April 2015 Dermatology Clinic
An African American man, aged 45 years, presented for evaluation of new lesions on the palms and soles. He reported that the rash began three weeks ago as “dark spots.” Over time, the lesions developed a scaly appearance. The lesions were asymptomatic. His medical history was notable for a recent diagnosis of human immunodeficiency virus infection. Physical examination revealed hyperpigmented macules and thin papules, many with collarettes of scale, that were scattered over the palmar and plantar surfaces. The oral and genital mucosal surfaces were not involved.
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Syphilis is an infectious disease caused by the spirochete Treponema pallidum. The majority of cases of syphilis in adults are attributed to intimate contact such as oral, anal, or genital sex.1
An understanding of syphilis remains relevant to clinical practice today as syphilis continues to be a public health concern. Diagnoses of the disease in the United States have rapidly increased following a historic low in 2000.2 Between 2005 and 2013, the number of cases of primary and secondary syphilis reported annually increased from 8,724 to 16,663.2 Men who have sex with men represent a rising proportion of these new syphilis cases, likely as a result of human immunodeficiency virus (HIV) infection and high-risk sexual behaviors.3
Health care providers should be aware of the basics of syphilitic staging and the associated cutaneous findings at each stage. The manifestations of symptomatic syphilis are classically divided into primary, secondary, and tertiary stages. Staging hinges upon both clinical findings and symptoms and the time since initial infection.3 Symptoms of primary and secondary syphilis manifest within one year of infection, whereas those of tertiary syphilis are notable more than one year after infection.3
From a cutaneous standpoint, primary syphilis is characterized by the development of a well-demarcated, painless ulcer known as a chancre.1 The chancre represents the site at which the spirochete entered the host; it is most often located on the external genitalia and appears between one week and three months after initial exposure.1 Although the chancre is classically an isolated lesion, multiple chancres have been reported in patients who are co-infected with HIV.4 Resolution typically occurs within three weeks even in the absence of treatment.1
Secondary syphilis presents between four and 10 weeks after infection; this stage may overlap with primary syphilis.4 Secondary syphilis may present with a myriad of cutaneous findings in combination with systemic findings such as fever, headache, malaise, pharyngitis, and painless lymphadenopathy.5 The early cutaneous findings of secondary syphilis include erythematous to copper-colored or hyperpigmented macules. These macules may affect the trunk and extremities with palmoplantar involvement seen in at least 50% of cases.4 Later in secondary syphilis, the rash is classically papular or papulosquamous and involves the trunk and extremities.5 Numerous other cutaneous findings may be seen in secondary syphilis, including but not limited to a “moth-eaten” alopecia, condyloma lata, photodistributed eruptions, and nodular, annular, and pustular lesions.5 Although widely variable in clinical presentation, the cutaneous findings of secondary syphilis are not vesicular.4 Secondary syphilis will resolve without treatment, but recurrences are common.4
Tertiary syphilis is an uncommon stage of syphilis that occurs more than one year after infection. Cardiovascular complications, such as aortitis and the formation of aneurysms, and neurological complications are characteristic of this stage of disease.1 Skin involvement is infrequent; however, granulomatous, destructive lesions called gummas may affect the skin, along with any other organ of the body.1
The differential diagnosis of syphilis is broad and varies depending on the syphilitic stage. Primary syphilis must be distinguished from other causes of genital ulceration such as herpes simplex virus, chancroid, lymphogranuloma venereum, neoplasia, and trauma.1 Secondary syphilis may be confused with pityriasis rosea or lichen planus. However, if palmoplantar involvement is prominent, then other rashes that characteristically involve the palms and soles should be considered such as Rocky Mountain spotted fever, measles, and hand, foot, and mouth disease.1 Finally, in tertiary syphilis, gummas may be mistaken for mycosis fungoides, sarcoidosis, tuberculosis, or Hodgkin disease.1
Given the wide range of cutaneous findings associated with syphilis, clinical diagnosis should be confirmed with supportive serologic assays.1 Screening conventionally begins with a nontreponemal test such as rapid plasma reagin (RPR) or the venereal disease research laboratory (VDRL) test. These tests identify antibodies to nonspecific antigens produced by the body in response to the foreign spirochete.1 Nontreponemal tests are 86% and 100% sensitive for primary and secondary syphilis, respectively.1 Although relatively specific, nontreponemal tests may be falsely positive in the setting of infection, chronic liver disease, and autoimmune disease.1 Nontreponemal tests correlate with disease activity and thus provide a means for monitoring disease activity and treatment response.1 Treponemal tests include the Treponema pallidum particle agglutination (TPPA), Treponema pallidum hemagglutination, and fluorescent treponemal antibody absorption (FTA-ABS) tests. These tests detect antibodies to specific components of Treponema pallidum and therefore can be used as a follow-up to a positive nontreponemal test to exclude a false-positive result.1 Treponemal tests tend to remain positive for life and thus should not be used to monitor disease activity.1
Penicillin is the preferred treatment for syphilis, but dosing varies based on disease stage.3 A single intramuscular injection of 2.4 million units of benzathine penicillin G (BPG) is recommended for the treatment of primary and secondary syphilis.3 Treatment of tertiary syphilis varies depending on involvement of the central nervous system and thus coordinating care with an infectious disease specialist may be beneficial. All individuals with syphilis should also be screened for HIV.6 Although serologic treatment failure may be more likely in HIV-infected individuals, those with primary or secondary syphilis have the same treatment recommendations as HIV-negative patients with primary or secondary syphilis.6
In our case, a clinical diagnosis of secondary syphilis was supported by both the presence of a newly elevated RPR titer (i.e., nonreactive on prior screening two months before presentation) and a reactive TPPA test. The patient did not recall a chancre but reported several “rashes” on the penis over the preceding one to two months. He was treated with intramuscular BPG (2.4 million units) with full resolution of the palmoplantar lesions six weeks later. The patient will continue seeing an infectious disease specialist to monitor his RPR titer and manage his HIV infection.
Jennifer Ruth, MD, is a third-year dermatology resident at Baylor College of Medicine in Houston.
- Cohen SE, Klausner JD, Engelman J, Philip S. Syphilis in the modern era: an update for physicians. Infect Dis Clin North Am. 2013;27(4):705-722.
- Patton ME, Su JR, Nelson R, Weinstock H; Centers for Disease Control and Prevention. Primary and secondary syphilis—United States, 2005-2013. MMWR Morb Mortal Wkly Rep. 2014;63(18):402-406. Available at cdc.gov/mmwr/preview/mmwrhtml/mm6318a4.htm
- Clement ME, Okeke NL, Hicks CB. Treatment of syphilis: a systematic review. JAMA. 2014;312(18):1905-1917.
- Zetola NM, Engelman J, Jensen TP, Klausner JD. Syphilis in the United States: an update for clinicians with an emphasis on HIV coinfection. Mayo Clin Proc. 2007;82(9):1091-1102. Available at mayoclinicproceedings.org/article/S0025-6196(11)61371-2/fulltext
- Balagula Y, Mattei PL, Wisco OJ, et al. The great imitator revisited: the spectrum of atypical cutaneous manifestations of secondary syphilis. Int J Dermatol. 2014;53(12):1434-1441.
- Workowski KA, Berman S; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010;59(RR-12):1-110. Available at cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm
All electronic documents accessed on March 30, 2015.