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LETTER TO THE EDITOR - OBSERVATION LETTER
Year : 2016  |  Volume : 82  |  Issue : 5  |  Page : 572-574

Vitiligo-like lesions following imiquimod 5% application for condyloma acuminata: An additional case


Department of Dermatology, Dermatologist - Venereologist, Hammoud Hospital University Medical Center, Beirut, Lebanon

Date of Web Publication4-Aug-2016

Correspondence Address:
Dr. IsmaŽl Maatouk
Department of Dermatology, Hammoud Hospital University Medical Center, Beirut
Lebanon
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0378-6323.182808

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How to cite this article:
Maatouk I. Vitiligo-like lesions following imiquimod 5% application for condyloma acuminata: An additional case. Indian J Dermatol Venereol Leprol 2016;82:572-4

How to cite this URL:
Maatouk I. Vitiligo-like lesions following imiquimod 5% application for condyloma acuminata: An additional case. Indian J Dermatol Venereol Leprol [serial online] 2016 [cited 2019 Sep 16];82:572-4. Available from: http://www.ijdvl.com/text.asp?2016/82/5/572/182808


Sir,

Among the many methods used in the treatment of condylomata acuminata, imiquimod 5% cream is the sole medication that is approved by the United States Food and Drug Administration.[1],[2] Since 2005, ten patients with condyloma acuminata have been reported to develop vitiligo or vitiligo-like depigmentation following the use of imiquimod.[3],[4],[5],[6],[7],[8],[9],[10],[11] Vitiligo is an acquired skin disorder characterized by the appearance of depigmented macules due to a reduction in the number and function of melanocytes. Although several hypotheses have been proposed, the mechanism of depigmentation remains uncertain and is thought to be due to an immune-mediated attack by auto-reactive cytotoxic T-cells on melanocytes. Like other autoimmune disorders, cytokines play a role in the recruitment of auto-reactive T cells to the skin, which in turn may be influenced by imiquimod.[12] An additional case of vitiligo-like lesions induced by imiquimod in a 26-year-old man is presented here with a short review of literature.

A 26-year-old Lebanese man presented with hypopigmented lesions on the penis. He had applied imiquimod 5% cream on three condyloma acuminata lesions on his penis, three months prior to presentation. He used to apply the cream at night and wash it off in the morning, once a week for 3 weeks. Although he noticed some irritation and excoriation in the treated areas, he continued the application. After stopping the application of imiquimod, he observed some hypopigmented lesions in the treated areas which did not expand in size; however, they did not repigment in the following 2 months. He and his family members had no history of skin disorders such as vitiligo, other depigmented dermatoses or autoimmune diseases. He denied use of any other topical treatment.

Clinical examination revealed the hypopigmented macules on the penile region [Figure 1] that were accentuated on Wood's light examination. Laboratory tests (blood counts, liver and kidney function tests, thyroid function tests, human immunodeficiency virus (HIV) and syphilis serologies, hepatitis B and C serologies) were completely normal and a skin biopsy was recommended but refused by the patient. He was clinically diagnosed with imiquimod-induced localized vitiligo-like lesions.
Figure 1: Hypopigmented macules on the sites of application of imiquimod for condyloma acuminata

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Imiquimod is an immune-response modifier that is generally well tolerated but has minor side effects like erythema, burning, blistering and excoriation.[13] Its mechanism of action in human papilloma virus (HPV) infection is by enhancing the host's innate and cellular immune response against the virus; it also stimulates peripheral blood monocytes, macrophages and dendritic cells to produce certain cytokines (interferon alfa, interleukins 12, 6 and 8, tumor necrosis factor alfa, nitric oxide).[14],[15]

We found 10 previous reports in English of Imiquimod-induced hypopigmented macules [Table 1]. There appear to be no specific criteria to differentiate among “depigmentation,” “hypopigmentation,” “vitiligo” or “vitiligo-like lesions” and these names were chosen at will by authors of the respective reports. Moreover, among the 10 patients previously reported, only one had agreed for a biopsy and the histopathologic examination findings were consistent with vitiligo.[14] Besides, family history of vitiligo or other autoimmune disorders was reported in only one case. Thus, the reported hypopigmented macules were most probably secondary to imiquimod application. For this reason, we feel “imiquimod-induced hypopigmented macules” would be a better name for this side effect.
Table 1: Summary of all reported cases of vitiligo-like lesions following imiquimod application

