- Email: [email protected]
Long-term prognosis of vitiligo patients on narrowband UVB phototherapy
J AM ACAD DERMATOL
326 Letters
FEBRUARY 2012
REFERENCES 1. Ly L, Christie M, Swain S, Winship I, Kelly JW. Melanoma(s) arising in large segmental speckled lentiginous nevi: a case series. J Am Acad Dermatol 2011;64:1190-3. 2. Barysch MJ, Dummer R. The spectrum of widespread hyperpigmentations from SLN to SUL. Arch Dermatol 2009;145:953-4. 3. Bauer AJ, Stratakis CA. The lentiginoses: cutaneous markers of systemic disease and a window to new aspects of tumourigenesis. J Med Genet 2005;42:801-10. 4. Schaffer JV, Orlow SJ, Lazova R, Bolognia JL. Speckled lentiginous nevus: within the spectrum of congenital melanocytic nevi. Arch Dermatol 2001;137:172-8. 5. Happle R. Speckled lentiginous nevi: no longer one single disorder. Arch Dermatol 2010;146:204. doi:10.1016/j.jaad.2011.08.029
Long-term prognosis of vitiligo patients on narrowband UVB phototherapy To the Editor: We read with interest the CME article on vitiligo that mentioned the paucity of long-term follow-up data of narrowband ultraviolet B (NBUVB) therapy in vitiligo.1 Although there are no established treatment caps for NB-UVB, the suggested limit for skin types I-III is arbitrarily set at 200 treatments. While there is no set limit for skin types IV-VI, the recommendation for number of treatments should be based on clinician discretion and patient consent. We have observed that longterm NB-UVB in vitiligo patients is safe. This is important because these patients often require more than 12 to 24 months of treatment for repigmentation. The University of California San Francisco Department of Dermatology Psoriasis and Skin Treatment Center has been treating vitiligo patients with NB-UVB for nearly a decade. A retrospective review of current NB-UVB vitiligo patients revealed 10 patients (6 female, 4 male; skin types II-IV) who had NB-UVB treatment for 33 to 93 months. Age at onset was from 8 to 59 years old, with disease duration between 3 and 33 years. Number of visits ranged from 201 to 744 with current dosing between 865 and 2,875 mJ/cm2 per treatment. Over time, none of our patients developed suspicious lesions or nonmelanoma skin cancer (NMSC). It has been reported from a review of vitiligo patients with skin types I-II (n ¼ 477), independent of whether or not they had used phototherapy, that individuals with vitiligo have a non-statistically significant increased risk of NMSC than the general population; however, no cases were reported in non-Caucasians.2 Only 2 of the 6 NMSCs identified were on vitiliginous skin, which supports existing evidence that NMSC in vitiliginous lesions is rare.3
Furthermore, vitiliginous skin is observed to be less susceptible to photodamage.3 After years of experience reviewing the available follow-up data drawn from all dermatology patients treated with NB-UVB phototherapy, we found that the general consensus is that NB-UVB does not significantly increase risk of NMSC compared with the general population. Furthermore, 3 of our patients (skin types II-IV) have a history of systemic psoralen and ultraviolet A (PUVA) therapy with treatment duration ranging from 24 to 60 months, followed by NB-UVB (52-72 months). We found no evidence of NMSC in these patients. In Caucasian-based population studies, long-term PUVA therapy is an established risk factor for NMSC, particularly in patients with skin types I-II.4 However, the carcinogenic risk of PUVA in Asian and Arabian-African populations is not substantiated; data suggest that pigmented skin may confer photoprotection.4 Moreover, it is common to use topical pimecrolimus and/or tacrolimus as adjuncts to NB-UVB. Recent evidence suggests that topical pimecrolimus and tacrolimus do not increase risk of NMSC in adults.5 Therefore, this combination should not have a cumulative carcinogenic effect. NB-UVB is likely to be a safe long-term phototherapy option for patients with vitiligo as it is expected that they will require more visits over a long period of time to appreciate the results of therapy. Current guidelines may not be adequate, and long-term follow-up data are needed. Kelly K. Park, MD,a Jenny E. Murase, MD,a,b and John Koo, MDa Department of Dermatology, University of California, San Francisco,a and the Department of Dermatology, Palo Alto Foundation Medical Group, Mountain View,b California Funding sources. None. Conflicts of interest: None declared. Reprint requests: Kelly K. Park, MD, Department of Dermatology, University of California San Francisco, 515 Spruce St, San Francisco, CA 94118 E-mail: [email protected] REFERENCES 1. Felsten LM, Alikhan A, Petronic-Rosic V. Vitiligo: A comprehensive overview Part II: Treatment options and approach to treatment. J Am Acad Dermatol 2011;65:493-514. 2. Hexsel CL, Eide MJ, Johnson CC, Krajenta R, Joacobsen G, Hamzavi I, et al. Incidence of nonmelanoma skin cancer in a cohort of patients with vitiligo. J Am Acad Dermatol 2009;60:929-33.
