Risk factors: As for other sexually transmitted diseases (>86).

Epidemiology: Common worldwide. 2 =500 in 2000, up from ==170 in 1995. Concurrent HIV infection alters the course of infection, with more frequent and rapid onset of neurological disease, and treatment failures with standard antibiotic regimens.

Transmission: By sexual contact and vertically. Very rarely by blood transfusion. Treponema pallidum cannot penetrate intact skin, but infection may occur through macroscopically invisible cuts and abrasions.

Clinical features: Primary syphilis: 14-20 days (range 10-90) after inoculation, a red painless papule develops and ulcerates to form a chancre, usually 0.5-2 cm in diameter, painless with a clean base and an indurated edge. Moderate bilateral local lymphadenopathy is usual. Chancres are usually located on penis, fourchette or cervix, but may be anywhere, e.g. mouth, hands, anus and rectum. Multiple chancres are sometimes seen. Spontaneous resolution occurs after 3-8 weeks.

Secondary syphilis follows systemic dissemination of organisms from the chancre; 4-10 weeks after the development of the chancre, a generalized symmetrical scaly papular rash develops, involving trunk and extremities including palms and soles. The papules may be smooth, pustular or itchy. Mucosal ulcers are common. Condylomata lata are raised grey-white lesions found in warm moist areas. Unlike the rash, they are highly contagious. Malaise, fever, sore throat, lymphadenopathy and myalgia are common, sometimes with subclinical hepatitis and periostitis. Neurological disease may rarely present during the secondary stage (‘early neurosyphilis’) with meningitis, headache, cranial nerve lesions, intranuclear ophthalmoplegia, cerebrovascular accident or signs of spinal cord involvement. Early neurosyphilis is more common in patients coinfected with HIV. Iritis, arthritis and glomerulonephritis occur infrequently. Spontaneous resolution occurs after 3-12 weeks, after which patients are said to have entered latency. Without treatment, 25% have recrudescence of secondary disease during the first year of latency.

After a variable latent period (2-20 yrs), tertiary syphilis (late benign syphilis, visceral syphilis, cardiovascular syphilis or neurosyphilis) develops in a minority of patients. Late benign syphilis describes the development of large granulomatous lesions (‘gumma’), in skin and soft tissues, particularly on the head, neck and arms. Gummata may be indurated, nodular or ulcerated. Visceral syphilis describes the development of gummata in the viscera and bones. Lesions affecting the palate, pharynx, nasal septum or tongue can be locally destructive. Bony lesions are particularly painful. Other organs that can be involved include liver, testis, eye, stomach and rarely lungs. Cardiovascular syphilis affects the aorta and is due to endarteritis of the vasa vasorum. Aortic regurgitation occurs more commonly than aneurysm and presents with angina and dyspnoea secondary to left ventricular failure. Aneurysm typically affects the ascending aorta, and may involve the ostia of the coronary arteries. The arch and descending aorta are less frequently affected. VDRL (Venereal Disease Reference Laboratory) may be negative, suggesting that development of aneurysm is due to ongoing mechanical damage in a previously inflamed aorta. Neurosyphilis includes asymptomatic latent syphilis in which the CSF is found to be abnormal, meningovascular syphilis, general paresis of the insane (GPI) andtabes dorsalis. Meningovascular syphilis presents approximately 5yrs after primary infection, either as a cerebral pachymeningitis with headaches, fits and limb paralysis, or more commonly as a chronic diffuse basal meningitis, causing headaches and isolated cranial nerve palsies. There may be mental changes, with memory impairment and poor concentration. In severe cases, there are multiple cranial nerve palsies and severe mental deterioration leading to stupor. Cerebral artery thrombosis can occur, leading to stroke. Meningovascular syphilis may also affect the spinal cord causing cervical myelopathy or hemiplegia. GPI describes severe cerebral atrophy developing 10-20 yrs after primary infection, with gradual onset of confusion, hallucinations, delusions, fits and severe cognitive deficit. On examination, there are coarse tremor of the lips and tongue, brisk tendon reflexes and extensor plantars. Tabes dorsalis develops 15-35 yrs after primary infection. There is atrophy of the dorsal columns of the spinal cord below the cervical region, with autonomic neuropathy and cranial nerve lesions. Patients present with ataxia, sensory loss, lightning pains and sphincter disturbance. Classical signs on examination include sensory loss, areflexia and Argyll Robertson pupils (irregular pupils that may constrict to accommodation but do not react to light).

