British Iournaf ofDermatobgy (1992)127, Supplement 41, 37-42.
The clinical identification and quantification of photodamage C.E .M .GRIFFITHS k~AbphArmaCOlOgyUnit. k p r t m e n t of Dermatology, University of Michigan Medical Center, Ann Arbor. Michigan. USA
Summary
The distinction between intrinsic and extrinsic ageing can be made on both histological and clinical grounds. Clinical criteria associated with the diagnosis of extrinsic ageing are coarse wrinkles, actinic lentigines, elastotic conditions, purpura, telangiectasia and cutaneous neoplasms. These parameters are always superimposed on changes associated with intrinsic ageing: namely, fine wrinkles and benign growths. There is heightened interest in extrinsic ageing as a result of studies demonstrating the efficacy of topical tretinoin in improving this condition. As a consequence, systems for grading extrinsic ageing have been developed, including a photographic standard scale which removes some of the subjectivity inherent to current methodology.
Cutaneous ageing is a process that is a seemingly inevitable consequence of senescence. However, this ‘natural’ event can be divided into two components: physiological and pathological. Intrinsic or chronological ageing, which is related purely to senescence, genetics accounting for the age of onset and susceptibility, occurs in its pure form in non-sun-exposed body areas, such as the buttocks. Extrinsic ageing, also known as photodamage. is directly related to environmental factors and occurs in habitually exposed areas of the body, such as the face, neck and arms. Extrinsic ageing will indubitably always be superimposed on a background of intrinsic ageing. The first descriptions of extrinsic ageing or photodamage became available from the end of the 19th century, when it was referred to as farmer’s or sailor’s skin.’ At that time, photodamage was only readily observed on people with outdoor occupations and, by and large, was not seen in the middle or upper social classes, except for golfers, cricketers and other sportsmen. Women from the non-working classes were rarely photodamaged because sensible sun avoidance was practised, as evidenced by the wearing of long skirts, long sleeves and hats, and the use of parasols. These features may have been the dictates of fashion and prudery, but were also very satisfactory sun-avoidance measures. Towards the middle of the 20th century, with the introduction of more leisure time and a life style centred around seaside vacations and outdoor pursuits, there was an inevitable increase in sun exposure. A sunCorrespondence.: Dr C.E.M.Gritfiths. Department of hmatoIogy, University of Michigan Medical Center, 19 10 Taubman Center, 1 500 East Medical Center Drive. Ann Arbor. Michigan 4 8 1 0 9 4 3 1 4 , usA.
tan became a desirable goal redolent of a ‘healthy’. monied existence:indeed, this aura of a sun-tan indicating a ‘jet-set’life style still persists. As a consequence,the effects of prolonged sun exposure became associated with the development of wrinkles and dyspigmentation-a process misinterpreted as accelerated ageing. The misconception persists today and is often referred to as ‘premature ageing’. This article delineates the clinical differences between intrinsic and extrinsic ageing, and discusses the technology currently available to help quantify extrinsic ageing.
Definition of cutaneous ageing Intrinsic or chronological ageing is observed on those areas of the skin that are habitually covered and not exposed to sun or other environmental factors. In these areas, ageing is characteristically manifested by smooth, pale and finely wrinkled skin, superimposed on which may be benign growths, such as cherry haemangiomas and seborrhoeic keratoses. By contrast, extrinsically aged or photodamaged skin is remarkable for its coarseness, the principle clinical features being roughness, sallowness, fine and coarse wrinkles, hyper- and hypopigmentation, purpura, telangiectasia and a variety of benign and malignant neopIasms (Table 1).2 The histological changes inherent to intrinsic and extrinsic ageing are dealt with in more detail elsewhere in this supplement in the article by Professor Marks.3 As a general rule, in intrinsic ageing there is a reduction in all histological parameters-to quote Kligmant4 ‘in intrinsic ageing everything shrinks’-whereas in extrin-
37
38
C.E.M.GRIFFITHS
Table 1. Clinical differentiation of extrinsically and intrinsically aged skin Extrinsically aged
Intrinsically aged ~~
Wrinkles--coarse and fine Rough and dry Dark, leathery Dyspigmentation Telangiectasia Actinic keratoses
Wrinkles-fine Smooth and soft Pale
sic ageing there is an increase in histological parameters. The salient histological features of extrinsically aged skin are an initial thickening of the epidermis, but at the endstages the epidermis becomes atrophic and is accompanied by keratinocyte atypia, actinic keratoses and neoplasms, such as basal and squamous cell carcinomas. Melanocytes increase in number, whereas there is a reduction in Langerhans cells by as much as 50% in photodamaged as compared with intrinsically aged skin.’ The most striking changes occur in the dermis. In intrinsically aged skin, there is a marked reduction and homogenization of collagen within the papillary dermis. In extrinsically aged skin, however, there is an initial excess deposition of microfibrillar elastic fibres proceeding to a disorganized mass of truncated. functionless elastic material. These profound changes in elastic tissue are set amidst a n increased deposition of proteoglycans and glycosaminoglycans.‘ In foetal skin these substances are greatly increased, gradually diminishing with age, whereas in photodamaged skin there is a n increase almost to prenatal values. The other salient
Figure 1. Actinic dyspigrnentation consisting of actinic lentigines and flat. pigmented seborrhoeic keratoses.
