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ContentsSynopsisCodesLook ForDiagnostic PearlsDifferential Diagnosis & PitfallsBest TestsManagement PearlsTherapyReferencesInformation for PatientsView all Images (234)
Secondary syphilis in Adult
See also in: Anogenital,Hair and Scalp,Oral Mucosal Lesion
Other Resources UpToDate PubMed

Secondary syphilis in Adult

See also in: Anogenital,Hair and Scalp,Oral Mucosal Lesion
Print Patient Handout Images (234)
Contributors: Susan Burgin MD, Belinda Tan MD, PhD, Lowell A. Goldsmith MD, MPH
Other Resources UpToDate PubMed


Syphilis (also known as lues) is a sexually transmitted infection (STI) caused by the bacterium Treponema pallidum and is characterized by a chronic, intermittent, clinical course. It is transmitted from person to person via direct contact with a syphilis ulcer during vaginal, anal, or oral sex. Hence, the locations for syphilitic ulcers include the vagina, cervix, penis, anus, rectum, lips, and inside of the mouth. Secondary syphilis is the second stage of the infection caused by the spirochete, which has spread throughout the entire body. It typically occurs approximately 1-3 months after the appearance of the primary syphilitic chancre.

Secondary syphilis usually presents with a generalized rash that includes the palms and soles. Condyloma lata may be seen in moist anogenital locations or in the mouth. They are teeming with spirochetes and are, therefore, extremely infectious. Symptoms may include malaise, appetite loss, fever, headache, stiff neck, myalgias, lacrimation, photophobia, red and painful eyes, back pain, arthralgias, pharyngitis, flu-like symptoms, pruritus (more common in immunocompromised patients), lymphadenopathy, splenomegaly, bursitis, and tenosynovitis. In late stages, blindness and epigastric pain may occur.

The lesions of secondary syphilis heal in 2-10 weeks, with or without treatment. If left untreated, up to 25% of patients will relapse within the first 2 years.

Ocular screening (eg, slit lamp examination) is advised for patients with suspected or proven syphilis.

The natural history of syphilis is as follows.

Primary stage:
  • Primary lesion develops 10-90 days (average of 3 weeks) after direct inoculation.
  • Primary lesion is a painless, asymptomatic papule, followed by ulceration (chancre) and regional lymphadenopathy.
  • Chancre lasts 3-6 weeks and heals spontaneously.
  • All patients with primary syphilis will go on to develop secondary syphilis if left untreated.
Secondary stage:
  • Characterized by hematogenous and lymphatic dissemination.
  • Wide range of clinical manifestations but dominated by mucocutaneous and prodromal symptoms 3-10 weeks after appearance of primary chancre.
  • Cutaneous manifestations – Generalized nonpruritic papulosquamous eruption including the palms and soles, with pink to violaceous, scaly papules. Patchy alopecia of the scalp is also observed in secondary syphilis.
  • Mucosal lesions – Ulcers, gray-colored plaques, and condyloma lata.
  • Prodromal symptoms – Fever, weight loss, malaise, lymphadenopathy, myalgias, and sore throat.
  • Malignant syphilis (lues maligna) is a rare noduloulcerative manifestation of secondary syphilis. A generalized eruption of papules and nodules progresses to pustules and then to ulcers with overlying thick or rupioid (darkly colored conical) crusts. Constitutional symptoms and generalized lymphadenopathy are usually seen. Most contemporary cases of malignant syphilis have been reported in the setting of underlying human immunodeficiency virus (HIV) infection.
  • Mucocutaneous manifestations and prodromal symptoms last 3-12 weeks and resolve spontaneously.
  • If left untreated, up to 25% of patients will relapse within the first 2 years.
Tertiary syphilis:
  • May appear months to years after secondary syphilis resolves and can involve the central nervous system, heart, bones, and skin.
According to the Centers for Disease Control and Prevention (CDC), primary and secondary syphilis rates have increased in the United States overall since 2005, primarily among men and particularly among men who have sex with men (MSM). Rates among men of all ages and races/ethnicities increased from 5.1 cases per 100 000 population in 2005 to 11.7 in 2014. An increased incidence of syphilis in the United States has been observed in black and Hispanic individuals, sex workers, individuals who sexually expose themselves to sex workers, and individuals with a history of other STIs and/or HIV.

Other related topics: Early Congenital Syphilis, Late Congenital Syphilis, Ocular Syphilis


A51.39 – Other secondary syphilis of skin

240557004 – Secondary syphilis

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

The following differential will be focused on the mucocutaneous findings of secondary syphilis.

  • Lichen planus – Very pruritic, associated with hepatitis C, violaceous, scaly papules; consider tissue biopsy.
  • Lichen amyloidosis – Monomorphous papules.
  • Pityriasis rosea – Look for herald patch, collarette of scale, and orientation of lesions (fir-tree pattern in skin tension lines).
  • Pityriasis rubra pilaris – Look for orange-red, waxy-like keratoderma of the palms and soles; consider tissue biopsy.
  • Guttate psoriasis – Systemic signs absent, palms and soles are spared; biopsy will aid in diagnosis.
  • Drug eruption – Cutaneous lesions of drug eruption tend to be different than those seen in syphilis. Drug eruptions often present with urticarial, exanthematous, or vesicular / bullous lesions. Eosinophilia on CBC and histology are often seen (but not an invariable finding). Look for nonsteroidal anti-inflammatory drugs, sulfonamides, and penicillin medication history.
  • Erythema multiforme – Characteristic target lesions (3 concentric colors that are round and well-demarcated) occur on the extremities more often than the trunk. Precipitating factors are infectious (herpes simplex virus, mycoplasma, etc) and usually not medication related.
  • Reactive arthritis (Reiter syndrome)
  • Tinea corporis – Check KOH.
  • Scabies – Check for scabies mite in mineral oil.
  • Sarcoidosis
  • Subacute cutaneous lupus erythematosus
Mucous membrane:
Patchy alopecia:

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Last Updated: 12/06/2017
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Secondary syphilis in Adult
See also in: Anogenital,Hair and Scalp,Oral Mucosal Lesion
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Secondary syphilis : Headache, Rash, Lymphadenopathy, Oral white plaque, Arthralgia, Myalgia, Pharyngitis, Sexual promiscuity, HIV+, Scaly papules
Clinical image of Secondary syphilis
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