Syphilis
Cheryl A. Glass and Leslie B. Norman
Definition
A.Syphilis is a systemic disease (sexually transmitted infection [STI]). The disease is divided into stages based on clinical finding, helping to guide treatment and follow-up. Syphilis is characterized by distinct primary, secondary, and tertiary stages that occur over several years or decades.
B.Because latent syphilis is not transmitted sexually, the objective of treating persons in this stage of disease is to prevent complications and transmission from a pregnant woman to her fetus:
1.Latent or inactive periods occur between the stages:
a.Early latent is less than 1 year after infection.
b.Late latent is more than 1 year after infection.
C.Health department notification of infection is required by law in all states.
Incidence
A.The Centers for Disease Control and Prevention (CDC) 2016 primary and secondary syphilis distribution of cases by sex and sexual behavior statistics note 52% of the cases are from men having sex with men (MSM) only, 6% are men who have sex with men and women, 14% are men who have sex with women only, 17% men without data on sex of sex partners, 11% women, and only 41 cases with unknown sex.
Pathogenesis
A.Treponema pallidum, a spirochete bacterium, is the causative organism that infects the mucous membrane through microscopic abrasions during intercourse. The growth characteristics and metabolism of T. palladium are due to the inability to grow the organism in a culture.
Predisposing Factors
A.History of STIs.
B.Multiple sexual partners.
C.Illicit drug use.
D.Trading sex for drugs or money.
E.Factors contributing to increase of STIs in older adults:
1.Undereducated: Older adults are less likely to perceive themselves at risk. Safe sex and STI prevention education came in the 1980s dealing with the HIV crisis during the time older adults were middle-aged and married. Seniors may feel sex education is only directed to youth and prevention of pregnancy.
2.Medications for erectile dysfunction have contributed to more men being able to engage in sexual activity throughout their older years.
3.Online dating lowers the chance that partners know the background and sexual history of people they date.
4.Women are postmenopausal and do not worry about getting pregnant with new partners
Common Complaints
A.Genital lesion, generalized rash involving palms and soles, mucous patches, and condyloma latum are common.
Other Signs and Symptoms
A.Primary syphilis:
1.Chancre: it is painless or minimally painful.
2.Round, indurated lesion with little or no purulent exudate.
3.Regional bilateral lymphadenopathy.
4.Skin rash.
B.Secondary syphilis:
1.Generalized maculopapular rash that is nonpruritic and copper colored, on palms or soles; may be erythematous or scaly.
2.Mucous patches: Painless, white, mucous membrane lesions.
3.Generalized lymphadenopathy: Flu-like syndrome including fever, headache, sore throat, and malaise.
4.Patchy alopecia.
C.Tertiary syphilis:
1.Cardiac gumma lesions: Locally destructive granulomatous tumors involving various organs or systems; commonly seen on liver but can occur on other organs (heart, brain, skin, bone, testis).
2.Cardiovascular: Aortic involvement, aneurysms, and valve insufficiency.
3.Neurologic: Tabes dorsalis (loss of coordination) and general paresis.
D.Latent syphilis: Asymptomatic, detected by serologic testing.
Latent-phase syphilis manifests itself after treatment failure or no history of treatment. Spirochete can lie dormant for years.
E.T. pallidum can infect the central nervous system (CNS) and result in neurosyphilis, which can occur at any stage of syphilis:
1.Early neurological clinical manifestations:
a.Cranial nerve dysfunction.
b.Meningitis.
c.Stroke.
d.Acute altered mental status.
e.Auditory or ophthalmic abnormalities.
2.Late neurological clinical manifestations:
a.Tabes dorsalis and general paresis occur 10 to 30 years after infection.
F.Congenital syphilis: Symptoms range from asymptomatic to fatal.
Subjective Data
A.Elicit history of onset, location, frequency, duration of symptoms; aggravating and alleviating factors; and associated symptomatology.
B.Question the patient about history of other STIs, illicit drug use, and sexual habits.
Physical Examination
A.Check temperature (if indicated), pulse, respirations, and blood pressure.
B.Inspect:
1.Inspect the skin; note lesions and rashes.
2.Observe the head; note patchy alopecia.
3.Ophthalmic examination.
4.Examine the mouth and throat; note lesions.
5.Inspect the perianal area, perineum, and vagina in women and underneath the foreskin in uncircumcised men to evaluate for mucosal lesions.
C.Palpate: Palpate the lymph nodes (neck, supraclavicular, axillary, epitrochlear, and inguinal regions).
D.Auscultate: Auscultate heart and lungs.
E.Neurologic exam:
1.Assess sensory functioning.
2.Test cranial nerves, first through twelfth.
Diagnostic Tests
A presumptive diagnosis of syphilis requires use of two tests: a nontreponemal test, venereal disease research laboratory (VDRL) or rapid plasma reagin (RPR), and a treponemal test, fluorescent treponemal antibody absorption (FTA-ABS). False-positive nontreponemal test results can be associated with various medical conditions and factors unrelated to syphilis including other
infections (e.g., HIV), autoimmune conditions, immunizations, injection drug use, and older age.
Evaluate for other STIs and HIV for patients presenting with syphilis.
A.Serology: Nontreponemal tests:
1.VDRL test.
2.RPR tests.
3.HIV.
