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Am Fam Physician. 2008;77(2):215-216

Author disclosure: Nothing to disclose.

A 42-year-old man presented with a nonhealing genital ulcer that persisted for six weeks. The erosion was initially small and painless, but rapidly developed into a superficial ulcer. The patient did not use condoms, but had no known history of sexually transmitted diseases. After further questioning, he admitted to having genital ulcers on the same area in the past but did not seek medical attention because they were painless and healed spontaneously.

Physical examination revealed a 2-cm superficial erythematous ulcer on the shaft of the penis (see accompanying figure). The ulcer had a firm base, indurated edges, and minimal drainage. There was bilateral, discrete, nontender enlargement of the inguinal lymph nodes. The patient had no urethral discharge, fever, or joint pain and no other rash or lesions on the skin and mucous membranes.

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Based on the patient's history and physical examination, which one of the following is the most likely diagnosis?


The answer is E: primary syphilis. Syphilis is caused by the spirochete Treponema pallidum. It is primarily a sexually transmitted disease, but transmission through blood transfusion or the placenta is possible.1 The overall rate of syphilis has increased since 2001, with a high incidence in men who have sex with men.2 Many patients diagnosed with syphilis also have human immunodeficiency virus (HIV).3

A primary syphilis lesion is an ulcer known as a chancre. It is typically indurated, with a clean base and rolled edges, and develops an average of three weeks after infection (10 to 90 days). The lesion may occur on any area of skin or mucous membrane but usually appears on or near the genitals. Typically, a single painless chancre appears unless there is a superinfection, and patients may miss the lesion if it is on the cervix, pharynx, or rectum.4 Nontender regional adenopathy is common, and secondary infection with bacteria or, occasionally, herpes viruses can occur. The chancre heals without scarring in two to six weeks and may periodically recur at the same site.4

A diagnosis of primary syphilis is based on clinical presentation, darkfield microscopy, and serology. Positive darkfield microscopy findings rule in the diagnosis, but the technique has limited accuracy.5 Nontreponemal test results, such as the rapid plasma reagin test, will be positive four to six weeks after infection or one to three weeks after the chancre appears. Treponemal antigen tests (e.g., microhemagglutination assay– T. pallidum, enzyme immunoassay for antitreponemal immunoglobulin G, T. pallidum particle agglutination test, fluorescent treponemal antibody absorption) are used to confirm the diagnosis in patients with a reactive nontreponemal test.5 After treatment, patients should be reexamined, and repeat serology should be performed six and 12 months after treatment.6

Treatment failure or reinfection is suggested if non-treponemal test titers fail to decrease by a factor of four within six months of therapy or if signs and symptoms of the disease persist.1,6 These patients should be retreated and retested for HIV, and lumbar puncture should be performed to rule out neurosyphilis.1

Behçet's syndrome is a noninfectious cause of genital ulcerations. Other noninfectious ulcers include fixed drug eruptions and traumatic ulcers.7

A chancroid ulcer begins as one or more papules that evolve into pustules. The subsequent ulcer is friable with soft, ragged, undermined edges; a granulomatous base; and surrounding erythema.8 The base of the ulcer is usually covered with a yellow-gray, purulent exudate and bleeds when scraped.9 Regional lymphadenitis and suppurative adenopathy can occur.8A probable diagnosis can be made from compatible findings plus darkfield microscopy negative for T. pallidum, serology negative for syphilis, and culture negative for herpes simplex virus (HSV) or a clinical presentation not typical of herpes.9

HSV lesions typically are groups of painful erosions or vesicles on an erythematous base. Tender regional lymphadenopathy is common, and primary infection is often associated with constitutional symptoms.10

Lymphogranuloma venereum is caused by Chlamydia trachomatis. Diagnosis usually relies on serology. Small, painless papules at the infection site erode to form shallow, rapidly healing ulcerations; painful unilateral lymphadenopathy develops two to six weeks later.8

Behçet's syndromeRecurrent oral aphthae plus two of the following: recurrent genital ulceration, eye lesions, skin lesions, or a positive pathergy test result
ChancroidPainful, friable ulcerations with soft, ragged, undermined edges; surrounding erythema; yellow-gray, purulent exudate; unilateral regional lymphadenitis
Herpes simplex virusUsually groups of painful lesions with or without tender regional lymphadenopathy or constitutional symptoms
Lymphogranuloma venereumPainless shallow ulcerations that heal quickly
SyphilisPainless lesions, typically indurated with a clean base and rolled edges; lesion is usually more than 0.5 cm in diameter; painless regional adenopathy

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This series is coordinated by John E. Delzell Jr., MD, MSPH, associate medical editor.

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