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Journal of the Laser and Health Academy Vol. 2010, No.1; www.laserandhealth.com Novel Laser Therapy in Treatment of Onychomycosis
Jasmina Kozarev,1 Zdenko Vižintin2
1Dr.Kozarev Dermatology Laser Clinic., Sremska Mitrovica, Serbia 2Fotona d.d., Ljubljana, Slovenia ABSTRACT
include dermatophytes (fungi that invade only dead A clinical study was performed in which 72 tissues of the skin, nails, or hair), nondermatophyte patients with 194 nails affected by onychomycosis moulds, and rarely, yeasts of the Candida species [4]. were treated with long pulse Nd:YAG laser light The dermatophytes Trichophyton rubrum and (Dualis SP, Fotona, Slovenia) at a single clinical site Trichophyton mentagrophytes are the most common (Dr. Kozarev's Dermatology and Laser Clinic) over a causative pathogens of onychomycosis, with T. period of 18 months. Mycotic cultures were taken rubrum responsible for approximately 90 percent of all from all affected nails and various fungal infections cases [1,2]. The overall prevalence of onychomycosis were positively diagnosed in all 72 patients. Laser ranges from 2 to 14 percent. The risk of infection treatment consisted of four sessions with one week increases with age: 15-20% of persons between the interval, during which all infected nails were irradiated ages of 40 and 60 have the condition, 32% of those three times with laser light so that the nail plate was who are between 60 and 70, and 48% of those older fully covered each time. Fluences of 35-40 J/cm2 were than 70 [1]. Recent evidence suggests that the applied at pulse duration of 35 msec to develop a nail- incidence of onychomycosis is increasing [1,2]. Several plate temperature of 45°C±5. Follow up was conditions can mimic onychomycosis, including performed at 3, 6, 9 and 12 months, with mycological psoriasis, atopic dermatitis, nail trauma, contact check ups at 3 and 6 months. At the 3 month fol ow irritants, and lichen planus. up point, 95,8% of patients were cleared of al fungal infections. The full procedure was performed again on the three patients in which infection persisted after 3 month fol ow up (4,2%). On 6 and 12 month fol ow up all patients (100%) were clear of all fungal infection. There were no noticeable side effects of treatment and all patients were satisfied with treatment. This clinical study demonstrates that fungal nail infections can be effectively and safely treated with VSP Nd:YAG 1064 nm laser.
Key words: onychomycosis, nails fungal infection,
Article: J. LAHA, Vol. 2010, No.1;pp. 1-8. Fig. 1: An example of severe distal subungual Received: April 03, 2010; Accepted: April 30, 2010. Therapeutic options for the treatment of Laser and Health Academy. Al rights reserved. Printed in Europe. www.laserandhealth.com onychomycosis include pal iative care, mechanical or chemical debridement, topical and systemic antifungal I. INTRODUCTION
agents, and various combinations of these modalities. The choice of therapy is influenced by the Onychomycosis, a persistent fungal infection of the presentation and severity of the disease, other nail bed, matrix or plate, is the most common nail medications that the patient is taking, which previous disorder in adults, accounting for one third of all therapies for onychomycosis have already been fungal skin infections and up to 50 percent of all nail attempted (and their effects), physician and patient diseases [1-3]. Toenails are affected more often than preference, and cost. [5] fingernails. The causative agents of onychomycosis Novel Laser Therapy in Treatment of Onychomycosis Novel Laser Therapy in Treatment of Onychomycosis Treatments of advanced onychomycoses are time- Exclusion criteria
fungal structures. Culture examination was executed Pro 2.8 software with which the level of temperature consuming, cost-intensive, and subject to relatively Patients who used systemic antifungal, oral by an independent microbiological laboratory increase was determined (see Fig.2 b) c) and Fig.4). high failure rates. Even drug courses of potent antifungal therapy, or isotretinoin within 6 months of (Mikrobioloska laboratorija Paster, Belgrade, Serbia). systemic antimycotics, delivered over a period of the first scheduled laser procedure were excluded. No local anesthesia was applied preoperatively. several months, have cure rates of only 40 to 80% [23- Some examples of drugs which were cause for Of the 110 patients who were initially recruited, 72 Cold air cooling was applied to the area during laser 25]. Among the orally delivered systemic drugs exclusion are griseofulvin or other cefalosporins, (65%) tested positive for, and were microbiologically treatment, (Cryo6, Zimmer, Germany used). No Terbinafine, Intraconazole and Fluconoazole are most minocyclin, or cytostatics (busulfa, 5-fluoroacil). confirmed as carrying, fungal cultures. All 72 patients postoperative analgesic treatment was required. No frequently used. Systemic drug therapy is associated Patients who used vasodilators were also excluded, were included in the study and completed all treatment prophylactic antibiotics or antiviral were given to any with several unpleasant side effects. Headache, rash because faster blood flow could increase heat transfer sessions and follow ups.
