- Email: [email protected]
Novel applications of Phototherapy
Phtotheray in Perspective: Commentary Tiago R. Matos MD, MSc, Vaneeta Sheth MD PII: DOI: Reference:
S0738-081X(16)30133-X doi: 10.1016/j.clindermatol.2016.05.001 CID 7049
To appear in:
Clinics in Dermatology
Please cite this article as: Matos Tiago R., Sheth Vaneeta, Phtotheray in Perspective: Commentary, Clinics in Dermatology (2016), doi: 10.1016/j.clindermatol.2016.05.001
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Phtotheray in Perspective: Commentary
Tiago R. Matos1,2 MD MSc, Vaneeta Sheth3 MD Department of Dermatology; Brigham and Women’s Hospital, Harvard Medical School,
RI PT
1
Boston, MA 02215, USA. 2
Academic Medical Center, Department of Dermatology, University of Amsterdam,
3
Newton-Wellesley Hospital
NU
Issue Title: Novel applications of Phototherapy
SC
Amsterdam, Netherlands.
Our human relationship with Light
MA
Phototherapy is perhaps the most ancient form of treatment in dermatology, being responsible for the management of a wide variety of skin diseases. It remains an extremely effective, safe and broadly used form
PT ED
of treatment.
Our relationship with the sun’s light and its popularity may seem to change almost as quickly as seasons or as fashion trends do. During winter, we fear the “winter blues” and even seasonal affective disorder (SAD), with advertisements making us believe that we need to expose ourselves to “happy light lamps” and take vitamin D supplements. In the summer, we are encouraged to cover up, avoid the midday sun, and use broad-spectrum
CE
sunscreen with high sun protection factor (SPF) to prevent skin cancer. Additionaly, throughout the year, it is still recommended to use broad-spectrum sunscreen daily to protect from the sun’s aging effects, such as
AC
rhytides (i.e. wrinkles) and uneven pigmentation. Such conflicting information may contribute to the general apprehension towards phototherapy.
Tanning has also come into and out of fashion. Until the end of the Victorian era, pallid skin was seen as a sign of "refinement, " because people with a lower social status tanned, as a result of outdoor exposure and work. With the onset of the 20th century, scientific evidence emerged to support the positive effects of ultraviolet radiation (UV) in health and as medical therapy. In 1903, Niels Finsen (1860-1904) was awarded the Nobel Prize in Medicine "in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation, whereby he has opened a new avenue for medical science".describing the “Finsen Light Therapy” that could cure diseases such as lupus vulgaris and rickets.
Fast forward to the 1920’,s when two women changed the perception of tanned skin, making it fashionable and luxurious. Parisians started to admire the “caramel” skin of the popular singer Josephine Baker (19061975) and the tanned skin of fashion-designer Coco Chanel (1883-1971), who developed her tan as result of an accidental sunburn in 1923, while visiting the French Riviera.
ACCEPTED MANUSCRIPT These contradictory attitudes towards UV radiation have also been and are still present among the medical community. The fear of phototherapy-induced skin cancer and the reports of fatal overexposure result in a significant geographic variation for the use of phototherapy. Additionally, there is also a wide discrepancy on
RI PT
protocols prescribed for the same medical indication despite the many studies published on these therapies.
Global awareness
As the importance of the therapeutic effects of the sun’s UV rays have grown, so has the development of artificial light sources, and the concept of phototherapy has greatly expanded. Since one of the first books
SC
on phototherapy, Die Heilkraft des Lichtes by Willibald Gebhardt (1861-1921) , published in 1898, 1
hundreds of new books have been written. A sign of growing interest in studying the effects of light was
NU
marked by the creation of sub-specialty areas like photobiology and photochemistry.
The demand for specific clinical-related information fueled the establishment of national and international
MA
photomedicine and photodermatology societies, including the British Photodermatology Group (1988), Photomedicine Society (1992), and European Society for Photodermatology (1995). Similarly, the recognition of the impact of UV radiation on human health by the World Health Organization in
PT ED
collaboration with the United Nations Environment Programme, the World Meteorological Organization, the International Agency on Cancer Research and the International Commission on Non-Ionizing Radiation 2
Protection led to the creation of INTERSUN, a global UV-focused program. Currently, there are regular meetings, journals, and publications focused on promotion, support, stimulatation and reporting on
CE
information about all aspects of the photosciences.
