Syphilis is a complex systemic illness caused by the spirochete Treponema pallidum. Some
reports in the literature suggest that, because of defects in cell-mediated and humoral immunity,
co-infection with HIV may alter the natural course of syphilis infection, leaving patients with HIV
vulnerable to a rapid clinical course characterized by unusual manifestations, with higher risk of
neurologic manifestations and higher rates of treatment failure. Thus both diagnostic and
treatment parameters for syphilis may be altered by the presence of HIV disease. Evaluate
patients carefully for ocular and neurologic abnormalities.
The natural course of untreated syphilis infection is arbitrarily divided into phases:
1. An incubation period lasting about 3 weeks (9-90 days)
2. A primary stage characterized by non-painful ulcer (chancre) at the site of sexual exposure,
associated with regional lymphadenopathy
3. A secondary disseminated stage accompanied by generalized mucocutaneous lesions and
4. Periods of subclinical infection (latent syphilis) detected only by confirmed serologic tests.
This is called early latent if known to be <1 year duration and late latent if known to be >1
year duration, or otherwise as latent syphilis of unknown duration.
5. Late or tertiary is stage characterized by progressive disease involving the CNS system and/or
ascending aorta, but virtually any organ in the body can be involved.
6. CNS disease, or neurosyphilis, may occur at any stage of infection. Neurosyphilis can be
asymptomatic, and HIV clients with latent or tertiary syphilis should have an LP prior to
S: In primary disease, patient complains of new sore (usually perigenital or perirectal, but can
be oral or other contact site); in secondary disease, patient complains of a new rash,
particularly on trunk or soles and/or palms, and may have fever; malaise; anorexia and
weight loss. Other possible secondary symptoms include arthralgias; hair loss; pharyngitis,
laryngitis, meningitis, or uveitis. CNS disease may present with problems with vision or
hearing, CVA, seizures, hyperactive reflexes, and changes in personality, affect or cognition.
Latent syphilis has no symptoms, though patient may recall chancre or rash.
HX: Previous exposure to syphilis or other STD's
Unprotected sex: specific practices such as oral, anal, or vaginal sexual contact
Multiple sexual partners
Injecting drug or crack use
History of positive serologic tests for syphilis (RPR or VDRL), with or without
O: PE: Thorough physical examination, including neuro; examine all visible mucous membranes
and skin, including palms and soles, for lesions or masses. Document presence/absence
of heart murmurs or other abnormalities; conjunctival and circumcorneal injection with
poor pupil responses suggest iritis.
Primary stage: papule; chancre - a firm, usually painless ulcerated lesion (~10% are painful)
with raised borders, clean appearance and no exudate; regional lymphadenopathy.
Secondary stage: multiple, widespread signs. Skin lesions begin on the trunk and proximal
extremities, and may be macular, maculopapular, papular or pustular. Rash on the palms and
soles is highly suggestive of secondary syphilis. Constitutional symptoms of fever, malaise,
anorexia, arthralgia, and pharyngitis/laryngitis are more common at this stage.
Latent stage: no signs beyond lab seropositivity (RPR/VDRL confirmed by a treponemal test).
If possible, determine duration of infection, using previous negative lab reports, history of
unequivocal symptoms of primary or secondary syphilis, duration of contact with sex partner
documented to have syphilis.
Tertiary stage: gumma or cardiovascular complications, such as aortic aneurysm and valvular
disease occur late in syphilis. Gumma can grow from skin or mucosal surfaces, destroy bone,
and may present in any organ system. Unusual presentations have included: hepatitis,
retinitis, posterior uveitis. Note that uveitis and other ocular manifestations are frequently
associated with neurologic involvement, and patients with these symptoms should have LPs,
and be treated for neurosyphilis.
Neurosyphilis: Can be associated with any stage of syphilis. Changes in personality, affect,
sensorium, intellect, insight and judgment; seizures; hyperactive reflexes; abnormal cranial
nerve function, with VII & VIII most commonly affected; unilateral facial palsy; hemiplegia;
hemiparesis; neurosensory hearing loss; visual changes such as blindness, chorioretinitis,
keratoderma; meningitis or encephalitis.
A: Rule out:
• other causes of neurologic disease • other dermatological conditions causing
• other causes of cardiac murmur maculopapular rashes
• other causes of ocular disease • constitutional HIV disease
1. Darkfield examination of exudate from suspicious chancres or other moist dermatologic
direct fluorescent antibody (DFA) staining of exudate (if available) are considered
2. RPR or VDRL (if not done as part of initial laboratory work-up). These tests may read falsely
negative in the presence of HIV infection if the patient has primary syphilis or is incubating
syphilis. Treponemal test to confirm positive PRP/VDRL (if not done previously). Specific
treponemal tests (Treponemal IgG or FTA-ABS) may become positive earlier in the course of
3. If darkfield and serologies are negative, but clinical suspicion of syphilis is high, rule out the
"prozone" phenomenon, which may occur when a nontreponomal serology is read as negative
because the specimen was not tested after sufficient dilution. Very high antibody
concentrations can prevent formation of detectable antigen-antibody complexes.