and gastrointestinal symptoms were reported in about in the nail plate, thereby adversely effecting therapy. 7 percent of patients treated with Intraconazole [23] Thicker nails were pretreated to achieve better laser Parallel to in-vivo therapeutic irradiation of nails and about 5 percent of patients treated with Permanent or semi-permanent discoloration of the light penetration. The patient's thick dystrophic nails infected with fungi an in-vitro experiment of laser Fluconoazole suffered nausea, headaches, pruritus and nail plate was another cause for exclusion. Such were treated with a preparation containing: 40% urea, irradiation effect on fungus culture was performed. An liver enzyme abnormalities [26]. The duration of discoloration can be caused by the use of therapeutics 20% anhydrous lanolin, 5% white wax, and 35% white isolate of fungal colonies obtained from a toenail systemic drug therapy is usually three months; the or cosmetics which effect nail pigmentation, for petrolatum for three successive nights, by applying the scraping were passed on Sabouraud Peptone-Glucose duration can be cut in half by using "pulse" therapy, in example the local antifungal therapy solutio Castel any, preparation to the nail under occlusion. This Agar. Ten days after isolation standardized which increased doses are administered. the use of nail dyes and polishes (especially those pretreatment was only needed for 3 patients of 72 photographs were obtained; the colonies were exposed which contain magnesium or iron). Discoloration can to laser irradiation with 1064 nm wavelength, fluence Topical antifungal preparations are also widely also be caused by professional exposure to dyes or of 40 J/cm2 and pulse duration of 35 msec. Three days used. Although safe and relatively inexpensive, topical asphalt. Treatment was performed using long pulse VSP after laser exposure a final examination was made and therapy is seldom effective [27]. 1064 nm Nd:YAG laser (Dualis SP; Fotona, Slovenia), standardized photographs were obtained. The fol owing conditions can cause various with fluences in the range of 35 to 40 J/cm², a spot The efficacy of the treatment can be improved and physiological changes to the nail plate in addition to size of 4 mm diameter, and pulse duration of 35 ms. Treatment Evaluation
its duration reduced by supplementing the discoloration and so were also cause for exclusion: The variations in fluence were selected based on the Fol ow-ups were done at 3, 6, 9 and 12 months. medicamentous therapy with some complementary subungual hematoma, nevoid subungual formation, thickness of the nail to be treated, with thicker nails The patients were evaluated for clearance of fungal (e.g. light) treatment. Photodynamic therapy has been bacterial nail infections, and concomitant nail requiring higher fluence. The pulse rate was 1 Hz. The infection clinically by the physician executing the recently proposed to treat T. rubrum infection, and disorders such as psoriasis of nail plate, lichen planus laser beam was applied to the entire nail plate by procedure and mycologically by analysis of the culture promising results have been obtained [6]. and atopic dermatitis. incrementally moving the beam in a spiral pattern as taken at 3 and 6 month follow-up visits made by In addition, pregnant women were excluded. shown on Fig. 2. After the entire nail plate was independent The direct effect of laser light on fungal isolates irradiated a 2 minute pause was taken and then the (Mikrobioloska laboratorija Paster, Belgrade, and and affected nails has not yet been rigorously Treatment procedure
treatment and pause were repeated twice more for a Bel adonna, Zemun, both Serbia). Photographs were examined for its possible inhibitory potential. The primary aim of this treatment regime was to total of three passes. The total therapy consisted of taken using the same camera settings, lighting, and nail restore the nail to ful health at 12 months. The four sessions with a one week interval between each position at baseline and at the 6, 9 and 12-month Although there are already two laser system secondary aim of treatment was to render the nail free follow-up visits. manufacturers promoting their systems for the of fungi at 3 months. treatment of onychmycosis, thus far neither has Also, all the patients were filling-in questionnaires delivered a clinical study with a significant number of In the first step samples were collected and the nail after each therapeutical session, evaluating the level of cases in which an efficacious outcome was achieved. area was thoroughly cleansed with alcohol to remove procedural pain (on a 5-point scale where 0 = no pain, contaminants. For distal subungual onychomycosis, 1 = mild pain, 2 = moderate pain, 3 = severe pain and II. MATERIALS AND METHODS
the infected nail was clipped proximally and the nail 4 = intolerable pain) as well as possible adverse 194 nails of 72 patients with clinically and bed and underside of the nail plate were scraped with effects, if any of such would occur. mycological y proven onychomycosis were exposed to a 1-2 mm serrated curette. For proximal subungual transcutaneous laser irradiation with the aim of onychomycosis, the normal surface of the nail plate III. RESULTS
deactivation and eradication of fungal infection. was pared down with a no.15 surgical blade at the lunula and the white debris was col ected with a sharp a) Types of onychomycosis treated
Inclusion criteria
curette from the deeper portion of the plate and the Treated patients had al four major clinical types of onychomycosis: total dystrophic form, distal To take part in the study each patient had to have proximal nail bed. The sampled material was divided subungual onychomycosis, proximal subungual one or more toenail and/or fingernail fungal infections into two portions: one for direct microscopy and the Fig. 2: Presentation of delivery of laser beam in spiral onychomycosis and endonyx onychomycosis. The of the fol ow types: total dystrophic form, distal remainder for culture. pattern on the nail plate surface (a) Thermal images of distribution of onychomycosis types in patient subungual onychomycosis, proximal subungual toenail surface before (b), and after (c) irradiation with VSP population is given in Table 1. onychomycosis and/or endonyx onychomycosis and Prior to laser treatment positive fungal cultures Nd:YAG laser beam. Temperature increase of the nail plate is clearly visible. be between 18-45 years of age. were obtained from al patients after direct microscopy Al patients signed written informed consent was used as a screening test. Scrapings were mounted For the first few patients the temperature increase statements before beginning laser treatment. for direct examination in 25% KOH mixed with 5% glycerol, heated (e.g., for 1 h at 51 to 54°C) to emulsify of the nail plate was measured during treatment using lipids, and examined under 3400x magnification for FLIR Thermal Imager and ThermaCAM Researcher Novel Laser Therapy in Treatment of Onychomycosis Novel Laser Therapy in Treatment of Onychomycosis Treatments of advanced onychomycoses are time- Exclusion criteria
fungal structures. Culture examination was executed Pro 2.8 software with which the level of temperature consuming, cost-intensive, and subject to relatively Patients who used systemic antifungal, oral by an independent microbiological laboratory increase was determined (see Fig.2 b) c) and Fig.4). high failure rates. Even drug courses of potent antifungal therapy, or isotretinoin within 6 months of (Mikrobioloska laboratorija Paster, Belgrade, Serbia). systemic antimycotics, delivered over a period of the first scheduled laser procedure were excluded. No local anesthesia was applied preoperatively. several months, have cure rates of only 40 to 80% [23- Some examples of drugs which were cause for Of the 110 patients who were initially recruited, 72 Cold air cooling was applied to the area during laser 25]. Among the orally delivered systemic drugs exclusion are griseofulvin or other cefalosporins, (65%) tested positive for, and were microbiologically treatment, (Cryo6, Zimmer, Germany used). No Terbinafine, Intraconazole and Fluconoazole are most minocyclin, or cytostatics (busulfa, 5-fluoroacil). confirmed as carrying, fungal cultures. All 72 patients postoperative analgesic treatment was required. No frequently used. Systemic drug therapy is associated Patients who used vasodilators were also excluded, were included in the study and completed all treatment prophylactic antibiotics or antiviral were given to any with several unpleasant side effects. Headache, rash because faster blood flow could increase heat transfer sessions and follow ups.
