RESULTS Sixty‐one children with recalcitrant warts were treated with PDL; 75% of them had total clearance of warts after an average of 3.1 treatment sessions. Overall success rates were 100% for both perineal and perianal and face‐only warts, 93% for hands, 69% for plantar warts, 67% when both face and extremities were involved, and 60% when multiple extremities were involved. Pain and other side effects were minimal. Mild scarring occurred in 2% of patients; 75% of patients remained free of warts after a follow‐up period of 24 months or longer.

METHODS AND MATERIAL Retrospective survey of the medical records of children with recalcitrant warts who were treated with PDL between March 1995 through January 1999 at the Children's Memorial Hospital outpatient subspecialty center, Chicago, Illinois.

Viral warts caused by the human papillomavirus (HPV) are a common problem in children.1 The prevalence in school children is 3% to 24%.2 The current treatment of choice in most pediatricians' and dermatologists' offices is cryotherapy, which involves freezing the warts with liquid nitrogen for 10 to 20 seconds every 2 to 3 weeks.3 The cure rate with cryotherapy varies from 40% to 82%.2 The other first‐line topical therapy consists of paints containing salicylic acid and lactic acid. The cure rate for salicylic acid is 48% to 87%.4 Duct tape occlusion therapy offers a cure rate of up to 85%.3 Other agents that are commonly used topically are 5‐fluorouracil (5FU), podophyllin, and cantharidin.1 Of all of these, 5FU has been studied in various randomized controlled trials (RCTs), and the cure rate is 50%.1 There are no published RCTs studying podophyllin and cantharidin (Cochrane database).1 Warts that fail to respond to the standard first‐line therapy are called recalcitrant warts.5 Treatment of these lesions is often frustrating to dermatologists and patients. These warts are usually treated with a combination of different therapies: topical or systemic immunotherapy, intralesional bleomycin, surgical excision, curettage, and cautery.1 Berth‐Jones and Hutchinson reported a cure rate of 41% to 52% using a combination of cryotherapy and topical paints.6 Imiquimod has been found to clear recalcitrant warts in only 30% of cases.7 A cure rate of 31.5% was noted with oral cimetidine alone in one study.8 If it is combined with levamisole, the cure rate is almost double (65%).8 Intralesional bleomycin is painful, especially in children, and the success rate varies from 33% to 92%.9 The success rate with surgical removal by curettage followed by cautery is 65% to 85%.10 Various lasers, especially carbon dioxide (CO 2 ) and pulsed dye laser (PDL), have also been used to treat recalcitrant warts. CO 2 laser has been found to have a cure rate between 52% and 64% in different studies,11, 12 but it is often associated with infection, delayed healing, scarring, and other complications. The PDL (585 nm) is reported to be safe, with a risk of scarring that is much lower. It has been used to treat recalcitrant warts in many recent studies, with clearance rates ranging from 68% to 93%.13, 14 Clearance rates vary depending on the site of the warts treated, the fluences used, and the follow‐up period. Although many studies using PDL in the treatment of warts have been performed in adults, there are few in children. Through retrospective review and follow‐up, we report the long‐term response rate of recalcitrant warts in children after treatment with PDL.

Materials and Methods All children with recalcitrant warts (defined as having >1 wart unresponsive to ≥1 types of physician‐directed destructive treatment modalities, other than PDL, over >2 months) treated with PDL at our pediatric dermatology laser treatment center between March 1995 and January 1999 were identified through chart review. The patients were divided into groups according to the body sites affected by the warts. The details of anesthesia and the laser parameters, including the number of treatments, spot size, energy, and number of pulses for each treatment with PDL, were analyzed from the medical records. Patients' parents were then interviewed over the telephone to obtain information about the success of treatment, side effects, and possible recurrences since the patient's last visit to the laser center. All previous treatments used were determined based on information from chart review and parent interviews. The end result of laser treatment was complete clearance of warts. Warts were considered 100% cleared if there was no recurrence and partially cleared if the patients did not clear completely or had recurrence within the documented follow‐up period. Follow‐up periods were rounded to the nearest month.

