| Onychomycosis is a fungal infection of the nail plate and subungual area, which is one of the most prevalent nail disorders in adults. An estimated 2-13% of the population suffers from onychomycosis (OM) which accounts for approximately half of all nail abnormalities. The most common causative pathogen is Trichophyton rubrum, followed by T.interdigitale (formerly T.mentagrophytes). The risk of infection increases with age:approximately 15%-20% for patients aged between 40-60 years,32% for those aged between 60-70 years, and more than 48% for patients aged over 70.The treatment of onychomycosis remains challenging due to the lack of safe and effective long-term treatment options. The elderly are at higher risk for diabetes, liver and kidney disease, nail trauma, poor peripheral circulation, compromised immune system, inactivity, larger nail surface, and slower growing nails, which may reduce the treatment efficacy for onychomycosis. If not treated in time, fungal invasion may further deteriorate until the nail plate is destroyed. The infected nails may serve as a fungal reservoir which facilitate their transmission to other areas of the body and even to other people.In this study we planned to evaluate the efficacy and safety of long pulse Nd:YAG 1064 nm laser in the treatment of onychomycosis for the elderly.Methods:The study was a controlled trial conducted at a single academic institution. A total of 104 patients (461 toenails) diagnosed of onychomycosis, who were positive in both potassium hydroxide test (KOH) and fungal cultures, were enrolled from The Third Affiliated Hospital of Southern Medical University between April 2011 and July 2014. Informed consent was obtained from all patients.Case Evaluation Criteria:Patients presenting with the following types of onychomycosis were included in the study:total dystrophic onychomycosis, distolateral subungual onychomycosis, proximal subungual onychomycosis and superficial white onychomycosis. Patients must not have taken any antifungal agents within six months before the first laser session or they had refused to take medication in previous treatments. They are aged between 10-90. The Scoring Clinical Index of Onychomycosis (SCIO) were rated between 1-30. The exclusion criteria were (1) patients discontinued the treatment procedure or follow-up plan; (2) patients had taken ongoing systemic antibiotic treatment within the last 6 months; (3) a history of trauma to the target nail; (4) existence of bacterial nail infection which resulted in nail pigmentation; (5) patients who were pregnant; (6) other clinical nail diseases, such as psoriasis, lichen planus or atopic dermatitis.Intervention ProcedureThe 104 patients with 461 affected toenails were prescribed with 1064nm Nd:YAG laser treatment. An antifungal cream was applied to the nail and its surrounding tissue twice a day between laser sessions as a preventive measure against re-infection. The 1064nm Nd:YAG laser (Harmony(?)XL, Alma Lasers Ltd) was used with the following settings:3mm spot size, fluences in the range of 40-60 J/cm2, 45ms pulse duration and 5Hz frequency, so as to ensure the treatment could be well tolerated by patients without any cooling sprays. Each infected nail was treated in a spiral pattern to cover the full nail including the areas of the hyponychium and the proximal and lateral nail folds. In one session two to three passes were performed with two minutes separation between each pass. Each treatment cycle involved four sessions at 1-week interval. All patients received 3 treatments (total 10-12 weeks).A total of 104 patients (461 toenails) were assigned to group 1 (y≥60) and group 2 (y<60).211 toenails from 40 elderly patients were included in group 1 while 250 toenails of 64 younger patients were included in group 2. Group1 was further divided to sub-groups A, B, C and D according to SCIO:sub-group A (SCIC<6), sub-group B (6≤SCIO<12), sub-group C (12≤SCIO<18) and sub-group D (SCIO≥18). Follow-ups were performed with clinical evaluations, mycological tests, SCIO scoring and photographic documentation using a high resolution digital camera at weeks 0,24 and 48. Mycological cure is defined as both fungal microscopic examination and fungal culture being negative.All of the included affected toenails were visually inspected and graded based on their overall improvement as follow:Marked improvement (>75% improvement), moderate improvement (50%-75% improvement), minor to moderate improvement (25%-50% improvement), minor improvement (<25% improvement), and no improvement (0% improvement). The treatment effectiveness was defined as the total rate of marked improvement and moderate improvement.ResultsIn follow-up of the 104 patients (461 toenails) the most severely affected nail of each patient was selected for mycological examination. The clinical effective rates and mycological cure rates showed better results in group 2 than group 1. The effective rates of subgroup A, B, C and D were 63.9%,71.0%,63.4% and 56.4% at week 48 respectively, which indicates no statistic difference in these 4 groups (p>0.05). In regard to the clinical manifestations, four different clinical types did not show significant difference between the different classification groups (p>0.05) at week 48.At week 24 and 48, the 2nd,3rd and 4th toenails were attended with higher clinical effective rates, while that for the 1st and 5th toenails were relatively lower (p<0.05). In our study, no serious adverse events related to laser treatment were reported during the 48-week study. None of the patients withdrew due to adverse events.Traditional therapeutic options for onychomycosis include nail removal, topical antifungal agents, systemic antifungal agents, and various combinations of the above. Nail removal, which can cause serious contusion, yields dissatisfied results that can affect patients’ quality of life. Though topical drugs often fail to infiltrate from nail plate into the underlying tissue, they are effective in preventing infection transmitted to other areas of the body and reducing recurrence and reinfection rate, which have proved their effectiveness as a preventive treatment option. The most effective treatment option for onychomycosis is oral intake of antifungal agents, which has been considered as the gold standard for years. In previous reports, onychomycosis was predominantly treated with peroral agents such as Terbinafine, Itraconazole, and Fluconazole, among which Terbinafine being the most common one due to its better fungistatic efficacy and