A 27-year-old man comes to the office due to a 2-week history of genital papules that are not painful or pruritic. Over this period, he has also had fatigue and mild, generalized arthralgia but no urethral discharge or dysuria. The patient had gonococcal urethritis 3 months ago, which was adequately treated, and tests for other sexually transmitted infections at that time were negative. He is sexually active with several male and female partners and reports using condoms consistently after the episode of gonorrhea. Temperature is 37.6 C (99.6 F). Physical examination shows a faint, diffuse maculopapular skin rash involving the trunk, extremities, palms, and soles. There are several enlarged, nontender inguinal lymph nodes. Genital examination reveals multiple elevated lesions on the scrotum and perineal region. Histopathologic evaluation of these lesions would most likely reveal which of the following in this patient?
Syphilis manifestations | |
Primary |
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Secondary |
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Latent |
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Tertiary |
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CNS = central nervous system. | |
Secondary syphilis is characterized by the spread of the causative spirochete, Treponema pallidum, through the blood to the skin and mucosal surfaces. Patients usually have a diffuse maculopapular skin rash that includes the palms and soles. They may also develop condylomata lata, which are painless, wart-like, elevated plaques, on moist areas of the skin such as the scrotum and perineum. Lymphadenopathy, fatigue, arthralgias, and mild fever are also common. Histopathologic examination of syphilitic lesions (at all stages) classically demonstrates proliferative endarteritis of small vessels with a surrounding plasma cell–rich infiltrate.
This patient was likely infected with syphilis at the same time he was infected with gonorrhea (coinfection is common). Serologic testing for syphilis (eg, rapid plasma reagin) is often falsely negative in early infection due to lag time between acquisition of T pallidum and the development of a measurable humoral antibody response. Patients who do not notice or ignore the genital chancre of primary syphilis often develop secondary syphilis 2 – 10 weeks later.
(Choice A) Pemphigus vulgaris is characterized by autoantibodies against epithelial cell surface antigens, leading to the formation of mucous membrane blisters that quickly erode; histopathology usually shows acantholysis (detached keratinocytes) with superficial dermal infiltrate.
(Choice B) Kaposi sarcoma (KS) lesions are histologically characterized by spindle-shaped endothelial cells that form vascular channels. KS is due to human herpesvirus 8 infection and most commonly occurs in the setting of advanced AIDS. Lesions typically appear as purplish or dark brown plaques and nodules on the lower extremities.
(Choice D) Biopsy of erythema nodosum lesions usually reveals septal panniculitis with multinucleated giant cells. Erythema nodosum is a delayed-type hypersensitivity reaction that can occur due to drugs or other antigenic stimuli. Patients usually present with tender nodules on the bilateral shins.
(Choice E) Biopsy of anogenital warts will demonstrate papillomatous epidermal hyperplasia with cytoplasmic vacuolization. Anogenital warts are caused by specific serotypes of human papillomavirus (eg, HPV-6, HPV-11). Anogenital warts are not typically associated with diffuse maculopapular rash or systemic symptoms.
Educational objective:
Histopathologic examination of syphilitic lesions classically demonstrates a proliferative endarteritis with a surrounding plasma cell infiltrate. Most of the manifestations of syphilis are due to localized tissue ischemia resulting from endarteritis.