CED
Clinical dermatology • Review article
Clinical and Experimental Dermatology
CPD
Targeted ultraviolet B phototherapy: definition, clinical indications and limitations D. Alshiyab,1 C. Edwards,2 M. F. Chin3 and A. V. Anstey2,4 1 Department of Dermatology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Academic Dermatology Unit, St Woolos Hospital, Newport, UK; 3Department of Dermatology, University Hospital of Wales, Cardiff, UK; and 4Cardiff University, Cardiff, UK
doi:10.1111/ced.12441
Summary
Targeted ultraviolet B (UVB) phototherapy is defined as UVB radiation applied only to clinically diseased skin, with sparing of adjacent normal skin, unlike conventional phototherapy, which involves irradiation of both diseased and normal skin. Targeted UVB radiation is a relatively new concept, which is now widely available because of advances in technology. Devices developed for targeted UVB phototherapy of the skin include the monochromatic excimer laser and lamp, both of which are now used by dermatologists in developed and developing countries. The aim of this review is to collate data from research studies on targeted phototherapy and to provide a concise description of currently available devices, their clinical indications and therapeutic efficacy. Additionally, potential adverse effects are summarized, and the limitations of these novel devices are highlighted.
Introduction
Mode of action
Conventional phototherapy involves irradiation of both diseased and clinically normal-looking skin. It can be delivered to the skin over a limited area (localized phototherapy) or to the whole body (generalized phototherapy) A range of devices is now available for targeted phototherapy, a method by which irradiation is delivered to diseased skin only, with sparing of clinically normal skin. Targeted phototherapy devices include very high fluence devices such as the monochromatic excimer laser and flashlamp,1–3 and very low output devices such as UVB light-emitting diodes (UVB-LED).4 The US Food and Drug Administration have approved the excimer laser for the treatment of psoriasis, vitiligo and atopic dermatitis.5
The mode of action of targeted phototherapy devices may be different from existing localized and whole body irradiation devices. This is likely for high fluence devices such as the monochromatic excimer laser or flashlamp. For low fluence devices such as UVB-LED, it is assumed that narrowband (NB)-UVB phototherapy (TL01) exerts its biological effect via suppression of the skin’s adaptive immune responses, induction of innate immunity or induction of photoadaptation.6 NB-UVB also induces apoptosis in T-cells within psoriatic plaques, which may also be important with localized irradiation devices. Furthermore, recent experimental research indicates that the therapeutic benefit of NBUVB administration in the treatment of psoriasis is mediated by induction of keratinocyte apoptosis.7
Correspondence: Prof Alexander V Anstey, Academic Dermatology Unit, Stow Hill, St Woolos Hospital, Newport NP20 4SZ, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 24 March 2014
ª 2014 British Association of Dermatologists
Clinical indications Targeted UVB phototherapy is indicated for limited, localized skin diseases, such as may occur in some patients with psoriasis, vitiligo or mycosis fungoides.
Clinical and Experimental Dermatology (2015) 40, pp1–5
1
Targeted UVB phototherapy D. Alshiyab et al.
Because targeted phototherapy is directed at diseased skin only, it is possible in psoriasis to give higher doses of UVB than would be tolerated by adjacent, unaffected skin. This has potential advantages for this mode of phototherapy in terms of therapeutic efficacy, tolerability and safety. Recent reports of targeted phototherapy describe its use in atopic dermatitis, mycosis fungoides, localized scleroderma, and genital and oral lichen planus.8
Targeted phototherapy and psoriasis Targeted phototherapy was first reported for psoriasis in 1997,9 and has subsequently been refined and extended.10–12 Targeted phototherapy has emerged as a potential option for psoriasis that is limited in extent or localized to sanctuary sites12 such as the flexures, scalp13 and genitalia. There are also reports of efficacy of targeted phototherapy in the treatment of palmoplantar psoriasis.13,14 Targeted phototherapy appears to have greater efficacy than whole-body UVB phototherapy;15 psoriatic plaques have been shown to tolerate much higher doses of UVB than nonpsoriatic skin. Furthermore, deeper penetration of UVB from high fluence devices may induce T-cell apoptosis in both the epidermis and dermis, leading to greater efficacy in some conditions. Palmoplantar pustular psoriasis was reported to respond well to targeted phototherapy in a small open study of 15 cases, with lower total cumulative doses than would be the norm for conventional localized phototherapy delivered by an array of TL01 fluorescent bulbs.13 Efficacy of targeted phototherapy may be enhanced when treating thick, scaly plaques by application of mineral oil or a topical keratolytic agent. A novel UVB-light-emitting diode (LED) device showed efficacy and safety in treating psoriasis. However, because of its very low output, the UVB-LED device must be strapped into position, with irradiation taking place over a number of hours. This treatment resulted in a significant reduction of inflammatory cells within psoriatic plaques.4
