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Microscopy of this patient's penis ulcer reveals a multinucleated giant cell with ground-glass intranuclear inclusions, raising strong suspicion for herpes simplex virus (HSV) infection.  Genital HSV is usually caused by HSV type 2, which is spread primarily via direct skin contact with herpetic sores or infected genital secretions during sexual activity.  Initial infection is often characterized by painful genital ulcers, fever, lymphadenopathy, and dysuria.  Symptoms typically resolve within a few weeks, but latent infection develops in the sacral dorsal root ganglia and can periodically reactivate, leading to recurrence.

HSV is generally diagnosed by cell culture or PCR, but Tzanck smear (as seen above) can reveal the cytopathic effects of the virus (eg, multinucleated giant cells, acantholytic cells, keratinocyte ballooning, nuclear molding).  Oral antiviral agents such as acyclovir, a competitive inhibitor of viral DNA polymerase, help speed symptom resolution.

(Choice B)  Azithromycin can be used to treat chancroid, which is characterized by the formation of a papule that evolves into a pustule and then an ulcer.  However, it is very rare in the United States and is caused by the gram-negative organism Haemophilus ducreyi; multinucleated giant cells would not be seen.

(Choice C)  Doxycycline can treat lymphogranuloma venereum, a genital infection caused by certain serotypes of Chlamydia trachomatis.  This disease is marked by the formation of a small genital ulcer, followed by significant lymph node inflammation and pain in the inguinal or femoral region.  C trachomatis appears as intravacuolar organisms in macrophages.

(Choice D)  Fluconazole can treat Candida balanitis, which is typically marked by a painful, pruritic, erythematous rash.  Yeasts and pseudohyphae can often be seen on microscopy.

(Choice E)  Penicillin can be used to treat syphilis, a spirochetal infection caused by Treponema pallidum that begins with the formation of a chancre (painless ulcer with heaped-up borders and a clean base) at the site of inoculation.  Diagnosis is generally made with serologic testing because T pallidum cannot be cultured; multiple ulcers and multinucleated giant cells are not typically seen.

(Choice F)  Permethrin can be used to treat pubic lice, which are associated with significant pruritus of hairy genital areas.  Lice can generally be visualized on the hair shaft.

Educational objective:
Herpes simplex virus is a common, sexually transmitted infection marked by the formation of painful genital ulcers.  Tzanck smear can reveal the characteristic cytopathic effects of the virus, including multinucleated giant cells, ground-glass intranuclear inclusions, acantholytic cells, keratinocyte ballooning, and nuclear molding.