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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
Contributors: David O'Connell MD, Samantha R. Pop MD, Belinda Tan MD, PhD, Susan Burgin MD
Other Resources UpToDate PubMed


Syphilis (also known as lues) is a sexually transmitted infection (STI) caused by the spirochete Treponema pallidum. Treponema pallidum is transmitted from person to person through contact with infectious lesions during vaginal, anal, or oral sexual activity, especially when there is disrupted epithelium, such as from minor trauma. Secondary syphilis is the second stage of the infection.

The natural history of syphilis is as follows:

Primary stage:
    • Primary lesion develops 10-90 days (average of 21 days) after direct inoculation.
    • Primary lesion is typically a painless, asymptomatic papule, followed by a painless ulcer (chancre) and regional lymphadenopathy.
    • Chancre lasts 3-6 weeks and heals spontaneously.
    • Locations for chancres may include the vagina, cervix, penis, anus, rectum, lips, and inside of the mouth.
      Secondary stage:
      • Secondary syphilis is caused by hematogenous dissemination of bacteria.
      • A wide range of clinical manifestations, dominated by prodromal symptoms and mucocutaneous manifestations 3-10 weeks after the appearance of the primary chancre.
      • Prodromal symptoms and signs – Malaise, appetite loss, fever, headache, stiff neck, myalgias, pharyngitis, and flu-like symptoms. Generalized lymphadenopathy is typically present.
      • Cutaneous manifestations – Generalized nonpruritic papulosquamous eruption including the palms and soles, with pink, violaceous, or copper-colored papules, each with a collarette of scale. Patchy alopecia of the scalp is also observed in secondary syphilis.
      • Mucosal lesions – Mucous patches and "snail-track" ulcers in the mouth, and condyloma lata (gray, flat, moist papules and plaques) may be seen in moist anogenital locations or, more rarely, in the folds. They are teeming with spirochetes and are, therefore, extremely infectious.
      • Ocular symptoms may include lacrimation, photophobia, and red, painful eyes.
      • Malignant syphilis (lues maligna) is a rare, noduloulcerative manifestation of secondary syphilis. A generalized eruption of papules and nodules progresses to painful, necrotic ulcers that may have overlying thick or rupioid (darkly colored and conical) crusts. Constitutional symptoms and generalized lymphadenopathy are usually seen. Most contemporary cases of malignant syphilis have been reported in the setting of underlying 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.
      Per the US Centers for Disease Control and Prevention (CDC), the majority of reported male primary and secondary syphilis cases where sex of sex partner is known are among men who have sex with men. An increased incidence of syphilis is associated with HIV positivity.

      Immunocompromised patient considerations: HIV infection can alter the clinical presentation of syphilis. Manifestations include multiple chancres, atypical cutaneous eruptions, increased severity of organ involvement (such as hepatitis and glomerulonephritis), and rapidly developing arteritis and neurosyphilis. Neurosyphilis can occur at any stage of syphilis.

      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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      Differential Diagnosis & Pitfalls

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

      • 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.
      • Lichen planus – Very pruritic, violaceous, scaly papules, associated with hepatitis C; consider tissue biopsy.
      • Lichen amyloidosis – Monomorphous papules.
      • Drug eruption general overview – Cutaneous lesions of drug eruption tend to be different than those seen in syphilis. Drug eruptions often present with urticarial, Exanthematous drug eruption, or vesicular / Bullous drug eruption lesions. Eosinophilia on CBC and histology are often seen (but eosinophilia is not an invariable finding). Look for NSAIDs, sulfonamides, and penicillin on 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 (eg, herpes simplex virus, mycoplasma) and usually not medication related.
      • Keratoderma blenorrhagica of Reactive arthritis (Reiter syndrome)
      • Tinea corporis – Check potassium hydroxide (KOH) test.
      • Scabies – Check for scabies mites in mineral oil.
      • Sarcoidosis
      • Subacute cutaneous lupus erythematosus
      Oral ulcers:
      • Orofacial herpes simplex virus
      • Aphthous stomatitis
      • Oral erythroplakia
      • Erosions due to Oral candidiasis
      • Oral lichen planus
      • Oral mucosal wart
      • Mucosal Lichen planus
      Genital ulcers:
      • Oral mucosal wart
      • Mucosal Lichen planus
      • Cutaneous Vulvovaginal candidiasis
      • Seborrheic keratosis
      • Extramammary Paget disease
      • Mpox
      Patchy alopecia:
      • Alopecia areata
      • Traction alopecia

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      Last Reviewed:08/24/2020
      Last Updated:09/05/2023
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      Patient Information for Secondary syphilis in Adult
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      Secondary syphilis in Adult
      See also in: Anogenital,Hair and Scalp,Oral Mucosal Lesion
      A medical illustration showing key findings of Secondary syphilis : Fever, Headache, Lymphadenopathy, Malaise, Oral white plaque, Widespread distribution, Arthralgia, Multiple sexual partners, Myalgia, Pharyngitis, Stiff neck
      Clinical image of Secondary syphilis - imageId=2848052. Click to open in gallery.  caption: 'Multiple brown papules and small plaques, some with overlying thick scales and others with collarettes, on the palm.'
      Multiple brown papules and small plaques, some with overlying thick scales and others with collarettes, on the palm.
      Copyright © 2024 VisualDx®. All rights reserved.