Viral warts are one of the most common dermatological diseases, which range in severity from a minor lesion that resolve spontaneously to a troublesome, chronic condition 1. Many different types of warts may exist at any site of the body, including common warts (Verruca vulgaris), plane or flat warts, myrmecia (single deep painful warts), plantar warts, coalesced mosaic warts, filiform warts, periungual warts and anogenital warts (venereal or condyloma acuminata) 2.
The persistence of human papilloma virus (HPV) infections is owing to the ability of viral genome to parasitize the stem cells and other long-lived cells in the basal epithelial layer and because the virus can evade the immune system by limiting both the gene expression and the replication of the virus in suprabasal cell layer. Most lesions resolve spontaneously presumably because the immune system eventually mounts a successful response 3.
Several factors control the choice of treatment for warts. The best modality of which should be individualized for each patient depending on morphology and extent of warts, patient preference, availability of the resources, and the experience of the healthcare provider. Generally, it is advised to start with the least painful, least expensive, and the least time-consuming methods 4.
Lasers have developed over the past decade, making them a valuable option for treatment. The CO2 laser has been used to treat warts since the 1980s and is still the gold standard in ablative lasers. It was the initial laser. It functions by emitting infrared light at 10 600 nm, a wavelength absorbed by water. Variable success rates have been reported in the literature, ranging from 32 to 100% 5.
Intracellular water and extracellular water are the targets for the CO2 laser, which emits an invisible infrared beam at 10 600 nm. When light energy is absorbed by water-containing tissue, skin vaporization occurs 6. A focused CO2 laser beam can be used as a scalpel to remove the wart down to the subcutaneous tissue after which the base of the wart is vaporized by a defocused beam 2.
Moghaddas 7 reported the complications of CO2 laser, which included delayed healing, high cost of instrumentation, damage to the nail and nail matrix, scarring, possibility of laser burn, practitioner infection from the HPV found in the laser plumes and postoperative pain.
The use of long-pulsed Nd:YAG at wavelength of 1064 nm for the treatment of vascular lesions such as telangiectasias and venous lakes has been studied. That is why 1064 nm Nd:YAG could be used in treatment of warts where the wart blood vessels are the target 8.
One of the adverse effects of 1064 nm Nd:YAG laser is the transient hypopigmentation, which occurs in 25–50% of patients, and also the hyperpigmentation owing to postinflammatory tissue changes. Nd:YAG laser may lead to scar formation especially when a high fluence or frequency is used. Mild reversible textural changes have been noted with this laser but are transient 9.
The aim of this work is to compare the therapeutic efficacy and adverse effects of long-pulsed Nd:YAG laser and ablative carbon dioxide laser in the treatment of recalcitrant warts.
Patients and methods
This study included 20 patients with recalcitrant warts of any type that were recruited from the outpatient clinic of Dermatology and Andrology in Benha University Hospital from January 2015 to June 2015.
Patients included those aged from 18 to 40 years, having duration of lesions more than 6 months, who did not respond to conventional therapies, or had lesions recurred after destructive procedures. Excluded patients were those having warts of less than 6-month duration, have been using other treatment modalities within the last 2 months, those who have used isotretinoin during the past 6 months, pregnancy, or had infection in the area to be treated.
Approval of the Dermatology and Andrology Department and the Ethics Committee in the Faculty of Medicine, Benha University, was taken for the study protocol. Informed written consent was taken from each participant.
All patients were subjected to the following:
- History including all demographic data, history of keloids and hypertrophic scars, history of isotretinoin intake, course and duration of warts and history of previous interventions.
- Dermatological examination, recording site, type, number, and size of warts.
- Photographic documentations before start of treatment, 1 week after the end of each treatment and after 3 months of follow-up.
- Treatment plan:
The areas of involved tissues were cleaned with povidone iodine solution 10%. Local anasthesia (mepivacaine hydrochloride) was injected to the treatment area. Both patient and operator used protective goggles during treatment. Patients were randomly divided into two groups:
- Group Ι: ablative CO2 laser (10 patients):
- CO2 laser 10 600 nm (SmartXide DOT; DEKA Laser, Florence, Italy) with a power of 2–4 W in a continuous mode for only one session.
- The warty tissue was removed by successive laser passes in the focused mode, taking care to remove any charred debris between passes using sterile gauze soaked with saline until complete removal of the wart. Any occasional bleeding points were coagulated by defocused mode.
- Group ΙΙ: long-pulsed Nd:YAG laser (10 patients).
The laser therapy was done by a 1064-nm long-pulsed Nd:YAG laser (Synchro Hp; DEKA laser) for one session per month for a maximum of three sessions. The following parameters were used: spot size 5 mm, fluence 200 J/cm2, pulse duration 30 ms and frequency 1 Hz/s. During treatment procedure, laser hand piece was held perpendicular to the skin surface to ensure maximum effect of laser beam.
