The Management of Diycult Anogenital Warts

192 Sex Transm Inf 1999;75:192–194

The management of diYcult anogenital warts

Clinical Sex Transm Infect: first published as 10.1136/sti.75.3.192 on 1 June 1999. Downloaded from A McMillan knots

Patients with anogenital warts present the extensive and persistent. As regression often healthcare professional with two major occurs within several weeks of delivery, treat- problems—recurrence and persistence. These ment is usually unnecessary. Occasionally, problems occur because of persistence of however, the warts cause discomfort, and these human papillomavirus in keratinocytes, defec- may be treated with cryotherapy or trichloro- tive immune responses in individuals with per- ethanoic acid (TCA). Conventional therapy is sistence and recurrence of warts, and the lack not uniformly successful in the treatment of of specific antiviral therapy. warts in the immunocompromised patient, In this article, the discussion will be confined including HIV infected individuals, and immu- to the management of lesions visible to the notherapy is generally unsatisfactory; it is not, naked eye and a scheme of management that I however, the purpose of this article to discuss have found useful is shown in figure 1. this issue further. The hyperplastic condylomata acuminata In deciding on treatment of persistent that have been present for less than 3 months, lesions, it is worth considering the following: often clear quickly after treatment with podo- Size and number of the lesions—Many indi- phyllin, podophyllotoxin, or cryotherapy. Podo- viduals have a few warts that are less than 1 mm phyllotoxin appears to be more eVective than in diameter and reassurance that spontaneous podophyllin in clearing warts and it has the regression will eventually occur, together with added advantage that the patient can apply it. counselling about reducing the risk of sexual Recurrence, either at the site of the initial transmission, may be all that is necessary. In lesions or on adjacent skin or mucosa, is addition to the psychological morbidity, larger common,1 and probably indicates active viral and more numerous warts, however, can cause activity in that area; therefore, repeated cycles discomfort, and, particularly at the urethral of treatment are often necessary before there is meatus and in the perianal region, they may complete eradication. As surrounding tissue bleed and become secondarily infected. necrosis may be a problem, I do not use podo- How the patient perceives his or her infection— phyllin or podophyllotoxin on warts in the Many patients seek some form of treatment vagina, anal canal, or on the uterine cervix. As because the presence of even the smallest wart lesions at these sites often regress spontane- causes considerable anxiety. Sometimes I find ously, I generally leave vaginal and anal warts that talking with the patient about the following http://sti.bmj.com/ untreated unless there are associated symp- is all that is required: toms such as anorectal bleeding or trouble- + the benign nature of the lesions some vaginal discharge. In my hospital, laser + feelings of guilt about having acquired a therapy is used less frequently in the treatment sexually transmitted infection and allaying of intravaginal or ectocervical warts but, these although ulceration can be a complication, I + the natural history of human papillomavirus have found 5-fluorouracil cream (5%) useful in infection on October 1, 2021 by guest. Protected copyright. the treatment of the former. Loop diathermy + treatment that is not curative for ectocervical warts has the advantage that + the possible adverse eVects of treatment of histological examination for cervical intraepi- small lesions; there may be damage to thelial neoplasia (CIN) is possible, and this is surrounding, latent virus-containing tissue my treatment of choice. Scissor excision under with the subsequent growth of warts at that local or general anaesthesia is my preferred site (Koebner phenomenon). treatment for intra-anal warts. Many patients, however, are not satisfied by Treatment with podophyllin or podophyllo- this approach. V toxin is less successful for sessile warts or What treatment, then, can be o ered to the lesions on dry skin surfaces, such as the shaft of individual with persistent warts? the penis, and I prefer to treat these by ablative methods. Extensive hyperplastic anogenital Ablative methods warts are often refractory to podophyllin, Cryotherapy can be very successful in clearing podophyllotoxin, and cryotherapy and are best warts that have failed to respond to podophyl- dealt with surgically or by the topical applica- lin, and is my first line ablative method; Genitourinary tion of 5-fluorouracil cream, an agent that I perianal warts, however, do not respond so 2 Medicine Unit, have found particularly useful. well. I have found scissor excision, either Department of Persistence at the same site for at least 6 under local or general anaesthesia, to be Medicine, Edinburgh months despite regular conventional treatment particularly helpful in the management of the Royal Infirmary is common and, in only very few cases, is a fea- latter and for sessile lesions of the labia majora A McMillan ture of immunodeficiency. A special case, how- and shaft of the penis. The results are generally Accepted for publication ever, is that of pregnancy when, with limited good with little scarring at the excision site. 20 April 1999 treatment options, anogenital warts can be Circumcision may be necessary in diabetic The management of diYcult anogenital warts 193