J AM ACAD DERMATOL
Letters 327
VOLUME 66, NUMBER 2
3. Nordlund JJ. Nonmelanoma skin cancer in vitiligo patients. J Am Acad Dermatol 2009;61:1080-1. 4. Murase JE, Lee EE, Koo J. Effect of ethnicity on the risk of developing nonmelanoma skin cancer following long-term PUVA therapy. Int J Dermatol 2005;44:1016-21.
RESEARCH Randomized study of topical tacrolimus ointment as possible treatment for resistant idiopathic pruritus ani To the Editor: Pruritus ani (PA) is a common and embarrassing proctologic condition, which can be difficult to treat if there are no obvious predisposing factors. There is little scientific evidence concerning the treatment of idiopathic PA. Randomized controlled studies have been published for both 1% hydrocortisone ointment1 (symptom reduction in 68% of patients after 2 weeks’ treatment compared with placebo) and capsaicin 0.006%2 (70% with relieved itching compared with 2% with placebo after 4 weeks 3 times daily). Intradermal injection of methylene blue is frequently reported, but no randomized studies have been done.3 Prolonged topical steroid use may provoke skin atrophy. Topical tacrolimus is proposed as an alternative treatment for inflammatory skin diseases in thin skin areas.4,5 In a personal pilot study, all patients with idiopathic PA received treatment with tacrolimus 0.1% ointment, administered locally on transitional mucosa and perianal skin and were symptom free within weeks. These encouraging results stimulated me to organize a randomized double-blind clinical trial of 21 new patients consulting for complaints of idiopathic PA (Fig 1). Our goal was to evaluate and compare the evolution of the intensity and frequency of anal itch during a 4-week treatment. This treatment was either topical tacrolimus 0.1% ointment daily or placebo ( petrolatum) daily, and then switched after 1 week without treatment (Fig 1). Sample size calculation was performed; for a crossover study able to detect a 3-point treatment difference (standard deviation [SD] ¼ 4; a ¼ 0.05; b ¼ 80%) a total of 16 patients was needed. The study was approved by the ethics committee of the UZ Brussels. Randomization and treatment allocation were carried out by the pharmacy department of the UZ Brussels. Patients as well as investigator were
5. Margolis DJ, Hoffstad O, Bilker W. Lack of association between exposure to topical calcineurin inhibitors and skin cancer in adults. Dermatology 2007;214:289-95. doi:10.1016/j.jaad.2011.10.022
LETTERS blinded throughout the study. Tacrolimus ointment was provided by Astellas Belgium. A Dermatology Life Quality Index (DLQI) questionnaire was filled in at the start of the study, at the second visit (during the week of treatment interval) and at the end of the study. In all patients pruritus existed daily at the start, but not continuously. A total of 14 men and 7 women were included, with the mean age of 48 6 12.3 years (95% confidence interval, 40.2-50.4). The analysis of variance of the placebo or tacrolimus 0.1% treatment showed a significant positive effect of tacrolimus 0.1% treatment on both itch intensity (e1.73 vs e0.05, P ¼ .044 for tacrolimus 0.1% vs placebo, respectively), and itch frequency (e1.71 vs 0.03, P ¼ .019 for tacrolimus 0.1% vs placebo, respectively). Although the evolution of the DLQI under tacrolimus 0.1% ointment was positive, the difference with placebo was not significant (e3.77 vs e1.04, P ¼ .146 for tacrolimus 0.1% vs placebo). One patient noticed a minor temporarily burning sensation. Similar to the two previously published randomized controlled trials, our study was placebo controlled and it included a crossover to the other treatment group after a 1-week wash-out period. Like the capsaicin study, we observed the treatment effect during a 4-week period. Our study suggests that tacrolimus 0.1% ointment may be an effective treatment for idiopathic PA, resulting in a symptom reduction in 68% of the patients in our study after 2 weeks of treatment. Erwin Suys, MD Private practice Funding sources: None. Conflicts of interest: None declared. Correspondence to: Erwin Suys, MD, Handelskaai 1G, 8500 Kortrijk, Belgium E-mail: [email protected]
326 Letters
FEBRUARY 2012
