Q- switched Nd:YAG laser versus itraconazole pulse therapy in treatment of onychomycosis: A clinical dermoscopic and mycologic study

Background: Onychomycosis (OM) represents about 50% of nail disorders. Oral antifungals have proven efficacy in the treatment of onychomycosis but their associated side effects limit their use. Accordingly, there is an increased need for a safe and effective therapy to induce clearance and improve the esthetic appearance of diseased nails. Objective: The current study is an attempt to evaluate and compare the efficacy of Q- Switched Nd:YAG (1064 nm) laser as monotherapy versus pulse itraconazole in the clearance of onychomycosis. Methods: In this prospective study, 40 onychomycosis patients were equally divided into two groups: Groups I (laser group) and II (Itraconazole group). Patients of Group I are treated with six biweekly sessions of Q- Switched Nd:YAG (1064 nm) laser. Patients of Group II are treated with itraconazole pulse therapy. The


| INTRODUC TI ON
Onychomycosis (OM) is a persistent chronic nail fungal infection, accounting for up to 50% of the nail disorders. It may lead to ungual pain, difficulties in performance of daily activities and impaired social interaction. 1 Dermatophytes represent the most common cause of onychomycosis in 85%-90% followed by the non-dermatophytic molds and Candida. 2 Onychomycosis can be classified into superficial white onychomycosis (SWO), proximal subungual onychomycosis (PSO), distolateral subungual onychomycosis (DLSO), endonyx onychomycosis (EO) and total dystrophic onychomycosis (TDO). 3 The treatment of onychomycosis is a challenge facing all dermatologists. It includes nail debridement, topical and systemic antifungals. The use of oral antifungals may be associated with multiple side effects, moreover the topical therapy are rarely effective when used as a monotherapy. 4 Itraconazole is a triazole antifungal agent available as oral and intravenous formulations. It has wide range of well-established efficacy against superficial fungal infections including the dermatophytes causing onychomycosis. It is usually used in a shortened treatment regimen, ranging from 1-day treatment in vaginal candidiasis to 1-week per month for 2-4 months, as a pulse therapy, in treatment of onychomycosis. 5 Non-pharmacological alternative treatment modalities such as long pulse and Q switched Neodymium-doped Yttrium Aluminium Garnet (Nd-YAG), photodynamic therapy, infradiode lasers, and fractional CO 2 lasers have been approved to increase the clearance of onychomycosis. 6 The efficacy of such lasers are attributed to their thermomechanical, photo-acoustic, photochemical effects, and photothermolysis toward the fungal cell wall components (chitin, xanthomegnin, and melanin). 7 This study was conducted aiming to study and compare the efficacy of Q-switched Nd:YAG laser as a monotherapy versus pulse itraconazole therapy in the clearance of onychomycosis caused by dermatophytes.

| PATIENTS AND ME THODS
Forty patients with onychomycosis were included in this study.
Patients with other nail conditions, the diabetic patients, who received any topical or systemic antifungal therapy within the previous 3 months, the pregnant females and patients on immunosuppressive therapies, were excluded from the study. The included patients signed an informed written consent before the beginning of the study, and the study was done under the approval of the ethical committee for Postgraduate Studies and Research of Faculty of Medicine, Minia University (apprpval no: 564/2023).
The diagnosis of onychomycosis was done clinically, and then was confirmed by dermoscopy, nail scrapping, and direct microscopy using 20% potassium hydroxide (KOH) in addition to culture on Sabouraud dextrose agar. Only the positive nails for both KOH and culture were included in the study.
Each nail plate was subjected to the laser beam in two passes across with 2 min intervals between each pass. The 1064 nm Nd:YAG laser was used in the first pass and each nail was fully covered with the laser beam, including the hyponychium and the proximal and lateral nail folds. After a pause of 2 min the second pass was performed using the 532 nm Nd:YAG (6.8 J/cm 2 fluence), fully covering the nail plate but not the hyponychium and nail folds. The laser sessions were performed without any pretreatment anathesia. 9 Group II (Itraconazole group); Each patient administered capsules of itraconazole in the dose of 200 mg twice daily for 1 week per month, for 3 consecutive months after screening of complete blood count, liver, and renal function tests. Patients were advised to record any side effects. 10

| Evaluation of clinical cure
Biweekly examination and digital photographing of the affected nails were done over a period of 6 months (3 months of treatment and 3 month of follow-up). The difference between OSI score at baseline and after 6 months of the treatment was calculated, and its percentage of reduction was used to assess the clinical cure. The obtained results were translated as (0%-25% change in OSI score = no improvement, 26%-50% = mild improvement, 51%-75% = moderate improvement, and 76%-100% = marked improvement). 11

| Patients' satisfaction
Six months after treatment, each patient was asked to evaluate his/ her satisfaction about the outcome of the used treatment by giving a score from 0 to 3 where 0 = not satisfied, 1 = mildly satisfied, 2 = moderately satisfied, and 3 = very satisfied. 12

| Evaluation of the complications of therapy
Moreover the patients were asked to record any emerging side effects during the course of treatment.