Targeted phototherapy and vitiligo Vitiligo is another potential clinical indication for targeted phototherapy, following the first report of efficacy in 2001.16 A number of studies have subsequently indicated efficacy of this treatment in vitiligo.17–19 Furthermore, two cases of recent-onset segmental vitiligo were reported to respond well to targeted phototherapy in combination with topical and systemic therapies.20 Although the mechanism of targeted phototherapy
2
Clinical and Experimental Dermatology (2015) 40, pp1–5
in vitiligo is unclear, it may be that in addition to producing a reduction in the number of cytotoxic T lymphocytes, high-intensity UVB leads to stimulation of melanocyte proliferation and migration to the epidermis from the hair follicles.21,22 Broadband UVB targeted phototherapy shows efficacy in vitiligo,23 albeit less than for targeted NB-UVB.24 Efficacy of the excimer laser and excimer lamp is almost equal to each other in the treatment of vitiligo.25 As with nontargeted phototherapy, anatomical location is important for predicting response in vitiligo; the face shows the best response, followed by the head and neck, while the trunk and proximal extremities respond less well, and the distal extremities and perioral areas are the least responsive.18,19,26 Skin type may also predict response, with darker skin types responding better than lighter skin types.17 Shorter disease duration and smaller lesions also tend to predict a better therapeutic response.18 The most common repigmentation pattern with targeted phototherapy is perifollicular, followed by a marginal pattern that may be associated with earlier and more enduring repigmentation.18,27
Combination with other treatments The evidence base for targeted phototherapy in combination with other treatments is mainly anecdotal. Some studies claim that combination therapy may enhance the response to treatment; however, small patient numbers and inadequate controls prevent clear conclusions being made.28–30
Adverse effects In general, targeted phototherapy appears to be welltolerated in most patients. The nature of targeted phototherapy means that adjacent normal skin is spared from potential acute and chronic effects of UV exposure. This is in contrast to localized or whole-body phototherapy, for which acute effects on clinically normal skin are common and chronic effects are a cause for caution. Despite this, adverse events may occur with targeted as with traditional UVB phototherapy. The most common acute adverse effect is erythema within areas of treated skin. Less common side effects include hyperpigmentation, burning, itching, erosions and blisters.10
Limitations Setting aside the issue of high cost of these devices, the main limitation of targeted phototherapy devices is that they treat such small areas of skin. This is not an
ª 2014 British Association of Dermatologists
Targeted UVB phototherapy D. Alshiyab et al.
issue if the skin disease is limited in extent. However, targeted phototherapy is not suitable as a monotherapy for more extensive disease. Another limitation is that Fitzpatrick skin phototype I may not tolerate high fluence targeted phototherapy because blistering may result when attempting to give more than one minimal erythema dose.
Conclusions Targeted phototherapy has clear advantages that suggest it should be added to conventional nontargeted phototherapies. It can be used to treat sanctuary sites such as flexures, hands, feet and scalp. It can also be used to treat skin disease of limited extent, where the advantages of higher dosage and efficacy outweigh the disadvantages of the time-consuming nature of this form of phototherapy. By using this form of phototherapy, healthy, apparently normal skin is spared, and clearance of skin lesions may occur more rapidly and with fewer treatment sessions. Finally, it remains to be seen if targeted phototherapy can be used as an alternative to conventional phototherapy for limited skin disease. This is only likely to be resolved by direct comparison in the form of a randomized study, with blinded assessment of clinical response. Another option would be a withinpatient comparison with targeted vs. conventional phototherapy using a left vs. right model for treating symmetrical skin disease. Importantly, patient preferences and patient-reported outcome should be included in any such comparative studies.
Learning points ● Targeted phototherapy is an emerging thera-
peutic option for skin disease. ● The main clinical indications for targeted
phototherapy are psoriasis and vitiligo. ● The high cost of targeted phototherapy devices
must be taken into account in future research aimed at establishing where this technique fits in to the spectrum of phototherapies for photoresponsive diseases.
References 1 Mudigonda T, Dabade T, Feldman S. A review of targeted ultraviolet B phototherapy for psoriasis. J Am Acad Dermatol 2012; 66: 664–72.