The patients of both groups were advised to use topical antibiotic cream (fusidic acid) twice daily for 3–5 days after treatment until complete healing occurred.
Patients of both groups were followed up monthly for 3 months after the last session to be inspected for any recurrence, complication or adverse effects.
- Clinical evaluation:
- Clinical evaluation of the treated cases was done by two blinded dermatologists who evaluated the clearance of the lesions 1 month after the last laser session. The response was categorized as follows:
- Complete response: complete resolution of the lesion (90–100%).
- Partial response: 50 to less than 90% resolution of lesions.
- Poor response: less than 50% resolution of lesions.
Patient satisfaction score
Patients assessed their response and recurrence of lesions using the Short Assessment of Patient Satisfaction test: 0–10=very dissatisfied, 11–18=dissatisfied, 19–26=satisfied, and 27–28=very satisfied 10.
Complications in the form of scarring, hypopigmentation, bleeding, hemorrhagic bullae, nail dystrophy, hyperpigmentation, or others were recorded.
The collected data were summarized in terms of mean±SD and range for quantitative data and frequency and percentage for categorical data. Comparisons between the different study groups were carried out using the Student t-test to detect differences in the means between two groups. The Fisher exact test was used to compare proportions. Statistical significance was accepted at P value less than or equal to 0.05, whereas a P value more than 0.05 was considered nonsignificant. All statistical analyses were carried out in STATA/SE, version 11.2 for Windows (STATA Corporation, College Station, Texas, USA).
The range of the age of patients in CO2 laser group was from 20 to 40 years with a mean of 28.5±7.6 years, whereas in the Nd:YAG laser group, it was from 22 to 40 years, with a mean of 33±6.7 years. Most patients were females in CO2 laser group (70%) and in Nd:YAG laser group (80%). There was no statistically significant difference in all demographic data between the two groups.
There was nonsignificant difference between the two groups regarding duration of warts, other clinical data including type and site and previous treatments of warts (Table 1).
All patients in group Ι showed complete healing (100%) after one session of ablative CO2 laser therapy (Fig. 1).
Patients in group ΙΙ were treated by long-pulsed Nd:YAG laser; six (60%) patients out of 10 showed complete healing after one session. Two (20%) patients showed complete healing after the second session. Only two (20%) patients had to receive the third session. Complete clearance rate after the first session was more in the common wart group (83.33%) than in the palmar warts group (25%) (Table 2 and Fig. 2).
Recurrence of lesions was noticed within 3 months after the end of treatment in 50% of patients treated by CO2 laser whereas in only one (10%) patient treated by Nd:YAG laser with statistically significant difference (P=0.02).
Secondary bacterial infection was not recorded in both groups. Scarring and hyperpigmentation were recorded more in group Ι (50 and 50%, respectively) compared with group II (20 and 10%, respectively), with no statistically significant difference. Bleeding and hemorrhagic bullae were the most common complications recorded in group II (50%), whereas they were not recorded in group I, with a statistically significant difference (P=0.003). Nail dystrophy was recorded in one patient with Nd:YAG laser (Table 3).
Patients treated with CO2 laser reported satisfaction range from 10 to 25 with mean 16.2±4.96, whereas patients treated with Nd:YAG laser reported satisfaction range from 11 to 28 with mean 23.2±5.96, with a statistically significant difference in patient satisfaction between the two groups (P=0.01) (Table 4).
This work aimed to compare the therapeutic efficacy and adverse effects of long-pulsed Nd:YAG laser versus ablative carbon dioxide laser in treatment of recalcitrant warts.
This study showed that all patients of group Ι who were treated with ablative CO2 laser showed complete healing (100%) after receiving only one session. This result was in agreement with Serour and Somekh 11, and also Azizjalali et al.12, who reported complete clearance of warts after a single treatment with ablative CO2 laser therapy.
Patients in group ΙΙ were treated by long-pulsed Nd:YAG laser; six (60%) of 10 patients showed complete healing after one session. Complete clearance was observed after the first session in the common warts (83.33%) than in the palmar warts (25%).
These results agreed with Han et al.13, who used the same parameters as in our study, and the clearance rate after the first treatment was higher in the verruca vulgaris group (72.6%) than in the periungual warts group (64.7%), whereas it was 44.1% in the deep palmoplantar warts group. The high success of clearance of warts in this study may be explained by the higher fluence used. Although the exact mechanism of Nd:YAG that makes it an effective treatment for many subtypes of warts is still unclear, the promising clearance rates reported by multiple studies advocate Nd:YAG laser over traditional therapies of recalcitrant warts.
These results were also in agreement with Bingol et al.14, who used different parameters and one laser application session was sufficient to successfully treat 129 (88.35%) of the 146 refractory hand warts, whereas the remaining 17 (11.65%) warts required two treatment sessions 1 month apart. A high clearance rate was achieved using an overlapped triple circle pulse technique in which the wart was aligned at the intersection of the circles of three laser pulses.
