Damage from Acute vs Chronic Solar Exposure

Antony R. Young

St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London School of Medicine at Guy's, King's College and St Thomas' Hospitals, King's College London, London, UK

Table of Contents

1.1. Introduction 5 1.2. Early Responses to Solar UV Radiation 5 1.2.1. Erythema 5 1.2.2. Pigmentary Changes 7 1.2.3. Hyperplasia 8 1.2.4. Early Responses that have a Direct Impact on Skin Cancer 8 1.2.4.1. DNA Photodamage 8 1.2.4.2. Immunomodulation 11 1.3. Late Responses to Solar UV Radiation 13 1.3.1. Adaptive Responses to Repeated Sub-erythemal Exposure 13 1.3.2. Photoaging 14 1.4. Beneficial Effects of Solar UV Radiation and the Need for Protection 15 1.4.1. Vitamin D Photosynthesis 15 1.4.2. The Role of Sunscreens in the Prevention of Acute and Chronic Photodamage 16 1.5. Concluding Remarks 17 References 18

1.1. Introduction

The acute and chronic effects of solar ultraviolet radiation (UVR) exposure are well established. The acute effects can be readily studied under controlled laboratory conditions whereas the chronic effects have been determined by epidemiology in the case of skin cancer and by clinical observation in the case of photoageing. Chronic exposure is, by definition, a series of acute (i.e. single) exposures; however, the relationship between photodamage by acute and chronic exposure is very poorly understood, mainly because this has not been extensively studied. The patterns of exposure seem to be important in long-term clinical outcome. Epidemiological research suggests that regular exposure is important in squamous cell carcinoma (SCC), which is often associated with signs of photoaging such as elastosis. In contrast, intermittent sunburning exposure seems to be important in malignant melanoma (MM) as does childhood exposure. There is also evidence that intermittent exposure is important in basal cell carcinoma (BCC).

Most UVR exposure in healthy people comes from the sun, but in recent years exposure from tanning devices has become increasingly widespread, especially amongst young women, and this has raised concern about long-term adverse effects such as MM and, to a lesser extent, SCC.

Controlled chronic UVR exposure to clinical outcome, such as skin cancer or photoageing, is neither ethical nor practicable in humans, but it is possible to carry out studies with repeated UVR exposure over relatively short periods. This mimics 'real life' more realistically than acute exposure experiments and also allows the study of adaptive responses that may influence the response to subsequent exposure. Furthermore, repeat exposure studies act as a bridge between the acute and the chronic effects of UVR and may provide a better understanding of how individual exposures result in long-term clinical outcome.

The discussion in this chapter will focus on the acute effects of physiologically and environmentally relevant UVR exposure on human skin and how these effects may be modified by repeated exposure. In addition, the possible effects of repeated exposure on long-term clinical outcome will be considered. The relationship between sunscreen photoprotection of acute and chronic photodamage will also be discussed.

1.2. Early Responses to Solar UV Radiation

1.2.1. Erythema

Erythema (inflammation) is the most obvious clinical sign of UVR exposure and is apparent from about 6 hours after exposure and is maximal at about 24 hours. Its action spectrum is maximal at about 300 nm, which is about three orders of magnitude more effective than UVA. This peak has been made into a plateau in the widely used mathematically derived curve known as the Commission Internationale de l'Eclairage (CIE) erythema reference action spectrum. The minimal erythema dose (MED) is used as a means of defining personal sensitivity to UVR, and is defined as the UVR dose (J/m2), of a given spectrum, that causes a (just) perceptible skin reddening. In other words, the MED is the visual threshold of UVR dose-response of which erythema becomes more intense with higher doses. This can be demonstrated by visual grading or by the measure of redness by reflectance spectroscopy. The MED is widely used as a biological dose unit of exposure in clinical and experimental photodermatology and is based on a single acute UVR exposure. The MED is also used in the determination of the sun protection factor (SPF) of a sunscreen.

Whilst the MED is convenient indicator of individual sensitivity to UVR, the classification of people into skin phototype, as shown in Table 1.1, is a useful way of defining population acute and chronic sensitivity to UVR, and has been valuable in skin cancer epidemiology. An acute erythemal exposure, whether caused by solar simulating radiation (SSR) or UVA, is also associated with significantly increased sensitivity to mechanical and thermal stimuli. In general, the higher the skin phototype the higher the MED but it must be stressed that neither skin phototype nor MED is predictive of each other on an individual basis because there is a considerable overlap of MED within skin phototypes. Furthermore, it must be stressed that difference between the mean MEDs of sun-tolerant and sun-sensitive white skin phototypes is relatively modest. Typically, the MED of phototypes III/IV is about twice that of phototypes I/II. Erythema from an acute erythemal exposure (5 MED) has been reported as being more persistent in skin phototype I compared with IV and this may be related, in some as yet unknown way, to skin cancer susceptibility.

By definition, a single sub-erythemal exposure is below the threshold of detection by the eye. However, this does not mean that it has no effects because repeated daily sub-erythemal exposure results in clinically visible erythema after 2–3 exposures especially in sun-sensitive...