Progress of Phototherapy in Dermatology
AC
Light has long played a significant role in the treatment of human diseases. The earliest registered information on heliotherapy in the treatment of skin diseases dates back to the fifteenth century BCE. This issue starts with a brief repost on the history of phototherapy by Grzybowski et al.; from the ancient use of heliotherapy 3
to the modern discoveries and inventions that have contributed to current artificial light therapies. Matos et al follow by elucidating the mechanisms of action of phothotherapy and its immunologic effects.
4
Ultraviolet radiation is also responsible for the photosynthesis of vitamin D and its active metabolites in the skin. Increasing controversy indicates that vitamin D produced during phototherapy may be responsible for some the positive effects. Juzeniene et al. review what is known about the use of phototherapy to enhance vitamin D levels, the use of vitamin D analogs with phototherapy, the efficacy of combination therapies and controversies regarding some of the outcomes.
5
Despite the beneficial biological impact of phototherapy, it can also lead to acute and long-term adverse effects. Coelho et al. thoroughly explore the “dark side of light” in two reviews: 1) placing in context the 6
adverse effects of each treatment modality, while specifying preventive and monitoring measures , and 2) focusing on the mechanisms of the most feared side effect: photocarcinogenesis.
7
Despite concerns over the
ACCEPTED MANUSCRIPT carcinogenic potential of ultraviolet radiation, most studies do not show an increased risk of non-melanoma or melanoma skin cancer in patients treated under controlled UVB (broadband and narrowband) and UVA1 phototherapy protocols.
RI PT
Photosensitivity can have an adverse effect on several drugs that induce photoallergic and phototoxic reactions. It remains a common clinical problem, frequently underdiagnosed. Monteiro et al. review the drugs, which have been implicated as photosensitizers, the involved mechanism, and their clinical presentations.
8
Brownell et al. discuss patient compliance rates. In order to optimize health outcomes, it is extremely
SC
important to account for patient compliance when tailoring therapy regimens and selecting patients. It can also influence the appearance of side effects and discomfort, grade of improvement, and even affinity with 9
NU
staff.
Phototherapy remains one of the most commonly utilized treatments for several diseases. Matos et al. provide
MA
an updated and comprehensive overview of UVB phototherapy for psoriasis in the pursuit of the optimal regime. It aims to help physicians optimize their choice of modality and dosing regimen to ensure optimal 10
outcomes for psoriasis patients. Even though there are a variety of wavelengths and modalities available to
PT ED
treat vitiligo, narrow-band UVB (NBUVB) remains the safest and most feasible line of treatment. Esmat et al. describe the most efficient protocols, while accounting for the heterogeneous population of vitiligo patients.
11
Eleftheriadou et al. follow by describing home portable devices available for vitiligo, which may overcome the need to treat vitiligo in hospital-based phototherapy cabinets, allowing early treatment at home that may 12
CE
enhance the likelihood of successful repigmentation. Rodenbeck et al. describe phototherapy dosing
AC
regimens and treatment concerns as a second-line treatment for moderate to severe atopic dermatitis.
13
Teske et al. has reviewed the current literature on phototherapy as an effective treatment strategy for a 14
variety of sclerosing skin conditions. Light therapy is also currently used for various modalities of cosmetic conditions, including acne vulgaris, solar lentigo, and melasma. Brownell et al. describe these as well as the 15
indications and mechanism of action for each cosmetic modality. Welsh discusses the potential therapeutic effect of UV in alopecia areata.
16
Crall et al. has focused on special considerations governing the use of phototherapy in pediatric populations.
17
These include the pediatric patient but also family and facility-based factors that are oriented around the heightened concerns for safety and tolerability of treatment. Lastly, Madigan et al. discuss the controversial 18
use of indoor tanning beds. Evidence-based research has shown an association between indoor tanning and negative health risks, such as melanoma and non-melanoma skin cancers, psychologic dependence, and propensity towards other high risk health behaviors.
