Effects of ultraviolet radiation, visible light, and infrared radiation on erythema and pigmentation: a review

Abstract

The effects of ultraviolet radiation, visible light, and infrared radiation on cutaneous erythema, immediate pigment darkening, persistent pigment darkening, and delayed tanning are affected by a variety of factors. Some of these factors include the depth of cutaneous penetration of the specific wavelength, the individual skin type, and the absorption spectra of the different chromophores in the skin. UVB is an effective spectrum to induce erythema, which is followed by delayed tanning. UVA induces immediate pigment darkening, persistent pigment darkening, and delayed tanning. At high doses, UVA (primarily UVA2) can also induce erythema in individuals with skin types I–II. Visible light has been shown to induce erythema and a tanning response in dark skin, but not in fair skinned individuals. Infrared radiation produces erythema, which is probably a thermal effect. In this article we reviewed the available literature on the effects of ultraviolet radiation, visible light, and infrared radiation on the skin in regards to erythema and pigmentation. Much remains to be learned on the cutaneous effects of visible light and infrared radiation.

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Introduction

Electromagnetic radiation emitted by the sun encompasses a wide spectrum of wavelengths. Only fractions of these wavelengths are able to penetrate the ozone layer to reach the surface of the earth; these include ultraviolet radiation (UVR; 280–400 nm), visible light (VL; 400–760 nm), and infrared (IR; 760 nm–1 mm) (Table 1). In the UVR range, only the longer spectra UV, i.e., UVB (280–315 nm) and UVA (315–400 nm), are able to reach the earth's surface, while UVC (100–280 nm) is absorbed by the ozone layers and is present in terrestrial sunlight only at high altitude.¹ It should be noted that while the above definition of UVR is that decided by the Second International Congress on Light in August, 1932, an alternate classification, widely used in photodermatology, is as follows: UVC (200–290 nm), UVB (290–320 nm), and UVA (320–400 nm).¹ In this article, the effects of UVB, UVA, visible light, and infrared radiation on erythema and pigmentation will be reviewed.

Table 1 UV, visible, and IR radiation with the corresponding wavelengths

UV, visible, and IR	Wavelength
UVC	100–280 nm
UVB	280–315 nm
UVA	315–400 nm
UVA2	320–340 nm
UVA1	340–400 nm
Visible light	400–760 nm
IR	760 nm–1 mm
IR-A	760–1400 nm
IR-B	1400–3000 nm
IR-C	3000 nm–1 mm

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Acute effects of UVR on erythema and pigmentation

Clinically, the acute effects of UVR include erythema, pigment darkening, delayed tanning, thickening of the epidermis, and vitamin D synthesis (Table 2). Erythema (redness of the skin that occurs with sunburn) (Table 3) is a cutaneous inflammatory reaction that can be accompanied by warmth and tenderness; severe cutaneous erythema may result in blister formation.^2–4 In fair skin types, sunlight may induce a transient flush of erythema during or immediately after exposure. A delayed erythema response is common in all skin types, and peaks between 6–24 h.^5,6

Table 2 Acute and chronic effects of UVR

Acute effects of UVR

Erythema (sunburn)

Pigmentation

 Immediate pigment darkening

 Persistent pigment darkening

Delayed tanning

Hyperplasia

Vitamin D synthesis

Immunosuppression

Nitric oxide induction

Heme oxygenase-1 expression

Decreased blood pressure

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Chronic effects of UVR

Photoaging

Photocarcinogenesis

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Table 3 Radiation-induced erythema

Radiation	Erythema
a UVA induces erythema in skin type I; in individuals with higher skin phototypes, it requires significantly high doses to do so. Some studies report a monophasic response.
UVA^a	Biphasic: peaks immediately to 4 h and then 6–24 h
UVB	In lighter skin types, fades within 1–2 weeks
	In darker skin types, fades within 1–3 days
Broadband UVB	Abrupt increase at 12 h and peaks at 6–24 h
	Immediate erythema only in skin types I and II
Narrowband UVB	Milder and shorter than BB-UVB
Visible light	Immediate, fades within 2 h
Infrared	Lasts less than 1 h

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Pigment darkening (Table 4), which should be differentiated from delayed tanning, demonstrates a biphasic response.^2,3,5–7 The immediate pigment darkening (IPD) occurs within minutes of exposure to UVA, and may last up to 2 h. IPD is followed by persistent pigment darkening (PPD), which may last for 24 h. Delayed tanning (DT) occurs between 3–5 days after sunlight exposure and may persist for several days to weeks, and sometimes even months.^3,5,8,9 In some, PPD may blend into DT. IPD, PPD, and DT are influenced by genetic factors and are more pronounced in darker skin types.^7,10