higher cure rates. In a clinical study by Tavakkol et al. patients aged over 60 with onychomycosis were treated with oral Terbinafine, which showed that 64% of patients achieved mycological cure and 41.3% achieved clinical cure by the 48th weeks.However, while oral antifungal agents can effectively eradicate fungal infection, side effects have hindered their use in the treatment of older patients. The US Food and Drug Administration (FDA) is concerned about that Lamisil (terbinafine) and Sporanox (Itraconazole) have been associated with serious hepatic toxicity leading to liver failure and death. This adverse side effect even affects patients who had neither pre-existing liver disease nor a serious underlying medical condition. Therefore physicians should be aware of the side effects of systemic antifungal therapies and require patients to take regular test of their liver function and kidney function.In addition, systemic antifungals are also associated with drug interactions. The majority of the aged population need to take multiple medicines on a daily basis, which exposes them to higher risk of interactions with oral antifungal drugs. Itraconazole can inhibit the activity of P450 enzyme, causing the increase of serum concentrations of drugs, such as astemizole, cisapride, digoxin, and quinidine, to an abnormally high or even toxic level. Adverse interactions with other drugs can limit antifungal’s use in patients receiving polypharmacy for predisposing conditions.Recently, investigations of laser-or light-assisted antifungal treatments have received much attention from researchers. In 2010, FDA approved the use of laser systems for treating patients with onychomycosis, with proven effectiveness stated as ’temporary increase in clear nails’(FDA USA 510K:K113810). Compared to oral agents, laser therapy is a local modality with no systemic side effects on body functions and metabolism, making it suitable for older patients. Though some patients reported to experience mild stinging pain during the first session, such symptom was relieved along with the increase of the course. There have been no reports of any other serious side effects.The healing mechanism of laser therapy is thought to be related to the following reasons. Firstly, laser can directly act on the structure of fungal cells and destruct the cell elements. Secondly, the 1064 nm radiation emitted by the Nd:YAG laser is primarily absorbed by melanin, an essential constituent of the fungal cell wall.The selective absorption of the brief radiation pulse generates heat energy in fungi and denaturizes their proteins, leading to the apoptosis of fungal cells.In recent papers, laser energy has been shown to have the potential to eliminate microorganisms. Kozarev et al. reported that 162 patients with 413 nails affected by onychomycosis were treated with long pulse Nd:YAG laser light (fluence:35-40 J/cm2, pulse duration:35ms) and achieved 98.8% mycological clearance after 6 months. Zhang RN et al. showed significant inhibition of fungal growth (Trichophyton species) after treatment with long-pulse 1064 nm Nd:YAG laser (fluence:240-324J/cm2, pulse duration:30ms, spot size:3 mm). The results showed that in group 1 where patients were given 8 treatments, the effective rates at the 8th, 16th and 24th week were 63%,62%,51%, respectively. In group 2 where patients were given 4 treatments, the effective rates were 68%,67% and 53%.In our study the mycological clearance rate in all patients (10-90 years old) at week 24 was 82.7%.Similar results (79.5%) were reported by Yan Li et al. (fluence: 50-60 J/cm2, pulse duration:35ms, spot size:2 mm) for patients aged between 18 to 75 at week 24. While in a study conducted by Kozarev J,98.8% patients showed negative fungal tests at week 24. The discrepancy between the overall effective rates in our research (82.7%) and Kozarev J’s (98.8%) might be explained by the fact that in our study,38.5% of the total samples consisted of patients aged over 60 who tend to show poorer response to the treatment. Inclusion of these old patients into the sample pool, who showed effective rate of 72.5% at week 24, can lower down the overall efficacy in the group when compared to Kozarev J’s results in which old patients were not included.In our results, the clinical effective rates showed better results in younger patients than older patients. Previous literature reported that the out growth rate of nails and peripheral circulation decreases with age. Nails that have a slower growth rate are likely to show poorer response to treatment than that of fast-growing nails. Therefore we advise oral intake of drug like vitamin for the elderly, which can increase the growth rate of nails and help to treat nail disorders. Our study also indicated that no statistically significant differences were observed in clinical effective rates between different clinical types or SCIO groups at week 48 (P>0.05). The present results showed that laser treatments might be effective to all onychomycosis with different clinical presentations and severity level.Literature showed the great toenail may have a poor prognosis due to slower growth among the toenails. In the elderly group, at week 24 and 48, the effective rates were 41.1%,57.1% for the great toenail,22.0%,46.3% for the fifth toenail and 63.3% (p<0.05),75.5%(p<0.05) for the rest. Lower clinical outcome rates observed in the great toenail and the fifth toenail may suggest the necessity for prolonged course of treatment or increased laser energy level in treating these two toenails.ConclusionIn an ageing society, onychomycosis will continue to be a focus of clinical concernfor the elderly. In fact, older patients are often not suitable for systemic antifungal therapies due to drug interactions and susceptibility to complication. Early diagnosis and treatment are fundamental to a successful cure. Although a significant number of onychomycosis cases using 1064 nm Nd:YAG laser modality have been reported, reliable clinical data of its effectiveness for the elderly are still lacking in literature. Our study is the first clinical trial to evaluate the safety and efficacy of long pulse 1064 nm Nd:YAG laser therapy for onychomycosis in the general aged population (y≥60). Although being small and open-label in design, this study has nevertheless contributed valuable new insight about the use of long pulse 1064 nm Nd:YAG laser therapy and provided a promising treatment option for the aged population. |
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