Medium-term antifungal effects of methylene blue versus flavin mononucleotide in the treatment of moderate toenail onychomycosis.

BACKGROUND: Methylene blue (MB) and flavin mononucleotide (FMN)-mediated photodynamic therapy (PDT) have demonstrated local antimicrobial effect, but no direct comparative study has been published so far for the treatment of toenail onychomycosis. OBJECTIVES: To directly compare the short and medium-term efficacy of MB versus FMN as photosensitizers in PDT for toenail onychomycosis by applying them in a 40% w/w urea cream in two different dye concentrations. METHODS: Forty toenails with distal and lateral subungual moderate onychomycosis due to dermatophyte fungi were randomised to receive 10 weekly sessions of PDT mediated by four topical formulations including MB or FMN at two different concentrations: Group I: 0.1% w/w MB; Group II: 2% w/w MB; Group III: 0.1% w/w FMN; and Group IV: 2% w/w FMN. Photographs were used for onychomycosis severity index (OSI) estimation allowing clinical assessment at any point of the study. Microscopic and microbiological evaluations were carried out at baseline, 27- and 35-week follow-ups. Side effects were recorded along with patient satisfaction. RESULTS: At week 27, mycological cure rates were 60%, 30%, 50% and 40% and complete cure rates were 0%, 20%, 10% and 20%, for Groups I, II, III and IV respectively. At week 35, mycological cure rates were 70%, 70%, 70% and 60% and complete cure rates were 30%, 50%, 70% and 30%, for Groups I, II, III and IV respectively. All cream formulations were safe and patients were fairly satisfied. CONCLUSIONS: Results of the present work confirm PDT as a therapeutic alternative for onychomycosis. Although all cream formulations were safe and effective, with a good degree of satisfaction, higher cure rates were obtained with 2% w/w MB cream and 0.1% w/w FMN cream.

Urea versus fractional Er:YAG laser pretreatment of methylene blue photodynamic therapy in the treatment of moderate toenail onychomycosis: short- and medium-term effects.

Keratolytic properties of urea 40% have long time used for the treatment of onychomycosis. Fractional ablative lasers enhance the delivery of topically applied photosensitizers improving photodynamic therapy (PDT) efficacy. The aim of this study was to compare the short- and medium-term efficacy of a pretreatment with urea 40% and fractional Er:YAG (Fr Er:YAG) laser radiation before PDT mediated by methylene blue (MB) for moderate toenail onychomycosis. Twenty-first-toe toenails were randomized to receive either urea 40% (Group I) or Fr Er:YAG laser (Group II) pretreatment and 9 sessions of MB/PDT over the course of 16 weeks. At baseline, 28- and 40-week follow-ups, clinical efficacy was assessed by digital photographs [allowing determination of the onychomycosis severity index (OSI)], whereas mycological efficacy was assessed by histological examination and fungal culture. Details of the side effects and patients' satisfaction were also recorded. In both groups, a significant decrease in OSI values was observed at the 28-week follow-up and a slight rebound at the 40-week follow-up. The percentage of nail involvement decreased significantly in both groups at the 28-week follow-up, to continue declining gently in Group I at 40 weeks, in contrast to the rebound observed during this period in Group II. The mycological cure rate was 20% and 30% at 28-week follow-up and 70% and 40% at 40-week follow-up, in Group I and II, respectively. Patients reported being fairly satisfied, and no side effects were detected in any groups. Although both pretreatments favor the action of PDT for the treatment of onychomycosis, the use of urea at 40% is more effective in the medium term.

Methyl aminolevulinate photodynamic therapy after partial debulking in the treatment of superficial and nodular basal cell carcinoma: 3-years follow-up.