Figure 2. Coarse wrinkling-the ageing.
characteristic feature of extrinsic
distinguishing feature of photodamaged skin is that of heliodermatitis.’ Within the dermis of early and moderately photodamaged skin such as ‘red neck’, there is a peri-appendageal and perivascular infiltrate composed of neutrophils, lymphocytes and degranulating mast cells. This infiltrate is not seen in chronological ageing. It is postulated that cytokines and enzymes released from these infiltrating cells are. at least in part, responsible for the degradation of elastic tissue.
Figure 3, Cut1.q rhomboldulls nuchne In nn outdcmr worker.
CLINICAL PHOTODAMAGE
39
Features of extrinsic ageing Hyperpigmcnted Iesiorts
Chronically sun-exposed skin is characteristically speckled with freckles. lentigines and flat seborrhoeic keratoses set in a background ofdiffuse mottling (Fig. 1). These pigmented lesions can be clinically very difficult to distinguish from one another. In a recent study of the efficacy of topical tretinoin in the treatment of actinic lentigines. despite careful clinical selection of what were perceived as lentigines. only hOO/,of these lesions fulfilled histological criteria for the diagnosis, the rest being classified as seborrhoeic keratoses. or unclassifiable.x Actinic lentigines are erroneously referred to as ‘age spots’ or ‘liver spots’, but are not so much a manifestation of age as of photodamage-they are not seen in sun-protected areas. Although seborrhoeic keratoses are frequently observed on photodamaged skin. they are also found in sun-protected areas and. as such, are a concomitant but not a diagnostic feature of extrinsic ageing. Wrirt kles
Coarse wrinkles are usually found on the forehead and in the periorbital and perioral areas, the so-called animation patterns. and are more indicative of extrinsic damage than are fine wrinkles.” The postulation for coarse wrinkles following these patterns is that the furrow of each wrinkle is relatively spared from ultraviolet exposure, in that solar elastotic material is greatest at the edge of wrinkles and least in the wrinkle floor.“’ Coarse wrinkles can be distinguished from fine wrinkles by the inability to efface them by stretching between two
Figure 5. Telangiectasia of the cheeks-an pathognomonic feature of extrinsic ageing.
associated but not a
fingers: fine wrinkles are completely effaced using this procedure. Coarse wrinkles must also be differentiated from the sags and jowls associated with gravitational pull-a feature of intrinsic ageing. Fine wrinkles, as well as being associated with intrinsic ageing, are a particular feature of photodamage in women, particularly a reticulate pattern on the cheeks, Coarse wrinkling per se is probably the pathognomonic feature of extrinsic ageing (Fig. 2), although it is not unique to sun damage.
40
C.E.M.GRIFFITHS
Kligman” has demonstrated in guinea pigs that heat in the form of infra-red radiation can produce similar increases in dermal elastic tissue to those observed with ultraviolet irradiation. Attention has recently been focused on the association between smoking and coarse facial wrinkling. The pathogenesis of this association is unknown at present, but is most probably multifactorial. relating to changes in dermal capillaries, direct oxidant effects of cigarette smoke, local heat and mechanical factors, such as squinting.I2 Elastotic conditions As previously mentioned, the major histoIogical change seen in photodamaged skin is one of increased, nonfunctional elastotic tissue which gives rise to a variety of clinical conditions in addition to a reduction in cutaneous elasticity. The back of the neck, with its continuous exposure to sun. particularly in the case of men working outdoors and golfers, initially manifests photodamage as ’red neck’, which in its latter stages takes on a characteristic appearance of deep geometric furrows set among yellowed elastotic skin-a condition known as cutis rhomboidalis nuchae (Fig. 3). The lateral periorbital region may develop a unique elastotic condition of its own, with the appearance of comedones and epidermoid cysts set in a deeply wrinkled sallow complexion. This constellation of features is known as the Favre-Racouchot syndrome (Fig. 41, which most probably arises as a result of ectatic sebaceous follicles developing into cysts or filling with keratinaceous debris and forming comedones. Solar elastosis in its commonest form occurs in fairskinned individuals and is observed as a pale yellow. copper-beaten appearance of the skin particularly overlying the temples-a result of increased visibility of yellow elastotic debris viewed through an atrophic epidermis and relatively avascular papillary dermis.
Sebaceous hyperplusia These distinctive. yellowish. umbilicated papules. 2-3 mm in diameter. often with a central punctum, occur most commonly on the forehead and cheeks. They result from enlargement of a single sebaceous gland comprising multiple lobules around a single enlarged duct.”
intrinsic ageing this is all that occurs and accounts for the pallor of intrinsically aged skin and, most probably. the sallowness of extrinsic ageing. In extrinsic ageing, the vessels become tortuous and dilated. producing telangiectasia, which is most commonly observed on the nose and cheeks (Fig. 51, but is not solely a result of environmental factors, since liver failure. high oestrogen concentrations and scleroderma, among other conditions, may produce the same appearance. On the pinna and lower lip. the vessels may break down further to produce venous lakes. In severe extrinsic damage, the vessel wall thickens as a result of reduplication of the basement ~nernbrane.~ This increased vascular rigidity coupled with a reduction in supportive, perivascular connective tissue results in fragility of the dermal vessels and, consequently, purpura following even the slightest injury. The purpura associated with photodamage is referred to as Bateman’s purpura (Fig. 6).