The results of this study were also in agreement with Shin et al.15, who compared the effectiveness of pulsed dye laser and long-pulsed Nd:YAG laser in the treatment of recalcitrant viral warts and reported at least 50% improvement from baseline in 20 (51.3%) patients in pulsed dye laser and 22 (66.7%) patients in long-pulsed Nd:YAG laser.
The efficacy of the Nd:YAG laser in the treatment of recalcitrant warts has been explained by its lower hemoglobin and melanin absorption coefficient, which enables the laser to penetrate deeper within the epidermis leading to higher clearance rates 13.
In this study, recurrence of the lesions in CO2 laser group was noticed within 3 months after the end of the treatment in five (50%) patients whereas in only one (10%) patient of Nd:YAG laser group, with statistically significant difference between the two groups.
Recurrence of warts after CO2 laser has been reported in many studies ranging from 11% 16 and up to 45% 5. The explanation of the recurrence could be owing to remaining HPV DNA or viral particles, which might be retransmitted to the ambient defective epidermis, resulting in recurrent warts 16. Moreover, Zeng et al.17 hypothesized that the vaporization of the entire wart during CO2 laser ablation was thought to eradicate both the visible and the underlying viral infection, but owing to lack of antiviral activity, the documented recurrence rates varied from 20 to 50%. Long duration of these lesions indicates a particularly weak recognition of the infected cells by the immune system.
In contrast, the use of long-pulsed Nd:YAG laser in the treatment of recalcitrant warts was not associated with any recurrence 18,19.
The low recurrence rate of Nd:YAG laser may be explained by a synergistic effect of Nd:YAG on the wart, deep penetration, and also its ability to target blood vessels of warts.
Multiple evaluations of warts after laser treatment revealed the destruction of blood vessels, which are characteristic of warts, causing insufficient nutrients to the warts, together with inflammatory infiltrate encapsulating the destructed blood vessels decreasing warts recurrence rate 20.
The HPV had been found to respond more to treatment with heat suggesting that Nd:YAG laser kills the virus more effectively. The long-pulsed 1064 nm Nd:YAG destructive technique creates tissue blistering that eventually slough off, leaving the dead tissues, that allows the immune system to destroy the remnant lesions and prevents further growth of the wart 19.
Regarding the adverse effects of CO2 laser, scarring and hyperpigmentation were recorded in 50% of patients. Hypopigmentation was recorded in only one patient.
The results were in agreement with Al-Dhalimi 21, and also with Esmat et al.22, who reported the same adverse effects in patients treated with CO2 laser.
The explanation for these adverse effects might be owing to the nonselective thermal damage that occurs with CO2 laser.
Regarding adverse effects of Nd:YAG laser, bleeding and hemorrhagic bullae were the most common complications (50%) in our study. Scarring was recorded in 20% whereas hyperpigmentation was recorded in 10%.
These results were in agreement with Bingol et al.14, as in their study, hemorrhagic blisters were observed in 27 (18.49%) warts. Hyperpigmentation was observed in only eight (5.48%) of the 146 treatment sites.
Han et al.13 reported adverse effects of Nd:YAG laser in the form of hemorrhagic bullae, hyperpigmentation, hypopigmentation, and nail dystrophy. Adverse effects were generally mild and did not prevent normal activity.
The longer wavelength of Nd:YAG allows delivery of the light energy deeper into the hyperkeratotic and thickened epidermis associated with warts. Moreover, decreased light absorption by melanin at 1064 nm reduces the risk of pigmentary adverse effects. Minimal destruction of the surrounding tissue in Nd:YAG treatment contributed to minimizing the risk of complications 23.
Satisfaction score was done after 3 months of follow-up after the end of treatment. The higher satisfaction score of Nd:YAG patients probably support the high cure rate with rapid healing time without need for downtime and acceptable adverse effects, which resolved within few weeks.
The important finding of this study was the low recurrence rate of verrucae in Nd:YAG laser group, which was the most satisfied issue to the patients, compared with the high recurrence rate in CO2 laser group. The lower satisfaction score with CO2 laser-treated patients probably support the slow healing, hyperpigmentation, scaring, high recurrence rate, and its harmful effect of its fumes on both patient and practioner. However, CO2 laser recorded higher clearance rate (100%) of verrucae with only one session, which was of lower cost than Nd:YAG laser, which needed more sessions for complete clearance.
Both treatments were safe, effective and highly tolerable. However, the Nd:YAG laser therapy had less adverse effects and less recurrence rate of verrucae.
No financial support.
Conflicts of interest
There are no conflicts of interest.
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Keywords:© 2018 Egyptian Women's Dermatologic Society
CO2; laser; Nd:YAG; recalcitrant warts