BACKGROUND: The increase in the number of basal cell carcinoma (BCC) lesions has prompted use of minimally invasive therapies, including Photodynamic therapy (PDT). . The objective of the present work was to analyze the efficacy of methyl aminolevulinate-mediated photodynamic therapy (MAL-PDT) in patients suffering from superficial or nodular BCCs. METHODS: A total of 220 BCC lesions (76 superficial and 144 nodular), clinically diagnosed and confirmed by histopathology analysis, were treated in 174 patients (mean age 72.5). Debulking using curettage was performed before two or three MAL-PDT sessions (λ = 630 nm; 90 J/cm2; 23 min) at 4-week intervals. Analyses of clinical clearance and cosmetic outcome were carried out by direct examination, dermoscopy, photographs, as well as by fluorescence diagnosis using a Wood's lamp. Evaluations were carried out at the different PDT sessions and follow-ups over a 3-year period. RESULTS: MAL-PDT was safe and highly tolerated. After an average of 2.6 MAL-PDT sessions, the overall clearance rate at 3-year follow-up was 96.1 % (95 % confidence interval [CI] 100 %-92 %) for superficial BCCs and 95.2 % (95 % [CI] 99 %-92 %) for nodular BCCs after an average of 2.7 sessions. Minimal side effects such as crushing, erythema and edema were reported. All BCC lesions showed excellent or good cosmetic results. CONCLUSION: The protocol followed in the present study has shown that MAL-PDT is a safe and effective treatment for superficial and nodular types of BCC.

Methylene blue vs methyl aminolevulinate photodynamic therapy in the treatment of mild-to-moderate toenail onychomycosis: Short- and medium-term effects.

Photodynamic therapy (PDT) has emerged as an interesting alternative option for onychomycosis treatment. The impact of a specific photosensitizer (PS) on the final result is an important factor to consider. We conducted a short- and medium-term controlled trial to compare the effectiveness of PDT in the treatment of mild-to-moderate onychomycosis when it is mediated by two different PSs. Twenty patients were randomized to receive nine sessions of PDT distributed over 16 weeks mediated either by methylene blue (MB/PDT group) or methyl aminolevulinate (MAL/PDT group). Onychomycosis severity index (OSI) and nail involvement were checked along the study. Complete cure, treatment success, and clinical improvement were tabulated at 16 and 40-week follow-ups. OSI scores decreased significantly along the study, from 12.1 ± 5.4 to 3.6 ± 3.2 (MB/PDT group) and from 14.8 ± 6.0 to 5.4 ± 4.4 (MAL/PDT group). At 16-week follow-up, only 20% of the patients in the MB/PDT group reached complete cure and none in the group of MAL/PDT. At 40-week follow-up, complete cure rates were 70% and 40% in the MB/PDT group and MAL/PDT group respectively. Both modalities showed good outcomes in treatment of moderate toenail onychomycosis. MB/PDT showed a faster action but with relapse rates slightly higher than MAL/PDT.

Methylene blue vs methyl aminolevulinate photodynamic therapy in combination with oral terbinafine in the treatment of severe dermatophytic toenail onychomycosis: Short- and long-term effects.

BACKGROUND: Photodynamic therapy (PDT) kills target microorganisms via reactive oxygen species (ROS) production. PDT seems to be a good alternative treatment option for onychomycosis. OBJECTIVE: To compare the efficacy of combined therapies based on oral terbinafine (TN) plus adjunctive PDT mediated by methylene blue (MB) (TN + MB/PDT) or methyl aminolevulinate (MAL) (TN + MAL/PDT) in the treatment of onychomycosis. METHODS: Twenty patients affected by severe dermatophyte onychomycosis in the nails of the big toe (>60% disease involvement of target nail) received oral TN for 12 weeks and concomitantly were randomly allocated to receive nine sessions, separated by 2-week intervals, of urea (40%) plus a PDT protocol mediated by MB (TN + MB/PDT: group I) or mediated by MAL (TN + MAL/PDT: group II). Clinical and mycological efficacy was evaluated at 16-, 40- and 52-week follow-up. RESULTS: Both protocols showed a significant decrease in Onychomycosis Severity Index (OSI) scores (P < .05), from 24.2 ± 4.6 to 0.7 ± 0.6 (group I)) and from 18.5 ± 10.1 to 2.1 ± 2.0 (group II). No side effects or complications were reported in any of the combinations used. Mycological cure rates were significantly higher during the last third of the evaluated period of time, reaching 100% and 90% in group I and group II, respectively, at the 52-week follow-up. In both modalities, complete cure was achieved in 70% of the patients at the 52-week follow-up. CONCLUSIONS: TN + MB/PDT and TN + MAL/PDT show similar outcomes in the treatment of toenails with severe onychomycosis. PDT is an effective method to accelerate the TN-mediated healing process.