Treatment Protocol Warts were pared with a #15 scalpel blade until punctate bleeding was apparent. The PDL was then used to irradiate the warts using a 5‐ or 7‐mm spot size. Energy ranged from 6.5 to 9.5 J/cm2, with the majority treated at 7 J/cm2. All warts were pulsed multiple times using a stacked pulse method with an average of three pulses per wart. Patients returned to the laser center for repeat treatment at 2.5‐ to 4‐week intervals until resolution of all warts occurred or the treatment modality was abandoned.

Results A total of 61 children were treated with PDL, ranging in age from 2 to 17 years (mean age 10 years); 33 (54%) patients were female and 28 (46%) male. None of the patients had any comorbid conditions such as immunosuppression or any systemic diseases. The duration of warts, despite prior therapy, ranged from 2 to longer than 60 months. Thirty‐nine (64%) patients had warts present for longer than 12 months at the time of PDL treatment. Before PDL, a variety of treatment modalities were attempted; 58 (93%) patients were treated with more than one modality, 14 (23%) patients had failed topical treatment and cryotherapy, and 27 (44%) patients had failed topical treatment, cryotherapy, and cimetidine. Fifty‐six patients were followed up for at least 1 year (range 12–66 months), and 77% were followed up for more than 2 years after PDL treatment. The overall clearance rate was 75%, with follow‐up ranging from 12 to 66 months. The remaining 25% had partial clearance. The average number of treatments for complete clearance of warts was 3.1. Total resolution of the warts with one treatment session was seen in 13% of patients. Body locations such as the face and perineum were most likely to clear in one treatment (50% and 20%, respectively). The clearance rate was highest for warts located on the perineum and only on the face (100%), followed by the hands (93%) (Figures 1 and 2). Plantar warts cleared completely in 69% of patients. Combined face and extremity warts cleared in 67% and combined arm and leg (or hands and feet) in 60% of patients. The results are summarized in Table 1. Figure 1 Open in figure viewer PowerPoint Periungual warts before pulsed dye laser. Figure 2 Open in figure viewer PowerPoint Periungual warts showing complete clearance after pulsed dye laser. Table 1. Details of Wart Clearance and Laser Parameters Site ofInvolvement Patients,n (%) Warts Cleared Patients Contacted, According toInterval Since Treatment, %* Patients 100%Cleared, n (%) Ave. Numberof LaserTreatments AverageJ/cm2 AverageNumber ofPulses perTreatment 12Months 13–36Months 37–66Months Hands 14 (23) 13 (93) 3.4 6.8 72 54 16 30 Combined extremities 15 (25) 9 (60) 5.3 7.6 116 56 33 11 Plantar warts 13 (21) 9 (69) 3.5 7.2 75 11 33 56 Combined face and extremities 12 (20) 8 (67) 2.8 7.1 56 25 50 25 Perineal and perianal warts 5 (8) 5 (100) 2.2 6.9 48.8 40 20 40 Face only 2 (3) 2 (100) 3.5 — — — 100 — All sites 61 (100) 46 (75) The side effects of the PDL treatments were minimal; 8% of patients had hypopigmentation, 2% had hyperpigmentation, 2% each had mild scarring and blistering, and 3% complained of an immediate itching after laser treatments. One patient, treated with general anesthesia, had a seizure from which he recovered uneventfully. This patient had no further seizures or other complications with subsequent treatments under general anesthesia. Pain management was excellent through varied uses of anesthesia, as shown in Figure 3. The majority of patients were treated with eutectic mixture of lidocaine and prilocaine (EMLA) alone before their laser treatment (49%), 33% were administered general anesthesia alone because of extensive verrucae or because of the inability to adequately locally anesthetize the area to be treated (perineal and perianal warts), and 15% had general anesthesia and EMLA over the course of their treatments. Nerve blocks were given to 3% of patients, and a combination of EMLA and nerve blocks was used in 1% of patients. None of the patients reported severe incapacitating postoperative pain or difficulty in performing normal activities. Figure 3 Open in figure viewer PowerPoint Types of anesthesia used during treatment with pulsed dye laser. The cost of PDL treatment was significant. At the laser center where these treatments were administered, the cost of therapy depended on the number of pulses delivered and the type of anesthesia given. The greatest cost was associated with the use of general anesthesia. When general anesthesia was given, the facility cost was $1,105 per session for 300 or fewer pulses, $1,454 for 301 to 600 pulses, and $1,855 for more than 600 pulses. With local anesthesia only, the facility cost was $100 for 1 to 10 pulses, $150 for 11 to 100 pulses, and $200 for 101 to 250 pulses. The fee for the physician delivering the services ranged between $300 and $829 per treatment session.

