BACKGROUND
A 52-year-old man with no clinically significant medical history presents to the emergency department (ED) with a chief complaint of a “rash” on his penis. The patient states that the rash first appeared 1 week before presentation. He denies any dysuria, urethral discharge, pruritus or pain in the area of the lesion. This is the first time he has had such a rash. He admits to having had several recent sexual partners.
{mosimage}On physical examination, his vital signs are normal. The patient has a well-demarcated, ulcerated lesion on the ventral aspect of his penis (see Image). The lesion is not tender to palpation. No other lesions are noted, and no discharge is observed from the urethra. The findings of his testicular examination are unremarkable, with the exception of bilateral prominent inguinal lymphadenopathy. The remaining physical findings, including the cardiac and abdominal findings, are unremarkable.
What is the diagnosis, and what empiric treatment is necessary?
HINT
The lesion is characteristically painless.
Authors:
Erick Miranda, MD, PGY4 Chief Resident, LAC/USC Department of Emergency Medicine, Los Angeles, CA.
Allison Richard, MD, Attending Physician, Assistant Professor of Emergency Medicine, Department of Emergency Medicine, LAC/USC Medical Center
eMedicine Editor:
Rick G. Kulkarni, MD, FACEP, Assistant Professor, Yale School of Medicine, Section of Emergency Medicine, Department of Surgery, Attending Physician, Medical Director, Department of Emergency Services, Yale-New Haven Hospital, CT
ANSWER
Primary syphilis: Syphilis, an infectious disease caused by the spirochete Treponema pallidum, is usually transmitted by means of sexual contact; the usual route of transmission is the skin or mucous membranes of an uninfected sexual partner coming in contact with the mucosal ulcerations (eg, in the genital area, mouth, or anus) of an infected partner.
In the United States, the rate of primary and secondary syphilis declined by 89% from 1990 to 2000; however, in November 2005, the Centers for Disease Control and Prevention (CDC) reported that the number of primary and secondary cases of syphilis had been increasing, from 2.6 cases per 100,000 population in 2002 to 4.7 cases per 100,000 population in 2004 (an increase of 87%). This rise was partially attributed to increased rates of infection among men who have sex with men, who in 2004 represented 64% (up from 5% in 1999) of all cases of primary and secondary syphilis in the United States.2
Primary syphilis manifests as a nonpainful ulcer (chancre) at the site of infection. The lesion is usually on the genital area, but it may also occur on the lips, tongue, cervix, or anus of the infected person. This lesion usually develops within 3-4 weeks after infection, but it may occur as long as 3 months after. The primary lesion spontaneously heals in 3-7 weeks, and it may go unnoticed, especially if it is on the cervix or anus; therefore, infected individuals may not realize that they have an infection. Unilateral or bilateral regional painless lymphadenopathy is also a characteristic finding of primary syphilis.
Secondary syphilis is the next phase of the disease, developing 4-10 weeks after the primary lesion appears. This phase is marked by nonspecific systemic complaints, such as fever, headache, fatigue, and lymphadenopathy. A characteristic rash that consists of round, discrete, nonpruritic macules on the trunk and proximal extremities and penny-sized, reddish-brown sores, appears on the palms, soles, scalp, and face in this phase. These sores may coalesce to form highly infectious lesions called condylomata lata. Symptomatic secondary syphilis also spontaneously resolves, and the disease then enters a latent period where few if any symptoms are seen; the latent phase is divided into “early” and “late” periods. Symptoms may recur in the early latent stage (during the first 2 years of infection). The disease then goes into the late latent phase, when patients remain asymptomatic and noninfectious.
About one third of patients with primary syphilis develop a form of the disease called tertiary syphilis, which is a chronic inflammatory process that progresses over years and decades and results in varied symptoms and physical findings, including mental illness, blindness, heart problems, and eventual death. Cardiovascular syphilis can cause devastating damage to the heart, including aortic endarteritis with medial necrosis and aneurysm formation. Gummatous syphilis manifests as coalescent granulomatous lesions affecting the bones, joints, skin, or almost any part of the body. Finally, symptomatic neurosyphilis can lead to meningitis, brain parenchymal infection, endarteritis, or stroke.
Standard treatment for primary syphilis or for syphilitic infection <1 year after exposure is benzathine penicillin G 2.4 million U given by intramuscular (IM) injection. Alternate regimens for patients allergic to penicillin are a 2-week course of doxycycline 100 mg given orally (PO) twice daily (BID) for 14 days, tetracycline 500 mg PO 4 times daily (QID) for 14 days, or ceftriaxone 1 g given IM or intravenously (IV) once a day for 8-10 days. A recent study also demonstrated efficacy with azithromycin 2 g PO as a single dose; however, the authors suggested caution in applying this finding to patients in the United States, because the trial was conducted in a geographically limited area outside of the US, and because macrolide resistance has already been demonstrated in the US.1
If the patient was infected for >1 year at the time of presentation, benzathine penicillin G (2.4 million U IM once a week for 3 consecutive weeks), or doxycycline for 4 weeks is recommended. Neurosyphilis requires treatment with aqueous crystalline penicillin G 2-4 million U IV every 4 hours for 10-14 days. Patients with neurosyphilis should also be followed up every 6 months for 3-4 years for cerebrospinal fluid (CSF) and serologic testing.
Given this patient’s allergy to penicillin and current social situation, he was treated with azithromycin 2 g PO instead of a 14-day course of doxycycline. The ulcerative lesion was swabbed and sent for darkfield microscopy. Rapid plasma reagin (RPR) and Venereal Disease Research Laboratories (VDRL) serum studies were also ordered. A urine sample was sent for Neisseria gonorrhoeae and Chlamydia polymerase chain reaction (PCR), and the patient was counseled about concomitant sexually transmitted diseases (STDs), including HIV. He was referred for HIV testing and given a fast-track follow-up appointment for the laboratory results.
Reference:
Riedner G, Rusizoka M, Todd J, Maboko L, Hoelscher M, Mmbando D, et al. Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis. N Engl J Med. 2005 Sep 22;353(12):1236-44. [MEDLINE: 16177249]
STD Surveillance 2004. Trends in Reportable Sexually Transmitted Diseases in the United States, 2004. National Surveillance Data for Chlamydia, Gonorrhea, and Syphilis. Atlanta, Ga: Centers for Disease Control and Prevention, US Dept. of Health and Human Services; 2005. Available at: http://www.cdc.gov/std/stats04/trends2004.htm#trendssyphilis.