Table 4 Radiation-induced pigmentation

Radiation	Pigmentation
UVA	Induces immediate pigment darkening that fades within 2 h
	Delayed tanning appears within 3–5 days after exposure, may persist for months
UVA1	Induces immediate pigmentation and delayed pigmentation in all skin types
UVA2	In skin types I and II erythema precedes pigmentation
	In skin types III and IV induces immediate pigmentation with no visible erythema
UVB	Pigmentation occurs when preceded by erythema
Narrowband UVB	Peaks between 3–6 days, pigmentation returns to baseline at 1 month
Broadband UVB	Peaks between 4–7 days, pigmentation returns to baseline at 3 months
Visible light	Immediate pigment darkening and delayed tanning in skin types IV–VI, pigmentation may last for 2 weeks
Infrared	None

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Chronic effects of UVR on erythema pigmentation, and skin carcinogenesis

While erythema, pigment darkening, and tanning are visible evidence of acute UV-induced injury to the skin, repeated injury may ultimately predispose one to the chronic effects of UVR (Table 2): photoaging (the development of deep wrinkles, leathery skin, dilatation of blood vessels, and multiple dark spots on the sun exposed skin), immunosuppression, and photocarcinogenesis (development of skin cancer).^6,11–14

Skin cancer is the most common malignancy in the United States, and the incidence of non-melanoma skin cancers (NMSCs) and melanoma is increasing.^10,15,16 It is estimated that over a million new cases of NMSC occur each year in the United States; the relationship between NMSC, especially squamous cell carcinoma, and sunlight exposure is evident.^17,18 The association between UV exposure and melanoma has been debated for decades; however, recent studies in an animal model,¹⁶ and on epidemiology of skin cancers in Norway and Sweden,¹⁹ and on individuals who are frequent users of tanning beds (which emit high doses of UVA)²⁰ have demonstrated that an association does exist.^16,19,20

UVB radiation induces direct damage to DNA, resulting in the formation of cyclobutane-pyrimidine dimers and thymine dimers. DNA damage secondary to UVA exposure is mediated by reactive oxygen species, resulting in the formation of oxidative products 7,8-dihydro-8-oxo-guanosine (8-oxoG) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG).^6,10 Incomplete repair of the DNA and removal of these mutagenic photoproducts result in uncontrolled proliferation of the cells, leading to the development of skin cancer.

While UV induced injury to the skin is an important etiologic factor for many types of skin cancers, in Caucasians it is the predominant predisposing factor.¹⁰ While Caucasians are estimated to be about 70 times more likely to develop skin cancer than blacks, when darkly pigmented individuals do develop skin cancer, it is often associated with increased morbidity and mortality.¹⁵ The association between UV exposure and non-melanoma skin cancers such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) is evident in lighter skin types, however in blacks, there is only an association between UV exposure and BCC.¹⁵ Intermittent sun exposure and sunburns that are intense, induce blistering, or occur early in life are major risk factors for melanoma in Caucasians, as is exposure to tanning beds.^15,16,20 Although UV exposure may play a role in the development of melanoma in dark skinned individuals, it does not appear to be a significant risk factor.¹⁵

The photoprotective function of the skin resides in the epidermis, where melanocytes are located. Melanocytes produce melanin, which is packaged in melanosomes and then transferred to keratinocytes. Melanin is a neutral density filter, capable of absorbing across the broad spectrum of UVR and visible light, hence acts to decrease damage in melanocytes and keratinocytes. As a result of the presence of larger, more dispersed melanosomes in darker skin types compared to in light skinned individuals, the epidermis of darker skin types transmits significantly less UVB and UVA compared to lighter skin types.^10,15 This accounts for the low incidence of skin cancer in darker skin types. In addition, Agar and Young suggest that another factor contributing to the lower incidence of skin cancer in darker skin individuals is a result of a greater ability to repair photodamaged DNA compared to those with lighter skin.⁷

UVR-induced immunosuppression is a major mechanism for photocarcinogenesis, as evidenced by the increased rates of skin cancer in immunosuppressed patients.^21,22 It has been shown that UVR suppresses the number and function of Langerhans cells (the antigen presenting cells) in the epidermis and T lymphocytes in peripheral blood.^23,24 Therefore, development of UVR-induced skin cancer is due to the combination of direct DNA damage as well as immunosuppression.

There is debate as to whether UV induced-tanning offers any protection against erythema, DNA damage, and other detrimental effects of UVR mentioned above. In IPD, UVR induces an oxidation of melanin and possibly a spatial redistribution of melanosomes.²⁵ IPD is believed by some investigators to offer no photoprotective effect.^7,26 Others, however, believe that the redistribution of melanin forms ‘nuclear caps’ in the basal cell layer of the epidermis, hence protecting the DNA from further UV damage.⁶ UVR also induces DT as a result of new melanin synthesis; this is a protective adaptation against sunburn and other UV-induced damage.^12,27 According to the Food and Drug Administration, the extra melanin in tanned skin offers a Sun Protection Factor (SPF) of about 2 to 4. However, the proposed protective adaptation of pigmentation is transitory and lasts no longer than 2 months.²⁸ UVR also induces thickening of the epidermis, especially the stratum corneum, and to a lesser extent, thickening of the dermis.^4,29,30 Some studies have shown that the photoprotective effect of tanning is primarily a result of epidermal thickening rather than melanin formation.^5,31 Other studies, however, have found no protective role of epidermal thickening.³²