Pseudoscurs These stellate or angulated lesions. typically found on photodamaged forearms, are true scars,14 developing from trauma and subsequent haemorrhage, the result of a reduction in both vascular supply and connective tissue due to poor wound healing. As a consequence, pseudoscars are frequently observed adjacent to Bateman’s purpura (Fig. 6 ) . Actinic keratoses
Also known as solar keratoses, these are a common premalignant condition. There is a strong relationship between exposure to ultraviolet radiation and actinic keratoses. although they may be associated with ingestion of arsenic and local heat to the skin, The correlation with skin type is high and Is particularly prevalent among skin types 1-11. A study by Marks and coll e a g u e ~ ’in ~ Australia found that actinic keratoses occurred in approximately hOo/, of white Australians aged 40 years or over. Actinic keratoses appear as small. pink, scaling papules. occasionally coalescing into plaques, on sun-exposed areas of the face and extremities. The potential to transform into tl squamous cell carcinoma is small, yet real, but it should be borne in mind that the ‘normal’, adjacent, sun-damaged skin is probably just as likely to produce a squamous cell carcinoma.
Vascular changes
In both intrinsic and extrinsic ageing. the superficial horizontal capillary plexus is markedly reduced. In
~ a s a cpIf l and syuumous cdl carcinomas A detailed discussion of these cutaneous malignancies is
CLINICAL PHOTODAMAGE beyond the scope of this article, but it should be stated that both these turnours are strongly correlated with chronic sun exposure and. as such, are more commonly, although not exclusively, found in areas of extrinsic ageing.
Assessment of photodamage The increasing public and medical awareness of cutaneous photodamage is partly a result of educational campaigns relating to skin cancer and the proven use of agents, such as topical tretinoin. to reverse some of the features of extrinsic ageing.16*’’Heightened awareness of this and resultant dermatopharmacological research into photodamage has made it necessary to clarify and quantify these changes in the form of grading scales. The assessment of extrinsic ageing is not a clinically taught skill and. until recently, has relied on the use of descriptive scales such as that developed by the R.W. Johnson Pharmaceutical Research Institute, which grades the various parameters of extrinsic ageing to produce an overall assessment on a 10-point scale, where 0 denotes none, 1-3 denotes mild, 4-6 denotes moderate and 7-9 denotes severe.18Although a satisfactory scale, this technique relies on the experience of the investigator and is somewhat subjective. Prior experience with photographic standard scales for the assessment of acne’8 demonstrated the usefulness of such visual scales for the grading of cutaneous disease. Such a scale had previously been described for the grading of wrinkles or the ‘crow’s feet’ of the lateral periorbital region of the face. This scale, developed by Daniell.” used a 1-6 grading scale for the quantitation of crow’s feet wrinkles associated with smoking, and demonstrated good reproducibility. In the author’s photoageing clinic, a photonumerical scale has been developed which is based on five photographic standards illustrating grades of facial photodamage from 0 (none) to 8 (severe). In a side-by-side comparison with the existing descriptive scale, the photonumerical scale was found to have superior inter-grader agreement. However, the repeatability between the two scales was not sign& cantly different 1 week later.” This scale is useful for categorizing subjects into different grades of photodamage. but can only be used to assess major improvements resulting from the use of skin repair agents, As a clinical measure, this is currently the best available, but is in itself a non-linear grading. and only semiquantitative. Quantitative methods available for determining the
41
severity of photodamage are reliant on image analysis and subsequent digitization; thus, the results are not often instantly accessible. One such method is optical Profi10meQ9 developed by Grove et d Zand 1 now used extensively in studies of photoageing treatment. This method measures both fine and coarse wrinkles by taking a silicone rubber cast of a ‘target area’ ofthe face and subjecting the resulting impression to computerized digital image processing. The wrinkles are read as ‘north-south’ or ‘east-west’ shadowing under oblique light, with the north-south facet showing the best correlation with a clinical grading based on the Daniel1 system.21A drawback of this system is that no objective units are given and, as such, it is diff?cultto interpret in isolation. Other methods for quantitation of. skin topography also rely on the use of skin surface replicas and subsequent computer-assisted analysis. The method described by Murphy et dZ2 which is reliant on these techniques, would most probably be of use in the assessment of skin texture. particularly the smoothness induced by topical tretinoin, one of the earliest and most consistent features of induced improvement. The development of high-resolution television pictures of the skin would allow subsequent digitization of wrinkles and quantification, although this technique is still dependent on the ability to assess the same area from visit to visit, i.e. its reproducibility. Although wrinkles are difficult to quantify, other features of photodamage-namely, actinic lentkinelend themselves more readily to quantification- In addition to straightforward counting of the individual lesions, there are measures of COlOUr. Calorimeters can be used as an objective measure of colour reflectance Or intensity. One particular form of colorimeter (ChromaMeter. CR, 200b. Minolta Camera Co., Osaka, Japan) is in constant use in the author’s photoageing clinic and has proved to be reliable in the documentation of pigment changes in actinic lentigines, melasma and post-inflammatory hyperpigmentation during studies on the use of topical tretinoin for these indications (S.M.Bulengo-Ransby, unpublished data). Epidermal pigment can be distinguished from dermal pigment by the use of a Woods light: epidermalpigment is enhanced under this form of lighting, whereas dermal pigment shows no discernible change. A Wood’s light also helps to visualize subclinical lesions such as ephelides or lentigines that are not readily discernible under normal lighting conditions, Indeed, when patients view their skin under Wood’s light, they are frequently astounded at the degree of photodamage not previously evident.