and gastrointestinal symptoms were reported in about in the nail plate, thereby adversely effecting therapy. 7 percent of patients treated with Intraconazole [23] Thicker nails were pretreated to achieve better laser Parallel to in-vivo therapeutic irradiation of nails and about 5 percent of patients treated with Permanent or semi-permanent discoloration of the light penetration. The patient's thick dystrophic nails infected with fungi an in-vitro experiment of laser Fluconoazole suffered nausea, headaches, pruritus and nail plate was another cause for exclusion. Such were treated with a preparation containing: 40% urea, irradiation effect on fungus culture was performed. An liver enzyme abnormalities [26]. The duration of discoloration can be caused by the use of therapeutics 20% anhydrous lanolin, 5% white wax, and 35% white isolate of fungal colonies obtained from a toenail systemic drug therapy is usually three months; the or cosmetics which effect nail pigmentation, for petrolatum for three successive nights, by applying the scraping were passed on Sabouraud Peptone-Glucose duration can be cut in half by using "pulse" therapy, in example the local antifungal therapy solutio Castel any, preparation to the nail under occlusion. This Agar. Ten days after isolation standardized which increased doses are administered. the use of nail dyes and polishes (especially those pretreatment was only needed for 3 patients of 72 photographs were obtained; the colonies were exposed which contain magnesium or iron). Discoloration can to laser irradiation with 1064 nm wavelength, fluence Topical antifungal preparations are also widely also be caused by professional exposure to dyes or of 40 J/cm2 and pulse duration of 35 msec. Three days used. Although safe and relatively inexpensive, topical asphalt. Treatment was performed using long pulse VSP after laser exposure a final examination was made and therapy is seldom effective [27]. 1064 nm Nd:YAG laser (Dualis SP; Fotona, Slovenia), standardized photographs were obtained. The fol owing conditions can cause various with fluences in the range of 35 to 40 J/cm², a spot The efficacy of the treatment can be improved and physiological changes to the nail plate in addition to size of 4 mm diameter, and pulse duration of 35 ms. Treatment Evaluation
its duration reduced by supplementing the discoloration and so were also cause for exclusion: The variations in fluence were selected based on the Fol ow-ups were done at 3, 6, 9 and 12 months. medicamentous therapy with some complementary subungual hematoma, nevoid subungual formation, thickness of the nail to be treated, with thicker nails The patients were evaluated for clearance of fungal (e.g. light) treatment. Photodynamic therapy has been bacterial nail infections, and concomitant nail requiring higher fluence. The pulse rate was 1 Hz. The infection clinically by the physician executing the recently proposed to treat T. rubrum infection, and disorders such as psoriasis of nail plate, lichen planus laser beam was applied to the entire nail plate by procedure and mycologically by analysis of the culture promising results have been obtained [6]. and atopic dermatitis. incrementally moving the beam in a spiral pattern as taken at 3 and 6 month follow-up visits made by In addition, pregnant women were excluded. shown on Fig. 2. After the entire nail plate was independent The direct effect of laser light on fungal isolates irradiated a 2 minute pause was taken and then the (Mikrobioloska laboratorija Paster, Belgrade, and and affected nails has not yet been rigorously Treatment procedure
treatment and pause were repeated twice more for a Bel adonna, Zemun, both Serbia). Photographs were examined for its possible inhibitory potential. The primary aim of this treatment regime was to total of three passes. The total therapy consisted of taken using the same camera settings, lighting, and nail restore the nail to ful health at 12 months. The four sessions with a one week interval between each position at baseline and at the 6, 9 and 12-month Although there are already two laser system secondary aim of treatment was to render the nail free follow-up visits. manufacturers promoting their systems for the of fungi at 3 months. treatment of onychmycosis, thus far neither has Also, all the patients were filling-in questionnaires delivered a clinical study with a significant number of In the first step samples were collected and the nail after each therapeutical session, evaluating the level of cases in which an efficacious outcome was achieved. area was thoroughly cleansed with alcohol to remove procedural pain (on a 5-point scale where 0 = no pain, contaminants. For distal subungual onychomycosis, 1 = mild pain, 2 = moderate pain, 3 = severe pain and II. MATERIALS AND METHODS
the infected nail was clipped proximally and the nail 4 = intolerable pain) as well as possible adverse 194 nails of 72 patients with clinically and bed and underside of the nail plate were scraped with effects, if any of such would occur. mycological y proven onychomycosis were exposed to a 1-2 mm serrated curette. For proximal subungual transcutaneous laser irradiation with the aim of onychomycosis, the normal surface of the nail plate III. RESULTS
deactivation and eradication of fungal infection. was pared down with a no.15 surgical blade at the lunula and the white debris was col ected with a sharp a) Types of onychomycosis treated
Inclusion criteria
curette from the deeper portion of the plate and the Treated patients had al four major clinical types of onychomycosis: total dystrophic form, distal To take part in the study each patient had to have proximal nail bed. The sampled material was divided subungual onychomycosis, proximal subungual one or more toenail and/or fingernail fungal infections into two portions: one for direct microscopy and the Fig. 2: Presentation of delivery of laser beam in spiral onychomycosis and endonyx onychomycosis. The of the fol ow types: total dystrophic form, distal remainder for culture. pattern on the nail plate surface (a) Thermal images of distribution of onychomycosis types in patient subungual onychomycosis, proximal subungual toenail surface before (b), and after (c) irradiation with VSP population is given in Table 1. onychomycosis and/or endonyx onychomycosis and Prior to laser treatment positive fungal cultures Nd:YAG laser beam. Temperature increase of the nail plate is clearly visible. be between 18-45 years of age. were obtained from al patients after direct microscopy Al patients signed written informed consent was used as a screening test. Scrapings were mounted For the first few patients the temperature increase statements before beginning laser treatment. for direct examination in 25% KOH mixed with 5% glycerol, heated (e.g., for 1 h at 51 to 54°C) to emulsify of the nail plate was measured during treatment using lipids, and examined under 3400x magnification for FLIR Thermal Imager and ThermaCAM Researcher Novel Laser Therapy in Treatment of Onychomycosis Novel Laser Therapy in Treatment of Onychomycosis Table 1: Clinical types of fungal nail infection in
and culture of nail specimens. Predisposing factors like diabetes, old age, hyperhidrosis, onychoglyphores, nail trauma, poor peripheral circulation are likely to be present. Several nail disorders that may mimic fungal nail infections must be correctly recognized and differentiated from onychomycosis to initiate the most appropriate therapy. They include psoriasis, lichen planus, bacterial infections, contact dermatitis, traumatic onychodystrophies, paronychia congenital, Fig. 5: Petri dish with T. mentagrophytes before and 3 days nail bed tumors, yellow-nail syndrome, idiopathic b) Types of diagnosed fungal infections
after long pulse VSP Nd:YAG laser irradiation. onycholysis etc. Fig. 4: Measured temperature at the nail plate during the As expected, the most frequent fungus found laser treatment. among treated patients was Trichophyton rubrum (in IV. DISCUSSION
There are a lot of factors which are contributing to 37 patients or 51,4%), fol owed by Trichophyton Working with laser energy delivery rate of 1 Hz Dermatophyte cel s infect skin by a process of fungal nail infection such as: diabetes, professional mentagrophytes (22 patient or 30,5%). Table 2 and using spot size of 4 mm, the nail plate was fully adherence to the cells of the epidermis followed by exposure to sugar (cooks, confectioneries, candy presents al fungi found in patient population. covered with laser energy in approximately germination, growth, and penetration by fungal makers, sportsmen), exposure to traumas (minor or 15 seconds. During that time the temperature in hyphae, both within and between cel s. The first phase mayor trauma like subungual hematomas), activities Table 2: Types of fungal nail isolates.
