Syphilis in pregnancy

Smita Oswal MD DA (UK) MRCA

Gordon Lyons MD FRCA

Key points For several decades, syphilis has been out of ulcer with a bright red margin.1 Chancres
sight, mind, and memory, but the incidence in appear on average about 3 weeks after sexual
There has been a
the Western world is now on the rise again and contact and heal in 3 –6 weeks. However, with
worldwide resurgence of

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syphilis in recent years, and it could once more become a major health a small inoculum, this incubation period may
it is likely to remain a concern. This change has followed the rapidly be as long as 90 days. One of the common sites
common disease rising number of human immunodeficiency for lesions is the cervix; therefore, the clinical
worldwide. virus (HIV) positive individuals worldwide, manifestations of primary syphilis may go
More than 80% of women together with the advent of health tourists, unnoticed by the patient and her partner.3
with syphilis are of economic migrants, asylum seekers, and the
reproductive age; therefore, easy availability of low-cost travel.
there is a serious risk of Just as syphilis has all but disappeared as an Secondary syphilis
vertical transmission to the entity in the working memory of most anaes-
Untreated patients will progress to secondary
fetus. thetists, it has suddenly re-emerged as a
syphilis after the signs for primary syphilis
There are no specific co-existing condition in women presenting for
resolve (within 4– 10 weeks3). The lesions are
contraindications to general Caesarean section. Figure 1 shows the changing
numerous, variable, and affect many systems.
anaesthesia or regional incidence of syphilis in the UK over the last 10
A symmetrically distributed, maculopapular,
blockade. However, HIV and years. This review is intended to inform anaes-
non-irritating rash is found on the palms and
syphilis affect the similar thetists caring for women with syphilis.
group of patients and co- the soles with painless lymphadenopathy. The
infection is common. highly infectious condyloma lata are found on
Universal precautions are Aetiology1 warm and moist areas such as genitalia, peria-
mandatory before nal region, perineum, and axillae. Both menin-
Treponema pallidum is the causative organism
anaesthetizing these gism and headache can occur, especially at
patients. for syphilis. It is a delicate, motile spirochete
night. Their cause can be confirmed by the pre-
bacterium. Humans are its only natural source.
sence of an elevated cell count and elevated
Syphilis is usually transmitted by sexual
proteins in cerebrospinal fluid. Less common
contact through exposure to mucocutaneous
accompaniments to secondary syphilis include
syphilitic lesions that contain infectious spiro-
alopecia, laryngitis, mild hepatitis, nephrotic
chetes. The infecting organism in body fluid
syndrome, bone pain, and uveitis.
gains access through microscopic abrasions in
skin or mucosal surfaces, and begins to repli-
cate locally. After inoculation, the incubation
Latent syphilis
period is around 3 weeks (10– 90 days), at the
end of which a primary sore develops at the The natural history of untreated secondary
Smita Oswal MD DA (UK) MRCA site of infection, usually the genitalia. syphilis is marked by spontaneous resolution
Staff Grade Anaesthetist
after a period of 3– 12 weeks, leaving the
Department of Anaesthesia patient entirely free of symptoms. This natu-
Bradford Royal Infirmary Classification rally attained asymptomatic state is called
Bradford BD9 6RJ
UK Syphilis is classified2 as congenital or acquired latency.4 The latency is arbitrarily subdivided
as shown in Figure 2. There are four stages of into early (,2 yr from the onset of the infec-
Gordon Lyons MD FRCA tion) and late (.2 yr) stages. During this time,
syphilis: primary, secondary, latent, and late
Consultant Anaesthetist
(tertiary). the patient remains serologically positive for
Department of Obstetric Anaesthesia
St James’s University Hospital syphilis. Approximately 60% of patients remain
Leeds LS9 7FT latent for the rest of their lives. In the early
UK Primary syphilis
latent stage, 25% will relapse with a secondary
Tel: þ44 (0113) 206 5371
Fax: þ44 (0113) 244 4538 The first development is a chancre at the site of syphilitic manifestation, whereas the likelihood
E-mail: [email protected] inoculation, classically in the anogenital region of such relapses in the late latent stage is
(for correspondence)
which is a painless, solitary, round indurated small.1
doi:10.1093/bjaceaccp/mkn042
224 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 8 Number 6 2008
& The Board of Management and Trustees of the British Journal of Anaesthesia [2008].
All rights reserved. For Permissions, please email: [email protected]
 Syphilis in pregnancy