ACCEPTED MANUSCRIPT Our goal Although UVR is also used in photochemotherapy (i.e. PUVA, using psoralen as a photosensitizer together with UVA radiation) and photodynamic therapy (PDT, UVA-1), the articles in this issue will mostly focus on phototherapy, alone. As such, this issue of Clinics in Dermatology
has been conceived as an
RI PT
updated comprehensive overview of the use of phototherapy in the most common skin conditions in order to provide the reader with a greater understanding of the photodermatology literature.
SC
We are most grateful for having superb collaborators who have given their valuable time, experience, and knowledge in reviewing the newest literature in order to present emerging
NU
evidence-based recommendations on remarkable core topics.
Vaneeta Sheth, MD
PT ED
Department of Dermatology Brigham and Women’s Hospital and Harvard Medical School Boston, MA Email: [email protected]
CE
Newton-Wellesley Dermatology Assoc. 65 Walnut Street Suite 520 Wellesley, MA 02481 Email: [email protected] Phone 781-237-3500
AC
MA
Tiago R. Matos, MD, MSc
ACCEPTED MANUSCRIPT References 1. Meffert H, Bahr T. Willibald Gebhardt (1861-1921). Sein Leben und seine Verdienste um die Photomedizin. Dermatol Monatsschr 1989;175:699-705.
AC
CE
PT ED
MA
NU
SC
RI PT
2. Ultraviolet radiation and the INTERSUN Programme [Internet]. Accessed on 12.12.2015. [Available from:http://www.who.int/uv/intersunprogramme/en/]. 3. Grzybowski A, Sak J, Pawlikowski J. A brief report on the history of phototherapy. Clin Dermatol. 2016. 4. Matos TR, Sheth V. Phototherapy: immunologic effects and xxxx. Clin Dermatol. 2016. 5. Juzeniene A, Grigalavicius M, Juraleviciute M, Grant WB. Phototherapy and Vitamin D. Clin Dermatol. 2016. 6. Coelho MMV, Apetato M. The dark side of the light: phototherapy adverse effects. Clin Dermatol. 2016. 7. Coelho MMV, Matos TR, Apetato . The dark side of the light: mechanisms of photocarcinogenesis. Clin Dermatol. 2016. 8. Monteiro AF, Rato A, Martins C. Drug-induced Photosensitivity: Photoallergic and phototoxic reactions. Clin Dermatol. 2016. 9. Brownell J,Wang S, Tsoukas MM. Patience compliance in Phototherapy. Clin Dermatol. 2016. 10. Matos TR, Ling TC, Sheth V. Ultraviolet B radiation therapy for psoriasis: Pursuing the optimal regime. Clin Dermatol. 2016. 11. Esmat S, Mostafa W, Hegazy RA, Shalaby S, Youssef R, El-Mofty M. Phototherapy: The Vitiligo Management Pillar. Clin Dermatol. 2016. 12. Eleftheriadou V, Ezzedine K. Portable home phototherapy for vitiligo. Clin Dermatol. 2016. 13. Rodenbeck DL, Silverberg SI, Silverberg NB. Phototherapy for Atopic Dermatitis. Clin Dermatol. 2016. 14. Teske NM, Jacobe HT. Phototherapy for Sclerosing Skin Conditions. Clin Dermatol. 2016. 15. Brownell J, Wang S, Tsoukas MM. Phototherapy in Cosmetic Dermatology. Clin Dermatol. 2016. 16. Welsh O. Phototherapy for Alopecia Areata. Clin Dermatol. 2016. 17. Crall CS, Rork JF, Delano S, Huang JT. Phototherapy in children: considerations and indications. Clin Dermatol. 2016. 18. Madigan LM, Lim HW. Tanning Beds: Impact on Health, and Recent Regulations. Clin Dermatol. 2016.
ACCEPTED MANUSCRIPT
AC
CE
PT ED
MA
NU
SC
RI PT
Figure 1. Dr. Tiago R. Matos and Dr. Vaneeta Sheth at the Department of Dermatology, Phototherapy Centre. Brigham and Women’s Hospital. A Harvard Medical School teaching hospital.
