Publish date: Posted on
Last updated: November 27, 2024
Keywords #
syphilis
T. pallidum
lues
sexually transmitted infection
chancre
gumma
Diagnosis #
Syphilis is an infection caused by the spirochete Treponema pallidum transmitted via direct contact with an infectious lesion during sexual intercourse. T. pallidum can infect any tissue on which inoculation occurs. T. pallidum is also capable of crossing the placenta and causing fetal infection. [1] Untreated syphilis progresses through three stages: primary, secondary, latent, and tertiary; the features of which are described in detail under “clinical manifestations.”
Key Concepts #
- Syphilis is on the rise both in the United States and worldwide.
- Untreated syphilis has significant morbidity and mortality.
- Cutaneous findings in syphilis are often the presenting sign prompting patients to seek care from a dermatologist. With timely diagnosis, treatment is simple and curative with antibiotics.
Epidemiology #
Syphilis has been listed in the Unites States as a nationally notifiable disease since 1944. Following the introduction of penicillin as a treatment for syphilis in 1943, infection rates plummeted until hitting a nadir in 2000. Since then, there has been a steady rise of primary and secondary syphilis each year until a steep upturn started in 2014. From 2014 to 2018, rates of primary and secondary syphilis increased 71.4%. Of the primary and secondary syphilis cases reported in 2018, men account for 85.7% of cases. The majority of primary and secondary syphilis cases occur among gay, bisexual and other men who have sex with men (MSM). There’s a high rate of HIV co-infection among MSM (~42%) and use of Truvada (tenofovir plus emtricitabine – pre-exposure prophylaxis for HIV) has been shown to significantly increase rates of syphilis, chlamydia, and gonorrhea. Infection rates in women increased by 172.7% from 2014-2018. Blacks are 4.7 times as likely to be diagnosed with primary or secondary syphilis than whites. In 2018, the CDC reported there were 30,065 cases of primary and secondary syphilis yielding a rate of 10.8 cases per 100,000 population. Rates of congenital syphilis and syphilitic stillbirths are also on the rise and there were 1,306 cases reported in 2018.[2]
Clinical Features #
Primary syphilis typically develops within 90 days (3 weeks on average) of infection and presents as a painless, round, well-circumscribed, indurated ulcer at the site of inoculation called a chancre.
- The chancre may go unnoticed by the patient, particularly when the site of inoculation involves the vaginal mucosae, cervix, anus or posterior pharynx.
- There may be associated regional lymphadenopathy.
- Within six weeks of their appearance and without intervention, chancres spontaneously heal. Resolution of the chancre marks hematogenous dissemination of spirochetes throughout the body.
Secondary syphilis develops 3-10 weeks after the chancre appears and manifests as the consequence of hematogenous dissemination of treponemes. [3]
- Common signs and symptoms of this systemic involvement include fever, headache, sore throat, weight loss, adenopathy, myalgias, arthralgias, hepatitis, glomerulonephritis, and conjunctivitis.
- While cutaneous findings vary, the most common clinical presentation is a widespread, nonpruritic, copper-colored papulosquamous eruption involving the palms and soles.
- Other cutaneous manifestations include: condyloma lata, nonscarring patchy alopecia, split papules at oral commissures, superficial mucosal ulcers, annular plaques with central hyperpigmentation on the face, granulomatous nodules and plaques, crusted necrotic lesions.
- Lues maligna, rarely observed but most often seen in HIV co-infected individuals, as widespread ulcerative lesions. [3]
Secondary syphilis is also self-limited usually resolving over weeks to months with occasional relapse (20%) if left untreated.
Resolution of secondary syphilis marks the development of latent syphilis, an asymptomatic stage. Early latent syphilis is defined by the first year of infection wherein 90% of relapses to secondary syphilis will occur. Late latent syphilis begins after the first year of infection and may last months to years. Only one third of patients who develop late latent syphilis will go on to demonstrate clinical signs of tertiary syphilis.
Tertiary syphilis is a rare consequence of untreated syphilis that can develop up to 30 years after the primary infection.
- There are a number of clinical presentations of tertiary syphilis with variable morbidity and mortality involving the skin, bones, central nervous system, heart and great vessels.
- About half of the patients develop “benign” late syphilis which is marked by nodular arciform or serpiginous lesions that may ulcerate called gummas. These can be found in skin and bones as well as other internal organs.