transmission of syphilis is more common in primary (50%) and

secondary syphilis (50%), compared with early latent (40%), late
latent (10%), and tertiary syphilis (10%). Seventy to one hundred
per cent of infants born to untreated infected mothers are infected.
Pregnancies complicated by syphilis may result in intrauterine
growth restriction, non-immune hydrops fetalis, stillbirth, preterm
delivery, and spontaneous abortion in up to 50% of pregnancies.
Women who had documented treatment for syphilis in the past do
not need treatment during current or subsequent pregnancies.

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Congenital syphilis
In spite of a downward trend in the incidence of syphilis, con-
Fig 1 Number of new syphilis cases seen at genitourinary medicine clinics genital syphilis, an infection passed from mother to child through
in the UK by sex, 1998–2007. (Source: Health Protection Agency, UK, the placenta during fetal development or birth, remains a great
http://www.hpa.org.uk/web/HPAweb&HPAwebStandard/HPAweb_C/ concern. An infected woman’s potential to infect her fetus remains
1195733775264)
for many years, although the risk of infecting a fetus declines
gradually during the course of untreated illness. After 8 yr, there is
little risk, even in the untreated mother. Nearly half of all children
infected with syphilis during gestation die shortly before or
after birth.
Infants who survive develop early-stage and late-stage symp-
toms of syphilis, if not treated. Early-stage symptoms include irrit-
ability, failure to thrive, non-specific fever, a rash and condyloma
lata on the borders of the mouth, anus, and genitalia. Some of
these lesions may resemble the wart-like lesions of adult syphilis.
A small percentage of infants have a watery nasal discharge (snif-
fles) and a saddle nose deformity resulting from destruction of the
cartilage of the nose. Bone lesions are common, especially in the
upper arm (humerus). Later signs appear as tooth abnormalities
Fig 2 WHO clinical classification of syphilis.
(Hutchinson teeth), bone changes (sabre shins), neurological invol-
vement, blindness, and deafness.
Late syphilis (tertiary syphilis)
Tertiary syphilis develops in 30–40% of untreated patients. The
Incidence of syphilis
three main manifestations of late syphilis are cardiovascular, gum- The 1999 WHO estimates suggest an annual rate for syphilis of
matous, and neurosyphilis. Cardiovascular syphilis usually occurs 12 million active infections. The risk of contracting syphilis
15 –30 yr after primary syphilis and may occur in any large vessel. through a sexual contact with a person with primary or secondary
It is characterized, by an aortitis, aortic incompetence, coronary syphilis is 30 –50%. More than 80% of women with syphilis are
ostial stenosis ( presenting as angina), and aortic medial necrosis in reproductive age; therefore, there is a serious risk of vertical
causing aortic aneurysm. Gummatous syphilis is granulomatous transmission to the fetus.6 Worldwide, a million pregnancies are
locally destructive lesions that usually occur 3–12 yr after inocu- adversely affected each year by syphilis because of maternal
lation. They can occur in almost any tissue. Neurosyphilis presents infection. About 270 000 babies are born with congenital syphilis,
with a variety of syndromes including general paresis, tabes dorsa- 460 000 pregnancies end in abortion or perinatal death, and
lis, syphilitic meningitis, and meningovascular syphilis. The incu- 270 000 babies are born prematurely or with low birth weight.7
bation period is 5 –12 yr.5
Laboratory diagnosis of syphilis
Syphilis in pregnancy
Diagnosis of syphilis is based on microscopy and serology. At the
Antenatal syphilis poses a significant threat to the pregnancy and first antenatal visit, all women in UK are screened for sexually
fetus. T. pallidum readily crosses the placenta, resulting in fetal transmitted diseases including syphilis and HIV. The serological
infection. Vertical transmission can occur at any time during preg- tests are repeated at three monthly intervals in cases of anogenital
nancy and at any stage of syphilis.6 Risk of transmission correlates ulceration if the initial tests are negative. All infants born to sero-
with the extent of spirochetal presence in the circulation. Vertical positive mothers should be examined at birth and at monthly