ª 2014 British Association of Dermatologists
2 Trehan M, Taylor CR. High-dose 308-nm excimer laser for the treatment of psoriasis. J Am Acad Dermatol 2002; 46: 732–7. 3 Chimento S.M, Newland M, Ricotti C et al. A pilot study to determine the safety and efficacy of monochromatic excimer light in the treatment of vitiligo. J Drugs Dermatol 2008; 7: 258–63. 4 Kemeny L, Csoma Z, Bagdi E et al. Targeted phototherapy of plaque-type psoriasis using ultraviolet B-light-emitting diodes. Br J Dermatol 2010; 163: 167–73. 5 Park KK, Liao W, Murase JE. A review of monochromatic excimer light in vitiligo. Br J Dermatol 2012; 167: 468–78. 6 Rivard J, Hexsel C, Owen M et al. Photoadaptation of vitiliginous skin to targeted ultraviolet B phototherapy. Photodermatol Photoimmunol Photomed 2007; 23: 258–60. 7 Weatherhead SC, Farr PM, Jamieson D et al. Keratinocyte apoptossis in epidermal remodeling and clearance of psoriasis induced by UV radiation. J Invest Dermatol 2011; 131: 1916–26. 8 Kassem R, Yarom N, Scope A et al. Treatment of erosive oral lichen planus with local ultraviolet B phototherapy. J Am Acad Dermatol 2012; 66: 761–6. 9 Weichenthal M, Schwarz T. Phototherapy: how does UV work? Photodermatol Photoimmunol Photomed 2005; 21: 260–6. 10 Gerber W, Arheilger B, Ha TA et al. Ultraviolet B 308-nm excimer laser treatment of psoriasis: a new phototherapeutic approach. Br J Dermatol 2003; 149: 1250–8. 11 Lapidoth M, Adatto M, David M. Targeted UVB phototherapy for psoriasis: a preliminary study. Clin Exp Dermatol 2007; 32: 642–5. 12 Toll A, Velez-Gonzalez M, Gallardo F et al. Treatment of localized persistent plaque psoriasis with incoherent narrowband ultraviolet B phototherapy. J Dermatolog Treat 2005; 16: 165–8. 13 Al-Mutairi N, Al-Haddad A. Targeted phototherapy using 308 nm Xecl monochromatic excimer laser for psoriasis at difficult to treat sites. Lasers Med Sci 2013; 28: 1119–24. 14 Aubin F, Vigan M, Puzenat E et al. Evaluation of a novel 308-nm monochromatic excimer light delivery system in dermatology: a pilot study in different chronic localized dermatoses. Br J Dermatol 2005; 152: 99–103. 15 Zakarian K, Nguyen A, Letsinger J, Koo J. Excimer laser for psoriasis: a review of theories regarding enhanced efficacy over traditional UVB phototherapy. J Drugs Dermatol 2007; 6: 794–8. 16 Baltas E, Nagy P, Bonis B et al. Repigmentation of localized vitiligo with the xenon chloride laser. Br J Dermatol 2001; 144: 1266–7. 17 Spencer JM, Nossa R, Ajmeri J. Treatment of vitiligo with the 308-nm excimer laser: a pilot study. J Am Acad Dermatol 2002; 46: 727–31.
Clinical and Experimental Dermatology (2015) 40, pp1–5
3
Targeted UVB phototherapy D. Alshiyab et al.
18 Hadi S, Tinio P, Al-Ghaithi K et al. Treatment of vitiligo using the 308-nm excimer laser. Photomed Laser Surg 2006; 24: 354–7. 19 Asawanonda P, Charoenlap M, Korkij W. Treatment of localized vitiligo with targeted broadband UVB phototherapy: a pilot study. Photodermatol Photoimmunol Photomed 2006; 22: 133–6. 20 Lee DY, Kim CR, Lee JH. Targeted phototherapy in combination with drug therapy for segmental vitiligo. Photodermatol Photoimmunol Photomed 2011; 27: 108–10. 21 Morelli JG, Kincannon J, Yohn JJ et al. Leukotrine C4 and TGF-alpha are stimulator of human melanocyte migration in vitro. J Invest Dermatol 1992; 98: 290–5. 22 Cui J, Shen LY, Wang GC. Role of hair follicles in the repigmentation of vitiligo. J Invest Dermatol 1991; 97: 410–16. 23 Asawanonda P, Kijluakiat J, Korkij W, Sindhupak W. Targeted broadband ultraviolet B phototherapy produces similar responses to targeted narrowband ultraviolet B phototherapy for vitiligo: a randomized, double-blind study. Acta Derm Venereol 2008; 88: 376–81. 24 Akar A, Tunca M, Koc E, Kurumlu Z. Broadband targeted UVB phototherapy for localized vitiligo: a retrospective study. Photodermatol Photoimmunol Photomed 2009; 25: 161–3.
