Pulsed dye laser treatment of recalcitrant verrucae: A preliminary report

Lasers in Surgery and Medicine 13:127-137 (1993)

Pulsed Dye Laser Treatment of Recalcitrant Ver r ucae :

A Preliminary Report O.T. Tan, MD, R.M. Hurwitz, MD, and T.J. Stafford, MD, PhD

Laser Research Laboratory (0. T. T.) and Department of Anesthesiology (T. J.S.), Boston City Hospital, Boston, Massachusetts 027 76, and Section of Dermatology

(R. M. H.), St. Vincent Hospital, Indianapolis, Indiana 48260

Patients with recalcitrant warts on the fingers and hands, periungual, and other parts of the body including verrucae plana and plantar surfaces were treated using the pulsed dye laser at 585 nm, 450 usec, and a spotsize of 5 mm diameter. Of the 39 patients treated, 28 (72%) were cleared of their warts after an average of 1.68 treatments at fluences of 6.25-7.5 J/cm2. Seven (18%) patients had a reduction of between 8%95% of their warts after 1.3 treatments, and verrucae reduced by 50% in four of the 39 patients after one treatment. The average follow-up period of the 28 cases cleared of their warts has been 5 months. Of this group, those with periungual warts have been followed for up to 6.4 months, compared to 4.8 months for those with warts on other parts of their body, 4.0 months for those with finger and hand warts, and 2.0 months for plantar warts. Only one of the 28 patients has had a recurrence after 3 months of clearance. o 1993 Wiley-Liss, Inc.

Key words: verrucae, pulsed dye laser, recalcitrant, vasculature

INTRODUCTION

Preliminary work had suggested that the pulsed dye laser at 585 nm was effective in the treatment of verrucae. However, since a wide range of treatment modalities currently exist, the precise role of any new treatment had to be iden- tified as to where such a new treatment might fit into the existing armementarium. It was decided to conduct a pilot study to confirm the early im- pressions of efficacy and that verrucae unrespon- sive to other conventional treatments might be the best test model.

Warts or verrucae that are induced by the human papilloma virus (HPV) are benign tumors of the skin occurring in children and adults at an estimated incidence of -10% [l l . Although com- monly more of cosmetic or nuisance significance, in subungual or plantar locations, warts can be painful or even disabling. They can present as venereal or nonvenereal warts. Of the estimated 4 million patient visits for nonvenereal warts reported in 1982, 70% of these patients were between 10 and 39 years old and 50% of these pre- sented to the dermatologists for treatment [2].

Warts are particularly common in immune- suppressed patients, especially those with im- paired cell-mediated immunity [31.

Many treatment modalities have been used to physically destroy the infected viral cells. These include the use of various caustic sub- stances such as salicylic and lactic acids, cryo- surgery, curettage, and electrocautery. Chemo- therapeutic agents such as 5-fluorouracil and bleomycin have also been reported to be effective in certain type of warts [4]. When these techniques fail, some clinicians surgically excise the warts. Over the past few years, the carbon dioxide laser (CO,) has become a relatively common modality in the treatment of warts, particularly in those lesions that have proven recalcitrant to other traditional therapies [51. The ability to op- erate in a bloodless field offers well-documented

Accepted for publication October 6, 1992. Address reprint requests to Dr. O.T. Tan, 29 Commonwealth Avenue, Suite 101, Boston, MA 02116.

0 1993 Wiley-Liss, Inc.

128 Tan et al.

Fig. 1. Black “crust” over the laser irradiated wart.

Fig. 2. Skin under the “crust” revealing either normal skin or remnants of wart (arrow- head).

Recalcitrant Verrucae Pulsed Dye Laser Treatment 129 advantages in this form of surgery. Certain draw- backs such as scarring of the laser-irradiated skin, a prolonged period of postoperative recov- ery, infection, late bleeding, as well as the presence of viable viral particles in the laser plume during the laser procedure have been described [6,71.

All of these techniques have concentrated upon physically destroying the infected cells. Whereas the viral DNA, virion antigens, and ma- ture virions have been detected only in keratinocytes at or above the granular layer in the epidermis [8], it has been assumed that the virus infects the basal cells and stimulate them to di- vide. For these reasons, the treatment modalities currently used to treat warts have concentrated upon nonselectively destroying the granular layer as well as all adjacent epidermal cells.

