Differential Diagnoses
The syphilitic chancre may be confused with genital herpes, chancroid (usually painful and uncommon in the United States), lymphogranuloma venereum, or neoplasm. Any genital ulcer should be considered a possible primary syphilitic lesion. Simultaneous evaluation for herpes simplex virus types 1 and 2 using PCR or culture should also be done in these cases.
Screening and/or Diagnostic Tests
Darkfield examinations and tests to detect T. pallidum directly from lesion exudate or tissue are the definitive methods for diagnosing early syphilis. Although no T. pallidum detection tests are commercially available, some laboratories provide locally developed and validated PCR tests for the detection of T. pallidum DNA. A presumptive diagnosis of syphilis requires use of two tests: a nontreponemal test (i.e., Venereal Disease Research Laboratory [VDRL] or Rapid Plasma Reagin [RPR]) and a treponemal test (i.e., fluorescent treponemal antibody absorbed [FTA-ABS] tests, the T. pallidum passive particle agglutination [TP-PA] assay, various enzyme immunoassays [EIAs], chemiluminescence immunoassays, immunoblots, or rapid treponemal assays). Although many treponemal-based tests are commercially available, only a few are approved for use in the United States. Use of only one type of serologic test is insufficient for diagnosis and can result in false-negative results in persons tested during primary syphilis and false-positive results in persons without syphilis. 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, pregnancy, injection-drug use, and older age. Therefore, persons with a reactive nontreponemal test should always receive a treponemal test to confirm the diagnosis of syphilis.
Well woman assessments should include screening, evaluation and counseling, and immunizations based on age and risk factors. Screening recommendations include: depression, obesity, alcohol misuse, HTN, tobacco use, Hep C, HIV infection, chlamydia, gonorrhea, sexually transmitted infection prevention, and intimate partner violence. These recommendations, based on age and risk factors, serve as a framework for care which may be provided by a single physician or a team of health care professionals.
Pathophysiology
Primary syphilis is characterized by ulceration and local lymphadenopathy. The primary syphilis ulcer or chancre containing the T pallidum spirochete is characterized by mononuclear leukocytic infiltration, macrophages, and lymphocytes. It heals spontaneously. The average time between infection with syphilis and the start of the first symptom is 21 days, but can range from 10 to 90 days. Syphilis blood test results will be negative during this time.
Secondary syphilis is caused by hematogenous spread of bacterium. This leads to a widespread vasculitis. The mucocutaneous lesions of secondary syphilis also contain treponemes. The reasons for the resolution of secondary syphilis are unclear but are likely to be related to a combination of macrophage-driven uptake of opsonized spirochetes and cell-mediated immunity. Symptoms last for 1 – 6 weeks (4-week average).
Perivascular infiltrates composed principally of lymphocytes, histiocytes (macrophages), and plasma cells, accompanied by varying degrees of endothelial cell swelling and proliferation, are the histologic hallmarks of primary and secondary syphilis lesions. Likewise, spirochetes are abundant in early syphilis lesions and often are observed in and around blood vessels and migrating from the dermis into the epidermis.
Most people with latent syphilis do not progress to late syphilis, although approximately 40% do progress. The argument that cell-mediated immunity is important in the control of T pallidum is supported by the observation that progression to neurosyphilis may be more common in patients coinfected with HIV. The interval between the resolution of secondary SX’s (up to 6.5 months after infection/exposure), and one year after infection/exposure. Late syphilis with clinical manifestations other than neurosyphilis becomes evident 15‐30 years after infection.
The hallmark of gummatous syphilis is the nodules that arise within skin, liver, bones, and testes, consisting of granulomatous rubbery tissue with a necrotic center. The destructive gumma may gradually replace normal tissue. Treponemes are rarely found within these lesions.