25 Shi Q, Li K, Fu J et al. Comparison of the 308-nm excimer laser with the 308-nm excimer lamp in the treatment of vitiligo – a randomized bilateral comparison study. Photodermatol Photoimmunol Photomed 2013; 29: 27–33. 26 Natta R, Somsak T, Wisuttida T, Laor L. Narrowband UltraViolet B radiation therapy for recalcitrant vitiligo in Asians. J Am Acad Dermatol 2003; 49: 473–6. 27 Yang YS, Cho HR, Ryou JH, Lee MH. Clinical study of repigmentation patterns with either narrow-band ultraviolet B (NBUVB) or 308 nm ecximer laser treatment in Korean vitiligo patients. Int J Dermatol 2010; 49: 317–23. 28 Amornpinyokeit N, Asawanonda P. 8-methoxypsoralen cream plus targeted narrowband ultraviolet B for psoriasis. Photodermatol Photoimmunol Photomed 2006; 22: 285–9. 29 Ozkan I, Kose O, Ozmen I, Arca E. Efficacy and safety of non-laser, targeted UVB phototherapy alone and in combination with psoralen gel or calcipotriol ointment in the treatment of localized, chronic, plaque-type psoriasis. Int J Dermatol 2012; 51: 609–13. 30 Kawalek AZ, Spencer JM, Phelps RG. Combined excimer laser and topical tacrolimus for the treatment of vitiligo: a pilot study. Dermatol Surg 2004; 30: 130–5.
CPD questions
(d) Psoriasis. (e) Vitiligo.
Learning objective
To show an understanding of targeted UVB phototherapy, including definition, clinical indications and limitations. Question 1
What is targeted ultraviolet (UV)B phototherapy? (a) UVB radiation applied directly to clinically diseased skin only. (b) UVB radiation delivered using a handheld device. (c) UVB radiation to a limited area of skin, which includes diseased and normal-looking skin. (d) Radiation with narrowband UVB. (e) UVB radiation that is applied to the entire body surface area.
Question 3
Why is targeted phototherapy more efficacious than traditional ultraviolet (UV)B therapy for psoriasis? (a) A higher cumulative dose of UVB can be delivered by targeted phototherapy. (b) Efficacy of targeted phototherapy may be enhanced by treating thick plaques with coal tar. (c) Higher fluences of UVB can be delivered to psoriatic plaques by targeted phototherapy. (d) T cell apoptosis only occurs in the epidermis when targeted phototherapy is used. (e) The UVB light-emitting diode device has a high output and only requires a short irradiation time.
Question 4 Question 2
Targeted phototherapy first became a recognized treatment option for which skin condition? (a) Eczema. (b) Localized scleroderma. (c) Mycosis fungoides.
4
Clinical and Experimental Dermatology (2015) 40, pp1–5
Which of the following is an advantage of targeted phototherapy over traditional ultraviolet (UV)B therapy? (a) It spares normal-looking adjacent skin from unnecessary irradiation.
ª 2014 British Association of Dermatologists
Targeted UVB phototherapy D. Alshiyab et al.
(b) It is more suitable for Fitzpatrick type 1 skin as it is less likely to cause blistering. (c) Side effects such as erythema, hyperpigmentation and blistering do not occur unlike in traditional UVB. (d) The patient spends less time in the phototherapy unit for each treatment. (e) The cost of the devices delivering targeted phototherapy is cheaper than for traditional UVB.
Question 5
The American Food and Drug Administration have approved the excimer laser for the treatment of which of the following? (a) Oral lichen planus. (b) Localized scleroderma. (c) Mycosis fungoides. (d) Granuloma annulare. (e) Vitiligo.
ª 2014 British Association of Dermatologists
Instructions for answering questions This learning activity is freely available online at http://www.wileyhealthlearning.com/ced. Users are encouraged to ● Read the article in print or online, paying particular attention to the learning points and any author conflict of interest disclosures ● Reflect on the article ● Register or login online at www.wileyhealthlearning.com/ced and answer the CPD questions ● Complete the required evaluation component of the activity Once the test is passed, you will receive a certificate and the learning activity can be added to your RCP CPD diary as a self-certified entry.