However, there are a number of cases where, in spite of apparently widespread and complete damage in the region of the verrucae and its adjacent tissues, the verrucae have persisted and remained resistant to treatment. In these cases the verrucae can be classified as recalcitrant and it was this class of presentation that was chosen for treatment using the pulsed dye laser in this study.

A characteristic histologic feature of verrucae has been the presence of prominent, dilated, and congested blood vessels in the dermal papillae extending up the elongated rete ridges [91. In searching for an alternative therapy to treat recalcitrant warts, which would obviate some of the morbidity and dangers of the CO, laser and other physical and chemotherapeutic agents already discussed, it seemed reasonable to target the laser energy at the prominent vessels present in these lesions. The goal of selectively destroying these vessels using the laser would be either to abolish the nutritional blood flow to the verrucae infected keratinocytes and/or to destroy the most rapidly replicating cells bearing the virus at the basal layer. In both cases, the ability to confine the laser energy solely to blood vessels would also min- imize the injury induced in healthy tissue such as dermal collagen [lo]. We have demonstrated in previous studies that blood vessels can be selectively destroyed using the pulsed dye laser [lo- 121. Such selectivity has localized injury just to the blood vessels, sparing unnecessary damage to healthy adjacent cellular structures. If the pulsed dye laser was successful in clearing the verrucae, it would avoid the scarring that has been reported to occur from some of the nonspecific treatments,

particularly from CO, laser treatment where it has been almost impossible to control the extent of thermal injury to healthy adjacent tissues [51.

The purpose of this study was to: (1) examine whether it might be possible to effectively clear recalcitrant warts using the pulsed dye laser, (2) determine whether equivalent fluence ranges as those used for PWS treatment would effectively clear these lesions, and (3) establish whether any advantages followed from this laser over other reported therapies such as the CO, laser.

MATERIALS AND METHODS

Thirty-nine patients presenting to two dermatology clinics with recalcitrant verrucae were included in the study. All of these subjects had been treated by other modalities, including cryo- therapy, caustic agents, and lasers as well as surgery. The subjects ranged in age from 5 to 59 years. Of these 39, 12 were under 18 years; 14 were males and 25 females. The warts treated were divided into those on the fingers and hands, plantar, periungual, and other parts of the body (Tables 1-4). Fourteen patients had finger and hand verrucae, 6 had plantar, 7 had periungual, and 12 had verrucae (including three with verrucae plana) on other parts of the body (including three with verrucae plana), such as the neck, face, legs, knees, and ear lobe (Tables 1-4).

After taking a careful history and following examination of the verrucae, photographic docu- mentation was taken at each visit to monitor change and/or improvement following laser treatment.

The hyperkeratosis and any redundant skin overlying the wart was carefully removed using a # 15 scalpel blade to the level of visualization of the blood vessels. In those with periungual verrucae extending under the nail, the latter was carefully trimmed to reveal as much of the wart as possible. Care was taken not to produce frank bleeding as any surface blood would have ab- sorbed the laser energy, preventing the laser light from penetrating deep into the wart vasculature.

Single 5 mm diameter spot-size pulses from the flashlamp pulsed dye laser at 585 nm over a pulse duration of 450 usec at fluences of between 6.25 and 7.5 J/cm2 were delivered to the wart and a small rim around it. Either a dry dressing or antibacterial ointment and cold pack were placed over the treated area. No special postoperative care was needed following this treatment as the epidermis remained intact in all the cases.

130 Tan et al. TABLE 1. Response of Finger and Hand Verrucae to Pulsed Dye Laser Subdivided According to Duration of Lesion

~

Finger and Hand Verrucae

Duration of No. F 1 u e n c e treatments Range Average warts (yr) cases (J/cm2) (mean) Results F/U (mo) F/U (mo) 6 mos-1 yr 4 6.25 -7.5 2.00 3 cleared 1-6 3.0

1-3 6 6.5-7.5 1.2 3 cleared 5-8 6.4

No.

