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Treatment of disseminated facial warts with diphenylcyclopropenone contact immunotherapy

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Treatment of disseminated facial warts through contact immunotherapy with diphenylcyclopropenone (DPCP)
Shahin Aghaei, MD
Dermatology Online Journal 12 (2): 10

Department of Dermatology, Jahrom Medical School, Jahrom, Iran.


This paper highlights the effect of diphenylcyclopropenone (DPCP) sensitization on warts resistant to other treatments and is interesting in views of the fact that all the facial warts apparently responded. To analyze the efficacy and side-effects of DPCP treatment of viral warts, a prospective study was designed to follow six patients with chronic and resistant facial warts through immunotherapy sensitization with diphenylcyclopropenone for 10 weekly sessions. Patients were first sensitized with 2 percent DPCP and then followed by weekly maintenance of 0.001-1 percent DPCP in acetone on facial warts until mild contact dermatitis was obtained. After application of DPCP to the warts of the face, all of the facial warts became inflamed and resolved. DPCP appears to be a valuable, safe, and well-tolerated treatment for resistant and chronic facial warts.


Warts are one of the most common problems in dermatological practice. In many cases warts are recalcitrant despite multiple therapeutic efforts including cryotherapy, electrosurgery, keratolytics, 5-flourouracil, bleomycin, antiviral agents, hypnosis, ultrasound, X-ray therapy, laser, photodynamic inactivation, levamisole, cimetidine, interferon, and retinoids [1].

Because many patients with multiple warts have defective cell-mediated mechanisms [1, 2], treatments have been attempted with various immunomodulator agents. The first to be tried was dinitrochlorobenzene (DNCB) [3, 4], which subsequently proved to be mutagenic [5]. Squaric acid dibutylester (SADBE) and diphenylcyclopropenone (DPCP) have no such risks [6]. Moreover, the latter substances, because their safety, were used in the treatment of resistant warts, as well as in alopecia areata [7, 8].

Considering the ethical problems arising from the use of substances whose long-term effects are still unknown [7], the author has only used DPCP in treating resistant and multiple facial warts as a last resort after the failure of other treatment with a view to assessing the effectiveness of this alternative treatment.


Six patients with recalcitrant facial warts (3 males and 3 females) with an age range of 11-31 years (mean age, 18.83 years) were treated with weekly applications of different concentrations of DPCP. The duration of disease before treatment was 9 months to 8 years (mean = 3.04 years). Sensitization was made with 2 percent DPCP in acetone on the medial arm. After 1 or 2 weeks the patients were sensitized and were able to start treatment with weekly application of DPCP solutions ranging between 0.001 percent and 1 percent according to the patient's ability to produce a mild inflammatory reaction. All the warts were treated weekly. The number of applications was restricted to no more than 10 weeks, which to be considered long enough for effective treatment. To the author knowledge no concurrent treatment was carried out. Four out of six patients had facial plane warts and two patients had verrucae vulgaris on the face.

Only patients over 10 years of age were included. Informed consent was obtained. All the patients were initially examined on complete blood count, sedimentation rate, blood chemistry, urinalysis, and anti-nuclear antigen (ANA), which all were within normal limits.


Figure 1Figure 2
Figure 1. Before treatment
Figure 2. After 10 sessions of treatment

All patients completed the treatment. Four patients were wart free after 8-10 sessions (see Table 1). Two patients improved after 10 sessions: the size and number of the warts were reduced (Figs. 1, 2). All patients became sensitized to 2 percent DPCP in 1-2 weeks. Sensitization manifested as a typical-IV reaction at the treated site with focal erythema, itching, edema and infiltration.

After sensitization has occurred a solution of DPCP was applied to the warts to induce a low grade inflammatory reaction. Initially, low concentrations were applied (0.001 %) and stronger or weaker solution used at subsequent visits depending on the severity of the inflammatory reaction. After 8-10 sessions of application, four of six patients with plane facial warts were completely cured and two other patients with common warts were improved. After 2 months the latter patients' lesions were completely gone. During the followup period, no recurrences were occurred within 6-12 months.

The complete response rate at the end of the investigation was 66.6 percent (4 of 6 patients). Side effects were not a problem in the majority of patients. Adverse effects included moderate to severe reactions at sensitization site or at the treatment site, or spreading of contact eczema to other parts of the body.


Immunotherapy has many advantages: many lesions can be treated simultaneously, and the frequency and size of relapsing warts are much reduced. However, regression after DPCP still needs to be clarified although many hypotheses have been put forward. It may well be that the wart is damaged by unspecific DPCP-induced inflammation. DPCP may bind to wart protein and subsequently induce a specific immune reaction [9]. An immune mechanism seems to be confirmed by the fact that untreated warts can also be rejected [10].

The role of lymphokines can not be excluded [3]. This may stimulate the host immune reaction to the wart. The longer the duration of the wart, the lower the possible effect of DPCP, probably because of its lower capacity to stimulate the immune system [11].

Although DPCP is restricted to the laboratory, personnel who prepare the concentrations may inadvertently be sensitized [12] (the author inadvertently was).

Not all patients manage to tolerate itching either on the challenge site or the sensitization site. But the possible effect to be feared the most is that this particular form of chronic immunostimulation may induce the onset of lymphomas even after a long period of time, especially the problem arises more with the treatment of alopecia areata than with the brief period of treatment for warts [1].

Immunotherapy with DPCP should not be used routinely as an initial therapy for facial warts, but is a possible alternative in selected patients with recalcitrant multiple facial warts.

This is the first clinical trials of successful topical immunotherapy with DPCP in disseminated facial warts and should be regarded as an effective therapeutic tool for this indication. DPCP appears to be a valuable, safe, and well-tolerated treatment for resistant facial warts and can be considered as a first line treatment.

Acknowledgment: All the patients gave informed consent, and the author thanks the patients and their parents.


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