42
C .E. M. GRIFFITHS
As research progresses, the molecular basis for intrinsic and extrinsic ageing will be elucidated, thereby helping to delineate even more accurately the differences between these two conditions. The ability to quantify the clinical changes inherent to extrinsic ageing are still rudimentary, but the application of sophisticated computer analysis to this problem will surely produce an objective, quantitative approach to classification in the near future.
Acknowledgment This study was supported in part by grants from the R.W.Johnson Pharmaceutical Research Institute, Raritan. N.J., and the Babcock Dermatologic Endowment, Ann Arbor, Michigan.
References 1 Unna RG. The Histopathology of the Diseases ofthe Skin. New York: Macmillan. 1896. 2 Lober DW. Fenske NA. Photoageing and the skin: differentiation and clinical response. Geriatrics 1990: 45: 36-42. 3 Marks R. Edwards C. The measurement of photodamage. Br / Dermatol 1992: 127(Suppl. 41): 7-13. 4 Kligman AM. Perspectives and problems in cutaneous gerontology. 1 Invest Dermatol 1979: 73: 39-46. 5 Gilchrest BA. Murphy G, Soter N. EKects ofchronologic ageing and ultraviolet irradiation on Langerhans cells in human epidermis. / Invest Dermatol 1982; 79: 85-8. 6 Smith JG. Davidson EA. Sams WM, Clark RD. Alterationsin human dermal connective tissue with age and chronic sun damage. 1 lnvest Dermatol 1962: 3 9 347-50.
7 Lavker RM. Kligman AM. Chronic heliodermatitis: a morphologic evaluation of chronic actinic dermal damage with emphasis on the role of mast cells. j Invest Dermatol 1988: 9 0 325-30. 8 Rafal ES, Griffiths CEM, Ditre CM et al. Topical tretinoin (retinoic acid) treatment for liver spots associated with photodamage. N Engl/ Med 1992: 326: 368-74. 9 Ellis DA. Masri H. The effect of facial animation on the aging upper half of the face. Arch Otolaryngol 1986: 1 1 5: 710-3. 1 0 Tsuji T, Yorifuji T, Hayashi Y et al. Light and scanning electron microscopicstudies on wrinkles in aged persons' skin. B r j Dermatol 1 9 8 6 : 114: 329-35.
1 1 Kligman LH. Intensification of ultraviolet-induced dermal damage by infrared radiation. Arch Dermatol Res 1982; 272: 229-38. 12 Kadance DP. Burr R.Cress R et al. Cigarette smoking: risk factor for premature facial wrinkling. Ann I n f m Med 1 99 1 : 1 14: 840-4. 1 3 Lever WF. Schaumburg-Lever G . Histopathology of the Skin. Philadelphia: J.B.Lippincott. I 990. 14 Marks R. Skin Disease in Old Age. Philadelphia: J.B.Lippincott. 1987. 1 5 Marks R , Ponsford MW. Selwood TS et al. Non-melanotic skin cancer and solar keratoses in Victoria. M d ] Aust 1983: 24: 61 922. 16 Weinstein CD, Nigra TP, Pochi PE et al. Topical tretinoin for treatment of photodamaged skin: a multicenter study. Arch Dermatol 1991: 127: 659-65. 17 Weiss JS. Ellis CN. Headington JT el al. Topical tretinoin improves photoaged skin in a double-blind, vehicle-controlled study. / A M A 1988: 259: 527-32. 18 Cook CH. Centner RC, Michaels SE. An acne grading method using photographic standards. Arch Brrnatol 1979: 1 1 5: 571-5. 19 Daniel1 HW. Smoker's wrinkles: a study in the epidemiology of 'crow's feet'. Ann Intern Med 1971: 75: 873-80. 20 GriffithsCEM, Wang TS, tlamilton TA ct al. A photonumeric scale for the assessment of cutaneous photodamage. Arch UPrmatol 1992: 128: 347-51. 21 Grove CL. Grove MI. Leyden jJ. Optical profilometry: an objective method for quantification of facial wrinkles. / Am Acad Dermatol 1989: 21: 531-7. 22 Murphy R. Cotton DWK, Wright AL. Bleehen SS. Computerassisted image analysis of skin surface replicas. Hr / fkrmatol199 1 : 1 8 4 571-5.