The epidermis contains several chromophores for UVR. These include nucleic acids, urocanic acid, aromatic amino acids, and melanin precursors.^2,10 It has been shown that DNA is the chromophore for UVR induced erythema.^6,7,33 The shape of the erythema action spectrum is identical to the action spectrum of UV-induced DNA damage for wavelengths less than 320 nm.³³ Because the predominant effect of UVA is oxidative damage to the DNA, it is possible that UVA-induced erythema is the result of oxidative damage.²

Factors influencing the effects of UVR on the skin

The Fitzpatrick classification of skin type is a numerical schema to describe response of skin to sunlight and skin color.³⁴ Skin types I and II burn more easily than tan; individuals with these skin types have an increased incidence of skin cancer compared to those with types III and IV skin, who tan more readily than burn.^35,36 The reason for this may be explained by the finding that darker skin types have reduced UV penetration, and have faster rates of DNA repair.^35,37 Kaidbey et al. demonstrated that 5 times as much UVA and UVB penetrates through the epidermis of Caucasians compared to that of blacks, primarily due to the increased melanin content in blacks.³⁷ Halder et al. demonstrated that dark skin allows 7.4% UVB and 17.5% UVA to penetrate compared to a much higher 24% UVB and 55% UVA penetration in white skin.³⁸ UV penetration also varies with different body sites due to the regional variation in the thickness of the stratum corneum and the entire epidermis.^2,3,39 Other factors such as skin hydration, age, UVR or VL dose in sunlight (varies with time of day), latitude, environmental surface reflection (e.g., sand vs. snow),² temperature,⁴⁰ certain medications,¹² as well as gender ⁴¹ play a role in the effects of UVR and VL on the skin.

Sunlight accounts for the majority of human UVR exposure. However, to examine the unique characteristics of UVA, UVB, VL, and IR, this review will focus on studies using artificial light sources emitting the specific wavelengths of interest.

UVB

The wavelength of UVB ranges from 280–315 nm. Narrowband UVB (NB-UVB), widely used for phototherapy, refers to UVB sources with specific wavelengths of 311–313 nm. Only 5% of the UVB emitted by the sun reaches the surface of the earth,⁴³ yet the relatively short wavelength of this radiation has much potential to induce harmful effects to the skin.

Erythema induced by UVB

UVB is more erythemogenic than melanogenic.^2,44 For Caucasian skin, the minimal erythema dose (MED) for UVB is 1000-fold less than that for UVA.^45,61 The erythema induced by UVB peaks between 6–24 h.^3,46,47 The time course and intensity of UVB-induced erythema are dependent on skin type, dose, and wavelength of UVB. For example, an immediate erythemogenic response is only seen in skin types I and II.² Suh and colleagues investigated the time course of pigmentation and erythema induced by two MEDs of narrowband UVB (NB-UVB) versus broadband UVB (BB-UVB; 315–400 nm). They found that NB-UVB induces erythema that is milder in intensity and shorter in time course compared to BB-UVB (maximum erythema observed at 1 and 2 days, respectively).³ In dark skin, UVB-induced erythema has been noted to fade within 1–3 days, however in fair skin, it may last for 1–2 weeks.²

It takes a higher dose of UVB to induce minimal erythema in darker skin tones because constitutional melanin pigment renders the skin less sensitive to UVR.⁴⁸ Henriksen et al. investigated the effect of daily exposure to NB-UVB in subjects with skin types II–V. As expected, they found that MED was higher in darker skinned individuals. They also found that after 4 consecutive days of UV exposures, there was a significant decrease in the MED of the dark skinned subjects, which was not observed in those with fair skin. The investigators postulated that 24 h was sufficient to repair the damage in fair skinned subjects, while the repairs took longer in those with dark skin.⁴⁸ It must be noted, however, that this theory contradicts the findings of other investigators that showed darker skin types are associated with faster rates of DNA repair.^35,37 While daily NB-UVB phototherapy is rarely used in the clinical setting, this finding needs to be taken into consideration to avoid sunburn reaction in dark skinned individuals when the daily treatment protocol is used, such as in outpatient day-hospitalization units.

Pigmentation induced by UVB

Pigmentation induced by UVB is delayed tanning (DT), which is preceded by erythema.^33,44,49,50 This is due to the fact that UVB is predominantly an erythemogenic spectrum. The intensity and timing of DT vary with UVB wavelength, dose, and skin type. Tan induced by NB-UVB is milder in intensity and is shorter lasting than BB-UVB.³ Suh et al. demonstrated a peak tanning response for NB-UVB to appear between 3–6 days and for BB-UVB, between 4–7 days.^3,42 The investigators also demonstrated that DT induced by NB-UVB and BB-UVB returned to baseline by 1 and 3 months, respectively. The absolute increase in pigmentation is independent of pre-exposure, constitutive skin pigmentation, and has been shown to increase linearly with increasing doses of UVB.⁵¹ The dose to induce minimal tanning however is shown to be dependent on pre-exposure skin pigmentation as well as constitutive skin type, and is higher for darker skin compared to lighter skin.⁴⁴ This was proven true for both single and multiple exposures.^44,51 These findings suggest that once the minimal melanogenic dose has been reached, which varies depending on pre-exposure and constitutive skin pigmentation, the subsequent absolute increase in pigmentation is equal for all skin types, and is only dependent on UVB dose.