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Concerning the pathomechanism of this side effect, many hypotheses were suggested. Imiquimod application induces antigen presentation that activates Langerhans cells. Consequently, destruction and apoptosis of the melanocytes can occur and this was confirmed by TUNEL assay.[16] Moreover, vitiligo pathogenesis involves pro-inflammatory cytokines such as interferon alfa, interleukin 6 and 8, tumor necrosis factor alfa and nitric oxide.[12] These cytokines can be induced by imiquimod application and may play a role in the development of hypopigmentation.[17] Third, the occurrence of these hypopigmented imiquimod-induced lesions has been exclusively reported in the genital area that has thin skin and this may also contribute to its development.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Shi H, Zhang X, Ma C, Yu N, Wang J, Xia L, et al. Clinical analysis of five methods used to treat condylomata acuminata. Dermatology 2013;227:338-45.  Back to cited text no. 1
    
2.
Chen FP. Efficacy of imiquimod 5% cream for persistent human papillomavirus in genital intraepithelial neoplasm. Taiwan J Obstet Gynecol 2013;52:475-8.  Back to cited text no. 2
    
3.
Brown T, Zirvi M, Cotsarelis G, Gelfand JM. Vitiligo-like hypopigmentation associated with imiquimod treatment of genital warts. J Am Acad Dermatol 2005;52:715-6.  Back to cited text no. 3
[PUBMED]    
4.
Stefanaki C, Nicolaidou E, Hadjivassiliou M, Antoniou C, Katsambas A. Imiquimod-induced vitiligo in a patient with genital warts. J Eur Acad Dermatol Venereol 2006;20:755-6.  Back to cited text no. 4
[PUBMED]    
5.
Al-Dujaili Z, Hsu S. Imiquimod-induced vitiligo. Dermatol Online J 2007;13:10.  Back to cited text no. 5
    
6.
Senel E, Seckin D. Imiquimod-induced vitiligo-like depigmentation. Indian J Dermatol Venereol Leprol 2007;73:423.  Back to cited text no. 6
[PUBMED]  Medknow Journal  
7.
Serrão VV, Páris FR, Feio AB. Genital vitiligo-like depigmentation following use of imiquimod 5% cream. Eur J Dermatol 2008;18:342-3.  Back to cited text no. 7
    
8.
Zhang R, Zhu W. Genital vitiligo following use of imiquimod 5% cream. Indian J Dermatol 2011;56:335-6.  Back to cited text no. 8
[PUBMED]  Medknow Journal  
9.
Wang HW, Miao F, Shi L, Lü T, Huang Z, Wang XL. Imiquimod-induced localized vitiligo in wife and lichen planus in husband. Chin Med J (Engl) 2013;126:2593.  Back to cited text no. 9
    
10.
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.  Back to cited text no. 10
    
11.
Serra MC, Menicanti C, Pennacchioli E, Tosti G. Vulvar vitiligo-like depigmentation and multiple halos of hypomelanosis at the trunk following treatment with imiquimod 5% cream for vulvar condylomata: Casual or related events? An Bras Dermatol 2014;89:806-7.  Back to cited text no. 11
    
12.
Ezzedine K, Sheth V, Rodrigues M, Eleftheriadou V, Harris JE, Hamzavi IH, et al. Vitiligo is not a cosmetic disease. J Am Acad Dermatol 2015;73:883-5.  Back to cited text no. 12
    
13.
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;23:909-10.  Back to cited text no. 13
    
14.
Schöfer H, Van Ophoven A, Henke U, Lenz T, Eul A. Randomized, comparative trial on the sustained efficacy of topical imiquimod 5% cream versus conventional ablative methods in external anogenital warts. Eur J Dermatol 2006;16:642-8.  Back to cited text no. 14
    
15.
Skinner RB Jr. Imiquimod. Dermatol Clin 2003;21:291-300.  Back to cited text no. 15
    
16.
Kim CH, Ahn JH, Kang SU, Hwang HS, Lee MH, Pyun JH, et al. Imiquimod induces apoptosis of human melanocytes. Arch Dermatol Res 2010;302:301-6.  Back to cited text no. 16
    
17.
Ueyama A, Yamamoto M, Tsujii K, Furue Y, Imura C, Shichijo M, et al. Mechanism of pathogenesis of imiquimod-induced skin inflammation in the mouse: A role for interferon-alpha in dendritic cell activation by imiquimod. J Dermatol 2014;41:135-43.  Back to cited text no. 17
    


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