Continuing Education in Anaesthesia, Critical Care & Pain j Volume 8 Number 6 2008 225
Syphilis in pregnancy

intervals for 3 months until it is confirmed that serological tests are antibodies as it is positive in earlier stages of syphilis. A positive
and remain negative. test is then confirmed with the TPHA/TPPA or VDRL/RPR tests.
FTA-ABS (fluorescent treponemal antibody absorption) assay:
Microscopy this uses the indirect fluorescent technique with killed T. palli-
dum as an antigen. The organisms are fixed on a slide to which
Microscopic demonstration of T. pallidum from the lesions or serum is added. The antibody in the serum unites with trepo-
infected lymph nodes in early syphilis depends on the following nemes. The test has been made more specific by absorbing the
three tests: group antibodies. This is the most sensitive and specific test
Dark-field microscopy: if a lesion such as chancre is present, available. It becomes positive earlier during the initial stage of
dark-field microscopy should be attempted to visualize the primary syphilis. However, it is not suitable for assessing the

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characteristic motile spirochetes in the exudates collected from activity, as the positive test persists long after successful
the lesion. The sensitivity rate5 is up to 97%, so failure to find treatment.1
the organism does not exclude a diagnosis of syphilis. (For an Neurological involvement9 is confirmed by a positive VDRL,
explanation of sensitivity and specificity, please see Lalkhen and raised cell count (.5/mm2), and raised protein (40 mg dl21) in the
McCluskey.8) CSF obtained by lumbar puncture. Chest X-ray, electrocardio-
Direct fluorescent antibody (DFA) test: this uses the indirect graphy, echocardiography, cardiac catheterization, and biopsy of
fluorescent technique with killed T. pallidum as antigen. The gumma can reveal involvement of other systems.
organisms are fixed on a slide to which serum is added. The
antibody in the serum unites with treponemes and is made Treatment of syphilis during pregnancy
visible with fluorescent stain.1
Penicillin is the drug of choice for treating all stages of syphilis.
Polymerase chain reaction (PCR) test: it may be useful for the
Parenteral rather than oral treatment has been the route of choice
detection of primary syphilis with sensitivity up to 98.6%.
as the therapy is supervised and bioavailability is guaranteed. Most
women treated during pregnancy will deliver before their serologi-
cal response to treatment can be assessed definitively. Neonates
Serological tests
born to such women should be evaluated for congenital syphilis.
Non-treponemal tests The UK national guidelines9 for the treatment of early syphilis
These tests detect the cross-reaction of antibody to syphilis with during pregnancy are described as follows:
cardiolipin. The result is reported as reactive or non-reactive; a
First-line therapy: intramuscular (i.m.) procaine penicillin
reactive test is accompanied by a quantitative titre and should be
750 mg daily for 10 days. If it is not possible to give daily pro-
confirmed with a treponemal test. False positive non-treponemal
caine penicillin on the weekend, then either long-acting procaine
tests may occur in patients who are pregnant, i.v. drug users, those
penicillin in aluminium stearate, 2 million units (MU) or long-
with systemic inflammatory diseases such as systemic lupus erythe-
acting benethamine penicillin 1.2 MU should be given IM on
matosus, or after a recent viral infection.3
the Friday.
VDRL (venereal disease research laboratory) test: this is
Patients with penicillin allergy: erythromycin 500 mg four times
simple and inexpensive and is the preferred test worldwide.
a day should be given for 14 days. Alternatively, azithromycin
RPR (rapid plasma reagin) test: this is used for screening pur-
500 mg should be given daily for 10 days. In addition to this,
poses and is the least technically demanding test as no micro-
examination, tests, and treatment of all babies at birth should be
scope is needed. It uses carbon-containing cardiolipin antigen
carried out. Desensitization to penicillin may be considered, fol-
and requires a minimal quantity of blood.
lowed by the first-line treatment. Mothers treated with erythro-
mycin or azithromycin may be considered for retreatment with
Treponemal tests doxycycline after delivery and when breast-feeding is stopped.
These tests specifically detect antibodies against T. pallidum and
Patients suspected of non-compliance: benzathine penicillin 2.4
are positive for life in the vast majority of infected patients regard-
MU i.m. on Days 1 and 8.
less of stage or treatment history.3
TPHA (T. pallidum haemagglutination assay) or TPPA
(T. pallidum particle agglutination assay): these are very valu-
Penicillin reactions
able and simple tests using an indirect haemagglutination
method with red cells or by gelatine particles. Together with Approximately 5–10% of pregnant women with syphilis report a
VDRL, it is probably the best combination for routine use. history of penicillin allergy. The Jarisch – Herxheimer reaction is
False positive reactions occur in up to 2%.1 an acute response that may occur after treatment for acquired early
EIA (enzyme immuno assay): treponemal enzyme immunoassay syphilis. It occurs in up to 45% of pregnant women and consists
is the screening test of choice and can detect IgG and IgM of fever, chills, myalgia, headache, hypotension, tachycardia, and