The clinical identification and quantification of photodamage C.E .M .GRIFFITHS k~AbphArmaCOlOgyUnit. k p r t m e n t of Dermatology, University of Michigan Medical Center, Ann Arbor. Michigan. USA
Summary
The distinction between intrinsic and extrinsic ageing can be made on both histological and clinical grounds. Clinical criteria associated with the diagnosis of extrinsic ageing are coarse wrinkles, actinic lentigines, elastotic conditions, purpura, telangiectasia and cutaneous neoplasms. These parameters are always superimposed on changes associated with intrinsic ageing: namely, fine wrinkles and benign growths. There is heightened interest in extrinsic ageing as a result of studies demonstrating the efficacy of topical tretinoin in improving this condition. As a consequence, systems for grading extrinsic ageing have been developed, including a photographic standard scale which removes some of the subjectivity inherent to current methodology.
Cutaneous ageing is a process that is a seemingly inevitable consequence of senescence. However, this ‘natural’ event can be divided into two components: physiological and pathological. Intrinsic or chronological ageing, which is related purely to senescence, genetics accounting for the age of onset and susceptibility, occurs in its pure form in non-sun-exposed body areas, such as the buttocks. Extrinsic ageing, also known as photodamage. is directly related to environmental factors and occurs in habitually exposed areas of the body, such as the face, neck and arms. Extrinsic ageing will indubitably always be superimposed on a background of intrinsic ageing. The first descriptions of extrinsic ageing or photodamage became available from the end of the 19th century, when it was referred to as farmer’s or sailor’s skin.’ At that time, photodamage was only readily observed on people with outdoor occupations and, by and large, was not seen in the middle or upper social classes, except for golfers, cricketers and other sportsmen. Women from the non-working classes were rarely photodamaged because sensible sun avoidance was practised, as evidenced by the wearing of long skirts, long sleeves and hats, and the use of parasols. These features may have been the dictates of fashion and prudery, but were also very satisfactory sun-avoidance measures. Towards the middle of the 20th century, with the introduction of more leisure time and a life style centred around seaside vacations and outdoor pursuits, there was an inevitable increase in sun exposure. A sunCorrespondence.: Dr C.E.M.Gritfiths. Department of hmatoIogy, University of Michigan Medical Center, 19 10 Taubman Center, 1 500 East Medical Center Drive. Ann Arbor. Michigan 4 8 1 0 9 4 3 1 4 , usA.
tan became a desirable goal redolent of a ‘healthy’. monied existence:indeed, this aura of a sun-tan indicating a ‘jet-set’life style still persists. As a consequence,the effects of prolonged sun exposure became associated with the development of wrinkles and dyspigmentation-a process misinterpreted as accelerated ageing. The misconception persists today and is often referred to as ‘premature ageing’. This article delineates the clinical differences between intrinsic and extrinsic ageing, and discusses the technology currently available to help quantify extrinsic ageing.
Definition of cutaneous ageing Intrinsic or chronological ageing is observed on those areas of the skin that are habitually covered and not exposed to sun or other environmental factors. In these areas, ageing is characteristically manifested by smooth, pale and finely wrinkled skin, superimposed on which may be benign growths, such as cherry haemangiomas and seborrhoeic keratoses. By contrast, extrinsically aged or photodamaged skin is remarkable for its coarseness, the principle clinical features being roughness, sallowness, fine and coarse wrinkles, hyper- and hypopigmentation, purpura, telangiectasia and a variety of benign and malignant neopIasms (Table 1).2 The histological changes inherent to intrinsic and extrinsic ageing are dealt with in more detail elsewhere in this supplement in the article by Professor Marks.3 As a general rule, in intrinsic ageing there is a reduction in all histological parameters-to quote Kligmant4 ‘in intrinsic ageing everything shrinks’-whereas in extrin-
37
38
C.E.M.GRIFFITHS
Table 1. Clinical differentiation of extrinsically and intrinsically aged skin Extrinsically aged
Intrinsically aged ~~
Wrinkles--coarse and fine Rough and dry Dark, leathery Dyspigmentation Telangiectasia Actinic keratoses
Wrinkles-fine Smooth and soft Pale
sic ageing there is an increase in histological parameters. The salient histological features of extrinsically aged skin are an initial thickening of the epidermis, but at the endstages the epidermis becomes atrophic and is accompanied by keratinocyte atypia, actinic keratoses and neoplasms, such as basal and squamous cell carcinomas. Melanocytes increase in number, whereas there is a reduction in Langerhans cells by as much as 50% in photodamaged as compared with intrinsically aged skin.’ The most striking changes occur in the dermis. In intrinsically aged skin, there is a marked reduction and homogenization of collagen within the papillary dermis. In extrinsically aged skin, however, there is an initial excess deposition of microfibrillar elastic fibres proceeding to a disorganized mass of truncated. functionless elastic material. These profound changes in elastic tissue are set amidst a n increased deposition of proteoglycans and glycosaminoglycans.‘ In foetal skin these substances are greatly increased, gradually diminishing with age, whereas in photodamaged skin there is a n increase almost to prenatal values. The other salient
Figure 1. Actinic dyspigrnentation consisting of actinic lentigines and flat. pigmented seborrhoeic keratoses.