1 cleared by 50%

2 cleared by 90% 1 cleared by 50%

3-5 1 7.5 1.0 1 cleared 5.0 5.0 >5 3 7.5 1.33 2 cleared 2-3 2.5

Total 14 1.4 9 cleared (64%) Average F/U cleared: 1 cleared by 50%

3 cleared by 90% (21.4%) 2 cleared by 50% (14.28%)

4.7 mo.

Average F/U for all cases: 4.0 mo

TABLE 2. Recalcitrant Plantar Verrucae Response to Pulsed Dye Laser at 585 nm

Plantar Verrucae

Duration of No. Fluence treatments Range Average warts (yr) cases (J/cm2) (mean) Results F/U (mo) F/U (mo) 6 mcr l yr 0 1-3 1 7.5 1 95% cleared 2.0 2.0 3-5 3 6.5 2 2 cleared 2-4 2.7

>5 2 6.75-7.5 1.00 1 cleared recurred 2-3 2.5

No.

1 cleared by 80%

3 mo later 1 cleared by 50%

1 cleared by 95% 1 cleared by 80% 1 cleared by 50%

Total 6 1.5 3 cleared (50%) Average F/U cleared: 3.0 mo


Patients returned between 1 to 3 weeks for follow-up and further laser treatment (s). At these visits, assessment of the clearance of the wart was made using clinical and photographic documenta- tion and, if necessary, further debridement with a #15 scalpel blade and laser treatment was given. All treatments followed the same protocol out- lined above. Particular attention was also paid to document adverse effects such as pain, period of forced inactivity through treatment discomfort, and scarring, etc. Even when lesions had cleared, follow-up visits were continued to ensure that recurrence would be noted.

Fifteen biopsy specimens were obtained from 10 patients of their warts immediately, 24 hours, 6 days, and 13 days following laser irradiation.

Each specimen was fixed in 10% formaldehyde solution, stained with eosin and hematoxylin, and processed for light microscopic examination.

RESULTS Clinical

Immediately following laser exposure, the wart turned light gray. In none of the patients treated was there any blistering, bleeding, or prolonged pain. The only discomfort felt by the patients was reported during the treatment procedure itself when each pulse produced an immediate “pinprick” sensation followed by a sensation of heat, which lasted for 5-15 minutes. No long-term effects were reported by any of the subjects. All were able to resume normal activities

Recalcitrant Verrucae Pulsed Dye Laser Treatment 131 TABLE 3. Verrucae in Other Parts of Body Apart From Limbs

Warts on Other Parts of the Body

Range Average Duration of No. Fluence treatments warts (yr) Site cases (J/cm2) (mean) Results F/U (mo) F/U (mo) 6 mo-1 yr leg 3a 6.25-7.5 1.33 2 cleared 1-7 4.3

No.

cheek 1 cleared by 95% legs & knee

neck 1 cleared by 95%

knee

knee & leg

1-3 ear lobe 7b 6.25-7.5 1.43 6 cleared 2-10 5.90

1%

3-5 knee 2 6.5-7.5 1.00 2 cleared 1-3 2.0

> 5 0 Total 12 1.40 10 cleared (83%) Average F/U clear:

2 cleared by 95% 4.7 mo

Average F/U for all cases:4.8 mo

(16.67%)

al patient had 35 lesions. bl patient had 112 lesions; 1 patient had 40 lesions.

TABLE 4. Periungual Verrucae Treated Using Pulsed Dye Laser

Periungual Verrucae

Duration of No. warts (yr) cases 6 mo-1 yr 2

1-3 yrs 4 3-5 yrs 0 > 5 yrs 1 Total 7

No. Range Average

F/U (mo) F/U (mo) Fluence treatments (J/cm2) (mean) Results 6.5-7.5 2.5 1 cleared 2-3 2.5

6.5-7.5 1.5 4 cleared 6-16 9.25 1 cleared by 50%

7.5 2.0 1 cleared 3.0 3.0

1 cleared by 50% 1.85 6 cleared (86%) Average F/U cleared

7.0 mo


following treatment of their warts. Over the 24 hours following laser exposure, the initial gray discoloration turned almost black and persisted for up to 2-3 weeks (Fig. 1). This black discoloration was often present when the patient returned for follow-up treatment. The altered tissue was easily removed using a #15 scalpel blade, revealing either “normal” tissue or, in some cases, remnants of wart tissue beneath (Fig. 2).

