Syphilis

From Ganfyd

The great imitator

Introduction

See also magic bullet. A sexually transmitted disease. The incidence of syphilis has varied through western history according to changes in behaviour and latterly treatment.

In the UK the incidence of syphilis fell to a minimum during the 1990s, and after some increases due to localised outbreaks rose in the first quinquenium of the 21st century. 1 million pregnancies affected worldwide, of which 50% will end in abortion or still birth, and the other 50% will result in congenital syphilis.

The largest number of cases currently arise in men who have sex, particularly oral sex, with men^[1].

Co-infection with HIV can bring earlier onset of tertiary syphilis^[2]

Aetiology

The spirochaete Treponema pallidum. Minimum infective dose known to be one !.

Clinical

Typical illustrative time courses for early syphilis

Primary

• Genital ulcer (Chancre)
  • Incubation about 3 weeks - can be up to about 90 days
  • Heals in about a month

Secondary

• Rash
  • Symmetrical generalised painless faint reddish macular
• Lymphadenopathy
  • Painless
• Systemic symptoms often absent or mild, perhaps with nocturnal emphasis as with headache or bone pain
• Occasional symptomatic meningitis acute phase (25% will have asymptomatic or symptomatic meningitis)
• Rarely alopecia, laryngitis, uveitis, hepatitis and nephrotic syndrome.
• Can overlap with primary stage but usually after 6 weeks
• Relapses in about 20% (infectious) - span between early latent and late latent which may progress in 40% to tertiary

Tertiary

• Gummas
  • Central necrosis
  • Perivasculitis
  • Obliterating endarteritis

Connective tissue

• 16.4% of those infected in Oslo study
• Skin
  • Gummas on extensor surfaces
    • Start as painless nodules
    • Punctured out ulcer
    • Secondary infection rare
• Mucous membranes
  • Syphilitic glossitis
  • Syphilitic leukoplacia
    • High risk malignant transformation
  • Condylomata lata
• Bones
  • Sabre tibia
  • Bone swelling
  • Bone defects eg skull

Visceral

• Paroxysmal cold haemoglobinuria
• hepar lobatum - irregular hepatomegaly
• Chorioretinitis, uveitis, optic atrophy
• Pseudolymphoma
  • Clinical catch^[3] - Non-Hodgkin's lymphoma like^[4]

Cardiovascular

• Usually fatal if untreated
• 10.4% of those infected in Oslo study but probably more in fact
• Aortitis
• Aortic regurgitation
• Aortic aneurysm
• Coronary ostial stenosis

Neurological

• If untreated 10% develop neurosyphilis

Asymptomatic

• +ive CSF serology

Meningovascular

• Usually about 12 years after primary infection but in HIV co infected patients can present within first year(1.7% of such patients with syphilis)^[5]
• Presents with:
  • Stroke
  • Cranial nerve palsy
  • Papillitis
  • Usually afebrile with headache and neck stiffness when evaluated fully

Parenchymatous

Grand paresis of insane

• Usually about 15-20 years after primary infection

everyone suffers in general paresis apart from the patient

• Dementia paralytica
  • CSF never normal

Syphilitic meningo-encephalitis

• As for meningovascular above but also manifestations essentially can mimic any CNS neuropsychiatric illness
  • Lues cerebri

Tabes dorsalis

• Usually about 10 to 25 years after primary infection. Can be over 60 years
  • Ataxia
  • Spincter disturbance
  • Lightning pains
    • Often down back/legs
    • Shoes/clothing trigger
  • Argyll Robinson pupils

Congenital

• Hutchinson's Triad
  • Deafness
  • Hutchinson's teeth (centrally notched, widely-spaced peg-shaped upper central incisors)
  • Interstitial keratitis (IK)
• Mulberry molars (sixth year molars with multiple poorly developed cusps)
• Frontal bossing
• Hypoplastic maxillae
• Hepatosplenomegaly
• Anaemia
• Lympadenopathy
• Jaundice
• Pseudoparalysis

Investigations

Direct dark field microscopy can be done from a chancre or mucous patch, but beware non pallidum treponemes found in normal flora esp mouth). PCR can be done from lesions too.

X-ray appearances may be characteristic.

Blood tests

Syphilis tests are either nontreponemal or treponemal:

• Nontreponemal eg VDRL, RPR are screening tests, 70% sensitive in primary, 99% in secondary. False positives - systemic lupus erythematosus, infection, recent immunization, pregnancy. Quantitative is useful for monitoring disease activity.
• Specific treponemal tests eg TPHA, TP immobilization (TBI), fluorescent T antibody absorption (FTA-Abs) used to confirm. False positives occur with borrelia and other treponemal disease eg yaws, pinta. Remain positive for life, and do not correlate with disease activity.

For disease monitoring, quantitative non-treponemal testing is useful: 4-fold rise in titre is seen early on in infection or in relapse, whereas a drop of 4-fold suggests adequate response to treatment. In secondary disease, titres are always high ie 1:32. Very high levels of antibody can cause false negative result so if high suspicion then do dilutions. Should become negative within 1 yr of treatment in primary, 2 yrs in secondary or congenital, 5 yrs in late.

Many Microbiology/Virology laboratories in the UK now use an ELISA serology test to screen for "syphilis" serology. All positives must be followed up by RPR/TPPA serological tests as described above.

NB: No routinely available "syphilis" serology can differentiate between Syphilis, Yaws and Pinta. The latter two diseases are caused by Treponema pallidum sub-species, which have avery high level of genetic homology to the type species of Treponema pallidum which causes Syphilis.

Radiology

Treatment

Medical

• Penicillin in variety of dose regimens cures rapidly the lesions of early syphilis and prevents progression of early and latent syphilis.
• Multiple other antibiotics have fair evidence base including doxycycline, azithromycin, erythromycin and ceftriaxone.

^[6]

• Early disease:
  • Benzathine penicillin (unlicensed in the UK) 2.4 million units IM (divided into 1.2 million units in each buttock) is treatment of choice for early syphilis.
  • Procaine penicillin 600,000 units IM daily for 10 days)
• Late latent:
  • Benzathine penicillin 2.4 megaunits IM on days 0, 7, 14 or
  • Procaine penicillin 900,000 units IM daily for 17 days
• Neurosyphilis
  • Procaine penicillin 2.4 units daily IM for 17 days with oral probenecid 500 mg four times a day
• Doxycycline for penicillin allergy
  • 100mg bd for 14 days in early disease
  • 200mg bd for 28 days in late disease

Surgical

Prevention

For screening adults, 1 step strip test available, and one off oral treatment effective (Azithromycin, 1.8g). Note that antibodies give only partial protection.

Notification

Notifiable disease in the UK.

External links

Until there is more content at Ganfyd, you might like to visit:

• Wöhrl S, Geusau A. Clinical update: syphilis in adults. Lancet. 2007 Jun 9; 369(9577):1912-4.(Link to article – subscription may be required.)
• French P. Syphilis. BMJ (Clinical research ed.). 2007 Jan 20; 334(7585):143-7.(Link to article – subscription may be required.)

References