Figure 2. Coarse wrinkling-the ageing.
characteristic feature of extrinsic
distinguishing feature of photodamaged skin is that of heliodermatitis.’ Within the dermis of early and moderately photodamaged skin such as ‘red neck’, there is a peri-appendageal and perivascular infiltrate composed of neutrophils, lymphocytes and degranulating mast cells. This infiltrate is not seen in chronological ageing. It is postulated that cytokines and enzymes released from these infiltrating cells are. at least in part, responsible for the degradation of elastic tissue.
Figure 3, Cut1.q rhomboldulls nuchne In nn outdcmr worker.
CLINICAL PHOTODAMAGE
39
Features of extrinsic ageing Hyperpigmcnted Iesiorts
Chronically sun-exposed skin is characteristically speckled with freckles. lentigines and flat seborrhoeic keratoses set in a background ofdiffuse mottling (Fig. 1). These pigmented lesions can be clinically very difficult to distinguish from one another. In a recent study of the efficacy of topical tretinoin in the treatment of actinic lentigines. despite careful clinical selection of what were perceived as lentigines. only hOO/,of these lesions fulfilled histological criteria for the diagnosis, the rest being classified as seborrhoeic keratoses. or unclassifiable.x Actinic lentigines are erroneously referred to as ‘age spots’ or ‘liver spots’, but are not so much a manifestation of age as of photodamage-they are not seen in sun-protected areas. Although seborrhoeic keratoses are frequently observed on photodamaged skin. they are also found in sun-protected areas and. as such, are a concomitant but not a diagnostic feature of extrinsic ageing. Wrirt kles
Coarse wrinkles are usually found on the forehead and in the periorbital and perioral areas, the so-called animation patterns. and are more indicative of extrinsic damage than are fine wrinkles.” The postulation for coarse wrinkles following these patterns is that the furrow of each wrinkle is relatively spared from ultraviolet exposure, in that solar elastotic material is greatest at the edge of wrinkles and least in the wrinkle floor.“’ Coarse wrinkles can be distinguished from fine wrinkles by the inability to efface them by stretching between two
Figure 5. Telangiectasia of the cheeks-an pathognomonic feature of extrinsic ageing.
associated but not a
fingers: fine wrinkles are completely effaced using this procedure. Coarse wrinkles must also be differentiated from the sags and jowls associated with gravitational pull-a feature of intrinsic ageing. Fine wrinkles, as well as being associated with intrinsic ageing, are a particular feature of photodamage in women, particularly a reticulate pattern on the cheeks, Coarse wrinkling per se is probably the pathognomonic feature of extrinsic ageing (Fig. 2), although it is not unique to sun damage.
40
C.E.M.GRIFFITHS
Kligman” has demonstrated in guinea pigs that heat in the form of infra-red radiation can produce similar increases in dermal elastic tissue to those observed with ultraviolet irradiation. Attention has recently been focused on the association between smoking and coarse facial wrinkling. The pathogenesis of this association is unknown at present, but is most probably multifactorial. relating to changes in dermal capillaries, direct oxidant effects of cigarette smoke, local heat and mechanical factors, such as squinting.I2 Elastotic conditions As previously mentioned, the major histoIogical change seen in photodamaged skin is one of increased, nonfunctional elastotic tissue which gives rise to a variety of clinical conditions in addition to a reduction in cutaneous elasticity. The back of the neck, with its continuous exposure to sun. particularly in the case of men working outdoors and golfers, initially manifests photodamage as ’red neck’, which in its latter stages takes on a characteristic appearance of deep geometric furrows set among yellowed elastotic skin-a condition known as cutis rhomboidalis nuchae (Fig. 3). The lateral periorbital region may develop a unique elastotic condition of its own, with the appearance of comedones and epidermoid cysts set in a deeply wrinkled sallow complexion. This constellation of features is known as the Favre-Racouchot syndrome (Fig. 41, which most probably arises as a result of ectatic sebaceous follicles developing into cysts or filling with keratinaceous debris and forming comedones. Solar elastosis in its commonest form occurs in fairskinned individuals and is observed as a pale yellow. copper-beaten appearance of the skin particularly overlying the temples-a result of increased visibility of yellow elastotic debris viewed through an atrophic epidermis and relatively avascular papillary dermis.
Sebaceous hyperplusia These distinctive. yellowish. umbilicated papules. 2-3 mm in diameter. often with a central punctum, occur most commonly on the forehead and cheeks. They result from enlargement of a single sebaceous gland comprising multiple lobules around a single enlarged duct.”
intrinsic ageing this is all that occurs and accounts for the pallor of intrinsically aged skin and, most probably. the sallowness of extrinsic ageing. In extrinsic ageing, the vessels become tortuous and dilated. producing telangiectasia, which is most commonly observed on the nose and cheeks (Fig. 51, but is not solely a result of environmental factors, since liver failure. high oestrogen concentrations and scleroderma, among other conditions, may produce the same appearance. On the pinna and lower lip. the vessels may break down further to produce venous lakes. In severe extrinsic damage, the vessel wall thickens as a result of reduplication of the basement ~nernbrane.~ This increased vascular rigidity coupled with a reduction in supportive, perivascular connective tissue results in fragility of the dermal vessels and, consequently, purpura following even the slightest injury. The purpura associated with photodamage is referred to as Bateman’s purpura (Fig. 6).
