Impact of microwave thermolysis energy levels on patient-reported outcomes for axillary hyperhidrosis and osmidrosis.

OBJECTIVE: Microwave thermolysis (MWT) is an emerging treatment for axillary hyperhidrosis reducing both sweat and odor. No prior studies have investigated and compared the different available energy settings of the MWT device. This study evaluated patient-reported outcome measures (PROMs) for axillary hyperhidrosis and osmidrosis following MWT treatment with two different energy levels. METHODS: Twenty adults with axillary hyperhidrosis and osmidrosis reported sweat on Hyperhidrosis Disease Severity scale (HDSS: 1-4) and odor on Odor scale (OS: 1-10), respectively, supplemented by overall Dermatology Life Quality Index (DLQI: 0-30). This was a prospective, randomized, patient-blinded and intraindividually controlled study with 3 months follow-up (FU). Randomization comprised MWT treatment of one axilla with a standard medium energy setting (energy level 3) and the contralateral axilla with a standard high energy setting (energy level 5). RESULTS: At baseline, patients reported substantial sweat and odor, negatively affecting their quality of life. At 3 months FU, PROMs showed improved quality of life with significantly reduced odor and sweat. Overall DLQI was reduced from a median of 10 to 4, with a median 6.5-point reduction (p = 0.0002). HDSS was reduced from a median of 4 to 2 on both sides, with a median reduction of 1 for medium energy level and 2 points for high energy level (p = 0.014). OS was reduced from a median of 8 to 3 for both energy levels, with a median reduction of 3.5 and 4.5 points for the medium and high energy level, respectively (p = 0.017). Local skin reactions were mild and transient, but slightly more pronounced following treatment with the high energy level. CONCLUSION: MWT effectively improved patients' quality of life, axillary sweat, and odor 3 months after on baseline treatment. Treatment with the high energy level presented a subtle but significant increase of efficacy based on PROMs for both sweat and odor. Patients were willing to accept a higher amount of temporary local skin reactions from a higher energy setting when experiencing greater odor and sweat reduction.

Efficacy and safety of daylight photodynamic therapy after tailored pretreatment with ablative fractional laser or microdermabrasion: a randomized, side-by-side, single-blind trial in patients with actinic keratosis and large-area field cancerization.

BACKGROUND: Physical pretreatments can potentiate the efficacy of daylight photodynamic therapy (dPDT), but clinical comparative studies remain limited. OBJECTIVES: Performed in large skin areas with actinic keratoses (AKs) and photodamage, this blinded, randomized clinical trial compared the efficacy and safety of dPDT after tailored skin pretreatment using ablative fractional laser (AFL) or microdermabrasion (MD). METHODS: Two ≥ 50-cm2 side-by-side skin areas were randomized to receive a single treatment with AFL-dPDT or MD-dPDT. Pretreatment parameters were tailored according to AK grade and skin constitution to ensure standardized immediate end points. Subsequently, methyl aminolaevulinate was applied, followed by 2-h daylight exposure. The primary outcome comprised blinded assessment of AK clearance at the 3-month follow-up. RESULTS: In 18 patients with 832 AKs, AFL-dPDT provided significantly higher AK clearance (81% vs. 60%, P < 0·001), led to fewer new AKs (P < 0·001) and showed superior improvement in dyspigmentation (P = 0·003) and skin texture (P = 0·001) vs. MD-dPDT. Peaking at days 3-6, AFL-PDT induced more intensified local skin responses (P = 0·004), including instances of Staphylococcus aureus infection (n = 3). Patients nonetheless preferred AFL-dPDT (P = 0·077), due to lower pretreatment-related pain (P = 0·002) and superior cosmesis (P = 0·035) and efficacy compared with MD-dPDT. CONCLUSIONS: AFL-dPDT is an effective treatment for patients with AK with extensive field cancerization, although AFL pretreatment is associated with intensified local skin reactions.

Photodynamic therapy is more effective than imiquimod for actinic keratosis in organ transplant recipients: a randomized intraindividual controlled trial.

