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The Great Imitator Revealed: Syphilis

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The Great Imitator Revealed: Syphilis Syphilis Volume 27 Issue 2 May 2019 Perspective The Great Imitator Revealed: Syphilis Rates of syphilis and other sexually transmitted infections are on the rise in the infections, some autoimmune condi- United States. The lesions of early syphilis can be mistaken for those of other tions, trauma, and malignancy. infections and conditions, and syphilis should be suspected in all sexually active When dark-field microscopy exam- patients presenting with a new skin rash or an oral or genital lesion. Rapid dia- ination of a syphilis lesion reveals un- gnosis and treatment of syphilis as well as rapid identification and treatment of dulating treponemes (Treponema palli- sexual contacts are needed to reverse the trend of increasing incidence. Avail- dum organisms, the cause of syphilis), a able data indicate success in reducing acquisition of syphilis with doxycycline diagnosis of primary syphilis is likely. pre- and postexposure prophylaxis. This article is based on a presentation by Figure 3 shows examples of clinical Jeffrey D. Klausner, MD, MPH, at the 2018 Clinical Conference at the National lesions positive for syphilis using dark- Ryan White Conference on HIV Care & Treatment in December 2018. field microscopy that could be mis- taken for genital herpes or chancroid. Keywords: syphilis, treatment, HIV, primary syphilis, secondary syphilis, latent For uncircumcised individuals, it is im- syphilis, prophylaxis, preexposure, postexposure portant to roll back the foreskin and examine the coronal sulcus. Epidemiology babies born with congenital syphilis According to Centers for Disease Con- over the same period. Some of that trol and Prevention (CDC) STD treat- Rates of sexually transmitted infec- increase is associated with the loss of ment guidelines, early syphilis of less tions (STIs) are increasing dramatically local public health capacity. Although than 1-year duration (ie, primary, sec- in the United States, including among health care practitioners may be test- ondary, or early latent syphilis) should newborns. As shown in Figure 1, rates ing individuals for syphilis, positive test be treated with a single intramuscular of primary and secondary syphilis in results are not being acted on in the (IM) injection of benzathine penicillin the United States are the highest since same manner as in the past by local G 2.4 MU, regardless of HIV serosta- 1994, a reversal of the dramatic de- public health departments. Patients tus. However, 3 injections of benza- cline observed with the emergence may not be coming back for treatment thine penicillin G 2.4 MU are recom- of HIV infection and resultant changes and sexual contacts are not being sought mended for individuals who have had in many individuals’ sexual behaviors.1 for testing and treatment. syphilis for more than 1 year. The effi- The recent increase in syphilis rates is cacy of single-dose benzathine penicil- likely multifactorial, including increases lin G for treatment of syphilis was re- in high-risk sexual behaviors, decreased Primary Syphilis confirmed in a study in Tanzania (more fear of HIV infection, substantial de- When a patient presents with a new than half of participants had HIV infec- clines in condom use among adults and oral or anogenital lesion, there must tion), in which the proportion cured adolescents, and a marked decline in be suspicion for STIs such as primary was 95% at 9 months.2 public health prevention services. Many syphilis, genital herpes, and chancroid, Any sexual contacts who may have counties and jurisdictions no longer although the latter is rare in the United been exposed within the past 90 days have sufficient staff or resources to per- States. Other potential causes of genital should receive prophylactic treatment form follow-up of individuals with syph- ulcers include fixed drug eruptions (eg, with a single injection of benzathine ilis and their sexual contacts, to support reactions to drugs, such as doxycy- penicillin G 2.4 MU. Medical practitio- prevention and education campaigns, line or nonsteroidal anti-inflammatory ners should make a reasonable effort or to promote syphilis testing in target drugs), staphylococcal or streptococcal to notify all sexual contacts exposed populations. Figure 2A shows the incidence of primary and secondary cases of syphi- 30 lis (acquired in the past 6 months) in 37 states between 2013 and 2017. Cases 20 of syphilis nearly doubled among men who have sex with men (MSM), and increased among women and among Cases per 10 men who have sex with women. The Population 100,000 increase in cases of syphilis among 0 women translated into an increase in 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 Year Dr Klausner is Professor of Medicine and Public Health at the University of California Figure 1. New cases of primary and secondary syphilis in the United States, 1956 to 