average increased to about 50°C. After the delivery of of fungal attack on the stratum corneum, the outer contributing to excessive sweating of feet and skin energy was stopped, the nail plate cooled, reaching layer of cornified cells, dead cel s fil ed with the maceration, visits to pedicure treatments. 40°C in about 1 minute after the beginning of fibrous protein, keratin, depends on this process of intercel ular adherence. Initial studies of this phenomenon utilized microconidia obtained from e) Treatment pain and adverse effect evaluation
pure dermatophyte cultures. [14] Patients evaluated the treatment pain level after each of the four sessions. Their evaluations were The principle means of defense against dermatophytes averaged and the results are presented in Table 3 identified at present involve both non-immunological below. Most of the patients reported mild pain, while processes such as the interaction between fungi and none reported severe or intolerable pain. unsaturated transferrin, activation of epidermal c) Eradication of nail fungal infections
peptides, the inhibitory effect of fatty acids in sebum, On 3 months fol ow up 95,83% patients were Table 3: Patients averaged evaluation of treatment
and immunological processes including fungal killing Fig. 7: Trichophyton mentagrophites treated with VSP cleared of all fungal infections. On 3 patients (4,17%) by polymorphonuclear leucocytes attracted into the Nd:YAG laser : before a) and 12 months after b) with still present infection the complete procedure was area of infection as well as the activation of T repeated. On 6 and 12 months fol ow ups al patients lymphocytes [14]. Each of the four clinical types of onychomycosis, as (100%) were fully cleared of all fungal infections.
defined by the route of fungal invasion, has a Increasingly onychomychosis is being viewed as more characteristic appearance, but other diseases, (2) Moderate pain than a mere cosmetic problem. Persons with unsightly, particularly psoriasis, may have a similar appearance. infected nails may suffer embarrassment. Fungi from Proper management, therefore, includes confirmation (4) Intolerable pain the nails may precipitate secondary bacterial infections, of fungal infection by potassium hydroxide slide Many of patients developed a kind of pain cellulitis, idiopathic reactions and chronic urticaria. preparation and culture. resistance during the therapy. Usually they felt the Infected toenails may act as a reservoir for fungi, highest level of pain during the first session. In facilitating their transmission to other areas of the Traditional y, pharmacologic treatment has been less following sessions patients' pain scores were usually body and even to other people. than optimal. In many cases, griseofulvin, the first oral lower, as they become "adapted", or they already knew agent approved for onychomycosis, must be given for what pain level they could expect. a year or more to be effective. Low cure rates are related to poor bioavailability and the fungistatic rather Fig. 3: Efficacy of laser treatment of onychomycosis, as Patients were also asked to report all adverse than fungicidal effect of the drug. Newer agents, such observed from mycological cultures taken on 3 and 6 effects. There were no reports of unwanted side as oral itraconazole and oral terbinafine, promise to months and clinical y evaluated on 12 months. effects resulting from treatment. substantial y increase cure rates while shortening d) Temperatures measured on the nail plate
treatment duration. Oral terbinafine is potently f) In-vitro fungus eradication
fungicidal against dermatophytes and has proven Measurements of the nail plate temperature All in-vitro irradiated samples of fungal cultures efficacious with regimens as brief as 12 weeks when showed similar behaviour on all tested specimens. were showing evident growth inhibition and colonies Fig. 6: Trichophyton rubrum treated with VSP Nd:YAG infection is not spread over the entire nail [23-25]. decay after single irradiation session. Example of an laser: before a), 6 months after b) and 12 months after c) in-vitro fungal colony development, prior to laser irradiation is shown on Fig.5 a) and its diminishing Clinical diagnosis of onychomycosis is based on the after the irradiation is shown on Fig.5 b). patients' history; a physical examination, microscopy Novel Laser Therapy in Treatment of Onychomycosis Novel Laser Therapy in Treatment of Onychomycosis Table 1: Clinical types of fungal nail infection in
and culture of nail specimens. Predisposing factors like diabetes, old age, hyperhidrosis, onychoglyphores, nail trauma, poor peripheral circulation are likely to be present. Several nail disorders that may mimic fungal nail infections must be correctly recognized and differentiated from onychomycosis to initiate the most appropriate therapy. They include psoriasis, lichen planus, bacterial infections, contact dermatitis, traumatic onychodystrophies, paronychia congenital, Fig. 5: Petri dish with T. mentagrophytes before and 3 days nail bed tumors, yellow-nail syndrome, idiopathic b) Types of diagnosed fungal infections
after long pulse VSP Nd:YAG laser irradiation. onycholysis etc. Fig. 4: Measured temperature at the nail plate during the As expected, the most frequent fungus found laser treatment. among treated patients was Trichophyton rubrum (in IV. DISCUSSION
There are a lot of factors which are contributing to 37 patients or 51,4%), fol owed by Trichophyton Working with laser energy delivery rate of 1 Hz Dermatophyte cel s infect skin by a process of fungal nail infection such as: diabetes, professional mentagrophytes (22 patient or 30,5%). Table 2 and using spot size of 4 mm, the nail plate was fully adherence to the cells of the epidermis followed by exposure to sugar (cooks, confectioneries, candy presents al fungi found in patient population. covered with laser energy in approximately germination, growth, and penetration by fungal makers, sportsmen), exposure to traumas (minor or 15 seconds. During that time the temperature in hyphae, both within and between cel s. The first phase mayor trauma like subungual hematomas), activities Table 2: Types of fungal nail isolates.