S0738-081X(16)30133-X doi: 10.1016/j.clindermatol.2016.05.001 CID 7049
To appear in:
Clinics in Dermatology
Please cite this article as: Matos Tiago R., Sheth Vaneeta, Phtotheray in Perspective: Commentary, Clinics in Dermatology (2016), doi: 10.1016/j.clindermatol.2016.05.001
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Phtotheray in Perspective: Commentary
Tiago R. Matos1,2 MD MSc, Vaneeta Sheth3 MD Department of Dermatology; Brigham and Women’s Hospital, Harvard Medical School,
RI PT
1
Boston, MA 02215, USA. 2
Academic Medical Center, Department of Dermatology, University of Amsterdam,
3
Newton-Wellesley Hospital
NU
Issue Title: Novel applications of Phototherapy
SC
Amsterdam, Netherlands.
Our human relationship with Light
MA
Phototherapy is perhaps the most ancient form of treatment in dermatology, being responsible for the management of a wide variety of skin diseases. It remains an extremely effective, safe and broadly used form
PT ED
of treatment.
Our relationship with the sun’s light and its popularity may seem to change almost as quickly as seasons or as fashion trends do. During winter, we fear the “winter blues” and even seasonal affective disorder (SAD), with advertisements making us believe that we need to expose ourselves to “happy light lamps” and take vitamin D supplements. In the summer, we are encouraged to cover up, avoid the midday sun, and use broad-spectrum
CE
sunscreen with high sun protection factor (SPF) to prevent skin cancer. Additionaly, throughout the year, it is still recommended to use broad-spectrum sunscreen daily to protect from the sun’s aging effects, such as
AC
rhytides (i.e. wrinkles) and uneven pigmentation. Such conflicting information may contribute to the general apprehension towards phototherapy.
Tanning has also come into and out of fashion. Until the end of the Victorian era, pallid skin was seen as a sign of "refinement, " because people with a lower social status tanned, as a result of outdoor exposure and work. With the onset of the 20th century, scientific evidence emerged to support the positive effects of ultraviolet radiation (UV) in health and as medical therapy. In 1903, Niels Finsen (1860-1904) was awarded the Nobel Prize in Medicine "in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation, whereby he has opened a new avenue for medical science".describing the “Finsen Light Therapy” that could cure diseases such as lupus vulgaris and rickets.
Fast forward to the 1920’,s when two women changed the perception of tanned skin, making it fashionable and luxurious. Parisians started to admire the “caramel” skin of the popular singer Josephine Baker (19061975) and the tanned skin of fashion-designer Coco Chanel (1883-1971), who developed her tan as result of an accidental sunburn in 1923, while visiting the French Riviera.
ACCEPTED MANUSCRIPT These contradictory attitudes towards UV radiation have also been and are still present among the medical community. The fear of phototherapy-induced skin cancer and the reports of fatal overexposure result in a significant geographic variation for the use of phototherapy. Additionally, there is also a wide discrepancy on
RI PT
protocols prescribed for the same medical indication despite the many studies published on these therapies.
Global awareness
As the importance of the therapeutic effects of the sun’s UV rays have grown, so has the development of artificial light sources, and the concept of phototherapy has greatly expanded. Since one of the first books
SC
on phototherapy, Die Heilkraft des Lichtes by Willibald Gebhardt (1861-1921) , published in 1898, 1
hundreds of new books have been written. A sign of growing interest in studying the effects of light was
NU
marked by the creation of sub-specialty areas like photobiology and photochemistry.
The demand for specific clinical-related information fueled the establishment of national and international
MA
photomedicine and photodermatology societies, including the British Photodermatology Group (1988), Photomedicine Society (1992), and European Society for Photodermatology (1995). Similarly, the recognition of the impact of UV radiation on human health by the World Health Organization in
PT ED
collaboration with the United Nations Environment Programme, the World Meteorological Organization, the International Agency on Cancer Research and the International Commission on Non-Ionizing Radiation 2
Protection led to the creation of INTERSUN, a global UV-focused program. Currently, there are regular meetings, journals, and publications focused on promotion, support, stimulatation and reporting on
CE
information about all aspects of the photosciences.