226 Continuing Education in Anaesthesia, Critical Care & Pain j Volume 8 Number 6 2008
 Syphilis in pregnancy

transient accentuation of the cutaneous lesions.6 It typically begins intubation during the induction of general anaesthesia.11 Syphilis
within several hours of treatment and resolves within 24–36 h. poses no specific problems for regional blockade. The three main
The release of T. pallidum lipoprotein, which possesses inflamma- manifestations of late syphilis (neuro-, cardiovascular, and gumma-
tory activity from dead or dying organisms, is implicated as a tous syphilis) can have a wide range of presentation. It is prudent to
likely inducer of this phenomenon. In pregnant women, the assess and document all existing signs and symptoms (including
Jarisch – Herxheimer reaction can cause uterine contractions and neurological examination) in the anaesthetic record. There is no evi-
precipitate labour. This is possibly mediated secondarily by prosta- dence to suggest that regional blockade can affect the extent or like-
glandins as the concentrations are increased during reactions.6, 10 lihood of neurosyphilis. The lesion in tabes dorsalis is concentrated
on the dorsal spinal roots and dorsal columns of the spinal cord,
Syphilis and HIV most often at the lumbosacral and the lower thoracic region. There

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have been reports that spinal anaesthesia induces severe lightning
Syphilis commonly co-exists in patients with HIV ( prevalence is pain in the lower limbs of patients with phantom limb pain, tabes
14 –36%). All HIV-infected patients under regular follow-up dorsalis, or causalgia. The exact mechanism of this phenomenon is
should have syphilis serology documented at baseline and sub- controversial. Some hypothesize that complete loss of sensory input
sequently 12 monthly thereafter. HIV-infected patients with early after spinal anaesthesia may decrease the level of inhibition and
syphilis have an increased risk of neurological involvement. increase the self-sustained neural activity.3
Features of syphilis in HIV include: generalized lymphadenopathy; Options for delivery include elective Caesarean section because
splenomegaly; hepatitis; skin rashes, alopecia or both; oral mani- it is associated with less vertical transmission. When considering
festations; cognitive impairment; meningitis; cranial nerve palsies; postoperative analgesia, those techniques that do not expose staff
myopathies; and uveitis. to needle-stick injury should be favoured.

Anaesthetic considerations References

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Update Ob/Gyns 2000; 7: 26–30
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7. Walker D, Walker G. Forgotten but not gone: the continuing scourge of
ing tests are routinely performed for evidence of donor infection congenital syphilis. Lancet Infect Dis 2002; 2: 432– 6
with syphilis.3 After storage in blood for more than 4 days at 4oC, 8. Lalkhen AG, McCluskey A. Statistics VI: Clinical tests: sensitivity and
spirochetes are non-viable. The risk of accidental infection by specificity. Contin Educ Anaesth Crit Care Pain 2008; 8: 221–3
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Such blood is used for exchange transfusion in neonates. Clinical Effectiveness Group (Association for Genitourinary Medicine
Cutaneous lesions of the breast and nipples carry a risk of trans- and the Medical Society for the Study of Venereal Diseases).
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single report of a 73-year-old woman with late congenital pharyngo-
laryngeal syphilis, who presented with a potentially difficult Please see multiple choice questions 23 –25

Continuing Education in Anaesthesia, Critical Care & Pain j Volume 8 Number 6 2008 227