average increased to about 50°C. After the delivery of of fungal attack on the stratum corneum, the outer contributing to excessive sweating of feet and skin energy was stopped, the nail plate cooled, reaching layer of cornified cells, dead cel s fil ed with the maceration, visits to pedicure treatments. 40°C in about 1 minute after the beginning of fibrous protein, keratin, depends on this process of intercel ular adherence. Initial studies of this phenomenon utilized microconidia obtained from e) Treatment pain and adverse effect evaluation
pure dermatophyte cultures. [14] Patients evaluated the treatment pain level after each of the four sessions. Their evaluations were The principle means of defense against dermatophytes averaged and the results are presented in Table 3 identified at present involve both non-immunological below. Most of the patients reported mild pain, while processes such as the interaction between fungi and none reported severe or intolerable pain. unsaturated transferrin, activation of epidermal c) Eradication of nail fungal infections
peptides, the inhibitory effect of fatty acids in sebum, On 3 months fol ow up 95,83% patients were Table 3: Patients averaged evaluation of treatment
and immunological processes including fungal killing Fig. 7: Trichophyton mentagrophites treated with VSP cleared of all fungal infections. On 3 patients (4,17%) by polymorphonuclear leucocytes attracted into the Nd:YAG laser : before a) and 12 months after b) with still present infection the complete procedure was area of infection as well as the activation of T repeated. On 6 and 12 months fol ow ups al patients lymphocytes [14]. Each of the four clinical types of onychomycosis, as (100%) were fully cleared of all fungal infections.
defined by the route of fungal invasion, has a Increasingly onychomychosis is being viewed as more characteristic appearance, but other diseases, (2) Moderate pain than a mere cosmetic problem. Persons with unsightly, particularly psoriasis, may have a similar appearance. infected nails may suffer embarrassment. Fungi from Proper management, therefore, includes confirmation (4) Intolerable pain the nails may precipitate secondary bacterial infections, of fungal infection by potassium hydroxide slide Many of patients developed a kind of pain cellulitis, idiopathic reactions and chronic urticaria. preparation and culture. resistance during the therapy. Usually they felt the Infected toenails may act as a reservoir for fungi, highest level of pain during the first session. In facilitating their transmission to other areas of the Traditional y, pharmacologic treatment has been less following sessions patients' pain scores were usually body and even to other people. than optimal. In many cases, griseofulvin, the first oral lower, as they become "adapted", or they already knew agent approved for onychomycosis, must be given for what pain level they could expect. a year or more to be effective. Low cure rates are related to poor bioavailability and the fungistatic rather Fig. 3: Efficacy of laser treatment of onychomycosis, as Patients were also asked to report all adverse than fungicidal effect of the drug. Newer agents, such observed from mycological cultures taken on 3 and 6 effects. There were no reports of unwanted side as oral itraconazole and oral terbinafine, promise to months and clinical y evaluated on 12 months. effects resulting from treatment. substantial y increase cure rates while shortening d) Temperatures measured on the nail plate
treatment duration. Oral terbinafine is potently f) In-vitro fungus eradication
fungicidal against dermatophytes and has proven Measurements of the nail plate temperature All in-vitro irradiated samples of fungal cultures efficacious with regimens as brief as 12 weeks when showed similar behaviour on all tested specimens. were showing evident growth inhibition and colonies Fig. 6: Trichophyton rubrum treated with VSP Nd:YAG infection is not spread over the entire nail [23-25]. decay after single irradiation session. Example of an laser: before a), 6 months after b) and 12 months after c) in-vitro fungal colony development, prior to laser irradiation is shown on Fig.5 a) and its diminishing Clinical diagnosis of onychomycosis is based on the after the irradiation is shown on Fig.5 b). patients' history; a physical examination, microscopy Novel Laser Therapy in Treatment of Onychomycosis Novel Laser Therapy in Treatment of Onychomycosis involving effector mechanisms that range from classified into one of three categories: induction by rescuing capacity of cells, induce cell death. Membrane accelerated epidermal turnover to production of direct DNA damage e.g. strand breaks, chromosomal lipid ceramide has been proposed as a signaling adhesion molecule-directed neutrophil trafficking in aberrations, induction by transduced signals e.g. molecule that converts extracellular stresses into the epidermis at the site of infection and subsequent FAS/APO-1 transmembrane signals, and stress (heat) intracellular signals. In response to heat shock, phagocyte-mediated fungal cell destruction. mediated apoptosis. Hyperthermia, a typical ceramide levels increased in normal HL-60 cells. environmental stress, has long been known as toxic to HSP70 in Trichophyton rubrum is already detected The 1064 nm radiation emitted by the Nd:YAG laser cells. It has been recognized the mode of cell killing to and careful y characterised. Reactive oxygen species is primarily absorbed by dark pigments. When an be influenced by severity of the heat treatment [18]. has recently been suggested as a second messenger Fig. 8: Candida species treated with VSP Nd:YAG laser: Nd:YAG laser is used at high power settings and for a A number of reports have been published to generated by growth factors and cytokines, including before a), 6 months after b) and 9 months after c) long time, the rise in temperature has deleterious demonstrate the induction of apoptosis by mild PDGF, EGF, angiopoietin-1, TNFơ, and IL-1 in effects on periodontal tissues [8]. It is generally agreed hyperthermia [19,20]. Some of the possibilities are that nonphagocytic cel s. Denatured proteins disrupt The successful clinical use of lasers largely depends that temperatures above 56-60°C cause denaturation thermal injury may initiate a death signal, target certain cellular redox homeostasis and increase ROS levels upon the wavelength, output power, pulse duration, of hard tissue proteins [7,8] Eriksson & Albrektsson heat labile proteins, or cause direct or indirect DNA and ROS induces protein misfolding. When misfolded exposure time, spot size, type, and color of the reported that 47°C temperature for 1 minute (only damage leading to apoptosis. Apoptosis is the result of proteins are produced, proteolytic machinery is turned targeted tissue [8,10,13]. 10°C above human body temperature) produced a combination of the thermal destruction (directly or on to remove them [16,20] persistent bone damage [11,12]. Levy et al. indirectly) of apoptosis protecting molecules with a Most severe protein denaturation leads apoptosis of One of main advantages of laser surgery is its demonstrated the level of energy is a critical factor to concurrent production of killing molecules which then fungal cel - a programmed cel death or sometimes bactericidal effect. Laser light causes local obtain safe treatment conditions [13]. execute the death sentence. cel suicide which plays an important role in a wide variety of normal and pathological processes. microorganisms, and stimulation of the reparative Local hyperthermia has been a common therapy in process [28]. Statistically significant growth inhibition Japan in the treatment of sporotrichosis since 1966, of T.rubrum was detected in colonies treated with the V. CONCLUSIONS