Progress of Phototherapy in Dermatology
AC
Light has long played a significant role in the treatment of human diseases. The earliest registered information on heliotherapy in the treatment of skin diseases dates back to the fifteenth century BCE. This issue starts with a brief repost on the history of phototherapy by Grzybowski et al.; from the ancient use of heliotherapy 3
to the modern discoveries and inventions that have contributed to current artificial light therapies. Matos et al follow by elucidating the mechanisms of action of phothotherapy and its immunologic effects.
4
Ultraviolet radiation is also responsible for the photosynthesis of vitamin D and its active metabolites in the skin. Increasing controversy indicates that vitamin D produced during phototherapy may be responsible for some the positive effects. Juzeniene et al. review what is known about the use of phototherapy to enhance vitamin D levels, the use of vitamin D analogs with phototherapy, the efficacy of combination therapies and controversies regarding some of the outcomes.
5
Despite the beneficial biological impact of phototherapy, it can also lead to acute and long-term adverse effects. Coelho et al. thoroughly explore the “dark side of light” in two reviews: 1) placing in context the 6
adverse effects of each treatment modality, while specifying preventive and monitoring measures , and 2) focusing on the mechanisms of the most feared side effect: photocarcinogenesis.
7
Despite concerns over the
ACCEPTED MANUSCRIPT carcinogenic potential of ultraviolet radiation, most studies do not show an increased risk of non-melanoma or melanoma skin cancer in patients treated under controlled UVB (broadband and narrowband) and UVA1 phototherapy protocols.
RI PT
Photosensitivity can have an adverse effect on several drugs that induce photoallergic and phototoxic reactions. It remains a common clinical problem, frequently underdiagnosed. Monteiro et al. review the drugs, which have been implicated as photosensitizers, the involved mechanism, and their clinical presentations.
8
Brownell et al. discuss patient compliance rates. In order to optimize health outcomes, it is extremely
SC
important to account for patient compliance when tailoring therapy regimens and selecting patients. It can also influence the appearance of side effects and discomfort, grade of improvement, and even affinity with 9
NU
staff.
Phototherapy remains one of the most commonly utilized treatments for several diseases. Matos et al. provide
MA
an updated and comprehensive overview of UVB phototherapy for psoriasis in the pursuit of the optimal regime. It aims to help physicians optimize their choice of modality and dosing regimen to ensure optimal 10
outcomes for psoriasis patients. Even though there are a variety of wavelengths and modalities available to
PT ED
treat vitiligo, narrow-band UVB (NBUVB) remains the safest and most feasible line of treatment. Esmat et al. describe the most efficient protocols, while accounting for the heterogeneous population of vitiligo patients.
11
Eleftheriadou et al. follow by describing home portable devices available for vitiligo, which may overcome the need to treat vitiligo in hospital-based phototherapy cabinets, allowing early treatment at home that may 12
CE
enhance the likelihood of successful repigmentation. Rodenbeck et al. describe phototherapy dosing
AC
regimens and treatment concerns as a second-line treatment for moderate to severe atopic dermatitis.
13
Teske et al. has reviewed the current literature on phototherapy as an effective treatment strategy for a 14
variety of sclerosing skin conditions. Light therapy is also currently used for various modalities of cosmetic conditions, including acne vulgaris, solar lentigo, and melasma. Brownell et al. describe these as well as the 15
indications and mechanism of action for each cosmetic modality. Welsh discusses the potential therapeutic effect of UV in alopecia areata.
16
Crall et al. has focused on special considerations governing the use of phototherapy in pediatric populations.
17
These include the pediatric patient but also family and facility-based factors that are oriented around the heightened concerns for safety and tolerability of treatment. Lastly, Madigan et al. discuss the controversial 18
use of indoor tanning beds. Evidence-based research has shown an association between indoor tanning and negative health risks, such as melanoma and non-melanoma skin cancers, psychologic dependence, and propensity towards other high risk health behaviors.