REFERENCES 1. Ly L, Christie M, Swain S, Winship I, Kelly JW. Melanoma(s) arising in large segmental speckled lentiginous nevi: a case series. J Am Acad Dermatol 2011;64:1190-3. 2. Barysch MJ, Dummer R. The spectrum of widespread hyperpigmentations from SLN to SUL. Arch Dermatol 2009;145:953-4. 3. Bauer AJ, Stratakis CA. The lentiginoses: cutaneous markers of systemic disease and a window to new aspects of tumourigenesis. J Med Genet 2005;42:801-10. 4. Schaffer JV, Orlow SJ, Lazova R, Bolognia JL. Speckled lentiginous nevus: within the spectrum of congenital melanocytic nevi. Arch Dermatol 2001;137:172-8. 5. Happle R. Speckled lentiginous nevi: no longer one single disorder. Arch Dermatol 2010;146:204. doi:10.1016/j.jaad.2011.08.029
Long-term prognosis of vitiligo patients on narrowband UVB phototherapy To the Editor: We read with interest the CME article on vitiligo that mentioned the paucity of long-term follow-up data of narrowband ultraviolet B (NBUVB) therapy in vitiligo.1 Although there are no established treatment caps for NB-UVB, the suggested limit for skin types I-III is arbitrarily set at 200 treatments. While there is no set limit for skin types IV-VI, the recommendation for number of treatments should be based on clinician discretion and patient consent. We have observed that longterm NB-UVB in vitiligo patients is safe. This is important because these patients often require more than 12 to 24 months of treatment for repigmentation. The University of California San Francisco Department of Dermatology Psoriasis and Skin Treatment Center has been treating vitiligo patients with NB-UVB for nearly a decade. A retrospective review of current NB-UVB vitiligo patients revealed 10 patients (6 female, 4 male; skin types II-IV) who had NB-UVB treatment for 33 to 93 months. Age at onset was from 8 to 59 years old, with disease duration between 3 and 33 years. Number of visits ranged from 201 to 744 with current dosing between 865 and 2,875 mJ/cm2 per treatment. Over time, none of our patients developed suspicious lesions or nonmelanoma skin cancer (NMSC). It has been reported from a review of vitiligo patients with skin types I-II (n ¼ 477), independent of whether or not they had used phototherapy, that individuals with vitiligo have a non-statistically significant increased risk of NMSC than the general population; however, no cases were reported in non-Caucasians.2 Only 2 of the 6 NMSCs identified were on vitiliginous skin, which supports existing evidence that NMSC in vitiliginous lesions is rare.3
Furthermore, vitiliginous skin is observed to be less susceptible to photodamage.3 After years of experience reviewing the available follow-up data drawn from all dermatology patients treated with NB-UVB phototherapy, we found that the general consensus is that NB-UVB does not significantly increase risk of NMSC compared with the general population. Furthermore, 3 of our patients (skin types II-IV) have a history of systemic psoralen and ultraviolet A (PUVA) therapy with treatment duration ranging from 24 to 60 months, followed by NB-UVB (52-72 months). We found no evidence of NMSC in these patients. In Caucasian-based population studies, long-term PUVA therapy is an established risk factor for NMSC, particularly in patients with skin types I-II.4 However, the carcinogenic risk of PUVA in Asian and Arabian-African populations is not substantiated; data suggest that pigmented skin may confer photoprotection.4 Moreover, it is common to use topical pimecrolimus and/or tacrolimus as adjuncts to NB-UVB. Recent evidence suggests that topical pimecrolimus and tacrolimus do not increase risk of NMSC in adults.5 Therefore, this combination should not have a cumulative carcinogenic effect. NB-UVB is likely to be a safe long-term phototherapy option for patients with vitiligo as it is expected that they will require more visits over a long period of time to appreciate the results of therapy. Current guidelines may not be adequate, and long-term follow-up data are needed. Kelly K. Park, MD,a Jenny E. Murase, MD,a,b and John Koo, MDa Department of Dermatology, University of California, San Francisco,a and the Department of Dermatology, Palo Alto Foundation Medical Group, Mountain View,b California Funding sources. None. Conflicts of interest: None declared. Reprint requests: Kelly K. Park, MD, Department of Dermatology, University of California San Francisco, 515 Spruce St, San Francisco, CA 94118 E-mail: [email protected] REFERENCES 1. Felsten LM, Alikhan A, Petronic-Rosic V. Vitiligo: A comprehensive overview Part II: Treatment options and approach to treatment. J Am Acad Dermatol 2011;65:493-514. 2. Hexsel CL, Eide MJ, Johnson CC, Krajenta R, Joacobsen G, Hamzavi I, et al. Incidence of nonmelanoma skin cancer in a cohort of patients with vitiligo. J Am Acad Dermatol 2009;60:929-33.