and good results have been obtained [21]. It was 1,064-nm Q-switched Nd:YAG laser at 4 and 8 J/cm2 applied with infra red and far infra red devices. The Nd:YAG 1064 nm laser irradiation with the [29]. This laser produced a significant inhibitory effect disadvantages of these methods were related to the capability of delivering destructive high energy pulses upon the fungal isolate T.rubrum in an in-vitro study. application of non sophisticated devices and the to specific targets with minimized surrounding tissue Meral, Tasar at al. reported a strong bactericidal effect necessity of daily applications. damage seems to be well suited for the task of on Candida albicans suspensions after Nd:YAG laser eradicating nail fungal infection. This wavelength irradiation [30]. photo-inactivate fungal pathogens to a depth below the nail tissue surface leaving the surrounding tissue The laser used in this study –VSP Nd:YAG 1064 nm, intact, using safe energy densities in-vitro and in-vivo penetrates through the nail plate and produces heat at physiologic temperatures. Reduction of nail plate deep within the dermis and nail tissue. thickness before laser treatment on severely distrophic enables the optimal effect of Nd:YAG laser The procedure is simple and quick with no Fig. 10: Candida species treated with VSP Nd:YAG laser : noticeable side effects and complications. VSP before a), 3 months after b) and 9 months after c) Nd:YAG laser therapy of onychomycosis is safe and very efficient method for treating al types of Desired average tissue temperature for laser irradiation onychomycosis caused by various fungal species. of onychomycotic nails is about 43-51°C, at a This method is useful for the broadest range of treatment time of at least 2-3 minutes; these patients and is special y beneficial in elderly, parameters provide an adequate therapeutic dose. compromised and hepatopathic patients for which Toleration of higher temperatures is possible with other alternative treatments could present some risks. desensitization of the treated area or with increased Fig. 9: Aspergilus niger treated with VSP Nd:YAG laser: The amount of laser energy that can deactivate 80- before a) and 6 months after b) Fig. 11: Trichophyton rubrum treated with VSP Nd:YAG 99% of the organisms present in an affected nail is the laser: before a) and 12 months after b) 1. Schlefman BS (1999) Onychomycosis: A compendium of facts deactivating dose. That dose does not instantly kill the and a clinical experience. J Foot Ankle Surg. 38:290–302. Melanin is an essential constituent of the fungal cell 2. Ghannoum MA,Hajjeh RA, Scher R, et al. (2000) A large-scale fungal colonies but results in their disability to wal that has been described in many pathogenic North American study of fungal isolates from nails: The replicate or survive according to apoptotic mechanism. External stresses including heat shock induce the frequency of onychomycosis, fungal distribution and species. The type of melanin varies although it is generation of reactive oxygen species (ROS) and antifungal susceptibility patterns. J Am Acad Dermatol. commonly Dopa or pentaketide melanin. Melanized Apoptosis, a physiological type of cell death, plays an denaturation of cel ular proteins. Activations of fungal cel s show enhanced capacity to resist T-cel 3. Zaias N, Glick B, Rebel G (1996) Diagnosing and treating important role in the selective deletion of cel s in signaling pathways in response to a stress vary mechanisms and neutrophil attack largely through onychomycosis. J Fam Pract. 42:513–518. divergent situation of various tissues (Levine et al, depending on the strength of stress resulting in the 4. Evans EG (1998) Causative pathogens in onychomycosis and neutralizing the effect of oxidative products such as 1991; White, 1995). The events that are able to induce generation of various amounts of ROS and denatured the possibility of treatment resistance: a review. J Am Acad superoxide or reactive oxygen. Dermatophyte apoptosis are incredibly diverse but are generally proteins. Strong stress which is overflowing the Dermatol. 38:S32–S56. infections are normal y eliminated through a Th1 path Novel Laser Therapy in Treatment of Onychomycosis Novel Laser Therapy in Treatment of Onychomycosis involving effector mechanisms that range from classified into one of three categories: induction by rescuing capacity of cells, induce cell death. Membrane accelerated epidermal turnover to production of direct DNA damage e.g. strand breaks, chromosomal lipid ceramide has been proposed as a signaling adhesion molecule-directed neutrophil trafficking in aberrations, induction by transduced signals e.g. molecule that converts extracellular stresses into the epidermis at the site of infection and subsequent FAS/APO-1 transmembrane signals, and stress (heat) intracellular signals. In response to heat shock, phagocyte-mediated fungal cell destruction. mediated apoptosis. Hyperthermia, a typical ceramide levels increased in normal HL-60 cells. environmental stress, has long been known as toxic to HSP70 in Trichophyton rubrum is already detected The 1064 nm radiation emitted by the Nd:YAG laser cells. It has been recognized the mode of cell killing to and careful y characterised. Reactive oxygen species is primarily absorbed by dark pigments. When an be influenced by severity of the heat treatment [18]. has recently been suggested as a second messenger Fig. 8: Candida species treated with VSP Nd:YAG laser: Nd:YAG laser is used at high power settings and for a A number of reports have been published to generated by growth factors and cytokines, including before a), 6 months after b) and 9 months after c) long time, the rise in temperature has deleterious demonstrate the induction of apoptosis by mild PDGF, EGF, angiopoietin-1, TNFơ, and IL-1 in effects on periodontal tissues [8]. It is generally agreed hyperthermia [19,20]. Some of the possibilities are that nonphagocytic cel s. Denatured proteins disrupt The successful clinical use of lasers largely depends that temperatures above 56-60°C cause denaturation thermal injury may initiate a death signal, target certain cellular redox homeostasis and increase ROS levels upon the wavelength, output power, pulse duration, of hard tissue proteins [7,8] Eriksson & Albrektsson heat labile proteins, or cause direct or indirect DNA and ROS induces protein misfolding. When misfolded exposure time, spot size, type, and color of the reported that 47°C temperature for 1 minute (only damage leading to apoptosis. Apoptosis is the result of proteins are produced, proteolytic machinery is turned targeted tissue [8,10,13]. 