Discussion Viral warts are a common dermatologic problem caused by HPV. HPV causes a spectrum of cutaneous warts such as verruca vulgaris, verruca plana, and palmoplantar warts.1 The different treatment options include physical destruction (e.g., surgical excision, electrodesiccation and electrocautery, and cryotherapy), chemical destruction (e.g., salicylic acid, cantharidin), chemotherapeutic agents (podophyllin, 5FU, and bleomycin) and various immunomodulating drugs (e.g., dinitrochlorobenzene, squaric acid dibutylester, interferons, retinoids, cimetidine, topical imiquimod). Warts that fail to respond to the conventional treatments are called recalcitrant warts.5 Different combination therapies, the newer immunomodulators, and cytotoxic drugs have been used with variable success.4 Lasers are an effective, safe, well‐tolerated procedure for the treatment of extensive recalcitrant warts. Several types of lasers have been used, especially CO 2 and PDL. The CO 2 laser emits infrared light (10,600 nm), which is absorbed by water. Hence, there is nonselective thermal tissue destruction. It has been shown to be associated with prolonged postoperative pain, delayed wound healing, scarring, and hypopigmentation.10, 15 PDL is an effective, safe, well‐tolerated procedure for the treatment of extensive, recalcitrant warts in the pediatric population. Especially important in the care of pediatric patients is the tolerability of pain associated with the PDL treatment compared with cryotherapy and CO 2 laser. PDL appears to clear the warts by producing selective photothermolysis of dermal blood vessels. Histologically, warts have a dilated congested capillary network in the dermal papillae that supply the warts. At 585 nm, oxyhemoglobin selectively absorbs PDL and is able to injure these feeding vessels without damaging surrounding structures. This type of selective damage gives PDL a distinct advantage over other destructive modalities by decreasing the risk of scarring.15 In addition to selective photothermolysis, PDL also has immunomodulating properties that contribute to wart healing. Ultrastructural studies have shown that, 1 week after laser therapy, all subjects were positive for interleukin (IL)2 messenger ribonucleic acid (mRNA) and IL4 mRNA. Levels of IL4 mRNA were higher, indicating an activated Th2 cell response.16 Activated Th2 cells are known to be important in fighting cutaneous viral infections. The overall clearance rate for common and recalcitrant warts with PDL varies from 0% to 100%.13-15, 17-26 Tan and colleagues,19 in their preliminary study, reported 72% clearance of recalcitrant warts with PDL after an average of 1.7 treatments. The energy fluence was 6.2 to 7.5 J/cm2, and the spot size was 5 mm. Kenton and Tan15 observed a higher clearance of 92% in their patients with 103 recalcitrant warts. Their fluence was 6 to 9 J/cm2, and the average number of treatments was 2.1. None of the warts relapsed during the follow‐up period of 7.2 months. Kauvar and colleagues14 studied 142 patients with 703 recalcitrant warts and 25 untreated warts and reported 95% clearance on the body and limbs and 78% clearance of plantar warts after one treatment session. Jacobson and colleagues13 observed a clearance of 68% for recalcitrant warts. Robson and colleagues,20 in their randomized series of recalcitrant and untreated warts, described 66% clearance with PDL. Passerson and colleagues,21 in their recent randomized comparative study of palmoplantar warts, reported 64% clearance with PDL. In