Neurosyphilis may occur at any stage of infection with syphilis, and may occur in up to 10% of patients with untreated syphilis. [16] Neurosyphilis is characterized by a chronic, insidious inflammation of the meninges and is caused by CNS invasion by treponemes. Early neurosyphilis syndromes are usually the result of meningovascular involvement; late neurosyphilis may occur due to meningovascular involvement or direct infection of the brain and spinal cord parenchyma. Parenchymal infection of the spinal cord by T pallidum results in tabes dorsalis. This condition is predominantly due to dorsal column loss. General paresis occurs with parenchymal involvement of the brain with neuronal loss.
Cardiovascular syphilis is characterized by aortic involvement as treponemes cause occlusion of the aortic vasa vasorum resulting in necrosis of the tunica media. Long-term inflammation and scarring weakens the aortic wall, leading to aneurysm formation, as well as aortic incompetence and angina due to narrowing of the coronary ostia.
Evidence-Based Treatment Guidelines
Antibiotic Therapy
Penicillin remains the preferred treatment for syphilis, since there have been no documented cases of penicillin resistant T pallidum. Benzathine penicillin G 2.4 million units IM in a single dose is the recommended regimen for adults. Data to support use of alternatives to penicillin in the treatment of primary and secondary syphilis are limited. However, several therapies might be effective in nonpregnant, penicillin-allergic persons who have primary or secondary syphilis. Regimens of doxycycline 100 mg orally twice daily for 14 days and tetracycline (500 mg four times daily for 14 days) have been used for many years. Compliance is likely to be better with doxycycline than tetracycline, because tetracycline can cause gastrointestinal side effects and requires more frequent dosing. Although limited clinical studies, along with biologic and pharmacologic evidence, suggest that ceftriaxone (1–2 g daily either IM or IV for 10–14 days) is effective for treating primary and secondary syphilis, the optimal dose and duration of ceftriaxone therapy have not been defined.
Public Health Measures
Patients with infectious syphilis must abstain from sexual activity for 7–10 days after treatment. All cases of syphilis must be reported to the appropriate local public health agency in order to identify and treat sexual contacts. In addition, all patients with syphilis should have an HIV test at the time of diagnosis. In areas of high HIV prevalence, a repeat HIV test should be performed in 3 months if the initial test result was negative.
Treating Syphilis Contacts
Patients who have been sexually exposed to infectious syphilis within the preceding 3 months may be infected but seronegative and thus should be treated as for early syphilis even if serologic tests are negative. Persons exposed more than 3 months previously should be treated based on serologic results; however, if the patient is unreliable for followup, empiric therapy is indicated.
Patient Education Plan
Patient counseling and education should cover the nature of the disease, transmission, treatment, follow-up, and risk reduction. Avoidance of sexual contact is the only completely reliable method of prevention but is an impractical public health measure. Latex or polyurethane condoms are effective but protect covered areas only. Patients treated for other sexually transmitted diseases should also be tested for syphilis, and persons who have known or suspected sexual contact with patients who have syphilis should be evaluated and presumptively treated to abort development of infectious syphilis.
Discuss the importance of abstaining from sexual activity until she and her partner are cured, and of using condoms to prevent reinfection. Explain the need to return for follow-up testing in 3 months and again at 6 months. Provide a copy of the STI prevention checklist, and document that reminders need to be sent at 3- and 6-month intervals. Notify sexual partners that they need to come to the clinic for testing. Refer to a social worker for counseling about the impact of the disease on their relationship.
Conclusion
Syphilis remains an important public health problem that is regularly encountered by clinicians working in a range of settings. It remains common in LMICs and rates are increasing in higher-income countries, particularly among MSM. Without a high index of suspicion and familiarity with the infection’s protean manifestations, syphilis diagnosis is sometimes missed. Obstetrician–gynecologists have the opportunity to provide holistic care for their patients. This includes taking a comprehensive history, diagnosing and treating conditions that are identified with a comprehensive history and focused examinations, and providing evidence-based and evidence-informed clinical preventive services. Although components of a physical examination may not be required at a well-woman visit, obstetrician–gynecologists can play a critical role in engaging patients in shared decision making, encouraging and facilitating healthy behaviors, and counseling about a wide array of effective preventive health practice.
Sample Solution