10°C above human body temperature) produced a combination of the thermal destruction (directly or on to remove them [16,20] persistent bone damage [11,12]. Levy et al. indirectly) of apoptosis protecting molecules with a Most severe protein denaturation leads apoptosis of One of main advantages of laser surgery is its demonstrated the level of energy is a critical factor to concurrent production of killing molecules which then fungal cel - a programmed cel death or sometimes bactericidal effect. Laser light causes local obtain safe treatment conditions [13]. execute the death sentence. cel suicide which plays an important role in a wide variety of normal and pathological processes. microorganisms, and stimulation of the reparative Local hyperthermia has been a common therapy in process [28]. Statistically significant growth inhibition Japan in the treatment of sporotrichosis since 1966, of T.rubrum was detected in colonies treated with the V. CONCLUSIONS
and good results have been obtained [21]. It was 1,064-nm Q-switched Nd:YAG laser at 4 and 8 J/cm2 applied with infra red and far infra red devices. The Nd:YAG 1064 nm laser irradiation with the [29]. This laser produced a significant inhibitory effect disadvantages of these methods were related to the capability of delivering destructive high energy pulses upon the fungal isolate T.rubrum in an in-vitro study. application of non sophisticated devices and the to specific targets with minimized surrounding tissue Meral, Tasar at al. reported a strong bactericidal effect necessity of daily applications. damage seems to be well suited for the task of on Candida albicans suspensions after Nd:YAG laser eradicating nail fungal infection. This wavelength irradiation [30]. photo-inactivate fungal pathogens to a depth below the nail tissue surface leaving the surrounding tissue The laser used in this study –VSP Nd:YAG 1064 nm, intact, using safe energy densities in-vitro and in-vivo penetrates through the nail plate and produces heat at physiologic temperatures. Reduction of nail plate deep within the dermis and nail tissue. thickness before laser treatment on severely distrophic enables the optimal effect of Nd:YAG laser The procedure is simple and quick with no Fig. 10: Candida species treated with VSP Nd:YAG laser : noticeable side effects and complications. VSP before a), 3 months after b) and 9 months after c) Nd:YAG laser therapy of onychomycosis is safe and very efficient method for treating al types of Desired average tissue temperature for laser irradiation onychomycosis caused by various fungal species. of onychomycotic nails is about 43-51°C, at a This method is useful for the broadest range of treatment time of at least 2-3 minutes; these patients and is special y beneficial in elderly, parameters provide an adequate therapeutic dose. compromised and hepatopathic patients for which Toleration of higher temperatures is possible with other alternative treatments could present some risks. desensitization of the treated area or with increased Fig. 9: Aspergilus niger treated with VSP Nd:YAG laser: The amount of laser energy that can deactivate 80- before a) and 6 months after b) Fig. 11: Trichophyton rubrum treated with VSP Nd:YAG 99% of the organisms present in an affected nail is the laser: before a) and 12 months after b) 1. Schlefman BS (1999) Onychomycosis: A compendium of facts deactivating dose. That dose does not instantly kill the and a clinical experience. J Foot Ankle Surg. 38:290–302. Melanin is an essential constituent of the fungal cell 2. Ghannoum MA,Hajjeh RA, Scher R, et al. (2000) A large-scale fungal colonies but results in their disability to wal that has been described in many pathogenic North American study of fungal isolates from nails: The replicate or survive according to apoptotic mechanism. External stresses including heat shock induce the frequency of onychomycosis, fungal distribution and species. The type of melanin varies although it is generation of reactive oxygen species (ROS) and antifungal susceptibility patterns. J Am Acad Dermatol. commonly Dopa or pentaketide melanin. Melanized Apoptosis, a physiological type of cell death, plays an denaturation of cel ular proteins. Activations of fungal cel s show enhanced capacity to resist T-cel 3. Zaias N, Glick B, Rebel G (1996) Diagnosing and treating important role in the selective deletion of cel s in signaling pathways in response to a stress vary mechanisms and neutrophil attack largely through onychomycosis. J Fam Pract. 42:513–518. divergent situation of various tissues (Levine et al, depending on the strength of stress resulting in the 4. Evans EG (1998) Causative pathogens in onychomycosis and neutralizing the effect of oxidative products such as 1991; White, 1995). The events that are able to induce generation of various amounts of ROS and denatured the possibility of treatment resistance: a review. J Am Acad superoxide or reactive oxygen. Dermatophyte apoptosis are incredibly diverse but are generally proteins. Strong stress which is overflowing the Dermatol. 38:S32–S56. infections are normal y eliminated through a Th1 path Novel Laser Therapy in Treatment of Onychomycosis Journal of the Laser and Health Academy Vol. 2010, No.1; www.laserandhealth.com 5. Gupta AK, Ryder JE, Baran R (2003) The use of topical 26. Scher RK (1999) Onychomycosis: therapeutic update. J Am therapies to treat onychomycosis. Dermatol Clin 21:481-9. Acad Dermatol 40(6 pt 2):S21-6. 6. Okunaka T, Kato H, Konaka C, Sakai H, Kawabe H, Aizawa 27. Ciclopirox (Penlac) nail lacquer for onychomycosis (2000) K (1992) A comparison between argon-dye and excimer-dye Med Lett Drugs Ther 42(1080):51-2. High Fluence, High Beam Quality Q-Switched Nd:YAG
laser for photodynamic effect in transplanted mouse tumor. 28. Dayan S, Damrose JF, Bhattacharyya TK, et al. (2003) Jpn J Cancer Res. 83(2):226-231. Histological evaluations fol owing 1,064-nm Nd:YAG laser Laser with Optoflex Delivery System for Treating Benign
7. Midda M, Renton-Harper P (1991) Lasers in dentistry. Br resurfacing. Lasers Surg Med 33: 126-31. Pigmented Lesions and Tattoos
Dent J. 11;170(9):343-6. 29. Vural E, Winfield HL, Shingleton AW, Horn TD, Shafirstein 8. Pick RM (1993) Using lasers in clinical dental practice. J Am G (2008) The effects of laser irradiation on Trichophyton Dent Assoc. 124(2):37-4. Review. rubrum growth, Lasers Med Sci 23: 349-353 9. Hay J R (2007) Immune Responses to Dermatophytoses In: 30. Meral G, Tasar F, Kocagoz S et. al. (2003) Factors affecting Boris Cencic1, Matjaz Lukac2, Marko Marincek1, Zdenko Vizintin1