Exposure of the epidermis to UVB and UVA results in the activation of protein 53 (p53) which up-regulates the gene encoding proopiomelanocortin (POMC).¹⁰ The POMC precursor polypeptide is processed into several bioactive products which include alpha-melanocyte stimulating hormone (alpha-MSH), adrenocorticotropic hormone (ACTH), and endorphin.¹⁰ After secretion, alpha-MSH binds to the melanocortin 1 receptor (MC1R) located on melanocytes and activates melanin production, clinically manifested as DT response.¹⁰ In addition, the anti-inflammatory effects of alpha-MSH and ACTH may help relieve irritation and local inflammation in UV-exposed skin.

UVB is a spectrum of wavelengths proven to cause skin cancer,⁵² as the carcinogenic action spectrum falls between 280–320 nm.^13,14 It has been shown that a UVB wavelength of 290 nm, in particular, may result in more harmful effects compared to UVB of longer wavelengths. Using human subjects, Phan and colleagues measured the melanin index by reflectance spectroscopy after 24 h of exposing subjects of skin types I–IV to graded doses of UV in the wavelengths of 290 and 310 nm. The investigators found that the melanin index correlated with the 310 nm wavelength but not the 290 nm wavelength.^53,54 Using subjects with skin types I and II, Young et al. demonstrated that wavelengths in the range of 300–360 nm can penetrate deep into the epidermis and be absorbed by melanin, which has its highest concentration at the basal cell layer, where most melanocytes are located; wavelengths of 280 nm and 290 nm have poor transmission into the basal layer.⁵⁵ The relatively short 290 nm wavelength penetrates the stratum corneum poorly and is therefore unable to significantly reach the basal layer where most melanin density is located.^53,54 However, this only applies to lower doses of the 290 nm wavelength. At super-erythemal doses of energy, melanin production can be induced by 290 nm. In essence, melanin is better able to protect against threshold erythema due to the longer wavelengths such as 310 nm. Melanin is not as protective against 290 nm wavelengths but these wavelengths are often filtered out by the stratum corneum.⁵⁴

Molecular and other effects of UVB

UVB-induced erythema is the result of vasodilation of the superficial blood vessels in the dermis.⁵ It is proposed that the vasodilation occurs in response to the cytokines, histamine, prostaglandins, and inflammatory mediators that are released into the skin following UVB exposure.²

Cyclobutane pyrimidine dimers (CPDs) and thymine dimers are the major DNA photoproducts after UVB exposure; these products are generated by direct effects of UVB on DNA, rather than mediated by reactive oxygen species.⁷ The UVB signature mutation (C → T or CC → TT) in the p53 gene was found in the majority of actinic keratoses (AKs) and squamous cell carcinomas (SCCs), and in approximately half of basal cell carcinomas (BCCs).⁵⁶ This mutation leads to apoptosis resistance which results in clonal expansion of the mutated keratinocytes.⁵⁶ UVB exposure may also play a role in melanoma.^16,19 Using an animal model to investigate melanoma induction by UVR, Noonan et al. reported that UVB was more effective than UVA in initiating melanoma, and that it did so in a skin pigment-independent manner associated with direct UVB induced DNA damage.¹⁶

UVB at 300 ± 5 nm is the spectrum responsible for cutaneous vitamin D synthesis, which has been shown to be important for bone health, as well as having effects on multiple diseases.⁵⁷

UVA

The wavelength of UVA ranges from 315–400 nm. UVA is further divided into UVA1 (340–400 nm) and UVA2 (320–340 nm); it is done because the biological properties of the shorter wavelength UVA2 are similar to that of UVB.

Erythema induced by UVA

Compared to UVB, the relatively longer wavelength of UVA is far less erythemogenic, but enables it to better penetrate the ozone layer; therefore, 95% of UVR reaching the earth's atmosphere is UVA and only 5% is UVB.^43,58,59 A biphasic erythema response to UVA has been reported in several studies. Diffey et al. observed an immediate erythemogenic response which fell to a minimum at 4 h and then intensified again to a plateau between 6–24 h.⁶² Parrish et al. confirmed the findings of a biphasic response by using a nitrogen laser to deliver monochromatic UVA radiation.⁶⁴ Pathak et al. described a transient flush of erythema that appeared within seconds of exposure to UVA, which was followed by a delayed erythema that peaked minutes to hours later.⁴² The initial flush was noted to only occur in skin types I and II, while the delayed erythema occurred in all skin types.⁶

