imiquimod 5% cream is an immune response modifier , currently approved for use in external genital and perianal warts , superficial basal cell carcinoma , and actinic keratoses . the antiviral and antitumoral activity seems to be dependent on focal activation of the immune system with induction , synthesis , and release of cytokines . local side effects , such as erythema , edema , erosion , and crusting are frequently observed . the induction of vitiligo - like depigmentation has been reported rarely.[38 ] in this paper , we describe two cases of genital vitiligo following use of imiquimod 5% cream . a 25-year - old chinese male with genital warts for 7 months was diagnosed as condyloma accuminatum and treated initially with external application of 5-fluorouracil injection , trichloroacetic acid solution , and so on . , new lesions appeared on his coronoid sulcus of penis and imiquimod 5% cream was prescribed for three times weekly . after 8 weeks of continuous use , the lesions gradually grew down and subsidized , erythema and anabrosis occurred in the areas treated with imiquiod . he was instructed to stop using imiquimod and provided rivanol solution and zinc oil for external using , but the patient persisted in using imiquimod cream up to 18 weeks for being afraid of recurrence of the lesions . one month after the drug withdrawal , the patient observed a depigmentation macula on his penis , which initially looked like a rice grain and gradually enlarged without subjective symptoms . dermatological inspection discovered an ivory - white patch of nearly 4 cm  2 cm with irregular edge on the patient 's coronoid sulcus and corpus penis [ figure 1 ] , without any vegetations in external genitals and vitiligo - like maculae on other sites . an ivory - white patch of nearly 4 cm  2 cm with irregular edge on the patient 's coronoid sulcus and corpus penis a 22-year - old male , with condyloma accuminata of the penis , treated initially with cryotherapy with only mild improvement . imiquimod 5% cream was applied to the warts every other night ; there was not significant side effect , except for moderate erythema and edema . after 12 weeks of continuous use , there was a complete resolution of lesions , without any pigmentary changes . new lesions appeared and imiquimod was used again . since moderate to severe local inflammatory reactions , and subsequently vitiligo - like patches in the areas treated with imiquimod , the patient stopped using imiquimod and returned to see us 2 months later . he complained that the vitiligo - like patches had been enlarging gradually , especially during the period of last weeks . on examination he had not previous history of vitiligo , and no other depigmented areas were found elsewhere . the patient refused our request for biopsies of these lesions and refused to have them photographed . a 25-year - old chinese male with genital warts for 7 months was diagnosed as condyloma accuminatum and treated initially with external application of 5-fluorouracil injection , trichloroacetic acid solution , and so on . , new lesions appeared on his coronoid sulcus of penis and imiquimod 5% cream was prescribed for three times weekly . after 8 weeks of continuous use , the lesions gradually grew down and subsidized , erythema and anabrosis occurred in the areas treated with imiquiod . he was instructed to stop using imiquimod and provided rivanol solution and zinc oil for external using , but the patient persisted in using imiquimod cream up to 18 weeks for being afraid of recurrence of the lesions . one month after the drug withdrawal , the patient observed a depigmentation macula on his penis , which initially looked like a rice grain and gradually enlarged without subjective symptoms . dermatological inspection discovered an ivory - white patch of nearly 4 cm  2 cm with irregular edge on the patient 's coronoid sulcus and corpus penis [ figure 1 ] , without any vegetations in external genitals and vitiligo - like maculae on other sites . an ivory - white patch of nearly 4 cm  2 cm with irregular edge on the patient 's coronoid sulcus and corpus penis a 22-year - old male , with condyloma accuminata of the penis , treated initially with cryotherapy with only mild improvement . imiquimod 5% cream was applied to the warts every other night ; there was not significant side effect , except for moderate erythema and edema . after 12 weeks of continuous use , there was a complete resolution of lesions , without any pigmentary changes . new lesions appeared and imiquimod was used again . since moderate to severe local inflammatory reactions , and subsequently vitiligo - like patches in the areas treated with imiquimod , the patient stopped using imiquimod and returned to see us 2 months later . he complained that the vitiligo - like patches had been enlarging gradually , especially during the period of last weeks . on examination he had not previous history of vitiligo , and no other depigmented areas were found elsewhere . the patient refused our request for biopsies of these lesions and refused to have them photographed . a 25-year - old chinese male with genital warts for 7 months was diagnosed as condyloma accuminatum and treated initially with external application of 5-fluorouracil injection , trichloroacetic acid solution , and so on . , new lesions appeared on his coronoid sulcus of penis and imiquimod 5% cream was prescribed for three times weekly . after 8 weeks of continuous use , the lesions gradually grew