Erosive Reaction After Imiquimod Treatment of Condylomata Acuminata
A 17-year-old adolescent presented to his family physician with a 9-month history of condylomata acuminata on the left side of the scrotum. The lesions had been treated with liquid nitrogen several times in the past. Two months ago, after treatment with liquid nitrogen, he had been advised to use imiquimod cream, 5%, three nights weekly to treat the warts and help prevent relapse. He had been told to wash off the cream in the morning, and he had followed the instructions. After 4 topical applications of imiquimod cream, erythema and erosions became evident in the treated areas. In spite of this, he continued to use the cream until his next follow-up appointment 1 month later. In the meantime, the eroded areas got bigger, coalesced, and became serosanguineous and painful.
His past health history was unremarkable, and he was not on any other medications. He had become sexually active a year ago and had had multiple sex partners, with only occasional condom use. His family history was noncontributory. Physical examination revealed a large, erosive, serosanguineous lesion on the left side of the scrotum in the area where the imiquimod cream had been applied. No clinical evidence of genital warts remained.
The patient was instructed to discontinue the imiquimod cream and was prescribed topical fusidic acid/hydrocortisone acetate cream with instructions to use it twice daily for 2 weeks. This regimen healed the lesion and cleared the discomfort, and no genital warts were evident at follow-up after the erosion had subsided.
Condylomata acuminata are anogenital warts that are most commonly caused by human papillomavirus (HPV) 6 and 11.1 Topical imiquimod, 5% and 3.75%, are immunomodulator creams that have been approved for the treatment of condylomata acuminata.2,3 Imiquimod, an aminoquinoline compound, enhances the host’s innate and cellular immune response and combats HPV infection by binding to the dermal dendritic cells and macrophages through toll-like receptor 7.2,3 This results in the production and release of proinflammatory cytokines such as interferon-α, tumor necrosis factor α, and interleukin (IL)-1, IL-6, IL-8, and IL-12.2,3 The secreted cytokines stimulate local immune effects that are cytotoxic against HPV.4 Imiquimod also acts on cell-mediated immunity by activating Langerhans cells, thereby increasing the presentation of antigens for the T cells.4
Although topical imiquimod is a relatively safe medication if used correctly, local and systemic adverse effects may occur. Local adverse effects can include itching, burning, soreness, pain, flaking/scaling/dryness, erythema, edema, vesicles, erosions, erosive pustular lesions, excoriation, ulceration, scabbing/crusting, and, rarely, induction of dermatoses such as vitiligo, urticaria, psoriasiform lesions, pemphigus-like lesions, lupus erythematosus-like lesions, lichenoid reaction, hyperkeratosis, and keratoacanthoma.2,3,5-8
The patient described here had an erosive serosanguineous reaction from imiquimod. Predisposing factors in this case included a raw area as a result of cryotherapy, and continued application of the medication despite the erosions.
Systemic adverse effects are rare, because there is only minimal absorption of imiquimod when it is used topically. Systemic adverse effects can include flulike symptoms such as fatigue, headache, fever, nausea, diarrhea, myalgia, and arthralgia.7-11 Rarely, chronic neuropathic pain, onset or exacerbation of autoimmune conditions (eg, thyroiditis, spondyloarthropathy, ulcerative colitis), erythema multiforme, or neuropsychiatric symptoms (eg, delirium, mania) can occur.7-11 It has been hypothesized that the systemic adverse effects are caused by the locally produced cytokines spreading into the systemic circulation.12
Because of its potential adverse effects, imiquimod should be avoided if possible for raw or large areas. The patient should avoid or minimize exposure to sunlight during treatment because of a concern for heightened sunburn susceptibility.6 The patient also should adhere to the proper dosage schedule and notify the physician of any adverse effects.
References
1. Varma S, Lathrop E, Haddad LB. Pediatric condyloma acuminata. J Pediatr Adolesc Gynecol. 2013;26(6):e121-e122.
2. Chan MP, Zimarowski MJ. Lupus erythematous-like reaction in imiquimod-treated skin: a report of 2 cases. Am J Dermatopathol. 2011;33(5):523-527.
3. Li W, Xin H, Ge L, Song H, Cao W. Induction of vitiligo after imiquimod treatment of condylomata acuminata. BMC Infect Dis. 2014;14:329.
4. Brandt HRC, Fernandes JD, Patriota RCR, Criado PR, Belda W Jr. Treatment of human papillomavirus in childhood with imiquimod 5% cream. An Bras Dermatol. 2010;85(4):549-553.
5. Bauza A, Del Pozo LJ, Saus C, Martin A. Pemphigus-like lesions induced by imiquimod. Clin Exp Dermatol. 2009;34(5):e60-e62.
6. Campalani E, Holden CA. Keratoacanthoma associated with the use of topical imiquimod. Clin Exp Dermatol. 2013;38(5):555-556.
7. Cantisani C, Lazic T, Richetta AG, Clerico R, Mattozzi C, Calvieri S. Imiquimod 5% cream use in dermatology, side effects and recent patents. Recent Pat Inflamm Allergy Drug Discov. 2012;6(1):65-69.
8. Kumar B, Narang T. Local and systemic adverse effects to topical imiquimod due to systemic immune stimulation [letter]. Sex Transm Infect. 2011;87(5):432.
9. Brett AS, Voss T, Ridley EP. Neuropsychiatric symptoms associated with topical imiquimod therapy: report of 2 cases. JAMA Dermatol. 2013;149(4):500-501.
10. Gupta AK, Cooper EA, Abramovits W. Zyclara (imiquimod) cream, 3.75%. Skinmed. 2010;8(4):227-229.
11. Yi BA, Nirenberg MJ, Goldstein SM, Berger TG. Chronic neuropathic pain associated with imiquimod: report of 2 cases. J Am Acad Dermatol. 2005;52(2):S57-S58.
12. Rosenblatt A, de Campos Guidi HG. Local and systemic adverse effects of imiquimod therapy for external anogenital warts in men: report of three cases. Int J STD AIDS. 2012;23(12):909-910.