ACCEPTED MANUSCRIPT Our goal Although UVR is also used in photochemotherapy (i.e. PUVA, using psoralen as a photosensitizer together with UVA radiation) and photodynamic therapy (PDT, UVA-1), the articles in this issue will mostly focus on phototherapy, alone. As such, this issue of Clinics in Dermatology
has been conceived as an
RI PT
updated comprehensive overview of the use of phototherapy in the most common skin conditions in order to provide the reader with a greater understanding of the photodermatology literature.
SC
We are most grateful for having superb collaborators who have given their valuable time, experience, and knowledge in reviewing the newest literature in order to present emerging
NU
evidence-based recommendations on remarkable core topics.
Vaneeta Sheth, MD
PT ED
Department of Dermatology Brigham and Women’s Hospital and Harvard Medical School Boston, MA Email: [email protected]
CE
Newton-Wellesley Dermatology Assoc. 65 Walnut Street Suite 520 Wellesley, MA 02481 Email: [email protected] Phone 781-237-3500
AC
MA
Tiago R. Matos, MD, MSc
ACCEPTED MANUSCRIPT References 1. Meffert H, Bahr T. Willibald Gebhardt (1861-1921). Sein Leben und seine Verdienste um die Photomedizin. Dermatol Monatsschr 1989;175:699-705.
AC
CE
PT ED
MA
NU
SC
RI PT
2. Ultraviolet radiation and the INTERSUN Programme [Internet]. Accessed on 12.12.2015. [Available from:http://www.who.int/uv/intersunprogramme/en/]. 3. Grzybowski A, Sak J, Pawlikowski J. A brief report on the history of phototherapy. Clin Dermatol. 2016. 4. Matos TR, Sheth V. Phototherapy: immunologic effects and xxxx. Clin Dermatol. 2016. 5. Juzeniene A, Grigalavicius M, Juraleviciute M, Grant WB. Phototherapy and Vitamin D. Clin Dermatol. 2016. 6. Coelho MMV, Apetato M. The dark side of the light: phototherapy adverse effects. Clin Dermatol. 2016. 7. Coelho MMV, Matos TR, Apetato . The dark side of the light: mechanisms of photocarcinogenesis. Clin Dermatol. 2016. 8. Monteiro AF, Rato A, Martins C. Drug-induced Photosensitivity: Photoallergic and phototoxic reactions. Clin Dermatol. 2016. 9. Brownell J,Wang S, Tsoukas MM. Patience compliance in Phototherapy. Clin Dermatol. 2016. 10. Matos TR, Ling TC, Sheth V. Ultraviolet B radiation therapy for psoriasis: Pursuing the optimal regime. Clin Dermatol. 2016. 11. Esmat S, Mostafa W, Hegazy RA, Shalaby S, Youssef R, El-Mofty M. Phototherapy: The Vitiligo Management Pillar. Clin Dermatol. 2016. 12. Eleftheriadou V, Ezzedine K. Portable home phototherapy for vitiligo. Clin Dermatol. 2016. 13. Rodenbeck DL, Silverberg SI, Silverberg NB. Phototherapy for Atopic Dermatitis. Clin Dermatol. 2016. 14. Teske NM, Jacobe HT. Phototherapy for Sclerosing Skin Conditions. Clin Dermatol. 2016. 15. Brownell J, Wang S, Tsoukas MM. Phototherapy in Cosmetic Dermatology. Clin Dermatol. 2016. 16. Welsh O. Phototherapy for Alopecia Areata. Clin Dermatol. 2016. 17. Crall CS, Rork JF, Delano S, Huang JT. Phototherapy in children: considerations and indications. Clin Dermatol. 2016. 18. Madigan LM, Lim HW. Tanning Beds: Impact on Health, and Recent Regulations. Clin Dermatol. 2016.
ACCEPTED MANUSCRIPT
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CE
PT ED
MA
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SC
RI PT
Figure 1. Dr. Tiago R. Matos and Dr. Vaneeta Sheth at the Department of Dermatology, Phototherapy Centre. Brigham and Women’s Hospital. A Harvard Medical School teaching hospital.