Results are reactive (positive) or nonreactive (negative). Titers correlate with active disease and should be quantitative. These tests are equally valid but cannot be compared because of titer differences (RPR is slightly higher than VDRL). All reactive results require confirmation with treponemal tests.
B.Serology: Treponemal tests:
1.FTA-ABS test.
2.Microhemagglutination assay for antibody to T. pallidum.
Once FTA-AB for antibody to T. pallidum,VDRL, and RPR are reactive, these tests usually remain reactive for life.
C.Cerebrospinal fluid (CSF) tests (CSF cell count or protein and a reactive CSF-VDRL). No single test can be used to diagnose neurosyphilis in all instances. The diagnosis of neurosyphilis depends on a combination of a CSF test in the presence of reactive serologic test results and neurologic signs and symptoms.
D.Microscopy: T. pallidum cannot be seen with light microscopy; dark-field microscopy exam of the serous exudate from lesions is the definitive test for early syphilis. Properly equipped labs with specially trained personnel must be available for this test.
Differential Diagnoses
A.Syphilis.
B.HSV.
Plan
A.General interventions: Staging of the disease may be difficult but guides management decisions.
B. 
See Section III: Patient Teaching Guide Syphilis
:
1.Advise the patient to abstain from sexual activity until treatment is completed.
2.Inform the patient of Jarisch–Herxheimer reaction (acute fever, headache, myalgia) that may occur within the first 24 hours of treatment. Antipyretics may be prescribed to manage symptoms, but have not be proved to prevent this reaction. The Jarisch–Herxheimer reaction occurs most frequently among persons who have early syphilis, presumably because bacteria burdens are higher during these states
3.Discuss the importance of partner notification. Refer to the CDC website for the management of sex partners at www.cdc.gov/std/tg2015/syphilis.htm.
4.Stress the importance of complying with follow-up regimen.
C.Pharmaceutical therapy.
Penicillin G administered parenterally is the preferred drug for treating all persons in all stages of syphilis. There are no proven alternatives to penicillin available for treating neurosyphilis and congenital syphilis in pregnant women. Penicillin is also recommended, whenever possible, for persons with HIV infection.
1.Primary syphilis, secondary syphilis, early latent syphilis:
a.Adults: Benzathine penicillin G 2.4 million units injected intramuscular (IM) in a single dose.
2.Late latent syphilis, latent syphilis of unknown duration, late syphilis (manage with expert consultation):
a.Adults: Benzathine penicillin G 50,000 units/kg IM up to the adult dose of 2.4 million units, administered as three doses injected IM at 1-week intervals (total 150,000 units/kg to the adult dose of 7.2 million units).
3.Tertiary syphilis (manage with expert consultation). Tertiary syphilis refers to gummas and cardiovascular syphilis but not to neurosyphilis:
a.Persons who are not allergic to penicillin and have no evidence of neurosyphilis (i.e., normal CSF examination), should be treated with benzathine penicillin G 7.2 million units total, administered at three doses of 2.4 million units IM at 1-week intervals.
4.Neurosyphilis (manage with expert consultation):
a.Refer to the CDC guidelines for treatment at www.cdc.gov/std/tg2015/syphilis.htm#Neurosyphilis.
5.Refer to the CDC guidelines for recommendation of the management of persons who have a history of penicillin allergy located at www.cdc.gov/std/tg2015/pen-allergy.htm.
6.Pregnancy: Parenteral penicillin G is the only therapy with documented efficacy for syphilis during pregnancy. For pregnant patients with penicillin allergy, penicillin treatment after desensitization is recommended.
Follow-Up
A.Primary and secondary syphilis: Clinical and serologic exams should be conducted at 6 and 12 months. Absence of fourfold decrease at 3 months is indicative of treatment failure.
B.Latent syphilis: Clinical and serologic exams should be conducted at 6, 12, and 24 months. Absence of fourfold decrease within 12 to 24 months is indicative of treatment failure.
C.Tertiary syphilis: Minimal evidence regarding follow-up exists. Follow-up largely depends on nature of lesions.
D.Neurosyphilis: CSF examination should take place every 6 months until cell count is normal.
Consultation/Referral
A.Consult or refer the patient to a physician when the recommended treatment fails and patient noncompliance and reexposure have been ruled out, or when neurosyphilis is diagnosed.
Individual Considerations
A.Pregnancy:
1.Draw blood samples for RPR/VDRL from all prenatal patients.
2.Administer appropriate regimen of penicillin for the patient’s stage of syphilis. Consider a second dose of penicillin 1 week after the initial treatment.
3.Patients who are allergic to penicillin should be desensitized and treated with penicillin during pregnancy.
4.Follow-up: Perform serologic tests monthly until adequacy of treatment has been ensured.
5.The Jarisch–Herxheimer reaction may predispose women to premature labor or fetal distress if treatment occurs in the second half of the pregnancy. Advise these patients to immediately seek medical attention if they experience uterine contractions or changes in fetal movement.
6.Abortions and stillbirths are common.
B.Partners: Identify at-risk partners who have had sexual contact with the patient within these time frames:
1.Primary syphilis: 3 months plus duration of symptoms.
2.Secondary syphilis: 6 months plus duration of symptoms.
3.Early latent syphilis: 1 year.
C.Geriatric.
1.Dementia, tremors, and pupillary changes are the result of long-term untreated syphilis.
2.The CSF should be tested using the FTA-ABS test. The VDRL is usually not adequate.