BACKGROUND: Actinic keratoses (AKs) in solid organ transplant recipients (OTRs) are difficult-to-treat premalignancies and comparison of topical therapies is therefore warranted. OBJECTIVES: In an intraindividual study to compare the efficacy and safety of field treatment with methyl aminolaevulinate photodynamic therapy (MAL-PDT) and imiquimod (IMIQ) for AKs in OTRs. METHODS: OTRs (n = 35) with 572 AKs (grade I-III) in two similar areas on the face, scalp, dorsal hands or forearms were included. All patients received one MAL-PDT and one IMIQ session (three applications per week for 4 weeks) in each study area according to randomization. Treatments were repeated after 2 months (IMIQ) and 3 months (PDT) in skin with incomplete AK response. Outcome measures were complete lesion response (CR), skin reactions, laboratory results and treatment preference. RESULTS: The majority of study areas received two treatment sessions (PDT n = 25 patients; IMIQ n = 29 patients). At 3 months after two treatments, skin treated with PDT achieved a higher rate of CR (AK I-III median 78%; range 50-100) compared with IMIQ-treated skin areas (median 61%, range 33-100; P < 0·001). Fewer emergent AKs were seen in PDT-treated skin vs. IMIQ-treated skin (0·7 vs. 1·5 AKs, P = 0·04). Patients developed more intense inflammatory skin reactions following PDT, which resolved more rapidly compared with IMIQ (median 10 days vs. 18 days, P < 0·01). Patient preference (P = 0·47) and cosmesis (P > 0·30) were similar for PDT and IMIQ. CONCLUSIONS: Compared with IMIQ, PDT treatment obtained a higher rate of AK clearance at 3-month follow-up and achieved shorter-lasting, but more intense, short-term skin reactions.

Primary prevention of skin dysplasia in renal transplant recipients with photodynamic therapy: a randomized controlled trial.

Organ transplant recipients (OTRs) are at high risk of developing cutaneous squamous cell carcinoma (SCC); prevention includes early treatment of premalignant actinic keratosis (AK). Photodynamic therapy (PDT) is a noninvasive field therapy that reduces new AKs in patients with existing AK and delays SCC development in mice. We investigated the effect of repeated PDT over 5 years for primary prophylaxis of skin dysplasia. These data represent an interim analysis of an on-going randomized controlled trial. During 2008-2011, 25 renal transplant recipients with clinically normal skin were randomized to split-side PDT of the face, forearm and hand, the contralateral side serving as untreated control. Patients received PDT on inclusion and at 6-monthly intervals for 5 years. Blinded evaluation was performed at each visit. We found that prophylactic PDT significantly delayed onset of AK compared with untreated skin, p = 0.020. At 3-year follow-up, we observed AK in 63% of patients in untreated skin areas compared with 28% of patients in PDT-treated skin, with a total number of cumulated AKs in untreated skin (n = 43) compared with PDT-treated skin (n = 8), p = 0.005. These preliminary data indicate a novel approach to early prevention of skin dysplasia that may reduce morbidity from multiple AKs and SCCs in OTR.

Fractional laser-mediated photodynamic therapy of high-risk basal cell carcinomas--a randomized clinical trial.

BACKGROUND: Photodynamic therapy (PDT) is approved for selected nodular basal cell carcinomas (nBCC) but efficacy is reduced for large and thick tumours. Ablative fractional lasers (AFXL) facilitate uptake of methyl aminolaevulinate (MAL) and may thus improve PDT outcome. OBJECTIVES: To evaluate efficacy and safety of AFXL-mediated PDT (AFXL-PDT) compared with conventional PDT of high-risk nBCC. METHODS: Patients with histologically verified facial nBCC (n = 32) defined as high-risk tumours were included; diameter > 15 mm, tumours located in high-risk zones, or on severely sun-damaged skin. Tumours were debulked and patients randomized to either AFXL-PDT (n = 16) or PDT (n = 16). Fractional CO2 laser treatment was applied at 5% density and 1000 µm (80 mJ) ablation depth. MAL was applied under occlusion for 3 h and illuminated with a 633-nm light-emitting diode source, 37 J cm(-2) . Clinical assessments were performed at 3, 6, 9 and 12 months and biopsies were taken at 12 months. RESULTS: Clinical cure rates at 3 months were 100% (16 of 16 AFXL-PDT) and 88% (14 of 16 PDT, P = 0·484). Recurrences tended to occur later and in lower numbers after AFXL-PDT at 6, 9 and 12 months (6%, 19%, 19%) than PDT (25%, 38%, 44%) (P = 0·114). Histology at 12 months documented equal tumour clearance after AFXL-PDT (63%, 10 of 16) and PDT (56%, 9 of 16). Cosmetic outcomes were highly satisfactory after both treatments (P > 0·090). CONCLUSIONS: Long-term efficacy was similar after PDT and AFXL-PDT with a trend for a favourable short-term cure rate after AFXL-PDT. AFXL-PDT needs further refinement for nBCC and at present is not recommended over PDT.

Combination of ablative fractional laser and daylight-mediated photodynamic therapy for actinic keratosis in organ transplant recipients - a randomized controlled trial.