Other studies have reported a monophasic response in UVA-induced erythema which is dose dependent. Using human subjects with skin types II–III, Kaidbey et al. observed a maximal erythemogenic response immediately after exposure which was not biphasic.⁶³ The investigators also found that when exposed to doses of 50 J cm⁻², the immediate erythema lasted for 24 h; however when exposed to threshold erythemal doses of 13 J cm⁻², the erythema faded within minutes, indicating that the duration of erythema may be dependent on the fluence.⁶³ Suh and colleagues conducted a study to investigate and compare the time course of erythema induced by BB-UVA and UVA1.³ Using male volunteers with skin types ranging from III–V, the investigators reported that after exposing the subjects to two minimal erythema doses (MED) of BB-UVA and UVA1, the intensity and time course of erythema induced by each are similar.³ They found the erythema to be most pronounced immediately and 1 h after exposure, then it rapidly faded.³

Unless exposed to extremely high fluences of UVA, and UVA1 in particular, erythema is generally induced only in fair skin types.^6,60 However, a study by Applegate et al. revealed that this may only hold true for areas of the skin that are exposed to sunlight, and that UVA-induced erythema is largely dependent on anatomical skin site.⁶⁰ Using a Uvasun 3000 lamp with a filter to permit UVA1 and another filter to permit UVA1 and UVA2 radiation, the investigators irradiated sun exposed (forearm) and sun protected (buttocks) sites of subjects with skin types I–IV with increasing doses of UVA1 and UVA1 + 2 radiation. For UVA1, all skin types were exposed to doses of 25, 50, 75, and 100 J cm⁻² except for skin type I for which 100 J cm⁻² was excluded. For UVA1 + 2, all skin types were exposed to doses of 20, 35, 50, and 70 J cm⁻². The investigators found a low erythema response on the forearms that was barely detectable to the naked eye, versus a readily detectable erythema response on the buttocks.⁶⁰ Furthermore, the UVA1-induced erythema was more intense in skin type I compared to skin type IV when given the same dose.⁶⁰ The investigators also found increased melanin production on sun exposed skin compared to non-sun exposed skin of subjects with types II and III when exposed to UVA1 + 2 for all doses.⁶⁰ Melanin therefore may act as a defense mechanism against UVA-induced erythema in chronically sun-exposed skin. A previous study by these investigators revealed that sun-exposed skin has higher levels of ferritin than does non-sun exposed skin, suggesting that ferritin may also act as a protective protein against UVA-induced erythema.⁶⁵

Pigmentation induced by UVA

As compared to UVB, UVA is more effective in inducing pigment darkening (both IPD and PPD) and delayed tanning (DT) than erythema; IPD, PPD and DT are more pronounced in dark skin compared to fair skin.² UVA1 induces immediate pigment darkening (IPD) response in all skin types.² IPD is grey in color; it occurs within minutes after exposure to UVA and visible light up to wavelengths of 470 nm, and it fades within a few minutes to a maximum of 2 h.^2,25,66–68 The maximum efficiency wavelength for IPD induction is noted to be 340 nm.²⁵ IPD is the result of a redistribution of melanosomes and photo-oxidation of melanin already present in the melanosomes; therefore, there is no new melanin synthesis during the IPD.^6,25 The threshold to induce IPD is 1–2 J cm⁻².^66,69 When skin is exposed to fluences of UVA greater than 10 J cm⁻², the IPD is more intense and fades over the next 2 h, leaving persistent pigment darkening (PPD) that may last for 24 h and may blend with the DT response.^2,3,9,67 Similar to IPD, PPD is due to the redistribution and oxidation of pre-existing melanin.

Delayed tanning (DT) appears within 3–5 days of UVA exposure, and persists for several days to weeks and sometimes months.^3,8,9 Unlike IPD and PPD, DT is due to a photochemical reaction which results in neo-melanogenesis. UVA-induced melanin accumulation is wavelength dependent: wavelengths between 340–400 nm increase melanin density in the basal cell layer, while wavelengths between 320–340 nm (which are less penetrating then 340–400 nm) increase the number of melanin granules in the more superficial layer of the epidermis.^2,5,6 This is the major reason that UVA-induced pigmentation lasts longer than UVB-induced pigmentation. UVA exposure results in increased melanin content in the deeper layer of the epidermis, while the UVB exposure induced pigmentation occurs in the superficial layer of the skin which is rapidly shed.³

Ravnbak et al. investigated pigmentation induced by BB-UVA and UVA1 in subjects with skin types II–V. They determined the minimal melanogenic dose (MMD) 7 days after exposure to incremental doses of UVA and UVA1. They found that for a single BB-UVA exposure, the dose to induce minimal pigmentation was higher in dark skinned subjects, whereas for a single UVA1 exposure, the dose to induce minimal pigmentation was independent of skin type. The investigators then exposed the subjects to multiple sub-minimal melanogenic doses (MMD) of BB-UVA and UVA1. They found the absolute increase in pigmentation to be independent of skin type and pre-exposure pigmentation for both BB-UVA and UVA1. The investigators also showed that fading of the delayed tanning response occurred at approximately 5–6 months and was independent of skin type.⁸

Pigmentation response induced by UVA2 is similar to that induced by UVB, and is dependent on skin type. In types I and II skin, erythema precedes the DT response, while in types III and IV, there is an immediate pigmentation response with no visible erythema, followed by DT.²