Pseudoscurs These stellate or angulated lesions. typically found on photodamaged forearms, are true scars,14 developing from trauma and subsequent haemorrhage, the result of a reduction in both vascular supply and connective tissue due to poor wound healing. As a consequence, pseudoscars are frequently observed adjacent to Bateman’s purpura (Fig. 6 ) . Actinic keratoses
Also known as solar keratoses, these are a common premalignant condition. There is a strong relationship between exposure to ultraviolet radiation and actinic keratoses. although they may be associated with ingestion of arsenic and local heat to the skin, The correlation with skin type is high and Is particularly prevalent among skin types 1-11. A study by Marks and coll e a g u e ~ ’in ~ Australia found that actinic keratoses occurred in approximately hOo/, of white Australians aged 40 years or over. Actinic keratoses appear as small. pink, scaling papules. occasionally coalescing into plaques, on sun-exposed areas of the face and extremities. The potential to transform into tl squamous cell carcinoma is small, yet real, but it should be borne in mind that the ‘normal’, adjacent, sun-damaged skin is probably just as likely to produce a squamous cell carcinoma.
Vascular changes
In both intrinsic and extrinsic ageing. the superficial horizontal capillary plexus is markedly reduced. In
~ a s a cpIf l and syuumous cdl carcinomas A detailed discussion of these cutaneous malignancies is
CLINICAL PHOTODAMAGE beyond the scope of this article, but it should be stated that both these turnours are strongly correlated with chronic sun exposure and. as such, are more commonly, although not exclusively, found in areas of extrinsic ageing.
Assessment of photodamage The increasing public and medical awareness of cutaneous photodamage is partly a result of educational campaigns relating to skin cancer and the proven use of agents, such as topical tretinoin. to reverse some of the features of extrinsic ageing.16*’’Heightened awareness of this and resultant dermatopharmacological research into photodamage has made it necessary to clarify and quantify these changes in the form of grading scales. The assessment of extrinsic ageing is not a clinically taught skill and. until recently, has relied on the use of descriptive scales such as that developed by the R.W. Johnson Pharmaceutical Research Institute, which grades the various parameters of extrinsic ageing to produce an overall assessment on a 10-point scale, where 0 denotes none, 1-3 denotes mild, 4-6 denotes moderate and 7-9 denotes severe.18Although a satisfactory scale, this technique relies on the experience of the investigator and is somewhat subjective. Prior experience with photographic standard scales for the assessment of acne’8 demonstrated the usefulness of such visual scales for the grading of cutaneous disease. Such a scale had previously been described for the grading of wrinkles or the ‘crow’s feet’ of the lateral periorbital region of the face. This scale, developed by Daniell.” used a 1-6 grading scale for the quantitation of crow’s feet wrinkles associated with smoking, and demonstrated good reproducibility. In the author’s photoageing clinic, a photonumerical scale has been developed which is based on five photographic standards illustrating grades of facial photodamage from 0 (none) to 8 (severe). In a side-by-side comparison with the existing descriptive scale, the photonumerical scale was found to have superior inter-grader agreement. However, the repeatability between the two scales was not sign& cantly different 1 week later.” This scale is useful for categorizing subjects into different grades of photodamage. but can only be used to assess major improvements resulting from the use of skin repair agents, As a clinical measure, this is currently the best available, but is in itself a non-linear grading. and only semiquantitative. Quantitative methods available for determining the
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severity of photodamage are reliant on image analysis and subsequent digitization; thus, the results are not often instantly accessible. One such method is optical Profi10meQ9 developed by Grove et d Zand 1 now used extensively in studies of photoageing treatment. This method measures both fine and coarse wrinkles by taking a silicone rubber cast of a ‘target area’ ofthe face and subjecting the resulting impression to computerized digital image processing. The wrinkles are read as ‘north-south’ or ‘east-west’ shadowing under oblique light, with the north-south facet showing the best correlation with a clinical grading based on the Daniel1 system.21A drawback of this system is that no objective units are given and, as such, it is diff?cultto interpret in isolation. Other methods for quantitation of. skin topography also rely on the use of skin surface replicas and subsequent computer-assisted analysis. The method described by Murphy et dZ2 which is reliant on these techniques, would most probably be of use in the assessment of skin texture. particularly the smoothness induced by topical tretinoin, one of the earliest and most consistent features of induced improvement. The development of high-resolution television pictures of the skin would allow subsequent digitization of wrinkles and quantification, although this technique is still dependent on the ability to assess the same area from visit to visit, i.e. its reproducibility. Although wrinkles are difficult to quantify, other features of photodamage-namely, actinic lentkinelend themselves more readily to quantification- In addition to straightforward counting of the individual lesions, there are measures of COlOUr. Calorimeters can be used as an objective measure of colour reflectance Or intensity. One particular form of colorimeter (ChromaMeter. CR, 200b. Minolta Camera Co., Osaka, Japan) is in constant use in the author’s photoageing clinic and has proved to be reliable in the documentation of pigment changes in actinic lentigines, melasma and post-inflammatory hyperpigmentation during studies on the use of topical tretinoin for these indications (S.M.Bulengo-Ransby, unpublished data). Epidermal pigment can be distinguished from dermal pigment by the use of a Woods light: epidermalpigment is enhanced under this form of lighting, whereas dermal pigment shows no discernible change. A Wood’s light also helps to visualize subclinical lesions such as ephelides or lentigines that are not readily discernible under normal lighting conditions, Indeed, when patients view their skin under Wood’s light, they are frequently astounded at the degree of photodamage not previously evident.