4. Clinical evidence of neurologic disease warrants lumbar puncture in all cases. LP is also
indicated when treatment for early syphilis fails (if titer does not decrease fourfold/2 dilutions
by 12 months), or if a substantial increase in titer occurs. See Treatment section, below, for
additional indications. Examine CSF for:
protein > 0.4mg/ml
5. All patients testing positive for syphilis should be tested for other STDs such as gonorrhea
TX: Note that up to 2/3 of patients with primary, secondary, or even latent syphilis can have a Jarisch-
Herxheimer reaction, with headache, chills, fever, arthralgias, malaise, tender lymphadenopathy,
and intensification of rash, that starts 2-8 hours after the first treatment dose, and resolves within
24 hours. This self-limited treatment effect is best treated with rest and acetaminophen, and
should not be confused with an allergic reaction to penicillin.
Non-neurologic syphilis <1 year's duration, i.e., primary, secondary, and early latent:
1. Benzathine penicillin G - 2.4 million units IM.
2. In penicillin-allergic, non-pregnant patients: Doxycycline 100mg PO BID x 2 weeks, or
Tetracycline 500mg PO QID x 2 weeks.
3. Refer penicillin-allergic pregnant women for desensitization to penicillin.
Non-neurologic syphilis >1 year's duration or of unknown duration, i.e., tertiary, late latent, or latent
syphilis of unknown duration:
1. CSF examination should be done on all patients with a history of syphilis of greater than one
year or of unknown duration.
2. If CSF exam is negative, treat with Benzathine penicillin G, 7.2 million units total (2.4 million
units IM weekly x 3 consecutive weeks).
3. In penicillin-allergic clients, refer to infectious disease specialist for desensitization to
Neurosyphilis, i.e., syphilis at any stage with neurologic or ocular symptoms:
1. Aqueous crystalline penicillin G: 18-24 million units IV/day (3-4 million units Q 4 hrs x 14
100000002.00 If compliance with therapy can be ensured, patients may be treated with the
following alternative: Procaine penicillin 2.4 million units IM per day, PLUS probenecid 500
mg po qid, both for 10-14 days.
3. Penicillin-allergic patients should be referred for desensitization. These patients require
hospitalization and 2 weeks of IV penicillin under close observation.
4. If CSF pleocytosis was initially present, the CSF should be rechecked every 6 months until the
cell count normalizes.
Pregnancy: Use penicillin regimen appropriate to stage of infection. Tetracycline and doxycycline should
not be used during pregnancy. Erythromycin does not reliably cure an infected fetus. Women treated
during the second half of pregnancy are at risk of Jarisch-Herxheimer reaction with resultant contractions,
fetal distress, and possible stillbirth. They should be instructed to seek obstetric attention in the event of
contractions or decreased fetal movements. This is a rare complication, but concern for this should not
delay treatment, given that syphilis can be even more devastating to an infant.
Sex partners: Sexual transmission of syphilis only occurs when mucocutaneous syphilitic lesions are
present, which is uncommon after the first year of infection. However, persons exposed sexually to a
patient who has syphilis in any stage should be evaluated as follows:
Persons exposed within the 90 days preceding the diagnosis of primary, secondary or early
latent syphilis might be infected even if seronegative; therefore, such persons should be treated
Persons exposed >90 days before the diagnosis of primary, secondary, or early latent syphilis
should be treated presumptively if serologic test results are not available immediately and the
opportunity for follow-up is uncertain.
All HIV-infected patients treated for syphilis should be clinically and serologically evaluated at 3,
6, 9, 12, and 24 months to rule out treatment failure. Any client with apparent treatment failure
should have LP and be re-treated as appropriate.
If, at any time, clinical symptoms develop or non-treponemal titers rise fourfold, a repeat CSF
examination should be performed and treatment administered accordingly.
For primary and secondary syphilis: If, between 6 and 12 months, the non-treponemal titer
fails to decline fourfold, the CSF exam should be done and treatment administered accordingly.
For latent syphilis: If, between 12 and 24 months, the non-treponemal titer fails to decline
fourfold, the CSF exam should be done or repeated, and re-treatment administered accordingly
1. As per state law, the health department will be notified (or client can be directly referred). A
communicable disease specialist will elicit sexual contacts from the previous 3 months (in the
case of primary syphilis), 6 months (for those with secondary syphilis) or 12 months (in the
case of latent syphilis), and refer them for workup and treatment.
2. Emphasize the need for careful follow-up of syphilis in HIV-infected patients to assure
adequate treatment of their infection. Report any recurrent symptoms or rashes.
3. Underline sexual transmissibility of both syphilis and HIV infection. Review patient's sexual
practices to assist them with negotiation skills for abstinence, condom use, or alternatives to
300000004. (For patients with primary, secondary, and latent syphilis, at the time of their first
treatment dose): You may notice within the next 2-8 hours that you have fever, chills,
headache, sore throat, swollen nodes, and worsening of any rashes. This is very common, and
seems to be a result of the medicine killing off the syphilis spirochetes. It is not an allergic
reaction. You may want to take aspirin or acetaminophen. It goes away within 24 hours; if
fever persists, return to clinic.
CDC. Sexually Transmitted Disease Treatment Guidelines 2002. MMWR 2002; 51 (No. RR-6).
Colven R, Spach DH. Generalized cutaneous manifestations of STD/HIV infection. In Holmes KK, Mardh
PA, Sparling PF, et al (Eds) 1999. Sexually Transmitted Diseases, 3rd Ed. New York: McGraw-Hill, Inc.
Musher, DM. Early syphilis. In Holmes KK, Mardh PA, Sparling PF, et al (Eds) 1999. Sexually
Transmitted Diseases, 3rd Ed. New York: McGraw-Hill, Inc. p. 484