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Tacalcitol and narrowband phototherapy in patients with vitiligo
P2533
P2535
THERAPEUTIC EVALUATION OF UVB-TARGETED PHOTOTHERAPY IN VITILIGO THAT AFFECTS LESS THAN 10% OF BODY SURFACE AREA Maira Herz Ruelas, MD, University Hospital ‘‘Dr. Jose´ Eleuterio Gonza´lez’’ U.A.N.L., Laredo, TX, United States; Oliverio Welsh Lozano, MD, PhD, Jorge ´ mez Flores, MD, University Hospital ‘‘Dr. Jose´ Ocampo Candiani, MD, Minerva Go Eleuterio Gonza´lez’’, U.A.N.L., Monterrey, Mexico Introduction: Vitiligo affects 1% to 2% of the population. Diverse mechanisms have been proposed to explain its cause: autoimmune, oxidative, genetic, neural, among others. Therapies for vitiligo include steroids, immunomodulators, grafts, phototherapy, and, recently, targeted phototherapy (TP). With TP, treatment is specific, increasing delivery of photostimulation to affected areas, thereby reducing the number of sessions required for significant repigmentation. The few studies reported of UVB TP for vitiligo have been combining it with topical medications, not specifying repigmentation rates in the diverse treated areas. Objective: To evaluate repigmentation induced by UVB TP as monotherapy in vitiligo affecting less than 10% of the skin surface.
UV-INDUCED PRODUCTION OF IMMUNOSUPPRESSIVE MEDIATORS IN HUMAN SKIN: PREVENTION BY A BROAD-SPECTRUM SUNSCREEN Thomas Luger, MD, Thomas Schwarz, MD, H. Kalden, MD, Thomas Brzoska, MD, University of Muenster, Muenster, Germany
Material and method: This study was an open, prospective, clinical trial that compared repigmentation between baseline lesions and at the end of 30 sessions. The UVB TP is mercury-based with a 290- to 320-nm wavelength, 0.5- to 2-second pulses, 50- to 800-mJ/cm2 fluences, and spot size of 16 3 16 mm.After obtaining signed informed consent forms, we included children, men, and nonpregnant women, 5 to 70 years old, with no treatment in the last month or contraindications for phototherapy. Patients were examined with Wood’s lamp; complete blood cell count, chemistry profile, and thyroid function tests were obtained. The minimal erythema dose (MED) was determined, and lesions were measured and photographed at baseline and after 30 sessions. On thin skin we started with 50% of MED and on the other lesions, 75% of MED. Sessions were twice a week, with 10- to 20mJ/cm2 increments until repigmentation or asymptomatic persistent erythema appeared. Evaluation was performed with the following scale: no repigmentation (0%), minimal (1%-25%), moderate (26%-50%), good (51%-75%), and excellent (76%100%). Lesions were divided into 3 regions (R): R1 (face), R2 (neck, trunk, genitalia), and R3 (extremities); in addition, 1 to 3 lesions were randomly selected from each area for follow-up, obtaining statistical analysis for R1 (20 lesions from 10 patients), R2 (12 lesions from 4 patients), and R3 (15 lesions from 5 patients). Evaluation was done by comparing baseline photographs and, after 30 sessions by 2 investigators, by morphometric assessment using a graduated grid. Results:We included 12 patients (5 females, 7 males; 5-62 years old; skin phototypes II-V). Duration of their vitiligo spanned 1 month to15 years. A total of 47 lesions were analyzed. Final repigmentation was 47.5%-73.5% on R1, 20.6%-39.5% on R2, and none on R3. After 6 months, 8 patients maintained their repigmentation and 4 worsened.