- The other half of patients with tertiary syphilis can develop cardiovascular syphilis or neurosyphilis, both with significant morbidity and mortality. These patients should be co-managed with infectious disease to arrange appropriate workup.
Differential Diagnoses #
- In primary syphilis, all causes of genital ulcers should be considered: genital herpes, trauma, fixed drug eruption, carcinoma, chancroid, lymphogranuloma venereum, primary EBV infection and Behcet disease.
- Secondary syphilis is known as “the great mimicker” as it can have a large variety of dermatologic manifestations. Differential diagnoses for more classic findings of cutaneous secondary syphilis include pityriasis rosea, guttate psoriasis, viral exanthem, lichen planus, pityriasis lichenoides chronica, primary HIV infection, drug eruption, nummular eczema, and folliculitis.
- Differential diagnoses for cutaneous tertiary syphilis include lupus vulgaris, chromoblastomycosis, dimorphic fungal infections, leishmaniasis, lupus erythematosus, mycosis fungoides, sarcoidosis, tumors and venous ulcers.
The differential diagnosis for syphilis depends on stage.
Diagnostic Workup #
Testing should be performed on any patient with signs or symptoms of syphilis, men who have sex with men, HIV-infected individuals, and pregnant patients. The most common method of diagnosis is via serologic testing, which consists of treponemal and non-treponemal studies.
Nontreponemal serologic tests measure the host’s response (IgM and IgG antibodies) to non-treponemal antigens. These include venereal disease research laboratory (VDRL) and rapid plasma regain (RPR). These tests are semi-quantitative as the amount of antibody present (reported as a titer) generally correlates with activity of infection and therefore can be used in both screening of acute infection and monitoring for treatment response. It’s important to note that there is a 2 week “window period” following inoculation during which neither IgM nor IgG antibody are detectable yet resulting in a false negative result. False positive rate for RPR and VDRL is ~1%.
Treponemal serologic tests use treponemal specific antigens to detect the presence of antibodies against T. pallidum in patient serum. These include Fluorescent treponemal antibody absorption (FTA-Abs), Treponema pallidum hemagglutination (TPHA), Treponema pallidum particle agglutination (TPPA), treponema pallidum enzyme immunoassay (TP-EIA) and treponema pallidum chemiluminescence immunoassay (TP-CIA). Treponemal serologic testing is more specific, remains positive indefinitely after infection and is often used as a confirmatory test following a positive non-treponemal study. However, since 2009, the CDC recommends consideration for using TP-EIA for screening in high-risk populations with RPR as confirmation of acute infection. TP-EIA and TP-CIA are qualitative tests more sensitive to early and late latent syphilis then RPR or VDRL.
All patients diagnosed with syphilis need to be reported to the state Department of Health.
Treatment #
The recommended treatment for primary, secondary, and early latent syphilis is a single intramuscular injection of Benzathine penicillin, 2.4 million units. If patients with a penicillin allergy are not amenable to de-sensitization, additional treatment options include doxycycline, tetracycline, azithromycin and ceftriaxone. Late latent syphilis requires three weekly doses of Benzathine penicillin and neurosyphilis requires IV penicillin. Most skin lesions will heal promptly with treatment. Patients with a high treponemal burden may experience a Jarisch-Herxheimer reaction with treatment which manifests as fever, headache, myalgias and hypotension. Sexual partner treatment should be arranged in conjunction with local health department officials.
Slide Viewer #
https://utahderm.med.utah.edu/image-viewer/References #
- Bolognia JL. Chapter 82: Sexually transmitted infections. In: Dermatology. Volume 2. 4th ed. London: Mosby; 2018.
- Syphilis – 2018 Sexually Transmitted Diseases Surveillance. Centers for Disease Control and Prevention. https://www.cdc.gov/std/stats18/syphilis.htm. Published October 1, 2019. Accessed April 20, 2020.
- Baughn RE, Musher DM. Secondary Syphilitic Lesions. Clinical Microbiology Reviews. 2005;18(1):205-216. doi:10.1128/cmr.18.1.205-216.2005.
- Soreng K, Levy R, Fakile Y. Serologic Testing for Syphilis: Benefits and Challenges of a Reverse Algorithm. Clinical Microbiology Newsletter. 2014;36(24):195-202. doi:10.1016/j.clinmicnews.2014.12.001.