Clinical and Experimental Dermatology (2015) 40, pp1–5
5
Clinical dermatology • Review article
Clinical and Experimental Dermatology
CPD
Targeted ultraviolet B phototherapy: definition, clinical indications and limitations D. Alshiyab,1 C. Edwards,2 M. F. Chin3 and A. V. Anstey2,4 1 Department of Dermatology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Academic Dermatology Unit, St Woolos Hospital, Newport, UK; 3Department of Dermatology, University Hospital of Wales, Cardiff, UK; and 4Cardiff University, Cardiff, UK
doi:10.1111/ced.12441
Summary
Targeted ultraviolet B (UVB) phototherapy is defined as UVB radiation applied only to clinically diseased skin, with sparing of adjacent normal skin, unlike conventional phototherapy, which involves irradiation of both diseased and normal skin. Targeted UVB radiation is a relatively new concept, which is now widely available because of advances in technology. Devices developed for targeted UVB phototherapy of the skin include the monochromatic excimer laser and lamp, both of which are now used by dermatologists in developed and developing countries. The aim of this review is to collate data from research studies on targeted phototherapy and to provide a concise description of currently available devices, their clinical indications and therapeutic efficacy. Additionally, potential adverse effects are summarized, and the limitations of these novel devices are highlighted.
Introduction
Mode of action
Conventional phototherapy involves irradiation of both diseased and clinically normal-looking skin. It can be delivered to the skin over a limited area (localized phototherapy) or to the whole body (generalized phototherapy) A range of devices is now available for targeted phototherapy, a method by which irradiation is delivered to diseased skin only, with sparing of clinically normal skin. Targeted phototherapy devices include very high fluence devices such as the monochromatic excimer laser and flashlamp,1–3 and very low output devices such as UVB light-emitting diodes (UVB-LED).4 The US Food and Drug Administration have approved the excimer laser for the treatment of psoriasis, vitiligo and atopic dermatitis.5
The mode of action of targeted phototherapy devices may be different from existing localized and whole body irradiation devices. This is likely for high fluence devices such as the monochromatic excimer laser or flashlamp. For low fluence devices such as UVB-LED, it is assumed that narrowband (NB)-UVB phototherapy (TL01) exerts its biological effect via suppression of the skin’s adaptive immune responses, induction of innate immunity or induction of photoadaptation.6 NB-UVB also induces apoptosis in T-cells within psoriatic plaques, which may also be important with localized irradiation devices. Furthermore, recent experimental research indicates that the therapeutic benefit of NBUVB administration in the treatment of psoriasis is mediated by induction of keratinocyte apoptosis.7
Correspondence: Prof Alexander V Anstey, Academic Dermatology Unit, Stow Hill, St Woolos Hospital, Newport NP20 4SZ, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 24 March 2014
ª 2014 British Association of Dermatologists
Clinical indications Targeted UVB phototherapy is indicated for limited, localized skin diseases, such as may occur in some patients with psoriasis, vitiligo or mycosis fungoides.
Clinical and Experimental Dermatology (2015) 40, pp1–5
1
Targeted UVB phototherapy D. Alshiyab et al.
Because targeted phototherapy is directed at diseased skin only, it is possible in psoriasis to give higher doses of UVB than would be tolerated by adjacent, unaffected skin. This has potential advantages for this mode of phototherapy in terms of therapeutic efficacy, tolerability and safety. Recent reports of targeted phototherapy describe its use in atopic dermatitis, mycosis fungoides, localized scleroderma, and genital and oral lichen planus.8
Targeted phototherapy and psoriasis Targeted phototherapy was first reported for psoriasis in 1997,9 and has subsequently been refined and extended.10–12 Targeted phototherapy has emerged as a potential option for psoriasis that is limited in extent or localized to sanctuary sites12 such as the flexures, scalp13 and genitalia. There are also reports of efficacy of targeted phototherapy in the treatment of palmoplantar psoriasis.13,14 Targeted phototherapy appears to have greater efficacy than whole-body UVB phototherapy;15 psoriatic plaques have been shown to tolerate much higher doses of UVB than nonpsoriatic skin. Furthermore, deeper penetration of UVB from high fluence devices may induce T-cell apoptosis in both the epidermis and dermis, leading to greater efficacy in some conditions. Palmoplantar pustular psoriasis was reported to respond well to targeted phototherapy in a small open study of 15 cases, with lower total cumulative doses than would be the norm for conventional localized phototherapy delivered by an array of TL01 fluorescent bulbs.13 Efficacy of targeted phototherapy may be enhanced when treating thick, scaly plaques by application of mineral oil or a topical keratolytic agent. A novel UVB-light-emitting diode (LED) device showed efficacy and safety in treating psoriasis. However, because of its very low output, the UVB-LED device must be strapped into position, with irradiation taking place over a number of hours. This treatment resulted in a significant reduction of inflammatory cells within psoriatic plaques.4