Irradiation of the skin with UV light is well known to cause local as well as systemic immunosuppression. Therefore the protective effect of a new broad-spectrum sunscreen on the UV-induced production of immunosuppressive mediators interleukin 10 (IL-10) and a-melanocyte stimulating hormone (aMSH) was investigated. The broad-spectrum sunscreen used has both a very high sun protection factor (SPF >60) and UVA protection factor (UVAPF = 28; persistent pigment darkening method [PPD]). Moreover, the UV filtering system (UVB filter [Octocrylene], UVA filters [Mexoryl SX, Mexoryl XL, Parsol 1789], TiO2) allows the formula to be photostable. Thirty minutes after the application (2 mg/cm2) of either the broad-spectrum sunscreen or its vehicle control, the volar side of the forearms of 4 human volunteers was irradiated with UV light (2 minimal erythema doses [MED]) using a solar simulator. Twenty-four hours after irradiation, sunction blister cups were placed on the test areas and by applying negative pressure, the formation of suction blisters was induced. Using a specific enzyme-linked immunosorbent assay, blister fluids were analyzed for IL-10 and aMSH. Total mRNA was isolated from the blister roofs, reversed transcripted, and the resulting cDNA was used for RT-PCR using primers specific for IL-10, aMSH, and bactin. Although the formation of erythema clearly was visible in the vehicle-controlled area,, it was suppressed on the broad-spectrum-treated area. Moreover, in comparison to untreated skin, IL-10 and aMSH expression were significantly up-regulated in UV-irradiated skin both at the protein and mRNA level. On treatment with the broad-spectrum sunscreen, the aMSH and IL-10 levels in the suction blister fluids were decreased in comparison to the untreated control area. Similarly, mRNA expression of IL-10 and aMSH was down-regulated when compared with untreated irradiated skin. These data provide the first evidence of induction of immunosuppressive mediators in vivo in the skin upon irradiation with UV light. In addition, there is evidence that the use of a highly effective sunscreen covering the entire UV spectrum (UVB + UVA) can inhibit the UV-mediated induction of these suppressor factors and thereby may prevent local UV-induced immunosuppression. Supported by La Roche-Posay Pharmaceutical Laboratories
Nothing to disclose.
P2534 TOPICAL PHOTOTHERAPY WITH METHYL AMINOLEVULINATE IN THE TREATMENT OF ACTINIC KERATOSIS IN TRANSPLANT RECIPIENTS Werner Kempf, MD, Galya Dragieva, MD, Bettina Prinz, MD, Department of Dermatology, Zurich, Switzerland; Ulrich Binswanger, 2 Division of Nephrology, Department of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland Background: Transplant recipients have an increased propensity to develop multiple actinic keratoses, which demonstrate an increased transformation rate into invasive squamous cell carcinoma. Objective: To evaluate the efficacy and tolerability of photodynamic therapy with methyl aminolevulinate (MAL-PDT) versus placebo in the treatment of actinic keratoses in transplant recipients.
P2536 TACALCITOL AND NARROWBAND PHOTOTHERAPY IN PATIENTS WITH VITILIGO Alessia Pacifico, MD, Andrea Paro Vidolin, MD, Paolo Iacovelli, MD, Giovanni Leone, MD, S. Gallicano Institute, Rome, Italy
Methods: Seventeen transplant recipients with a total of 129 mild to moderate actinic keratoses were included in this prospective, randomized, double-blind, placebo-controlled study. Two lesional areas within a patient were randomized for two consecutive treatments of topical MAL-PDT or placebo were selected. Sites were illuminated with 75 J/cm2 of visible light delivered at 80 mW/cm2 by an incoherent light source. Measurements included complete resolution and reduction in number or size of actinic keratoses within the lesional area relative to baseline evaluated at weeks 1, 4, 8, and 16 after treatment.
Vitiligo is a common skin disease characterized by loss of normal melanin pigments in the skin, and its pathogenesis is still unclear. Several treatments exist, but none of them are really efficient. Recently, perturbation of calcium homeostasis in vitiliginous epidermis has been described. On the basis of these findings, several clinical studies suggested that topical vitamin D3 analogue calcipotriol in association with psoralen plus ultraviolet A (PUVA) therapy induces repigmentation of lesional skin. The aim of this prospective open study was to compare the effectiveness of narrowband ultraviolet B (NB UVB) alone and the combination of NB UVB and the topical vitamin D3 analogue tacalcitol in the treatment of vitiligo.
Results: The lesional areas treated with MAL were clinically cleared in 76% of patients at 16 weeks. Partial response was recorded in an additional 18%. No reduction in size or number of actinic keratoses was observed in 6% of patients treated with MAL-PDT and in all placebo-treated areas. Adverse events, such as erythema, edema, and crust formation, were mild to moderate, and treatment was well tolerated by all patients. Conclusion: Photodynamic therapy using MAL is safe and effective for actinic keratoses in transplant recipients. It could reduce the risk for transformation of actinic keratoses to invasive, potentially fatal, squamous cell carcinoma.
Thirty-two patients with generalized vitiligo and with symmetric lesions were taken into the study. NB UVB was applied on a twice-weekly schedule. Tacalcitol ointment was applied to one of the two symmetric lesions of each patient once daily. The repigmentation percentage was estimated on both sides by clinical examination at the beginning and at the end of treatment. Our results showed that the addition of topical tacalcitol to NB UVB treatment led to a significant increase in the response rate of patients with vitiligo compared with NB UVB treatment alone. In conclusion, our data suggest that combination therapy with topical vitamin D3 ointment and NB UVB can be used as an alternate therapy for vitiligo.
