A 25-year-old previously healthy man comes to the office due to penile lesions. The patient first noticed a nontender papule on his penis a month ago, and it has progressively increased in size and number. He reports no fever, dysuria, or penile discharge. The patient is sexually active with multiple partners and uses condoms inconsistently. Physical examination reveals 3 soft, flesh-colored, papillary lesions measuring <1 cm on the dorsum of the penis. There are no enlarged inguinal lymph nodes, and the remainder of the examination is normal. Treatment is started with a topical agent that acts as a toll-like receptor agonist to increase antiviral cytokine production. Which of the following medications was most likely prescribed to this patient?
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Imiquimod is a topical immunomodulatory drug that is used to treat many common dermatologic disorders associated with abnormal cell proliferation, including anogenital warts (ie, human papillomavirus infection), superficial basal cell carcinoma, and actinic keratosis. The antiviral and antiproliferative effects of imiquimod are primarily mediated through activation of toll-like receptor 7, which upregulates the proinflammatory transcription factor nuclear factor-kappa B (NF-κB).
NF-κB increases transcription of proinflammatory genes, activating antigen-presenting cells (eg, Langerhans cells in the skin) and initiating an immune response involving natural killer cells, cytotoxic T cells, and type 1 helper T cells. This results in increased cytokine production (eg, IL-1, IL-12, interferon-alfa/gamma, tumor necrosis factor-alpha) and enhanced immune-mediated killing of aberrant cells (eg, cancer cells, virus-infected cells).
Other antiproliferative effects of imiquimod include:
Induction of apoptosis of aberrant cells through caspase activation via inhibition of BCL-2
Inhibition of angiogenesis by downregulating proangiogenic factors (eg, fibroblast growth factor) and upregulating angiogenesis inhibitors (eg, interferon-gamma, IL-12)
(Choice A) Calcipotriene is a vitamin D analog (ie, activates the vitamin D receptor, a nuclear transcription factor) used to treat plaque psoriasis. It acts by inhibiting T-cell and keratinocyte proliferation and stimulating keratinocyte differentiation.
(Choice C) Pimecrolimus is a calcineurin inhibitor used to treat atopic dermatitis (eczema). It acts by blocking the translocation of NFAT (nuclear factor of activated T cells), resulting in reduced transcription of IL-2.
(Choice D) Topical salicylic acid is a keratolytic agent that acts by increasing sloughing of virus-infected epidermal cells. It is widely used to treat common warts but is not recommended for anogenital warts.
(Choice E) Silver nitrate is a caustic agent that coagulates cellular proteins to form an eschar. It is used to cauterize wounds to stop bleeding (eg, epistaxis) and to remove excess granulation tissue.
Educational objective:
Imiquimod is a widely used topical immunomodulatory agent that stimulates a potent cellular and cytokine-based immune response to aberrant cells (eg, human papillomavirus-infected cells in anogenital warts) by activating toll-like receptors and upregulating NF-κB. Other antiproliferative effects of imiquimod include inhibition of angiogenesis and induction of apoptosis.