Gange et al. investigated the protective effect of UVA- and UVB-induced tanning against erythema and DNA damage induced by subsequent exposure to UVB. Protection against erythema was measured by comparison of the MED of UVB in tanned and untanned skin, and protection against DNA damage was measured by comparing the numbers of endonuclease-sensitive sites in epidermal DNA extracted from biopsies taken from tanned and untanned sites exposed to the same dose of UVB.⁷⁰ After inducing tanning by either UVA or UVB, they exposed the UVA-induced tanned area, the UVB-induced tanned area, and the untanned area to 1 minimal erythema dose (MED) of UVB. They found UVB-induced tan to offer more protection (protection factor of 3) against erythema as compared with the UVA-induced tan (protection factor of 1.3). This different effect is most likely due to the more superficial localization of melanin accumulation following UVB exposure, and due to the fact that UVB can induce thickening of the epidermis more efficiently than UVA.² This finding has been confirmed by others.^26,71,72

As reviewed recently, exposure to UVA can induce an antioxidant, heme oxygenase-1, in vitro and in animal models, hence could potentially provide a protective effect on UVB-induced immunosuppression;⁷³ however, it should be emphasized that the clinical relevance of this finding is currently unclear.

In a study of 12 subjects exposed to repeated sub-erythemogenic doses of UVA from 4 different sources for 4 weeks, Bech-Thomsen and colleagues concluded that melanogenesis accounted for 63–95% of the total protection against the erythemogenic effect of UVA.⁷⁴ Miyamura et al. exposed human skin to sub-erythemogenic doses of UVA or UVB for 2 weeks, followed by exposure to a challenge dose of UVA or UVB. They confirmed that the melanin content and UV-protective effects against DNA damage in UVB-tanned skin were significantly higher compared to UVA-tanned skin.⁷²

Molecular effects of UVA

UVA has been implicated as the major spectrum of wavelengths that induces almost all of the oxidative damage to DNA following exposure to sunlight.⁷⁵ Similar to UVB, UVA can also generate the formation of DNA pyrimidine dimers, although it is not nearly as efficient as UVB in doing so.^76,77

It should be noted that UVA exposure may result in harmful effects due to the presence of melanin and intermediates in melanin biosynthesis.^7,16 Upon UVA exposure, melanin can generate reactive oxygen species, that in turn can induce single strand breaks in DNA. Reactive oxygen species, such as hydrogen peroxide, are cytotoxic and capable of inducing cell death at high levels.⁷

UVA radiation has been shown to lead to high levels of heme oxygenase-1 levels in the skin which has antioxidant and anti-inflammatory properties.⁷³ Other studies have shown that UVA induces nitric oxide release in the skin.^78–80 Oplander et al. showed that irradiation with biologically relevant doses of UVA can lead to a rapid reduction in systolic and diastolic blood pressure by 11 ± 2% that may last up to an hour. The investigators also showed that this reduction in blood pressure correlated with increased plasma concentrations of nitrosated species.⁷⁹ Feelisch and colleagues also proposed this cardiovascular benefit to be attributed to UVA-induced mobilization of nitric oxide, nitrite/nitrate in the skin which releases into the systemic circulation to exert a vasodilator effect.⁸¹ While nitric oxide is a gaseous free radical and its direct toxicity is modest, the toxicity is greatly enhanced when combined with cytotoxic free radical species such as superoxide anions. Such combination results in the formation of the potent oxidant peroxynitrite, which can promote oxidative damage to blood vessels, DNA, and melanosomes in the skin.^7,81

Recent studies have suggested that UVA exposure is also a risk factor for melanoma.^16,19 In a mouse model, Noonan et al. reported that melanoma caused by UVA requires the presence of melanin pigment and that it is associated with oxidative DNA damage within melanocytes.¹⁶ In an attempt to investigate the association between UVR and melanoma, Moan et al. analyzed epidemiological data from cancer registries in Norway and Sweden and their findings also suggest that UVA may play a role in melanoma induction.¹⁹ Data from analysis of tanning bed users also strongly suggest that exposure to UVA in tanning lamps is associated with an increased risk for melanoma.^20,82–85

Runger et al. recently compared DNA damage responses following equi-mutagenic doses of UVA and UVB. The investigators analyzed the cell cycle regulation, DNA repair, and apoptosis in human fibroblasts after UVA and UVB exposure. They demonstrated that UVA-induced dimers induced a less effective anti-mutagenic cellular response compared to the response induced by UVB-induced dimers, suggesting that the former is more mutagenic than the latter. They further demonstrated that this only applies to exposure of pure UVA since the concomitant presence of UVB would protect against formation of additional UVA-induced mutations.⁷⁷

Visible light (VL)

Visible light (400–760 nm) comprises 38.9% of the solar radiation that reaches the surface of the earth.⁶⁷