down and subsidized , erythema and anabrosis occurred in the areas treated with imiquiod . he was instructed to stop using imiquimod and provided rivanol solution and zinc oil for external using , but the patient persisted in using imiquimod cream up to 18 weeks for being afraid of recurrence of the lesions . one month after the drug withdrawal , the patient observed a depigmentation macula on his penis , which initially looked like a rice grain and gradually enlarged without subjective symptoms . dermatological inspection discovered an ivory - white patch of nearly 4 cm  2 cm with irregular edge on the patient 's coronoid sulcus and corpus penis [ figure 1 ] , without any vegetations in external genitals and vitiligo - like maculae on other sites . an ivory - white patch of nearly 4 cm  2 cm with irregular edge on the patient 's coronoid sulcus and corpus penis a 22-year - old male , with condyloma accuminata of the penis , treated initially with cryotherapy with only mild improvement . imiquimod 5% cream was applied to the warts every other night ; there was not significant side effect , except for moderate erythema and edema . after 12 weeks of continuous use , there was a complete resolution of lesions , without any pigmentary changes . new lesions appeared and imiquimod was used again . since moderate to severe local inflammatory reactions , and subsequently vitiligo - like patches in the areas treated with imiquimod , the patient stopped using imiquimod and returned to see us 2 months later . he complained that the vitiligo - like patches had been enlarging gradually , especially during the period of last weeks . on examination he had not previous history of vitiligo , and no other depigmented areas were found elsewhere . the patient refused our request for biopsies of these lesions and refused to have them photographed . imiquimod is an immune - response modifier for the topical treatment of external genital and perianal warts . it is generally a well - tolerated drug , its most frequent side effects are erythema , flaking , scabbing , edema , and excoriation . the us food and drugs administration lists 68 reports of pigmentary changes related to imiquimod from 1997 to 2003 , including 43 reports of depigmentation , 7 of vitiligo , 1 of hypopigmentation , and 17 of hyperpigmentation . other four cases of vitiligo - like depigmentation following use of imiquimod have been reported.[38 ] the possible mechanisms of hypopigmentation associated with imiquimod treatment include antibodies found in sera of patients with vitiligo to nonpigment cell antigens , cytoplasmic pigment cell antigens and pigment cell - surface antigens , stimulation by imiquimod of both the innate immune response and cell - mediated adaptive immunity , and increased sensitivity of melanocytes to oxidative stress . furthermore , imiquimod enhances antigen presentation by stimulating cd8 t - cell activation and inducing langerhans cell maturation . vitiligo - like depigmentation may result from the destruction of melanocytes by cd8 t - cells directed to melanocyte surface antigens after antigen presentation is enhanced by imiquimod . in addition , the release of no was promoted indirectly by imiquimod ; it induced cascade reaction of free radical and resulted in apoptosis of melanocytes . some authors speculated that imiquimod might have acted as a triggering factor in a susceptible patient who had a positive family history of vitiligo . they also suggested that clinicians should be cautious when prescribing imiquimod in patients with a personal of family history of vitiligo . however , our patient and other reported case had no personal or family history of vitiligo . in addition , the depigmentation did not extend beyond the treatment area , suggesting a local factor was responsible . in case 1 , during the period of using imiquimod , erythema , dropsy or anabrosis appeared on the treated areas several times , without pigmentary changes were observed . however , 1 month after discontinuing imiquimod , there was a depigmented macula appeared and primarily confined to the site of imiquimod treatment and enlarged gradually . we presume that imiquimod as a precipitating factor induced local immunologic abnormality , eventually , vitiligo - like lesions were caused . in view of the mode of action of imiquimod , vitiligo - like hypopigmentation following a course of topical imiquimod treatment is , therefore , not unexpected . as the use of imiquimod expands , clinicians should be made aware of the possible pigmentary changes associated with its use , particularly when used in visible areas . furthermore , clinicians should keep in mind that not all individuals treated with imiquimod will result in pigmentary change . each case should be individually examined , the course of action determined , and the patient monitored while receiving imiquimod therapy .
imiquimod is a small molecule with adjuvant pro - inflammatory effects that can be topically delivered as a cream for treating external genital and perianal warts . in our report , 
 two chinese males at the ages of 25 and 22 years were treated with imiquimod 5% cream for recurrent condyloma accuminatum , three times per week for 18 and 12 . 
 weeks , respectively . 
 depigmentation were noted and gradually enlarged in the treated areas after the two patients discontinued imiquimod . 
 therefore , clinicians should be made aware of the possible pigmentary changes associated with application of this cream .