Syphilis

Introduction

Syphilis is a systemic contagious disease caused by the bacteria Treponema Pallidum. The disease
is characterized by periods of active manifestations of symptoms and periods of symptomless
latency.

Syphilis is classified as of being congenital or acquired. In the early infection of the disease,
diagnosing and treating it is straightforward, but if left untreated it can cause complex sequellae in
many different organs and eventually death.

Etiology and Pathophysiology

Syphilis is caused by the bacterium Treponema Pallidum, which is a motile spirochete that is
acquired either by sexual contact or can be transmitted by trans-placentally. T. pallidum rapidly
penetrates intact mucous membranes or microscopic abrasions in skin and, within a few hours,
enters the lymphatics and blood to produce systemic infection and metastatic foci long before the
appearance of a primary lesion. Blood from a patient with incubating or early syphilis is infectio us.
The generation time of T. pallidum during early active disease in vivo is estimated to be ∼30 h,
and the incubation period of syphilis is inversely proportional to the number of organis ms
inoculated.
Clinical features

Acquired syphilis (if untreated) passes thorough different stages with different clinical features.

a) Primary syphilis

Between 10 to 90 day after exposure to pathogen, a papule develops at the site of inoculation. This
ulcerates to become painless firm chancre. The papule then rapidly becomes eroded and usually
becomes indurated, with a characteristic cartilaginous consistency on palpation of the edge and
base of the ulcer. Multiple primary lesions are seen in a minority of patients. It’s usually associated
with painless regional lymphadenopathy with rubbery, discrete and nontender to palpation.
Primary chancres are found primarily on the penis, and cervix/vulva but may also be found on the
lips. Healing occurs spontaneously within 2–3 weeks.
 b) Secondary syphilis

Between 4 and 10 weeks after the appearance of the primary lesion constitutional symptoms with
fever, sore throat, malaise and arthralgia appear. At this point, any organ can be affected which
then (in addition to general features), the patient may also present clinical features of diseased
organ. General features include, generalized lymphadenopathy (in contrast to regional
lymphadenopathy in primary syphilis), generalized skin rashes that spares the face, condylomata
Lata, and snail track ulcers. Alopecia and acute neurological sign can present.
c) Latent syphilis
Again, without treatment, symptoms and signs abate over 3–12 weeks, but in up to 20% of
individuals, may recur during a period known as early latency. In this stage, the patient is
asymptomatic and if lucky enough can be life-long. Early latent syphilis is limited to first year
after infection while late latent syphilis is after one year of infection or when initial infection date
cannot be established. Even though the patient is asymptomatic clinically in the latent syphilis,
he/she is syphilitic in laboratory wise (positive serologic test).
d) Tertiary syphilis
Benign tertiary syphilis develops 3–20 years after the initial infection; typical lesion is the gumma
(a chronic granulomatous reaction) found in any tissue or organ, which will heal spontaneously
and leave a scar. Cardiovascular manifestations of the tertiary syphilis include: aortitis, aneurysm,
aortic regurgitation, and myocarditis. Neurological involvements include: meningeal syphilis,
meningovascular syphilis and parenchymatous syphilis in which each one of them causes
neurological findings. Patients are not contagious at the tertiary syphilis.
Congenital syphilis has two stages.
Congenital syphilis usually becomes apparent between the 2nd and 6th week after birth, early signs
being nasal discharge, skin and mucous membrane lesions and failure to thrive. Signs of late
syphilis generally do not appear until after 2 years of age and take the form of ‘stigmata’ relating
to early damage to developing structures, particularly teeth and long bones. Other late
manifestations parallel those of adult tertiary syphilis.
Diagnosis
a) Screening of syphilis is done through VDRL and PRL. The Venereal Disease Research
Laboratory (VDRL) and rapid plasma regain (RPR) tests are nonspecific, becoming positive
within 3–4 weeks of the primary infection. They are quantifiable tests which can be used to
 monitor treatment efficacy and are helpful in assessing disease activity. They generally
become negative by 6 months after treatment in early syphilis. The VDRL may also become
negative in untreated patients (50% of patients with late-stage syphilis) or remain positive
after treatment in late stage.
b) Specific tests of syphilis: The T. pallidum enzyme immunoassay (EIA). T. pallidum
haemagglutination or particle agglutination assay (TPHA/TPPA) and fluorescent treponemal
antibodies absorbed (FTA-abs) test are both highly specific for treponemal disease but will
not differentiate between syphilis and other treponemal infection such as yaws. These tests
usually remain positive for life, even after treatment.
Treatment
Penicillin is the drug of choice for all stages of syphilis.
• Primary, secondary, and latent syphilis are treated with 2.4 million units of intramusc ular
benzathine penicillin given once a week. Primary and secondary syphilis receive 1 week
of therapy. Late latent syphilis is treated with 3 weeks of therapy and diagnosed when the
VDRL or RPR titers are elevated >1:8 without symptoms.
• Tertiary syphilis is treated with penicillin 10–20 million units/day IV for 10 days.
• Penicillin-allergic patients receive doxycycline for primary and secondary syphilis, but
must be desensitized in tertiary syphilis. Pregnant patients must also undergo
desensitization.
A reaction called Jarisch- Herxheimer can occur in >50% of patients (general malaise, fever,
headache, sweating rigors, and temporary exacerbations of the syphilitic lesions 6–12 hours after
initial treatment).

References:
1. Harrison’s principle of internal medicine 19 th Ed
2. Kumar and Clark’s clinical medicine 8th Ed
3. USMLE Step 2 CK Lecture Notes 2018
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2624832/