Erythema induced by VL

At high doses, VL causes skin erythema.¹⁰ Using a light source that emits 98.3% VL, 1.5% infrared radiation, and 0.19% UVA1, Mahmoud et al. demonstrated that skin type plays a major role in the intensity and timing of erythema.⁶⁷ In skin types IV–VI, VL induced a halo of erythema that surrounded the IPD response; the erythema resolved within 2 h. For these skin types, the degree of erythema increased with increasing doses of VL. However, erythema could not be induced in type II skin, even at 480 J cm⁻², the highest fluence tested. The authors proposed that perhaps the VL induces a reaction within the chromophores that generates heat, and that increased concentrations of melanin in darker skin types result in greater heat production, resulting in vasodilation and the appearance of erythema.⁶⁷ In another study, using a light source that emits 385–690 nm, Porges et al. found that in skin types II–IV, an immediate erythema was observed which faded within 1 day.⁸⁶ It should be noted that unlike the first study, the light source used in this study did contain a greater output of UVA1. Similar to the first study, the authors also suggested that the erythema response may have represented thermal effects.^67,86

Pigmentation induced by VL

In 1984, Kollias and Baqer used a polychromatic light source of 390–1700 nm to demonstrate that pigmentation could be induced by VL in the absence of significant UVR. They reported that VL at doses greater than 720 J cm⁻² could induce pigment that lasted for up to 10 weeks.⁴⁰ Using a xenon–mercury arc lamp that emits a beam through a grating holographic monochromator to select wavelengths of 334, 365, 405, 435, or 549 nm, Rosen et al. showed through spectrophotometric analysis of skin reflectance that VL, up to 470 nm, can potentially induce an IPD response.⁶⁶ Using a fixed exposure of 45 J cm⁻², Pathak et al. showed that the peak IPD response occurred at wavelengths between 380 and 500 nm.⁸⁷

In a recent study on skin types IV–V, Ramasubramaniam et al. used mid-day sunlight in Bangalore, India with filters to evaluate the cutaneous effects of electromagnetic radiation of wavelengths greater than 420 nm, and wavelengths of less than 400 nm. They reported that the IPD induced by VL is not significantly different from that induced by UVR, and that the shapes of the action spectra of VL and UV induced IPD are similar.⁶⁹ However, compared to VL, UV is 25 times more efficient in inducing pigmentation.⁶⁹ The investigators also found that the PPD response induced by VL is significantly less intense than that induced by UVR; however the similarity of the shapes of the absorption spectra curves indicated that the same type of pigment was being formed.⁶⁹ After analyzing the similarities in the diffuse reflection spectra and decay kinetics of VL and UV induced pigmentation, the investigators concluded that VL and UV likely interact with the same melanin precursor to induce IPD and PPD responses that are similar in nature.⁶⁹ This work corroborates work by Mahmoud et al. who showed that pigmentation can be induced by visible light.⁶⁷ However, Mahmoud's work used artificial light sources while Ramasubramaniam et al. used natural sunlight with filters. In addition, Mahmoud et al. noted more intense pigment that lasted for 2 weeks or more. The studies differed in the dose of visible light applied to the subjects’ skin with Mahmoud using a 4-fold higher dose of visible light than Ramasubramaniam et al.

Porges et al. used a solar simulator that emits radiation in the range of 385–690 nm on individuals with skin types II–IV to show that the threshold dose for IPD is between 40–80 J cm⁻² and that for PPD is greater than 80 J cm⁻².⁸⁶ The IPD faded within 24 h but the tanning response persisted for 10 days.⁸⁶ Using a light source that emits 98.3% VL, a study by Mahmoud et al. showed that in skin types IV–VI, the pigmentary response, which was dark brown in color, was observed immediately and lasted 2 weeks with no signs of fading.⁶⁷ This finding extends the findings of the previous study conducted by Porges, which used a light source that emitted wavelengths between 385 nm to 690 nm.⁸⁶ The difference, however, was that the light source used by Porges et al. was able to induce pigmentation in skin types II–IV while the light source used by Mahmoud et al. that emits close to pure VL was unable to induce significant pigmentation in type II skin. Once again, this finding may be a result of contamination by wavelengths out of the VL spectrum; alternately, it could be related to the very limited infrared radiation present in the study done by Mahmoud et al.⁶⁷

In the study by Mahmoud et al., the pigmentation induced by VL in skin types IV–VI was darker and more sustained in darker skin types, compared to that induced by UVA1.⁶⁷ Confocal microscopy revealed a VL-induced redistribution of melanin, which migrated from the basal layer to the upper epidermal layers. An increased melanin content directly related to the dose of VL light delivered was also revealed via diffuse reflectance spectroscopy.⁶⁷

The clinical relevance of the ability of VL to induce pigmentation, especially in darker skin types, is the possible role of VL in the pathogenesis of photo-induced pigmentary disorders, such as melasma or post inflammatory hyperpigmentation. These conditions are much more pronounced in darker skin types, and it is known that in many, the use of sunscreens, which protect against UVR but not VL, does not fully prevent the progression of these conditions. In fact, in melasma, it has been proposed that even indoor VL is sufficient to cause interaction with potential photoallergens resulting in worsening of hyperpigmentation.⁸⁸