2016. Los Angeles in Los Angeles, California. Adapted from Kojima et al.1 71 IAS–USA Topics in Antiviral Medicine A B Primary and Secondary Syphilis Primary and Secondary Syphilis 15,000 1,000 CS cases P&S rate 8 Cases Women per 100,000 7 12,500 800 6 10,000 MSM 600 5 7,500 4 400 3 5,000 Number of Cases Syphilis Cases 2 MSW 2,500 200 Women Number of Congenital 1 0 0 0 2013 2014 2015 2016 2017 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 Year Year Figure 2. A: Cases of primary and secondary (P&S) syphilis in 37 states, 2013 to 2017. Of note, 37 states were able to classify 70% or more of reported cases of P&S syphilis as either men who have sex with men (MSM), men who have sex with women only (MSW), or women for each year between 2013 and 2017. B: Cases of P&S syphilis among women aged 15 to 44 years and cases of congenital syphilis (CS) in the United States, 2008 to 2017. Adapted from the US Centers for Disease Control 2017 Sexually Transmitted Disease Surveillance Report. in the past 90 days. Although health de- strongly recommended—to contact the The rapid TP test is a 10-minute point-of- partments have often performed such county or state public health depart- care assay that can be used in the clinic. notifications in the past, some of them ment and check if a patient with sus- It is more sensitive than and becomes have been defunded or lost staff, and pected latent syphilis is entered in the positive earlier than an RPR test. Posi- do not have the same resources they syphilis reactor registry, which may con- tive treponemal test results indicate had 10 or 20 years ago. tain details of any prior reports on the past or current infection. Treponemal patient. antibodies may remain detectable for Secondary Syphilis According to CDC guidelines, the re- life, although about 15% of people might commended treatment for latent syph- actually become seronegative if treated Figure 4 shows a rash associated with ilis of unknown duration is a weekly IM early. In practice, it is prudent to order secondary syphilis on the chest and injection of benzathine penicillin G 2.4 both a nontreponemal test and a trepo- back that consists of nonspecific mac- MU for 3 weeks. Sexual contacts within nemal test to ensure the best likelihood ulopapular lesions. In addition to sec- the prior 90 days should be found and of obtaining serologic confirmation. ondary syphilis, the differential diagno- treated with prophylactic benzathine sis of such a trunk rash includes viral penicillin G, and contacts within the Neurosyphilis exanthem, including acute HIV infec- past 12 months should be notified and tion; pityriasis rosea; drug eruption; tested. Indications for analysis of cerebrospinal lichen planus; psoriasis; and sarcoid- Given the absence of signs and sym- fluid (CSF) in CDC treatment guidelines osis. Examination of the palms and ptoms in latent syphilis, diagnosis de- include neurologic findings (including soles in Figure 4 shows classic ery- pends on syphilis testing. Nontrepo- auditory findings); ocular abnormalities thematous, somewhat copper-colored nemal tests, such as the rapid plasma (including visual loss, uveitis); tertiary lesions. Presence of a palmar-plantar reagin (RPR) and Venereal Disease Re- disease (eg, dementia, aortic disease, rash is indicative of secondary syphilis. search Laboratory tests, detect antibody gumma); and treatment failure (lack of Other, rarer causes include erythema to cardiolipin, with levels rising and fall- 4-fold decline at 6 [early], 12 [late or multiforme or Rocky Mountain spot- ing with infection and treatment over HIV-infected early], or 24 [HIV-infected ted fever. time. A 4-fold change in titer (1:2 to 1:8 late] months). The CSF can serve as a Oral and other secondary lesions in or 1:64 to 1:16) is significant. Those tests sanctuary for untreated infection. Neu- syphilis are shown in Figure 5, including have a specificity of 98%, with false- rosyphilis in early disease can cause split papules, “moth-eaten” alopecia, positive results seen in injection drug meningovascular syndrome and stroke. mucous patches, and condyloma lata. users, some autoimmune conditions, The most common presentations of The split papule presentation can be viral infections and in cases of recent neurosyphilis are the different mani- mistaken for oral herpes labialis. The vaccination.4 festations of ocular syphilis, with the white plaque lesions can be mistaken Treponemal tests are more specific, primary complaint of red eye, blurry for thrush or oral hairy leukoplakia. including the T. pallidum particle agglu- vision or decreased visual acuity fol- tination assay, fluorescent treponemal lowed by hearing loss. CSF analysis Latent Syphilis antibody absorption test, T. pallidum helps rule out other conditions and enzyme immunoassay (TP EIA), and provides a baseline for following CSF Latent syphilis presents with no signs, rapid treponemal test, each of which titers to determine if there is improve- symptoms, or sores.
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