The risk of congenital syphilis is highest during early syphilis (1° or 2°). Treatment of the mother before 16 weeks’ gestation will prevent congenital disease. Neonates may present with fulminant disease; hepatitis, pulmonary haemorrhage and intercurrent bacterial infection are common and mortality is high. In less severe early congenital syphilis, signs develop over the first 2-10 weeks of life, including vesicular or bullous rash involving the sole and palms, rhinitis (snuffles) and evidence of widespread visceral involvement. Features of late congenital syphilis develop throughout childhood and include interstitial keratitis, Clutton’s joints, Hutchinson’s teeth, meningoencephalitis and skeletal changes. Diagnosis is by serology or dark-ground examination of material from mucosal lesions.

Organisms: Treponemapallidum (>322).

Microbiological investigations: Diagnosis of primary syphilis is confirmed by dark-ground microscope examination of material from the base of the chancre forspirochaetes. An alternative method of identifying T. pallidum from lesions is direct fluorescent antibody testing (DFA-TP). This technique has the advantage of permitting the identification of the organism when smears cannot be examined immediately and is specific for T. pallidum antigens. PCR is sometimes used to confirm diagnosis, particularly in oral lesions which can be contaminated by oral communal spirochaetes.

Two types of serological tests are used (Table Serological diagnosis of syphilis). Non-specific tests include VDRL and RPR (Rapid Plasma Reagin). These tests are based on the original Wassermann reaction (WR) and detect antibodies against cardiolipin, which is found in mammalian cell membranes, and is incorporated by the spirochaete into its outer membrane. False positives in non-specific tests are seen in a large number of conditions, including acute viral infections, connective tissue diseases, pregnancy and leprosy. The value of non-specific tests is that titres fall after successful treatment of syphilis. A reappearance or fourfold rise in titre of VDRL is regarded as evidence of relapse or reinfection. Specific tests, including fluorescent Treponema antigen tests (FTA and FTA-ABS), Treponema pallidum haemagglutination test (TPHA) and treponemal enzyme immunoassay (EIA) use Treponema pallidum antigens as targets. They are specific for syphilis, but remain positive for life and are not useful for assessing success of treatment. Their value lies in confirming the diagnosis of primary syphilis, as they become positive before VDRL in this situation, and excluding syphilis in suspected secondary and tertiary disease. False-positive reactions occur in Lyme disease (>323) and other spirochaetal infections (>322). Patients with syphilis and late-stage HIV infection may lose all antibody responses (>165).

Table Serological diagnosis of syphilis

Clinical situation Non-specific serology (e.g. VDRL) Specific serology (e.g. TPHA)
Primary syphilis* Positive in  ~75% Positive in ~90%
Secondary syphilis Positive at high titre in ~100% Positive in ~100%
Latent infection May remain positive. Titre falls with time and after treatment. Rise in titre suggests reinfection Remains positive
Late benign syphilis Usually strongly positive Remains positive
Syphilitic aortitis Positive in only 60% of cases Remains positive
Late neurosyphilis** May be negative or weakly positive Remains positive

* Definitive disgnosis by dark-ground examination of chancre.

** CSF may show pleocytosis with raised protein and positive VDRL.

Antibiotic management: Referral to genitourinary medicine clinic is essential. Published guidelines all stipulate benzathine penicillin as first line, but this is no longer available in the UK. Most now use (and BNF recommends) doxycycline or tetracycline or erythromycin. Early syphilis is treated for 14 days; late latent syphilis is treated with doxycycline for 28 days.

Isolation: Body fluid precautions should be observed for the first 24 h of treatment of patients with primary and secondary disease.

Complications: Jarisch-Herxheimer reaction is a hypersensitivity reaction precipitated by lysis of organisms. It occurs 1-6 h after initiating treatment in many patients and consists of fever, rash, lymphadenopathy and hypotension.

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