Immune Responses to Dermatophytoses 226-233, Springer the antibacterial effects of NdYAG laser in vivo. Lasers in 10. Brooks SG, Ashley S, Fisher J, et. Al (1992) Exogenous Surg Med. 32(3):197-202. Fotona d.d., Stegne 7, Ljubljana, Slovenia chromophores for the argon and Nd:YAG lasers: a potential 31. Smijs TG, Schuitmaker HJ (2003) Photodynamic inactivation 2Institut Josef Stefan, Department for Complex Matter, Jamova 39, Ljubljana, Slovenia application to laser-tissue interactions. Lasers Surg Med. of the dermatophyte Trichophyton rubrum. Photochem Photobiol 77:556–560 11. Eriksson A, Albrektsson T, Grane B, et. al. (1982) Thermal injury to bone. A vital-microscopic description of heat effects. Int J Oral Surg. 11(2):115-21. 12. Eriksson A, Albrektsson T (1983) Temperature threshold ABSTRACT
I. INTRODUCTION
levels for heat-induced bone tissue injury: a vital-microscopic study in the rabbit. J Prosthet Dent. 50(1):101-7. Q-switched neodymium (Nd:YAG) lasers are very Extremely short pulse, Q-switched (QS) laser 13. Levy G (1992) Cleaning and shaping the root canal with a effective in the treatment of benign pigmented lesions systems can successfully lighten or eradicate a variety Nd:YAG laser beam : a comparative study. J Endodon; and tattoos. For effective and safe clearance or of pigmented lesions. Pigmented lesions that are eradication of pigments an Nd:YAG laser system must treatable include freckles and birthmarks including 14. Rosenberg HF, Gal in JI (1999) Inflammation. In be able to deliver nanosecond pulses with a very high some congenital melanocytic naevi, blue naevi, naevi Fundamental Immunology, ed Paul WE. Lippincott-Raven Publishers, Philadelphia, 1051–1066. pulse energy, and a uniform beam profile. However, a of Ota/Ito and Becker naevi.[1-11] 15. Jiang Q, Cross AS, Singh IS, Chen TT, Viscardi RM, Hasday host of technical challenges are associated with Q- The QS laser systems can also selectively destroy JD (2000). Febrile core temperature is essential for optimal switched Nd:YAG lasers which are capable of tattoo pigment without causing much damage to the host defense in bacterial peritonitis. Infect Immun 68: 1265– sufficiently high energies at short, nanosecond laser surrounding skin.[12-15] The altered pigment is then 16. Dubois MF, Hovanessian AG, Bensuade O1 (1991) Heat pulses. The optical components of a Q-switched laser removed from the skin by scavenging white blood cel s shock-induced denaturation of proteins. Characterization of are exposed to extremely high (several hundred MW) and tissue macrophages. the insolubilization of the interferon-induced p68 kinase. J Biol powers that are very close to, or above, their damage Q-switching, sometimes known as giant pulse Chem 266: 9707- 9711 thresholds. In addition, high powers may lead to formation, is a technique by which a laser can be made 17. Elia G, Santoro MG (1994) Regulation of heat shock protein optical breakdown and plasma formation in the air, to produce a pulsed output beam.[16] The technique synthesis by quercetin in human erythroleukemia cel s. Biochem J 300:201-209 thereby reducing transmission and deforming the al ows the production of light pulses with extremely 18. Armour EP, McEachern D, Wang Z, Corry PM, Martinez A beam. For these reasons, some commercially available short (on the order of nanoseconds) pulse duration (1993) Sensitivity of human cel s to mild hyperthermia. Cancer devices use a rapid sequence of two, or more, low and high (megawatt) peak power, much higher than Res 53: 2740-2744 power laser pulses, instead of a single giant pulse, to can be produced by the same laser operating in 19. Cuende E, Ales-Martinez JE, Ding L, Gonzalez-Garcia M, Martinez-A C, Nunez G (1993) Programmed cel death by bcl- increase the total delivered laser fluence to the treated continuous wave mode (constant output), or Variable 2-dependent and independent mechanisms in B lymphoma tissue without increasing the instantaneous laser pulse Square Pulse (0.1-300 ms) mode. [17-20] cel s. EMBO J 12:1555-1560 power. In this paper, we report on a study in which the The high power, short pulse QS laser systems are 20. Deng G, Podack ER (1993) Suppression of apoptosis in a efficacy of pigment clearance by a single giant pulse effective because they confine their energy to the cytotoxic T-cel line by interleukin 2-mediated gene was compared to the efficacy of clearance under treated pigments. The time duration (pulse duration) of transcription and deregulated expression of the protooncogene bcl-2. Proc Natl Acad Sci USA 90: 2189-2193 multiple pulse conditions. Results are presented that the QS laser energy is so short that the extremely smal 21. Hiruma W, Kavada A et al. (1992)Hyperthermic treatment of show that multiple pulsing is not effective, and that pigments of 10-100 nm size are heated to sporotrichosis: Experimental use of infra red and far infra red high-power, single pulses are mandatory for effective fragmentation temperature before their heat can reys. Mycoses 35, 293-299 pigment removal. Further, a novel laser delivery dissipate to the surrounding skin. This prevents 22. Gupta AK, Ahmad I, Borst I, Summebrbell RC (2000) Detection of xanthomegnin in epidermal materials infected approach is described that enables reliable delivery of heating of the surrounding tissue that could potentially with Trichophyton rubrum. J Invest Dermatol 115:901–905 giant laser pulses with very high beam quality. lead to burns or scars. 23. Gupta AK, De Doncker P, Scher RK, Haneke E, Daniel CR The most likely cause of pigment destruction under 3d, Andre J, et al (1998) Itraconazole for the treatment of Key words: laser pigment treatments; Q-switched QS laser pulses are shockwave and/or cavitation
onychomycosis. Int J Dermatol 37:303-8. laser; Nd:YAG laser; KTP laser; Optoflex, tattoo damage, the photomechanical physical effects 24. Havu V, Brandt D, Heikkila H, Hol men A, Oksman R, Rantanen T, et al. (1997) A double-blind, randomised study produced from thermal expansion, and/or the extreme comparing itraconazole pulse therapy with continuous dosing Article: J. LAHA, Vol. 2010, No.1, pp. 9-18. temperature gradients created within the melanosome for the treatment of toe-nail onychomycosis. Br J Dermatol or tattoo pigment. Melanin absorbs and localizes the Received: April 12, 2010; Accepted: May 6, 2010. high-intensity irradiation from Q-switched lasers, 25. De Doncker P, Decroix J, Pierard GE, Roelant D, Woestenborghs R, Jacqmin P, et al. (1996) Antifungal pulse Laser and Health Academy. Al rights reserved. thereby creating a sharp temperature gradient between therapy for onychomycosis. A pharmacokinetic and Printed in Europe. www.laserandhealth.com the melanosome and surrounding structures. This pharmacodynamic investigation of monthly cycles of 1-week gradient leads to thermal expansion and the generation pulse therapy with itraconazole. Arch Dermatol 132:34-41.

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