Targeted phototherapy and vitiligo Vitiligo is another potential clinical indication for targeted phototherapy, following the first report of efficacy in 2001.16 A number of studies have subsequently indicated efficacy of this treatment in vitiligo.17–19 Furthermore, two cases of recent-onset segmental vitiligo were reported to respond well to targeted phototherapy in combination with topical and systemic therapies.20 Although the mechanism of targeted phototherapy
2
Clinical and Experimental Dermatology (2015) 40, pp1–5
in vitiligo is unclear, it may be that in addition to producing a reduction in the number of cytotoxic T lymphocytes, high-intensity UVB leads to stimulation of melanocyte proliferation and migration to the epidermis from the hair follicles.21,22 Broadband UVB targeted phototherapy shows efficacy in vitiligo,23 albeit less than for targeted NB-UVB.24 Efficacy of the excimer laser and excimer lamp is almost equal to each other in the treatment of vitiligo.25 As with nontargeted phototherapy, anatomical location is important for predicting response in vitiligo; the face shows the best response, followed by the head and neck, while the trunk and proximal extremities respond less well, and the distal extremities and perioral areas are the least responsive.18,19,26 Skin type may also predict response, with darker skin types responding better than lighter skin types.17 Shorter disease duration and smaller lesions also tend to predict a better therapeutic response.18 The most common repigmentation pattern with targeted phototherapy is perifollicular, followed by a marginal pattern that may be associated with earlier and more enduring repigmentation.18,27
Combination with other treatments The evidence base for targeted phototherapy in combination with other treatments is mainly anecdotal. Some studies claim that combination therapy may enhance the response to treatment; however, small patient numbers and inadequate controls prevent clear conclusions being made.28–30
Adverse effects In general, targeted phototherapy appears to be welltolerated in most patients. The nature of targeted phototherapy means that adjacent normal skin is spared from potential acute and chronic effects of UV exposure. This is in contrast to localized or whole-body phototherapy, for which acute effects on clinically normal skin are common and chronic effects are a cause for caution. Despite this, adverse events may occur with targeted as with traditional UVB phototherapy. The most common acute adverse effect is erythema within areas of treated skin. Less common side effects include hyperpigmentation, burning, itching, erosions and blisters.10
Limitations Setting aside the issue of high cost of these devices, the main limitation of targeted phototherapy devices is that they treat such small areas of skin. This is not an
ª 2014 British Association of Dermatologists
Targeted UVB phototherapy D. Alshiyab et al.
issue if the skin disease is limited in extent. However, targeted phototherapy is not suitable as a monotherapy for more extensive disease. Another limitation is that Fitzpatrick skin phototype I may not tolerate high fluence targeted phototherapy because blistering may result when attempting to give more than one minimal erythema dose.
Conclusions Targeted phototherapy has clear advantages that suggest it should be added to conventional nontargeted phototherapies. It can be used to treat sanctuary sites such as flexures, hands, feet and scalp. It can also be used to treat skin disease of limited extent, where the advantages of higher dosage and efficacy outweigh the disadvantages of the time-consuming nature of this form of phototherapy. By using this form of phototherapy, healthy, apparently normal skin is spared, and clearance of skin lesions may occur more rapidly and with fewer treatment sessions. Finally, it remains to be seen if targeted phototherapy can be used as an alternative to conventional phototherapy for limited skin disease. This is only likely to be resolved by direct comparison in the form of a randomized study, with blinded assessment of clinical response. Another option would be a withinpatient comparison with targeted vs. conventional phototherapy using a left vs. right model for treating symmetrical skin disease. Importantly, patient preferences and patient-reported outcome should be included in any such comparative studies.
Learning points ● Targeted phototherapy is an emerging thera-
peutic option for skin disease. ● The main clinical indications for targeted
phototherapy are psoriasis and vitiligo. ● The high cost of targeted phototherapy devices
must be taken into account in future research aimed at establishing where this technique fits in to the spectrum of phototherapies for photoresponsive diseases.
References 1 Mudigonda T, Dabade T, Feldman S. A review of targeted ultraviolet B phototherapy for psoriasis. J Am Acad Dermatol 2012; 66: 664–72.
