Successful management of recalcitrant perianal warts with two sessions of intralesional 5-fluorouracil.

Sir,

Genital warts (GWs) have been associated with high recurrence rates even following treatment. Managing these patients, therefore, still remains a challenge. Nonablative methods for managing GWs include podophyllin, podophyllotoxin, imiquimod, trichloroacetic acid, bleomycin, interferons, synecatechins, cidofovir, and 5-fluorouracil (5-FU).[1] Intralesional instillation of 5-FU has recently demonstrated promising results for managing GW.

A 25-year-old male presented to the Department of Dermatology with the complaints of a foreign body sensation in the perianal area. Otherwise, he was asymptomatic. His sexual history revealed frequent episodes of receptive anal intercourse. Clinical examination demonstrated perianal aggregates of verrucous papules and plaques [Figure 1]. A diagnosis of GW was made and his blood sent for Venereal Disease Research Laboratory (VDRL) and HIV 1 and 2 examination. Reports showed a negative retro status and a nonreactive VDRL. After patient counseling and taking an informed consent podophyllin in tincture, benzoin was applied over the lesions at weekly intervals. However, even after 8 sessions of podophyllin application, the status of his lesions remained unaltered. Treatment, therefore, was switched to topical 5% imiquimod cream 3 days a week on alternate nights. The patient was followed up every month till the duration of treatment which lasted for 16 weeks. However, the lesions showed no regression. Intralesional instillation of 5-FU was therefore contemplated on. A volume of 2 ml of 5-FU was infiltrated into the entire lesion using an insulin syringe. After 1 month of follow-up, more than 50% of warts had disappeared [Figure 2]. A second session of intralesional 5-FU heralded complete clearance of lesions [Figure 3]. Patient has been on regular follow-up, and even after 1 year, there has been no recurrence [Figure 4].

Figure 1

Perianal warts seen in our patient at his first visit. The status of his lesions remained the same even after post podophyllin and imiquimod usage

Figure 2

Status of perianal warts after a month of intralesional instillation of 5-fluorouracil

Figure 3

Status of perianal warts after 1 month of the second session of intralesional 5-fluorouracil

Figure 4

Patient's perianal region after 1 year of follow-up, with no recurrence

5-FU is a pyrimidine antagonist, specifically targeting thymidylate synthetase and disrupting DNA synthesis in mitotically active cells.[2] It has been used topically in wart management. However, owing to poor penetration topical 5-FU has not been very effective. Intralesional instillation of 5-FU, on the other hand, allows for therapeutic concentrations to effectively reach the diseased site, thereby facilitating wart regression. The beneficial properties of intralesional 5-FU for GW have been elaborated by Swinehart et al.[3] and Pall et al.[4] However, there have been subtle differences in 5-FU administered by both authors [Table 1].

Table 1

Brief overview of studies conducted by Swinehart et al.[3] and Pall et al.[4] utilizing intralesional 5-fluorouracil for genital warts

My patient was infiltrated with aqueous solution of 5-FU only after failure of podophyllin and imiquimod. In general, following 6 weekly applications of podophyllin visible changes demonstrating regression of GW is noted.[5] However, if no changes are evident, treatment needs revision. Imiquimod, on the other hand, is an immune response modifier which after 16 weeks of regular protocol usage culminates in appreciable wart regression. In some patients, although, there could be lack of response following imiquimod usage, which has been attributed to regional drug resistance.[6] Recently, intralesional usage of 5-FU at weekly intervals has been utilized for GW.[34] I, however, utilized 5-FU on a monthly basis. The reason for using this schedule was excruciating pain complained by my patient following the first intralesional session. Other likely complications with intralesional 5-FU include edema, erythema, ulceration, necrosis, and skin discoloration which however was not encountered by me. Following two sessions of intralesional 5-FU complete regression of all GW was witnessed. Now, whether previous therapies, with podophyllin and imiquimod, played a synergistic role, facilitating wart regression with just two sessions of intralesional 5-FU or monthly intralesional injections using 5-FU as the sole therapy could be effective enough similar to weekly therapy, needs contemplation. Advantages seen with intralesional 5-FU include its nonsurgical nature, tissue sparing character, the simplicity of the technique, excellent cosmesis, and site specific with drug concentrations being localized to the diseased site thereby minimizing the risk of systemic toxicity. Overall, this modality of treatment shows promise. However, more comparative studies utilizing 5-FU intralesionally, at monthly intervals independently, or following the usage of two failed nonsurgical treatment techniques, would further help in delineating the exact therapeutic protocol of intralesional 5-FU for GW in future.

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Conflicts of interest

There are no conflicts of interest.