Histopathology Histopathologic changes observed immedi-

ately following pulsed dye laser treatment re-

vealed the presence of agglutinated red blood cells in the papillary vessels accompanied by stream- ing of the adjacent keratinocytes (Fig. 3A,B). Twenty-four hours later, the keratinocytes and blood vessel walls appeared vacuolated and necrotic. Marked intravascular agglutination of the red blood cells (thrombosis) accompanied by endo- thelial cell necrosis of blood vessel walls were still evident at 6 and 13 days after pulsed dye laser irradiation of the warts. These vessels were also surrounded by necrotic keratinocytes as well as extravasated red blood cells within the papillary dermis and epidermis (Fig. 3C).

Figs. 3A and B.

Recalcitrant Verrucae Pulsed Dye Laser Treatment 133

Fig. 3. A Normal verrucae revealing the presence of large blood vessels in dermal papillae extending up the elongated rete ridges (arrowheads). B: Agglutinated red blood cells (arrowheads) in verrucae blood vessels immediately following laser irradiation. c: Thrombosed blood vessels in laser irradiated verrucae accompanied by extravasation of red blood cells and necrotic adjacent keratinocytes.

Outcome Of the 39 patients treated, 28 (72%) were

cleared of their wart(s) after an average of 1.68 treatments using the pulsed dye laser at fluences of between 6.25-7.5 J/cm2 (Figs. 4, 5 ) . There was

a reduction in wart size by 80-95% after 1.3 treatments in seven (18%) patients, and four had their warts reduce in size by 50% after 1 laser treatment (Table 5).

Six of the seven patients (86%) with periun

134 Tan et al. TABLE 5. Number Treatments Required to Clear or Reduce Size of Warts Using Pulsed Dye Laser

Cleared 80-95% cleared 50% cleared No. No. No. No. No. No.

Site patients treatments patients treatments patients treatments Fingers & hands 9 16 3 3 2 2 Plantar 3 4 2 4 1 1 Periungual 6 12 0 0 1 1 Other parts 10 15 2 2 0 0 Total 28 47 I 9 4 4 Average no. treatments: 1.68 1.3 1.0 Average FIU cleared: 5.0 mo

TABLE 6. Summary of Patients With Verrucae Treated Using Pulsed Dye Laser and Their Response to This Treatment Modality

Results No. No. Site cases treatments Cleared 80-95% 50% Fingers & hands 14 1.40 9 (64%) 3 (21%) 2 (14%) Plantar 6 1.50 3 (50%) 2 (33%) 1(17%) Periungual 7 1.85 6 (86%) 1(14%) Other parts of body 12 1.40 10 (83%) 2 (17%) Total 39 28 (72.0%) 7 (18%) 4 (10%)

gual warts cleared after 1.85 treatments, and 10 of the 12 patients (83%) with warts on other parts of their body (including the verrucae plana) (Fig. 4) apart from hands, feet, and periungual areas were also cleared after 1.40 treatments. Of the cohort with warts on their fingers and hands, 64% (9 of 14) were cleared after 1.40 treatments, and 50% (3 of 6) with plantar warts cleared after 1.50 treatments (Fig. 5; Table 6). Although in patients with previously untreated verrucae, response to treatment resulting in 50% clearance would be considered a failure, the warts being treated here were recalcitrant and had failed to respond to all other conventional treatments. Hence, 50% clearance in this cohort was considered a good response.

The average follow-up period of the 28 cases cleared of their warts has been 5 months (Table 5). Of this group, those with periungual warts have been followed for up to 6.4 months (Table 4) compared to 4.8 months for those with warts on other parts of their body, 4.0 months for those with finger and hand warts (Table 11, and 2.0 months for plantar warts (Table 2). Only one of these 28 patients had a recurrence after 3 months (Table 2).

DISCUSSION

In this clinical report describing the results of a new form of treatment of recalcitrant warts,

we are aware that we cannot from this clinical data claim that this particular laser represents an optimal treatment modality.