Infrared

Infrared constitutes the wavelengths longer than 760 nm and up to 1 mm. It accounts for approximately 40% of the solar radiation reaching the earth. It has been divided into IR-A (760–1400 nm), IR-B (1400–3000 nm), and IR-C (3000 nm–1 mm). IR-A and IR-B can penetrate the epidermis, dermis, and subcutaneous tissue, whereas IR-C is almost completely absorbed by the epidermis due to the presence of water. Exposure to IR is perceived as heat.⁸⁹

In a recent review on the effects of IR radiation on the skin, Piazena et al. suggest that single exposures to IR are capable of inducing acute changes such as erythema, thermal pain caused by over-warming of tissues, and cardiovascular collapse. The authors also state that excessive and repeated exposures may cause chronic damage such as erythema ab igne and squamous cell carcinoma.⁹⁰

IR can cause temporary erythema lasting less than 1 h. Pujol and Lecha used this temporary erythema to define a standard radiation dose (the minimal response dose) to measure IR radiation.⁹¹ This erythema might be due to vasodilatation secondary to the thermal effect of IR.⁹² At 24 h, there was no observable erythema or pigmentation.⁹¹ Lee et al. suggested the use of a new biological unit to measure IR radiation which they called the minimal heating dose. They exposed the skin of subjects to IR radiation at a fixed irradiance of 2.02 W cm⁻² with a maximum emission at 1100–1200 nm, and they measured the skin temperature every 30 s. The temperature of the skin increased until it reached a plateau at 652 ± 22 s of exposure time. The IR dose when the temperature of the skin reached a plateau was defined as the minimal heating dose. They also found that the minimal heating dose increased on increasing the irradiance of the IR source.⁹²

IR induced photoaging

The cutaneous effects of IR were first suggested by Kligman when she demonstrated that the combination of IR and UV can cause more photodamage than UV alone.⁹³ More recently, studies have investigated the effect of IR-A on photoaging after the introduction of an irradiation device capable of emitting only IR radiation.⁹⁴ The suggested mechanism of photoaging induced by IR includes the induction of MMP-1 without the induction of its inhibitor TIMP-1, which results in the degradation of collagen.⁹⁵ It has recently been shown that chronic heat exposure to the skin may cause skin wrinkling through heat-induced increased expression of matrix metalloproteinases and decreased antioxidant enzyme activity.⁹⁶ Krutmann et al. suggest that IR-induced photoaging may be the result of a disturbance of the electron flow of the mitochondrial electron transport chain caused by IR radiation. The investigators propose that this results in an inadequate energy production in dermal fibroblasts, and that mitochondrial signaling pathways are triggered which result in functional and structural alterations in the skin.⁹⁷ IR has also been shown to stimulate angiogenesis and increase the number of mast cells, both of which have been associated with skin aging.⁹⁴

IR-induced cytotoxicity and DNA damage

Studying the effects of IR on in vivo human skin fibroblasts, Menezes et al. demonstrated that IR irradiation induced a long lasting partial protection from UVA- and UVB-induced cytotoxic damage.⁹⁸ Several studies have investigated the relationship between IR exposure alone and DNA damage, however none have found a positive association.^90,98,99 Using a mouse model in which in vivo mouse skin and in vivo mouse keratinocytes were analyzed, Jantschitsch et al. found that exposure with IR-A prior to UVB exposure decreases UVB-induced apoptosis and UVB-induced DNA damage.⁹⁹ This finding confirmed the earlier finding of Frank et al. who revealed that IR exposure decreased UVB-induced DNA damage using in vitro human skin fibroblasts.^90,100

IR-induced oxidative stress

Several studies have investigated the association between IR exposure and oxidative stress. Studying in vitro human skin cells, Applegate et al. found no IR-A induction of oxidative stress proteins.¹⁰¹ In contrast, Schroeder et al. found that IR-A exposure causes a decrease in antioxidant content in human skin.⁹⁵ Several years later, Zastrow et al. and Darvin et al. confirmed these findings when they reported an IR induced increased free radical formation in human skin.^102,103 Zastrow et al. and Darvin et al. proposed that the observed free radical formation may be influenced by the temperature increase that occurred during IR irradiation. Jung et al. examined the effect of heat stress on the association between IR and free radical formation in an in vitro human fibroblast model. They found that IR exposure at a temperature of 37 °C did not induce free radicals, however, at temperatures of 39 °C or higher, free radicals were induced.¹⁰⁴

Conclusion

The biologic effects of the interaction of UVR, VL, and IR with skin, namely, erythema and pigmentation induced, are influenced by a variety of factors. Different spectra of UVR induce unique effects on the localization of melanin within the epidermis, and changes in epidermal structure and thickness. The time course of exposure, specific chromophores, dosage of each wavelength, constitutional skin type, and pre-exposure skin pigmentation all play a role in this interaction. VL is now known to induce erythema and pigmentation in dark skinned subjects. Erythema induced by IR is well documented. More studies still need to be done on the cutaneous effects of VL and IR.

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Footnote

† This article is published as part of a themed issue on current topics in photodermatology.

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