J AM ACAD DERMATOL
Letters 327
VOLUME 66, NUMBER 2
3. Nordlund JJ. Nonmelanoma skin cancer in vitiligo patients. J Am Acad Dermatol 2009;61:1080-1. 4. Murase JE, Lee EE, Koo J. Effect of ethnicity on the risk of developing nonmelanoma skin cancer following long-term PUVA therapy. Int J Dermatol 2005;44:1016-21.
RESEARCH Randomized study of topical tacrolimus ointment as possible treatment for resistant idiopathic pruritus ani To the Editor: Pruritus ani (PA) is a common and embarrassing proctologic condition, which can be difficult to treat if there are no obvious predisposing factors. There is little scientific evidence concerning the treatment of idiopathic PA. Randomized controlled studies have been published for both 1% hydrocortisone ointment1 (symptom reduction in 68% of patients after 2 weeks’ treatment compared with placebo) and capsaicin 0.006%2 (70% with relieved itching compared with 2% with placebo after 4 weeks 3 times daily). Intradermal injection of methylene blue is frequently reported, but no randomized studies have been done.3 Prolonged topical steroid use may provoke skin atrophy. Topical tacrolimus is proposed as an alternative treatment for inflammatory skin diseases in thin skin areas.4,5 In a personal pilot study, all patients with idiopathic PA received treatment with tacrolimus 0.1% ointment, administered locally on transitional mucosa and perianal skin and were symptom free within weeks. These encouraging results stimulated me to organize a randomized double-blind clinical trial of 21 new patients consulting for complaints of idiopathic PA (Fig 1). Our goal was to evaluate and compare the evolution of the intensity and frequency of anal itch during a 4-week treatment. This treatment was either topical tacrolimus 0.1% ointment daily or placebo ( petrolatum) daily, and then switched after 1 week without treatment (Fig 1). Sample size calculation was performed; for a crossover study able to detect a 3-point treatment difference (standard deviation [SD] ¼ 4; a ¼ 0.05; b ¼ 80%) a total of 16 patients was needed. The study was approved by the ethics committee of the UZ Brussels. Randomization and treatment allocation were carried out by the pharmacy department of the UZ Brussels. Patients as well as investigator were
5. Margolis DJ, Hoffstad O, Bilker W. Lack of association between exposure to topical calcineurin inhibitors and skin cancer in adults. Dermatology 2007;214:289-95. doi:10.1016/j.jaad.2011.10.022
LETTERS blinded throughout the study. Tacrolimus ointment was provided by Astellas Belgium. A Dermatology Life Quality Index (DLQI) questionnaire was filled in at the start of the study, at the second visit (during the week of treatment interval) and at the end of the study. In all patients pruritus existed daily at the start, but not continuously. A total of 14 men and 7 women were included, with the mean age of 48 6 12.3 years (95% confidence interval, 40.2-50.4). The analysis of variance of the placebo or tacrolimus 0.1% treatment showed a significant positive effect of tacrolimus 0.1% treatment on both itch intensity (e1.73 vs e0.05, P ¼ .044 for tacrolimus 0.1% vs placebo, respectively), and itch frequency (e1.71 vs 0.03, P ¼ .019 for tacrolimus 0.1% vs placebo, respectively). Although the evolution of the DLQI under tacrolimus 0.1% ointment was positive, the difference with placebo was not significant (e3.77 vs e1.04, P ¼ .146 for tacrolimus 0.1% vs placebo). One patient noticed a minor temporarily burning sensation. Similar to the two previously published randomized controlled trials, our study was placebo controlled and it included a crossover to the other treatment group after a 1-week wash-out period. Like the capsaicin study, we observed the treatment effect during a 4-week period. Our study suggests that tacrolimus 0.1% ointment may be an effective treatment for idiopathic PA, resulting in a symptom reduction in 68% of the patients in our study after 2 weeks of treatment. Erwin Suys, MD Private practice Funding sources: None. Conflicts of interest: None declared. Correspondence to: Erwin Suys, MD, Handelskaai 1G, 8500 Kortrijk, Belgium E-mail: [email protected]