BACKGROUND: Topical photodynamic therapy (PDT) for actinic keratoses (AK) is hampered by pain during illumination and inferior efficacy in organ-transplant recipients (OTR). OBJECTIVES: We assessed ablative fractional laser (AFL)-assisted daylight photodynamic therapy (PDT) (AFL-dPDT) compared with daylight PDT (dPDT), conventional PDT (cPDT) and AFL alone (AFL) in field treatment of AK in OTR. METHODS: In each patient, four areas in the same region were randomized to one treatment with AFL-dPDT, dPDT, cPDT and AFL. AFL was delivered with a 2940-nm AFL at 2·3 mJ per pulse, 1·15 W, two stacks, 50-µs pulse-duration, 2·4% density. In dPDT and AFL-dPDT, methyl aminolaevulinate (MAL) was applied for 2·5 h without occlusion during daylight exposure. For cPDT, MAL was occluded for 3 h followed by red-light (630 nm) irradiation at 37 J cm(-2). The primary end-point was complete response (CR) 3 months post-treatment. RESULTS: Sixteen patients with 542 AK (grades I-III) in field-cancerized skin of the scalp, chest and extremities were treated during August and September 2012. After 3 months, CR (AK I-III) rates were 74% after AFL-dPDT, 46% after dPDT, 50% after cPDT and 5% after AFL (P < 0·001). CR rates in AFL-dPDT, dPDT and cPDT were also significantly different (P = 0·004). Median maximal pain scores differed significantly during AFL-dPDT (0), dPDT (0), AFL (0) and cPDT (5) (P < 0·001). Erythema and crusting were more intense following AFL-dPDT than dPDT and cPDT, but only transient hypopigmentation was observed. CONCLUSIONS: AFL-dPDT is a novel PDT modality that enhances CR with excellent tolerability compared with dPDT and cPDT in difficult-to-treat AK in OTR.

Intensified fractional CO2 laser-assisted photodynamic therapy vs. laser alone for organ transplant recipients with multiple actinic keratoses and wart-like lesions: a randomized half-side comparative trial on dorsal hands.

BACKGROUND: Photodynamic therapy (PDT) is a well-documented treatment for actinic keratosis (AK), but achieves inferior efficacy in organ transplant recipients (OTRs), particularly in acral regions. Ablative fractional laser (AFXL) intensifies the PDT response and may improve the efficacy of AK clearance when used as monotherapy. OBJECTIVES: To compare the efficacy of a single treatment with AFXL-assisted PDT vs. AFXL alone for difficult-to-treat AKs and wart-like lesions (WLLs) in OTRs. METHODS: Ten OTRs were included with a total of 680 AKs (severity grade I-III) and 409 WLLs on the dorsal hands. Both hands were initially treated with targeted fractional ablation of thick keratotic lesions followed by AFXL field treatment. Treatment regions were then randomized to (i) PDT (AFXL-PDT) or (ii) no further treatment (AFXL). The primary end point was complete response (CR) at 4 months after treatment; secondary end points were improvement of AK severity grade, overall patient assessment of efficacy and tolerability of treatments. RESULTS: CR of AKs was significantly higher for AFXL-PDT (73%) compared with AFXL alone (31%) (P = 0·002). AFXL-PDT improved 82% of AKs to lower lesion grades compared with 52% after AFXL alone (P = 0.008). For WLLs, the rate of CR was 37% for AFXL-PDT compared with 14% for AFXL (P = 0·02). Overall assessment showed a preference for AFXL-PDT compared with AFXL (AFXL-PDT, n = 8; AFXL, n = 0; equal, n = 2). Mild pigment changes were observed in four patients (AFXL-PDT, n = 3; AFXL, n = 1). No scarring was observed. CONCLUSIONS: AFXL-PDT is more effective than AFXL in the treatment of acral AKs and WLLs in OTRs.

Intensified photodynamic therapy of actinic keratoses with fractional CO2 laser: a randomized clinical trial.

BACKGROUND: Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is effective for thin actinic keratoses (AKs) in field-cancerized skin. Ablative fractional laser resurfacing (AFXL) creates vertical channels that facilitate MAL uptake and may improve PDT efficacy. OBJECTIVES: To evaluate efficacy and safety of AFXL-assisted PDT (AFXL-PDT) compared with conventional PDT in field-directed treatment of AK. METHODS: Fifteen patients with a total of 212 AKs (severity grade I-III) in field-cancerized skin of the face and scalp were randomized to one treatment with PDT and one treatment with AFXL-PDT in two symmetrical areas. Following curettage of both treatment areas, AFXL was applied to one area using 10 mJ per pulse, 0·12 mm spot, 5% density, single pulse (UltraPulse(®), DeepFx handpiece; Lumenis Inc., Santa Clara, CA, U.S.A.). MAL cream was then applied under occlusion for 3 h and illuminated with red light-emitting diode light at 37 J cm(-2). Fluorescence photography quantified protoporphyrin IX (PpIX) before and after illumination. RESULTS: At 3-month follow-up, AFXL-PDT was significantly more effective than PDT for all AK grades. Complete lesion response of grade II-III AK was 88% after AFXL-PDT compared with 59% after PDT (P = 0·02). In grade I AK, 100% of lesions cleared after AFXL-PDT compared with 80% after PDT (P = 0·04). AFXL-PDT-treated skin responded with significantly fewer new AK lesions (AFXL-PDT n = 3, PDT n = 11; P = 0·04) and more improved photoageing (moderate vs. minor improvement, P = 0·007) than PDT-treated skin. Pain scores during illumination (6·5 vs. 5·4; P = 0·02), erythema and crusting were more intense, and long-term pigmentary changes more frequent from AFXL-PDT than PDT (P = not significant). PpIX fluorescence was higher in AFXL-pretreated skin [7528 vs. 12,816 arbitrary units (AU); P = 0·003] and photobleached to equal intensities after illumination (AFXL-PDT 595 AU, PDT 454 AU; P = 0·59). CONCLUSIONS: AFXL-PDT is more effective than conventional PDT for treatment of AK in field-cancerized skin.

