Transplantation Dermatology

P. Häusermann, J. Steiger, J. Passweg, P., Häusermann, J., Steiger, J., Passweg, P. Itin, G. B. E. Jemec, P., Itin, G.B.E., Jemec

• Publisher: S. Karger
• Year: 2012
• Print ISBN: 9783805598552
• eBook ISBN: 9783805598569
• Topic: Medicine
• Subtopic: Cardiology

Patients undergoing solid organ and hematopoietic stem cell transplantation frequently develop skin diseases that can be challenging to themselves and their doctors. In the first part of this volume, prevalent epidemiological, clinical and histological skin problems of solid organ recipients are discussed. Pre- and posttransplant management as well as follow-up programs are presented focusing on European and Swiss guidelines. A special chapter is dedicated to immunosuppressive drugs considering current standards, and new and upcoming medication. The second part starts with a summary of historical aspects of hematopoietic stem cell transplantation, and proceeds with a description of skin manifestations of graft-versus-host disease and their therapy. Covered are early, late and very late periods after transplantation with a focus on recent consensus classification and treatment aspects of chronic graft-versus-host disease. The publication ends with a comprehensive review and practical guidance on photoprotection in transplant recipients. This book covers all the important dermatological aspects that should be considered in diagnosis and treatment of recipients of solid organ and hematopoietic stem cell transplants. It is intended as a guide for dermatologists, nephrologists, hemato-oncologists and all specialists involved in the field of transplantation.

Photoprotection

Häusermann P, Steiger J, Passweg J (eds): Transplantation Dermatology.
Curr Probl Dermatol. Basel, Karger, 2012, vol 43, pp 171-196

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Photoprotection in Transplant Recipients

Christian Surber^a · Mark Pittelkow^c · Stephan Lautenschlager^b

^aDepartment of Dermatology, University Hospital of Basel, Basel,^bOutpatient Clinic of Dermatology, Triemli Hospital, Zurich, Switzerland;^cDepartments of Dermatology and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minn., USA

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Abstract

Skin cancers remain the most commonly diagnosed neoplasms among organ transplant recipients (OTRs), comprising nearly 40% of all posttransplant malignancies. The occurrence of skin tumors has a considerable impact on the quality of life and the overall survival of OTRs. Ultraviolet radiation (UVR) is the major environmental cause of nonmelanoma skin cancers, and it is therefore pivotal to protect the skin from UVR in order to prevent de novo and progression of preinvasive and invasive malignancies. The present chapter delivers background information on UVR, photoprotection and accompanying concerns regarding vitamin D, as well as educational and behavioral aspects of photoprotection in OTRs; some common misconceptions and mistakes regarding photoprotection are addressed as well.

Copyright © 2012 S. Karger AG, Basel

Skin cancers remain the most commonly diagnosed neoplasms among organ transplant recipients (OTRs), comprising nearly 40% of all posttransplant malignancies [1]. The occurrence of skin tumors has a considerable impact on the quality of life and the overall survival of OTRs [2]. In addition to the increased incidence of these tumors in the OTR population, the tumors tend to behave more aggressively than those in nontransplants. Most of the cutaneous malignancies diagnosed in OTRs are nonmelanoma skin cancers (NMSC), with squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) accounting for more than 90% of the total (table 1) [3].

The reported average time to develop NMSC is estimated to range from 3 to 10 years after organ transplantation [2, 8-12]. Male gender, older age at transplantation, and longer follow-up after transplantation are independently associated with the onset of NMSC [10]. Other predictors of NMSC after organ transplantation are skin phototypes I—III according to the Fitzpatrick scale, an excessive sun exposure history, ‘aggressive’ immunosuppressive medication and genetic factors [8, 13, 14].

Cumulative ultraviolet radiation (UVR) is the primary responsible carcinogen for the induction and promotion of NMSC, as suggested by the fact that the lesions almost exclusively appear on UV-exposed skin [15]. Hence, patients working in typical outdoor occupations or spending most of their leisure time outdoors and patients living in countries with high UV indices are at higher risk. The determinants of skin cancer development in OTRs are well defined (table 2).

Table 1. Population-based standardized incidence ratios of skin cancers in OTRs [4-7].

Skin cancer	Increase in incidence (x)
SCC	>65-220
BCC	>10-16
Melanoma	>2.2-8
Kaposi sarcoma	>84

Table 2. Risk factors for the development of skin cancer after organ transplantation

Skin cancer
Exposure to UVR
Fitzpatrickskin types I-III
Increased age at transplantation
Duration, degree, and type of immunosuppression
Type of organ transplant
Previous organ transplant
Personal history of actinic keratosis
HPV infection
UVR is presumably the only factor that is to a certain degree ‘avoidable’. Sun avoidance and sun protection measures, including sunscreen application, are usually the cornerstones of dermatological education programs designed for OTRs (see the section ‘Educational and Behavioral Aspects in Skin Cancer Prevention’).

The significance of UVR is further emphasized by the observation that after the first SCC, the rate of subsequent NMSC can be decreased if patients change their behavior and protect themselves from the sun [16]. Unfortunately, several studies highlighted the poor compliance among OTRs with advice of sun protection measures [17, 18]. In addition, a high number of OTRs are no longer integrated into a daily occupational routine after transplantation. Recreational sun exposure - either in their home environment or during prolonged vacations - gains predominant importance for OTRs. This is supported by previous findings that OTRs who participated in outdoor recreation were more likely to subsequently develop NMSC [17, 19]. UVR is presumably the only factor that is to a certain degree ‘avoidable’. Sun avoidance and sun protection measures, including sunscreen application, are usually the cornerstones of dermatological education programs designed for OTRs.