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C .E. M. GRIFFITHS
As research progresses, the molecular basis for intrinsic and extrinsic ageing will be elucidated, thereby helping to delineate even more accurately the differences between these two conditions. The ability to quantify the clinical changes inherent to extrinsic ageing are still rudimentary, but the application of sophisticated computer analysis to this problem will surely produce an objective, quantitative approach to classification in the near future.
Acknowledgment This study was supported in part by grants from the R.W.Johnson Pharmaceutical Research Institute, Raritan. N.J., and the Babcock Dermatologic Endowment, Ann Arbor, Michigan.
References 1 Unna RG. The Histopathology of the Diseases ofthe Skin. New York: Macmillan. 1896. 2 Lober DW. Fenske NA. Photoageing and the skin: differentiation and clinical response. Geriatrics 1990: 45: 36-42. 3 Marks R. Edwards C. The measurement of photodamage. Br / Dermatol 1992: 127(Suppl. 41): 7-13. 4 Kligman AM. Perspectives and problems in cutaneous gerontology. 1 Invest Dermatol 1979: 73: 39-46. 5 Gilchrest BA. Murphy G, Soter N. EKects ofchronologic ageing and ultraviolet irradiation on Langerhans cells in human epidermis. / Invest Dermatol 1982; 79: 85-8. 6 Smith JG. Davidson EA. Sams WM, Clark RD. Alterationsin human dermal connective tissue with age and chronic sun damage. 1 lnvest Dermatol 1962: 3 9 347-50.
7 Lavker RM. Kligman AM. Chronic heliodermatitis: a morphologic evaluation of chronic actinic dermal damage with emphasis on the role of mast cells. j Invest Dermatol 1988: 9 0 325-30. 8 Rafal ES, Griffiths CEM, Ditre CM et al. Topical tretinoin (retinoic acid) treatment for liver spots associated with photodamage. N Engl/ Med 1992: 326: 368-74. 9 Ellis DA. Masri H. The effect of facial animation on the aging upper half of the face. Arch Otolaryngol 1986: 1 1 5: 710-3. 1 0 Tsuji T, Yorifuji T, Hayashi Y et al. Light and scanning electron microscopicstudies on wrinkles in aged persons' skin. B r j Dermatol 1 9 8 6 : 114: 329-35.
1 1 Kligman LH. Intensification of ultraviolet-induced dermal damage by infrared radiation. Arch Dermatol Res 1982; 272: 229-38. 12 Kadance DP. Burr R.Cress R et al. Cigarette smoking: risk factor for premature facial wrinkling. Ann I n f m Med 1 99 1 : 1 14: 840-4. 1 3 Lever WF. Schaumburg-Lever G . Histopathology of the Skin. Philadelphia: J.B.Lippincott. I 990. 14 Marks R. Skin Disease in Old Age. Philadelphia: J.B.Lippincott. 1987. 1 5 Marks R , Ponsford MW. Selwood TS et al. Non-melanotic skin cancer and solar keratoses in Victoria. M d ] Aust 1983: 24: 61 922. 16 Weinstein CD, Nigra TP, Pochi PE et al. Topical tretinoin for treatment of photodamaged skin: a multicenter study. Arch Dermatol 1991: 127: 659-65. 17 Weiss JS. Ellis CN. Headington JT el al. Topical tretinoin improves photoaged skin in a double-blind, vehicle-controlled study. / A M A 1988: 259: 527-32. 18 Cook CH. Centner RC, Michaels SE. An acne grading method using photographic standards. Arch Brrnatol 1979: 1 1 5: 571-5. 19 Daniel1 HW. Smoker's wrinkles: a study in the epidemiology of 'crow's feet'. Ann Intern Med 1971: 75: 873-80. 20 GriffithsCEM, Wang TS, tlamilton TA ct al. A photonumeric scale for the assessment of cutaneous photodamage. Arch UPrmatol 1992: 128: 347-51. 21 Grove CL. Grove MI. Leyden jJ. Optical profilometry: an objective method for quantification of facial wrinkles. / Am Acad Dermatol 1989: 21: 531-7. 22 Murphy R. Cotton DWK, Wright AL. Bleehen SS. Computerassisted image analysis of skin surface replicas. Hr / fkrmatol199 1 : 1 8 4 571-5.