Successful treatment of Pityriasis Versicolor by photodynamic therapy mediated by methylene blue.

BACKGROUND: Although systemic therapies are recommended for severe or recalcitrant cases of pityriasis versicolor (PV), they are not free of important side effects and drug interactions. Photodynamic therapy (PDT) utilizes the action of singlet oxygen and free radicals produced by a light-activated photosensitizer to kill viruses, bacteria, or fungi. In this study, the effect of a PDT mediated by methylene blue (MB) in PV was evaluated. METHODS: Five women with PV disseminated on the back and diagnosed by fresh microscopic analysis were treated with a solution of MB (2%) applied to the PV lesions for 3 minutes. Next, a red LED lamp (λ = 630±5 nm, 37 J/cm2 ), placed 100 mm from the skin for 10 minutes, was applied on the dyed PV lesions. Six sessions of MB/PDT were implemented with a 2-week interval in between. Wood's lamp examination was used to monitor fungal infection at each time point. RESULTS: Complete cure was observed in the five women at the 4 weeks post-treatment follow-up. Fluoresce images from PV lesions by Wood's lamp allowed to evaluate whether the lesions were healed or not at each time point. No patient showed relapse at the 6-month follow-up. The patients did not have any adverse effect, and good cosmetic outcome was observed. CONCLUSIONS: Six sessions of MB/PDT spaced at 14-day intervals are sufficient for the treatment for PV in healthy patients.

Methyl aminolevulinate-based photodynamic therapy of Bowen´s disease: Observational study of 21 lesions.

BACKGROUND: Although surgical removal is the treatment of choice in Bowen's disease (BD), there are cases in which by age, comorbidities, use of anticoagulants, location, cosmetic result, or size, it is preferable to use other treatments such as cryotherapy, 5-fluorouracil cream, imiquimod 5% cream or photodynamic therapy (PDT). Efficacy of PDT in BD is supported by substantial research and clinical data. OBJECTIVES: This study aimed to evaluate the long term effectiveness of methyl aminolevulinate-PDT (MAL/PDT) on a wide range of Bowen lesions in different locations and sizes. METHODS: Patients diagnosed with BD were treated in 3 sessions with a 4-week interval in between with MAL/PDT between January 2016 and January 2017 in a private clinic. Clinical response and relevant patient and tumour characteristics were analyzed during the first year after start of the PDT sessions. RESULTS: In total, 21 BD lesions in 18 patients were included in the study. Complete regression (CR) after 3rd PDT session was 87.5% and 100% at the 6-month follow-up. Treatment was well tolerated and local adverse reactions were very scarce. No recurrence was observed at 12-month follow-up. Cosmetic outcome at 12 months was good or excellent in 100% of patients. CONCLUSIONS: MAL/PDT is an effective, non invasive and safe treatment modality for BD with excellent cosmesis.

Efficiency of methylene blue-mediated photodynamic therapy vs intense pulsed light in the treatment of onychomycosis in the toenails.

BACKGROUND: Photodynamic therapy (PDT) or intense pulsed light (IPL) are efficient therapeutic methods in the treatment of superficial skin infections, and thus, they could be good options for onychomycosis treatment, the most common nail disorder. METHODS: Forty patients, affected with different diagnosed types of onychomycosis in nails of the first toe, were randomly divided into two groups of 20 patients to be treated by PDT or IPL. Nail plates were softened with urea 40% by occlusive dressing for 12 hours during 3-7 days before treatments. Then, eight sessions separated by an interval of 2 weeks of a PDT protocol mediated by methylene blue (MB) and red laser diode (Periowave® , λ = 670 nm, 200 mW) or an IPL protocol based on 10 pulses/cm2 (Dye-VL-F module, Alma Lasers, λ = 500-600 nm, 10 J) were applied. RESULTS: Both treatments reduced significantly the Onychomycosis Severity Index (OSI) (P < 0.05). In terms of complete cure: 70% (PDT) and 80% (IPL) of the patients reached it after 12 weeks post-treatment. No patient reported any adverse effects or complications, although in the IPL Group, some referred pain sensation during light irradiation and hematomas apparition. CONCLUSIONS: Photodynamic therapy and IPL were effective for onychomycosis cure of any etiology.