Newly diagnosed patient with anogenital warts No treatment or Yes Sex Transm Infect: first published as 10.1136/sti.75.3.192 on 1 June 1999. Downloaded from cryotherapy Pregnant woman? or No TCA Local sepsis? Yes Specific therapy eg balanitis No

Hyperplastic warts Sessile, keratotic warts Extensive < 3 months’ duration? on dry skin surface > 3 months’ duration? anogenital warts? No Yes External warts only? Cryotherapy OR electrocautery Scissor excision OR TCA (general anaesthesia) OR scissor excision OR CO2 laser Podophyllin OR 5-FU OR podophyllotoxin Recurrence? OR cryotherapy Yes

Urethral Anal Is treatment necessary? Success? Vagina Ectocervix meatus canal (see text) Yes Recurrences? Persistence? Repeat initial therapy Podophyllotoxin Submucous CO2 laser CO2 laser OR resection OR OR Yes cryotherapy 5-FU loop diathermy Repeat initial or Recurrences? OR alternative first line electrocautery therapy Yes Consider imiquimod No OR intralesional Recurrences? Persistence Success? Recurrences? interferon-α or β

Repeat initial Consider Consider Success? treatment 5-FU No imiquimod No Further ablative therapy and consider cyclic systemic interferon-α http://sti.bmj.com/ Figure 1 Flow chart of management of anogenital warts. TCA = trichloroethanoic acid, 5-FU = 5-fluorouracil cream (5%). men with preputial warts and phimosis. Trials of interferons in the treatment of Electrocautery and, where available, diathermy refractory warts have yielded conflicting re- and laser therapy are alternative treatment sults, and the place for such therapy is not well methods but, if the lesions are extensive, there established. may be considerable pain at the operation site on October 1, 2021 by guest. Protected copyright. and the wounds may heal more slowly than SYSTEMIC INTERFERONS after scissor excision. Monotherapy with systemic interferon-á is The topical application of trichloroethanoic ineVective. acid may be successful in the treatment of small persistent lesions, but painful ulceration may INTRALESIONAL INTERFERONS result, and I rarely use this agent. Small series of patients with refractory warts I have found the topical application of treated with intralesional interferon-á have 5-fluorouracil (5%) cream useful in the treat- shown a significant advantage over placebo in ment of refractory condylomata of the urethral producing regression. In a placebo controlled meatus and of the perianal area. Local adverse trial of intralesional interferon-â given three eVects, particularly ulceration, are common times per week for 3 weeks, Dinsmore et al 3 and the patient should be warned about these. reported significantly better results with inter- Even with ablative methods, recurrence is feron than with placebo, with the complete dis- not uncommon, and, if further ablative treat- appearance of the treated warts or at least a ment fails, immunomodulatory therapy may be 50% reduction in their area; this eVect was tried to reduce the risk of further recurrence. particularly noted in women.