Pulsed dye laser vs. intense pulsed light for port-wine stains: a randomized side-by-side trial with blinded response evaluation.

BACKGROUND: Pulsed dye lasers (PDLs) are considered the treatment of choice for port-wine stains (PWS). Studies have suggested broadband intense pulsed light (IPL) to be efficient as well. So far, no studies have directly compared the PDL with IPL in a randomized clinical trial. OBJECTIVES: To compare efficacy and adverse events of PDL and IPL in an intraindividual randomized clinical trial. METHODS: Twenty patients with PWS (face, trunk, extremities; pink, red and purple colours; skin types I-III) received one side-by-side treatment with PDL (V-beam Perfecta, 595 nm, 0.45-1.5 ms; Candela Laser Corporation, Wayland, MA, U.S.A.) and IPL (StarLux, Lux G prototype handpiece, 500-670 and 870-1400 nm, 5-10 ms; Palomar Medical Technologies, Burlington, MA, U.S.A.). Settings depended on the preoperative lesional colour. Treatment outcome was evaluated by blinded, clinical evaluations and by skin reflectance measurements. RESULTS: Both PDL and IPL lightened PWS. Median clinical improvements were significantly better for PDL (65%) than IPL (30%) (P = 0.0004). A higher proportion of patients obtained good or excellent clearance rates with the PDL (75%) compared with IPL (30%) (P = 0.0104). Skin reflectance also documented better results after PDL (33% lightening) than IPL (12% lightening) (P = 0.002). Eighteen of 20 patients preferred to receive continued treatments with PDL (P = 0.0004). No adverse events were observed with PDL or IPL. CONCLUSIONS: Both the specific PDL and IPL types of equipment used in this study lightened PWS and both were safe with no adverse events. However, the PDL conveyed the advantages of better efficacy and higher patient preference.

Evidence-based review of lasers, light sources and photodynamic therapy in the treatment of acne vulgaris.

Background There is a considerable need for effective and safe treatment for acne vulgaris. Objective In a systematic review with an evidence-based approach to assess the effects of optical treatments for acne vulgaris. Methods Original publications of controlled clinical trials were identified through searches in PubMed and the Cochrane Library. Results A total of 16 randomized controlled trials (RCT) and 3 controlled trials (CT) were identified, involving a total of 587 patients. Interventions included photodynamic therapy (PDT; 5 RCTs), infrared lasers (4 RCTs), broad-spectrum light sources (3 RCTs, 1 CT), pulsed dye lasers (PDL; 2 RCTs, 1 CT), intense pulsed light (IPL; 1 RCTs, 2 CTs), and potassium titanyl phosphate laser (1 RCT). The randomization method was mentioned in 6 of 16 RCTs, and one trial described adequate allocation concealment. Most trials were intraindividual trials (12 of 19), which applied blinded response evaluations (12 of 19) and assessed a short-term efficacy up to 12 weeks after treatment (17 of 19). Based on the present best available evidence, we conclude that optical treatments possess the potential to improve inflammatory acne on a short-term basis with the most consistent outcomes for PDT [up to 68% improvement, aminolevulinic acid (ALA), methyl-aminolevulinic acid (MAL) and red light]. IPL-assisted PDT seems to be superior to IPL alone. Only two trials compare optical vs. conventional treatments, and further studies are needed. Side-effects from optical treatments included pain, erythema, oedema, crusting, hyperpigmentation, pustular eruptions and were more intense for treatments combined with ALA or MAL. Conclusion Evidence from controlled clinical trials indicates a short-term efficacy from optical treatments for acne vulgaris with the most consistent outcomes for PDT. We recommend that patients are preoperatively informed of the existing evidence, which indicates that optical treatments today are not included among first line treatments.