severe liver impairment), used cautiously in severe regurgitation with echocardiography monitoring. Ramipril 2.5 mg once daily, increased every 2 to 4 weeks to 10 mg once daily (maximum 10 mg daily, 5 mg daily at creatinine clearance under 30 mL/min), with potassium and creatinine 1 to 2 weeks after each change.
• Heart failure: furosemide 40 mg orally once daily in the morning, increased to 80 to 120 mg daily as needed (higher doses in renal impairment under specialist care), with sodium, potassium and creatinine monitoring.
• After a mechanical valve: warfarin 5 mg orally once daily at the start (2 to 3 mg in older adults, liver impairment or interacting drugs), adjusted to an INR of 2.5 (2.0 to 3.0) for a bileaflet valve without risk factors or 3.0 (2.5 to 3.5) with risk factors, no fixed maximum, with INR every 2 to 3 days at the start, weekly until stable, then every 4 to 12 weeks.

Public health. Test sexual partners and treat contacts. Offer HIV testing. Report cases as required.

Special groups. HIV infection: give benzathine benzylpenicillin 2.4 million units intramuscularly once weekly for 3 weeks, with a lumbar puncture, antiretroviral therapy and closer serological follow up. Pregnancy: penicillin is the only treatment accepted for the foetus, and the infant is assessed after birth.

Monitoring. Non-treponemal titre at 3, 6, 12 and 24 months, expecting a fall of at least fourfold by 12 to 24 months, though some patients stay serofast. CSF re-examination at 6 months if abnormal. Imaging yearly for aneurysm.

Referral and escalation. Refer to infectious diseases and a cardiothoracic or aortic team. Urgent for neurological or visual symptoms, ischaemia, rupture or progressive aortic regurgitation.