| Evaluation of mycological cure
Fungal cultures were performed before the start of treatment (at baseline) and 6 months after treatment for detection of mycological cure; which equals negative microscopy and culture.

| Statistical analysis
The data were statistically analyzed using SPSS for Windows (version 16.0.1; SPSS Inc.). Descriptive statistics were done for parametric quantitative data by mean ± SD, whereas number and percentage were used for qualitative data. For non-parametric data, Mann-Whitney test was used to compare between variables of both treatment modalities, whereas Wilcoxon signed-rank test was used to compare between before and after data within the same treatment.
Fisher's exact test was used to compare qualitative data. Significance was expressed in terms of the p-value, which was considered significant when it was ≤0.05.

| Baseline characteristics
There was no significant statistical difference in the demographic data regarding the age, sex, and duration of onychomycosis between the patients of both groups ( Table 1).
Disto-lateral onychomycosis was the most common form (12 in both groups); without any statistically significant difference in the types of onychomycosis between the two groups ( Table 1). Fingernail infection was seen in 15 patients in group I and 12 in group II, with no statistical significant difference in both groups ( Table 1).

| Clinical assesment
As regards the OSI score, the median OSI score before treatment in laser group was 24.5 and in itraconazole group was 24 without any statistical difference between the groups (p = 0.845) ( Table 2). All the included patients in the two groups had a significant decrease in the median OSI scores when compared with their baseline OSI scores (p ˂ 0.001), with a median percentage of reduction of 100% in the OSI score in both groups, with no statistical significant difference in both groups (p = 0.721) ( Table 2).
Regarding the clinical response of treatment, there was a statistically significant increase in the clinical response in both groups as in group I (19 patients had marked response and one patient had moderate response). Moreover in group II (15 patients had marked response and five patients had moderate response), with no statistical significant difference in both groups with (p = 0.181) ( Table 3; Figures 1 and 2).
No statistically significant difference in clinical improvement between the fingernails and toenails, was found in both groups with (p = 0.063).

| Patients' satisfaction
Assessment of the patients' satisfaction revealed that in the laser group (19 patients were very satisfied and only one patient was moderately satisfied) and the itraconazole groups revealed that (15 patients were very satisfied and five patients were moderately satisfied) with no significant difference was detected between both groups (p = 0.181) ( Table 4).

| Dermoscopic assessment
Dermoscopic examinations performed at the baseline were all positive for criteria of onychomycosis. A statistically significant disappearance of the diagnostic dermoscopic criteria was detected in both groups with no statistical significant difference between them (p = 0.181) ( Table 5; Figures 3 and 4).

| Mycologic assessment
The fungal cultures performed at the baseline were all positive for dermatophytes. Tricophyton Mentagrophytes was detected in 12 (60%) patients in group I and 11 patients (55%) in group II and Tricophyton Rubrum was detected in 8 (40%) patients in group I and nine patients (45%) in group II, with no statistical significant difference in both groups ( Table 1).
A statistically significant mycological cure in culture was detected in both groups with no statistical significant difference between them (p = 0.181) ( Table 5).
Most of side effects that were reported by the patients in both groups where minimal, transient, and did not affect the patient compliance to continue treatment protocols.

| DISCUSS ION
Lasers became a famous treatment modality of onychomycosis, owing to their minimally invasive mode and the ability to restore the normal nail growth with a small number of sessions. 15 The efficacy of lasers is attributed to their thermal effects; which can be either selective or nonselective. Most of the current laser systems used in the treatment of dermatophytes acts TA B L E 1 Demographic data of the patients of both groups.

TA B L E 2
The onychomycosis severity index scoring before and after treatment.
through the nonspecific bulk heating technique. In such lasers the direct elimination of dermatophytes cannot be obtained without damaging the surrounding structures. 16 The 532 nm Nd-Yag laser is postulated to be a better targeting of the fungal pigment xanthomegnin, while the 1064 nm is preferably absorbed by the fungal cell wall. 17 In the present study, the laser group patients showed a significant decrease in the mean OSI score (p < 0.001), with a marked clinical, dermoscopic, and mycological cure detected in 100% of Very satisfied 19 15 Note: Fisher exact test.

TA B L E 4
The patient satisfaction to the used treatment in both groups.

TA B L E 5
The assessment of dermoscopic and mycological cure in both groups.  To the best of our knowledge this is the first study comparing the efficacy of Q-Switched Nd:YAG 1064 nm/532 nm laser versus itraconazole pulse therapy in treatment of onychomycosis caused by dermatophytes in the Egyptian patients.

| CON CLUS ION
In order to summarize, the current study revealed that Q-Switched The future studies need to be applied on a larger number of patients in order to give more confirmation of our results.

AUTH O R CO NTR I B UTI O N S
All the authors have made a significant scientific contribution to the research.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author upon reasonable request.

E TH I C A L A PPROVA L
The study was done under the approval of the ethical committee