A wide range of distinct methods from folk medicine “nostrums” to lytic agents, immuno- therapy, to lasers have been used to treat verrucae. One difficulty in arriving at preferred modalities lies in the idosyncratic nature of warts, independent of location, histopathology, and the viral type strain, by which certain individuals will respond well to particular treatments but not to others, or alternatively the lesions may “spon- taneously” regress and clear. Clinicians are thus prepared to try a variety of treatments depending on the response. A wide variety of “success rates” for each of the different methods of treatment have been documented (perhaps not surprisingly in view of the above), but there is a paucity of comparative studies [131 and even they have been less than comprehensive. Ideally, any comprehensive assessment of different methods should include the “efficacy,” morbidity of treatment, and its aftereffects.

“Efficacy” of treatment should define for a consistent and reproducible technique, not just the degree of regression, but also the time-course of such improvements. With virion-containing tissue outside of the visible lesion [7], with the possibility of reinfection, and with a latency period of the virus in the skin lasting up to 2 months [ll,

Recalcitrant Verrucae Pulsed Dye Laser Treatment 135

studies are necessarily protracted. For these reasons, it was important even in this preliminary work to monitor the patients’ posttreatment.

Similarly, distinct morbidities do associate with particular treatment forms. Logan et al. [51 brought attention to significant problems associated with postoperative pain, scarring, bleeding, and infection, which accompanied a series of warts treated with the C 0 2 laser. As one probably could have foreseen, pulsed dye laser treatments of warts produce minor acute pain similar to that associated with PWS treatment using this laser, with none of the morbidities of nonselective tissue destruction.

Thus, whereas it would be premature to define the role of the pulsed dye laser among all other modalities in the treatment of verrucae, nevertheless we can state that what appears at this time to be extremely good clinical results follow from a laser treatment that is radically different from the GO2 laser. The pulsed dye laser (585 nm) in selectively destroying the prolifera- tive vasculature underlying warts does not cause the postoperative pain, scarring, bleeding infection, etc., which are often associated with the CO, laser and other treatment modalities 151.

The mechanism of success of this treatment is not altogether clear. The planned selective con- centration of the laser energy to the dermal blood vessels certainly results in their thrombosis and destruction as shown in Figure 3 and is then followed by necrosis of the wart infected keratinocytes. One possibility could lie in the thermal effects of the laser pulse being specifically de- structive to the virus; the virion of the HPV being known to be heat sensitive [141.

Another possibility might conclude that the linking here for the first time of a purely vascular-specific injury to regression and resolution of the wart is that the viability of the wart depends heavily on this prominent underlying dermal blood supply. It might therefore be hypothecated that those successful treatments by other agents, podophyllin, salicylic acid, etc., also require ex- tensive obliteration of this blood supply for their success. Similarly, efficacy with the CO, laser might again rely on these vascular effects, at the cost, however, in this case of more widespread tissue destruction with its attendant morbidity.

In this preliminary study, we used equivalent laser parameters as those for treating portwine stains. We did not attempt to explore whether varying laser parameters such as wave- length might have distinct effects on the pathology of warts. We find the results described in this

study interesting because they demonstrate that the selective vascular effect of the pulsed dye laser is effective not only in PWS but also in this very distinct pathology of verrucae. A larger study, examining the effects of the laser on verrucae and the mechanism(s) responsible for the effectiveness of this therapy, is currently under- way in our laboratory and clinics. Unlike the treatment of PWS where the abnormal blood vessels in this birthmark define the pathology and treatment involves their destruction by 577685 nm laser light being directly targeted at them, warts have totally distinct pathology and appear to be cleared by a secondary effect that nevertheless similarly involves the absorption of the laser light by the verrucae blood vessels.

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Fig. 4. A Verrucae plana prior to laser treatment. B: Close-up of verrucae prior to laser treatment. C: Same area following a single pulsed dye laser treatment a t 7.5 J/cm2.

Recalcitrant Verrucae Pulsed Dye Laser Treatment

Fig. 5. A Plantar verrucae prior to laser irradiation. 8: Site of plantar verrucae following two laser treatments at 6.5 J/cm2. Note the presence of a residual scar, which was produced by previous surgical removal of the wart. Warts have been cleared for 6 months.

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Pulsed dye laser treatment of recalcitrant verrucae: A preliminary report