Supported by Photocure ASA
Supported by Abiogen Pharma
P166
J AM ACAD DERMATOL
MARCH 2005
P2535
THERAPEUTIC EVALUATION OF UVB-TARGETED PHOTOTHERAPY IN VITILIGO THAT AFFECTS LESS THAN 10% OF BODY SURFACE AREA Maira Herz Ruelas, MD, University Hospital ‘‘Dr. Jose´ Eleuterio Gonza´lez’’ U.A.N.L., Laredo, TX, United States; Oliverio Welsh Lozano, MD, PhD, Jorge ´ mez Flores, MD, University Hospital ‘‘Dr. Jose´ Ocampo Candiani, MD, Minerva Go Eleuterio Gonza´lez’’, U.A.N.L., Monterrey, Mexico Introduction: Vitiligo affects 1% to 2% of the population. Diverse mechanisms have been proposed to explain its cause: autoimmune, oxidative, genetic, neural, among others. Therapies for vitiligo include steroids, immunomodulators, grafts, phototherapy, and, recently, targeted phototherapy (TP). With TP, treatment is specific, increasing delivery of photostimulation to affected areas, thereby reducing the number of sessions required for significant repigmentation. The few studies reported of UVB TP for vitiligo have been combining it with topical medications, not specifying repigmentation rates in the diverse treated areas. Objective: To evaluate repigmentation induced by UVB TP as monotherapy in vitiligo affecting less than 10% of the skin surface.
UV-INDUCED PRODUCTION OF IMMUNOSUPPRESSIVE MEDIATORS IN HUMAN SKIN: PREVENTION BY A BROAD-SPECTRUM SUNSCREEN Thomas Luger, MD, Thomas Schwarz, MD, H. Kalden, MD, Thomas Brzoska, MD, University of Muenster, Muenster, Germany
Material and method: This study was an open, prospective, clinical trial that compared repigmentation between baseline lesions and at the end of 30 sessions. The UVB TP is mercury-based with a 290- to 320-nm wavelength, 0.5- to 2-second pulses, 50- to 800-mJ/cm2 fluences, and spot size of 16 3 16 mm.After obtaining signed informed consent forms, we included children, men, and nonpregnant women, 5 to 70 years old, with no treatment in the last month or contraindications for phototherapy. Patients were examined with Wood’s lamp; complete blood cell count, chemistry profile, and thyroid function tests were obtained. The minimal erythema dose (MED) was determined, and lesions were measured and photographed at baseline and after 30 sessions. On thin skin we started with 50% of MED and on the other lesions, 75% of MED. Sessions were twice a week, with 10- to 20mJ/cm2 increments until repigmentation or asymptomatic persistent erythema appeared. Evaluation was performed with the following scale: no repigmentation (0%), minimal (1%-25%), moderate (26%-50%), good (51%-75%), and excellent (76%100%). Lesions were divided into 3 regions (R): R1 (face), R2 (neck, trunk, genitalia), and R3 (extremities); in addition, 1 to 3 lesions were randomly selected from each area for follow-up, obtaining statistical analysis for R1 (20 lesions from 10 patients), R2 (12 lesions from 4 patients), and R3 (15 lesions from 5 patients). Evaluation was done by comparing baseline photographs and, after 30 sessions by 2 investigators, by morphometric assessment using a graduated grid. Results:We included 12 patients (5 females, 7 males; 5-62 years old; skin phototypes II-V). Duration of their vitiligo spanned 1 month to15 years. A total of 47 lesions were analyzed. Final repigmentation was 47.5%-73.5% on R1, 20.6%-39.5% on R2, and none on R3. After 6 months, 8 patients maintained their repigmentation and 4 worsened.