Fig. 1. UVR refers to solar radiation with wavelengths in the 200 to 400 nm range. Radiation in the 400 to 700 nm range is referred to as visible light. UVR is subdivided into UVC, UVB and UVA radiation. Penetration of UVR into skin is wavelength dependent and hence leads to different biological effects (e.g. sunburn, DNA damage, immune suppression, formation of free radicals, oxidative damage of DNA and other biomolecules). SPF is largely a measure of UVB protection. In Europe, a sufficient UVA protection of a sunscreen product is labeled with a dedicated UVA label as depicted above.

In this chapter, background information on (A) UVR, (B) photoprotection and accompanying concerns regarding vitamin D, as well as educational and behavioral aspects of photoprotection in OTRs will be delivered - some common misconceptions and mistakes regarding photoprotection are addressed as well.

Ultraviolet Radiation

Physics of Ultraviolet Radiation

The electromagnetic spectrum covers a wavelength band of radiation ranging from 10^-14 m (gamma radiation) to 10⁴ m (radio waves). UVR refers to solar radiation with wavelengths in the 200 to 400 nm range. Radiation in the 400 to 700 nm range is referred to as visible light. UVR is subdivided into UVC, UVB and UVA radiation (fig. 1). Penetration of UVR into skin is wavelength dependent and hence leads to different biological effects [20-22]. The UVC band (200-290 nm) is known as the germicidal band and is primarily absorbed by the ozone layer (NB: industrial workers may experience UVC exposure, e.g. welding, UV drying of paint or finish). The UVB band (290-320 nm) - reaching the epidermis - is known as the erythemal band and is significantly attenuated by the atmosphere. UVA (320-400 nm) - reaching the basal layer of the epidermis and the upper dermis - is known as black light. It is further subdivided into UVA-1 (340-400 nm) and UVA-2 (320-340 nm). The shorter wavelengths of UVA-2 are more erythemogenic than UVA-1. Although UVA is more prevalent at the earth’s surface, it is less effective than UVB in eliciting erythema in human skin [23].

Biological Effects of Ultraviolet Radiation

UVR exerts a number of important biological effects on the skin, influencing the immune system and vitamin D metabolism, as well as causing DNA damage, photoaging, skin cancer, and pigmentary changes through biologically complex mechanisms [24]. In addition, there are psychological effects, with many people reporting enhanced well-being after sun exposure, and social influences, with 20th and 21st century fashion dictating that in some cultures a suntan is attractive and a sign of increased socioeconomic status [25].

Since the 1890s, even before the discovery of DNA and the concept of genetic mutations, sunlight exposure was implicated in the etiology of skin cancer [26, 27]. Over time, significant scientific evidence has been collected and has linked UVR with skin cancer formation [28].

The exact mechanism of UVR-induced cutaneous carcinogenesis is multifactorial and has not been totally elucidated. It is a complex interplay between gene mutation, inflammation, and immunosuppression. Erythema is the clinically visible immediate effect on the skin from UVR. Evidence suggests that clinical erythema correlates with DNA damage. Wavelengths of UVR that are most efficient at producing erythema are also the most efficient at producing pyrimidine dimers [29, 30]. However, some of the deleterious effects of UVR occur before the erythema threshold is reached. Such suberythemal effects of UVR include inflammation, photoaging, diminished antigen responsiveness and depletion of epidermal Langerhans cells [31]. The tumor suppressor, p53 protein, is also induced, which is a strong indication that DNA damage is occurring during suberythematous ultraviolet (UV) exposures [32]. Although much of the literature documents the effects of UVB on skin, many studies in recent years have highlighted the role UVA radiatio...

Table of contents

• Cover Page
• Front Material
• Organ Transplantation and Skin – Principles and Concepts
• Skin Problems in Immunodeficient Patients
• Critical Skin Cancer in Organ Transplant Recipients – A Dermatopathological View
• Immunosuppressive Drugs in Organ Transplant Recipients – Rationale for Critical Selection
• Human Papillomavirus and Squamous Cell Cancer of the Skin – Epidermodysplasia Verruciformis-Associated Human Papillomavirus Revisited
• Pre- and Posttransplant Management of Solid Organ Transplant Recipients: Risk-Adjusted Follow-Up
• Future Trends in Organ Transplant Recipients – Important Issues for Dermatologists
• History of Hematopoietic Stem Cell Transplantation: Evolution and Perspectives
• Acute and Chronic Skin Graft-versus-Host Disease - Pathophysiological Aspects
• Cutaneous Graft-versus-Host Disease - Clinical Considerations and Management
• UV Treatment of Chronic Skin Graft- versus-Host Disease - Focus on UVA1 and Extracorporeal Photopheresis
• Late Effects after Hematopoietic Stem Cell Transplantation - Critical Issues
• Drug Hypersensitivity Reactions during Hematopoietic Stem Cell Transplantation
• Future Trends in Hematopoietic Stem Cell Transplantation
• Photoprotection in Transplant Recipients
• Author Index
• Subject Index