our pediatric group, we achieved 75% clearance of warts after an average number of treatments of 3.1; the mean fluence was 7.1 J/cm2. Facial (only) and perineal warts cleared completely (100%). Table 2 summarizes the response to treatment in different reported series. Table 2. Response to Treatment in Various Reported Series Tanet al. 19 Kauvaret al. 14 Jain andStorwick 23 Jacobsonet al. 13 Rosset al. 17 KentonandTan 15 Robsonet al. 20 Vargaset al. 18 Kopera 24 Parket al. 26 Schellhaaset al. 5 Presentstudy Cases, n 39 142 28 32 33 28 15 12 134 56 73 61 Age, range 5–59 7–56 3–72 11–67 5–69 >18 18–47 4–65 2–12 6–75 2–17 Types of wart R R (mostly) P R, UT R (mostly) R, C R, UT Face R, UT R, C R R Clearance, % 72 93 95 68 R47 UT 48 92 R75 C 66 100 62.69 48.1 89 73% Fluence,J/cm2 6.25–7.5 Up to 9.5 8.1–8.4 8 9.4 6–9 9.5 9–13 8 8.5–9.5 8–12 7.1 Average of treatments 1.68 2.5 2.6 1.84 R1.61 UT 3.4 2.1 R1.6 C 2 1–3 3.38 3.1 3.7 3.45 Spot size, mm 5 5–7 5 5–7 5–7 5 5 7 5 5 5–7 Treatment interval, weeks, range 1–3 2–4 1–4 4–8 2–4 6–8 4 3–4 3.26 2–3 2 2.5–4 Follow‐up period, months 5 0.5–6 — 5.4 7.2 11 10.33 5.38 3–20 6 12–66 Recurrence % 3.5 14 lesions recurred — Nil Nil 30–40 Nil 0.79 0 (within 3 months 1 8 Side effects were minimal. Eight percent of patients experienced hypopigmentation. One patient each noted scarring and blistering. The presence of minimal side effects found in our study and others13-15, 17-26 in association with a high wart clearance rate is in sharp contrast to reports using CO 2 laser to treat recalcitrant warts. We attribute the minimal complications of the PDL to the selective destruction of the wart vasculature. The low incidence of recurrences noted even as far out as 66 months after PDL in our study is encouraging. These findings add credibility to the findings of other authors reporting clearance with PDL over shorter follow‐up periods. Our long‐term follow‐up study showed a recurrence rate of 8% for all patients whose warts resolved with PDL therapy. When general anesthesia is used for treatment of warts with PDL, several safety issues must be considered. Fretzin and colleagues27 and Epstein and colleagues28 reported incendiary potential of the PDL in association with 100% oxygen delivery and hair‐bearing surfaces. Epstein and colleagues28 noted that green nasal cannulae were much more flammable in oxygen than clear nasal cannulae. The PDL at 585‐nm put out light in the visible spectrum, which darker materials absorb, producing enough heat for combustion. An additional risk of 1:10,000 of a major anesthetic complication is added. A pediatric anesthesiologist should always be involved when this is necessary, and no anesthetic should be given unless the child is completely healthy to minimize risk. In conclusion, PDL appears to be a promising modality for the treatment of recalcitrant warts. It is safe and is particularly useful in children because of the tolerability of pain. The only limiting factor is the cost. Hence it is not recommended as a first‐line treatment for warts in children. New warts should be treated first with standard conventional therapy, with topical or cryotherapy if they are few in number. For patients with many warts for whom topicals or cryotherapy are not reasonable, oral cimetidine and immunotherapy are excellent therapeutic options, but when these therapies fail in the pediatric population, PDL stands out as the most efficacious and safest treatment currently available, with minimal side effects and a low, long‐term recurrence rate.