ª 2014 British Association of Dermatologists
2 Trehan M, Taylor CR. High-dose 308-nm excimer laser for the treatment of psoriasis. J Am Acad Dermatol 2002; 46: 732–7. 3 Chimento S.M, Newland M, Ricotti C et al. A pilot study to determine the safety and efficacy of monochromatic excimer light in the treatment of vitiligo. J Drugs Dermatol 2008; 7: 258–63. 4 Kemeny L, Csoma Z, Bagdi E et al. Targeted phototherapy of plaque-type psoriasis using ultraviolet B-light-emitting diodes. Br J Dermatol 2010; 163: 167–73. 5 Park KK, Liao W, Murase JE. A review of monochromatic excimer light in vitiligo. Br J Dermatol 2012; 167: 468–78. 6 Rivard J, Hexsel C, Owen M et al. Photoadaptation of vitiliginous skin to targeted ultraviolet B phototherapy. Photodermatol Photoimmunol Photomed 2007; 23: 258–60. 7 Weatherhead SC, Farr PM, Jamieson D et al. Keratinocyte apoptossis in epidermal remodeling and clearance of psoriasis induced by UV radiation. J Invest Dermatol 2011; 131: 1916–26. 8 Kassem R, Yarom N, Scope A et al. Treatment of erosive oral lichen planus with local ultraviolet B phototherapy. J Am Acad Dermatol 2012; 66: 761–6. 9 Weichenthal M, Schwarz T. Phototherapy: how does UV work? Photodermatol Photoimmunol Photomed 2005; 21: 260–6. 10 Gerber W, Arheilger B, Ha TA et al. Ultraviolet B 308-nm excimer laser treatment of psoriasis: a new phototherapeutic approach. Br J Dermatol 2003; 149: 1250–8. 11 Lapidoth M, Adatto M, David M. Targeted UVB phototherapy for psoriasis: a preliminary study. Clin Exp Dermatol 2007; 32: 642–5. 12 Toll A, Velez-Gonzalez M, Gallardo F et al. Treatment of localized persistent plaque psoriasis with incoherent narrowband ultraviolet B phototherapy. J Dermatolog Treat 2005; 16: 165–8. 13 Al-Mutairi N, Al-Haddad A. Targeted phototherapy using 308 nm Xecl monochromatic excimer laser for psoriasis at difficult to treat sites. Lasers Med Sci 2013; 28: 1119–24. 14 Aubin F, Vigan M, Puzenat E et al. Evaluation of a novel 308-nm monochromatic excimer light delivery system in dermatology: a pilot study in different chronic localized dermatoses. Br J Dermatol 2005; 152: 99–103. 15 Zakarian K, Nguyen A, Letsinger J, Koo J. Excimer laser for psoriasis: a review of theories regarding enhanced efficacy over traditional UVB phototherapy. J Drugs Dermatol 2007; 6: 794–8. 16 Baltas E, Nagy P, Bonis B et al. Repigmentation of localized vitiligo with the xenon chloride laser. Br J Dermatol 2001; 144: 1266–7. 17 Spencer JM, Nossa R, Ajmeri J. Treatment of vitiligo with the 308-nm excimer laser: a pilot study. J Am Acad Dermatol 2002; 46: 727–31.
Clinical and Experimental Dermatology (2015) 40, pp1–5
3
Targeted UVB phototherapy D. Alshiyab et al.
18 Hadi S, Tinio P, Al-Ghaithi K et al. Treatment of vitiligo using the 308-nm excimer laser. Photomed Laser Surg 2006; 24: 354–7. 19 Asawanonda P, Charoenlap M, Korkij W. Treatment of localized vitiligo with targeted broadband UVB phototherapy: a pilot study. Photodermatol Photoimmunol Photomed 2006; 22: 133–6. 20 Lee DY, Kim CR, Lee JH. Targeted phototherapy in combination with drug therapy for segmental vitiligo. Photodermatol Photoimmunol Photomed 2011; 27: 108–10. 21 Morelli JG, Kincannon J, Yohn JJ et al. Leukotrine C4 and TGF-alpha are stimulator of human melanocyte migration in vitro. J Invest Dermatol 1992; 98: 290–5. 22 Cui J, Shen LY, Wang GC. Role of hair follicles in the repigmentation of vitiligo. J Invest Dermatol 1991; 97: 410–16. 23 Asawanonda P, Kijluakiat J, Korkij W, Sindhupak W. Targeted broadband ultraviolet B phototherapy produces similar responses to targeted narrowband ultraviolet B phototherapy for vitiligo: a randomized, double-blind study. Acta Derm Venereol 2008; 88: 376–81. 24 Akar A, Tunca M, Koc E, Kurumlu Z. Broadband targeted UVB phototherapy for localized vitiligo: a retrospective study. Photodermatol Photoimmunol Photomed 2009; 25: 161–3.