Immunomodulatory therapy ADJUVANT THERAPY Inosine pranobex was one of the first such Interferons have also been used as adjuvant to agents to be used in clinical practice. While other therapy. Although some workers have appearing in some trials to show some benefit, shown significant benefit over placebo in the place of inosine pranobex in the manage- patients given systemic interferon-á three times ment of recurrent or persistent anogenital per week in addition to laser therapy, others warts is still uncertain have failed to show such advantage. 194 McMillan

Adopting a diVerent approach, Gross et al 4 and clearance between those treated with obtained reasonably good results with cyclic imiquimod and those treated with placebo; this administration of interferon-á. Patients with was particularly so in women. Of the patients

refractory warts that had been treated with who had complete wart clearance and who Sex Transm Infect: first published as 10.1136/sti.75.3.192 on 1 June 1999. Downloaded from carbon dioxide laser were given daily subcutan- were followed up for 12 weeks, 19%, however, eous injections of interferon-á, 1 MIU, in three had recurrence. It is important to note, cycles consisting of 5 days of therapy with a 4 however, that this trial included individuals week interval between each cycle. The recur- with previously untreated and treated warts. rence rate in the interferon treated group was Erythema developed in the majority of indi- lower than that in the placebo group and it was viduals, but excoriation and erosion were concluded that such cyclic application of low found in fewer than 50% of imiquimod recipi- dose interferon-á adjuvant to laser therapy was ents. superior to continuous interferon treatment. Although these studies are encouraging, the As it has been shown that patients with warts place of imiquimod, alone or in combination that respond to interferon therapy already have 5 with other agents, in the primary management enhanced cell mediated immune responses, it of anogenital warts is as yet unclear, but it is an is unlikely that this form of therapy will be uni- agent that I have used successfully when versally successful, irrespective of the mode of conventional therapy for persistent warts has administration of interferon. failed. As the results of treatment with interferons, Preliminary results of the treatment of either alone or as adjunct therapy, are uncer- anogenital warts with cidofovir and the retin- tain, as subcutaneous and intralesional injec- oids are encouraging, and the results of tions are not always be acceptable to the patient, as therapy is expensive, and as there are ongoing clinical trials are awaited with interest. frequent systemic side eVects I only use these Interestingly, cidofovir may have a place in the agents when all else fails and the patient management of warts in HIV seropositive demands further therapy. I have not been patients. impressed with the outcome in the patients I have treated. 1 Beutner KR, Wiley DJ. Recurrent external genital warts: a Imiquimod is an immune response modiﬁer literature review. Papillomavirus Report 1997;8:69–74. 2 Thomson JPS. Perianal and anal condylomata accuminata. that has potent antitumour and antiviral activ- In: Smith R, Rob C, eds. Operative surgery.Colon,rectum and ity. It induces interferon-á, interleukin 1 anus. London: Butterworths, 1977:376–8. 3 Dinsmore W, Jordan J, O’Mahony C, et al. Recombinant (IL-1), and tumour necrosis factor á (TNF-á) human interferon-â in the treatment of condylomata in peripheral blood, and human keratinocytes acuminata. Int J STD AIDS 1997;8:622–8. exposed to imiquimod show an increase in 4 Gross G, Roussaki A, Baur S, et al. Systemically adminis- tered interferon alfa-2a prevents recurrence of condylo-

mRNA for IL-2, IL-6, and IL-8. Arany and mata acuminata following CO2-laser ablation. The inﬂu- Tyring5 showed that wart clearance was associ- ence of the cyclic low-dose therapy regimen. Results of a multicentre double-blind placebo-controlled clinical trial. ated with tissue production of interferons á, â, Genitourin Med 1996;72:71. and ã, and TNF-á. 5 Arany I, Tyring SK. Activation of local cell-mediated immu-

nity in interferon-responsive patients with human http://sti.bmj.com/ In a placebo controlled trial of imiquimod papillomavirus-associated lesions. J Interferon Cytokine Res cream (5%), applied daily for a maximum of 16 1996;16:453–60. 6 6 Beutner KR, Spruance SL, Hougham AJ, et al. Treatment of weeks, Beutner et al reported a signiﬁcant dif- genital warts with an immune-response modiﬁer (imiqui- ference with respect to reduction in wart area mod). J Am Acad Dermatol 1998;38:230–9. on October 1, 2021 by guest. Protected copyright.