Irradiation of the skin with UV light is well known to cause local as well as systemic immunosuppression. Therefore the protective effect of a new broad-spectrum sunscreen on the UV-induced production of immunosuppressive mediators interleukin 10 (IL-10) and a-melanocyte stimulating hormone (aMSH) was investigated. The broad-spectrum sunscreen used has both a very high sun protection factor (SPF >60) and UVA protection factor (UVAPF = 28; persistent pigment darkening method [PPD]). Moreover, the UV filtering system (UVB filter [Octocrylene], UVA filters [Mexoryl SX, Mexoryl XL, Parsol 1789], TiO2) allows the formula to be photostable. Thirty minutes after the application (2 mg/cm2) of either the broad-spectrum sunscreen or its vehicle control, the volar side of the forearms of 4 human volunteers was irradiated with UV light (2 minimal erythema doses [MED]) using a solar simulator. Twenty-four hours after irradiation, sunction blister cups were placed on the test areas and by applying negative pressure, the formation of suction blisters was induced. Using a specific enzyme-linked immunosorbent assay, blister fluids were analyzed for IL-10 and aMSH. Total mRNA was isolated from the blister roofs, reversed transcripted, and the resulting cDNA was used for RT-PCR using primers specific for IL-10, aMSH, and bactin. Although the formation of erythema clearly was visible in the vehicle-controlled area,, it was suppressed on the broad-spectrum-treated area. Moreover, in comparison to untreated skin, IL-10 and aMSH expression were significantly up-regulated in UV-irradiated skin both at the protein and mRNA level. On treatment with the broad-spectrum sunscreen, the aMSH and IL-10 levels in the suction blister fluids were decreased in comparison to the untreated control area. Similarly, mRNA expression of IL-10 and aMSH was down-regulated when compared with untreated irradiated skin. These data provide the first evidence of induction of immunosuppressive mediators in vivo in the skin upon irradiation with UV light. In addition, there is evidence that the use of a highly effective sunscreen covering the entire UV spectrum (UVB + UVA) can inhibit the UV-mediated induction of these suppressor factors and thereby may prevent local UV-induced immunosuppression. Supported by La Roche-Posay Pharmaceutical Laboratories
Nothing to disclose.
P2534 TOPICAL PHOTOTHERAPY WITH METHYL AMINOLEVULINATE IN THE TREATMENT OF ACTINIC KERATOSIS IN TRANSPLANT RECIPIENTS Werner Kempf, MD, Galya Dragieva, MD, Bettina Prinz, MD, Department of Dermatology, Zurich, Switzerland; Ulrich Binswanger, 2 Division of Nephrology, Department of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland Background: Transplant recipients have an increased propensity to develop multiple actinic keratoses, which demonstrate an increased transformation rate into invasive squamous cell carcinoma. Objective: To evaluate the efficacy and tolerability of photodynamic therapy with methyl aminolevulinate (MAL-PDT) versus placebo in the treatment of actinic keratoses in transplant recipients.
P2536 TACALCITOL AND NARROWBAND PHOTOTHERAPY IN PATIENTS WITH VITILIGO Alessia Pacifico, MD, Andrea Paro Vidolin, MD, Paolo Iacovelli, MD, Giovanni Leone, MD, S. Gallicano Institute, Rome, Italy
Methods: Seventeen transplant recipients with a total of 129 mild to moderate actinic keratoses were included in this prospective, randomized, double-blind, placebo-controlled study. Two lesional areas within a patient were randomized for two consecutive treatments of topical MAL-PDT or placebo were selected. Sites were illuminated with 75 J/cm2 of visible light delivered at 80 mW/cm2 by an incoherent light source. Measurements included complete resolution and reduction in number or size of actinic keratoses within the lesional area relative to baseline evaluated at weeks 1, 4, 8, and 16 after treatment.
Vitiligo is a common skin disease characterized by loss of normal melanin pigments in the skin, and its pathogenesis is still unclear. Several treatments exist, but none of them are really efficient. Recently, perturbation of calcium homeostasis in vitiliginous epidermis has been described. On the basis of these findings, several clinical studies suggested that topical vitamin D3 analogue calcipotriol in association with psoralen plus ultraviolet A (PUVA) therapy induces repigmentation of lesional skin. The aim of this prospective open study was to compare the effectiveness of narrowband ultraviolet B (NB UVB) alone and the combination of NB UVB and the topical vitamin D3 analogue tacalcitol in the treatment of vitiligo.
Results: The lesional areas treated with MAL were clinically cleared in 76% of patients at 16 weeks. Partial response was recorded in an additional 18%. No reduction in size or number of actinic keratoses was observed in 6% of patients treated with MAL-PDT and in all placebo-treated areas. Adverse events, such as erythema, edema, and crust formation, were mild to moderate, and treatment was well tolerated by all patients. Conclusion: Photodynamic therapy using MAL is safe and effective for actinic keratoses in transplant recipients. It could reduce the risk for transformation of actinic keratoses to invasive, potentially fatal, squamous cell carcinoma.
Thirty-two patients with generalized vitiligo and with symmetric lesions were taken into the study. NB UVB was applied on a twice-weekly schedule. Tacalcitol ointment was applied to one of the two symmetric lesions of each patient once daily. The repigmentation percentage was estimated on both sides by clinical examination at the beginning and at the end of treatment. Our results showed that the addition of topical tacalcitol to NB UVB treatment led to a significant increase in the response rate of patients with vitiligo compared with NB UVB treatment alone. In conclusion, our data suggest that combination therapy with topical vitamin D3 ointment and NB UVB can be used as an alternate therapy for vitiligo.
Supported by Photocure ASA
Supported by Abiogen Pharma
P166
J AM ACAD DERMATOL
MARCH 2005