25 Shi Q, Li K, Fu J et al. Comparison of the 308-nm excimer laser with the 308-nm excimer lamp in the treatment of vitiligo – a randomized bilateral comparison study. Photodermatol Photoimmunol Photomed 2013; 29: 27–33. 26 Natta R, Somsak T, Wisuttida T, Laor L. Narrowband UltraViolet B radiation therapy for recalcitrant vitiligo in Asians. J Am Acad Dermatol 2003; 49: 473–6. 27 Yang YS, Cho HR, Ryou JH, Lee MH. Clinical study of repigmentation patterns with either narrow-band ultraviolet B (NBUVB) or 308 nm ecximer laser treatment in Korean vitiligo patients. Int J Dermatol 2010; 49: 317–23. 28 Amornpinyokeit N, Asawanonda P. 8-methoxypsoralen cream plus targeted narrowband ultraviolet B for psoriasis. Photodermatol Photoimmunol Photomed 2006; 22: 285–9. 29 Ozkan I, Kose O, Ozmen I, Arca E. Efficacy and safety of non-laser, targeted UVB phototherapy alone and in combination with psoralen gel or calcipotriol ointment in the treatment of localized, chronic, plaque-type psoriasis. Int J Dermatol 2012; 51: 609–13. 30 Kawalek AZ, Spencer JM, Phelps RG. Combined excimer laser and topical tacrolimus for the treatment of vitiligo: a pilot study. Dermatol Surg 2004; 30: 130–5.
CPD questions
(d) Psoriasis. (e) Vitiligo.
Learning objective
To show an understanding of targeted UVB phototherapy, including definition, clinical indications and limitations. Question 1
What is targeted ultraviolet (UV)B phototherapy? (a) UVB radiation applied directly to clinically diseased skin only. (b) UVB radiation delivered using a handheld device. (c) UVB radiation to a limited area of skin, which includes diseased and normal-looking skin. (d) Radiation with narrowband UVB. (e) UVB radiation that is applied to the entire body surface area.
Question 3
Why is targeted phototherapy more efficacious than traditional ultraviolet (UV)B therapy for psoriasis? (a) A higher cumulative dose of UVB can be delivered by targeted phototherapy. (b) Efficacy of targeted phototherapy may be enhanced by treating thick plaques with coal tar. (c) Higher fluences of UVB can be delivered to psoriatic plaques by targeted phototherapy. (d) T cell apoptosis only occurs in the epidermis when targeted phototherapy is used. (e) The UVB light-emitting diode device has a high output and only requires a short irradiation time.
Question 4 Question 2
Targeted phototherapy first became a recognized treatment option for which skin condition? (a) Eczema. (b) Localized scleroderma. (c) Mycosis fungoides.
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Clinical and Experimental Dermatology (2015) 40, pp1–5
Which of the following is an advantage of targeted phototherapy over traditional ultraviolet (UV)B therapy? (a) It spares normal-looking adjacent skin from unnecessary irradiation.
ª 2014 British Association of Dermatologists
Targeted UVB phototherapy D. Alshiyab et al.
(b) It is more suitable for Fitzpatrick type 1 skin as it is less likely to cause blistering. (c) Side effects such as erythema, hyperpigmentation and blistering do not occur unlike in traditional UVB. (d) The patient spends less time in the phototherapy unit for each treatment. (e) The cost of the devices delivering targeted phototherapy is cheaper than for traditional UVB.
Question 5
The American Food and Drug Administration have approved the excimer laser for the treatment of which of the following? (a) Oral lichen planus. (b) Localized scleroderma. (c) Mycosis fungoides. (d) Granuloma annulare. (e) Vitiligo.
ª 2014 British Association of Dermatologists
Instructions for answering questions This learning activity is freely available online at http://www.wileyhealthlearning.com/ced. Users are encouraged to ● Read the article in print or online, paying particular attention to the learning points and any author conflict of interest disclosures ● Reflect on the article ● Register or login online at www.wileyhealthlearning.com/ced and answer the CPD questions ● Complete the required evaluation component of the activity Once the test is passed, you will receive a certificate and the learning activity can be added to your RCP CPD diary as a self-certified entry.
Clinical and Experimental Dermatology (2015) 40, pp1–5
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