Update June 20, 2019
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Sunburn is an acute inflammatory response of the skin, predominantly to UV-B.
Generally, an individual’s ability to tolerate sunlight is inversely proportional to that individual’s degree of melanin pigmentation.
Melanin, a complex polymer of tyrosine derivatives, is synthesized in specialized epidermal dendritic cells known as melanocytes and is packaged into melanosomes that are transferred via dendritic processes into keratinocytes, thereby providing photoprotection (dissipating the vast majority of absorbed UVR in the skin) and simultaneously darkening the skin. Sun-induced melanogenesis is a consequence of increased tyrosinase activity in melanocytes.
Central to the suntan response is the melanocortin-1 receptor (MC1R), and mutations in this gene contribute to the wide variation in human skin and hair color; individuals with red hair and fair skin typically have low MC1R activity.
In the skin there are two main types of melanin: eumelanin (providing brown and black pigmentation associated with high MC1R activity) and pheomelanin (providing red pigmentation associated with low MC1R activity).
Pheomelanin is a cysteine-containing red polymer of benzothiazine units and has much weaker shielding capacity against UVR compared to eumelanin. This may explain why individuals with a higher proportion of pheomelanin (red hair/fair skin appearance) have an increased risk of melanoma formation. In addition, pheomelanin may also promote melanoma formation through induction of oxidative damage by amplifying UV-A-induced ROS but also through UVR-independent mechanisms.
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Genetic studies have revealed additional genes that influence skin color variation in humans, such as the gene for tyrosinase (TYR) and the genes APBA2[OCA2], SLC45A2, and SLC24A5. The human MC1R gene encodes a G protein–coupled receptor that binds α-melanocyte-stimulating hormone (α-MSH), which is secreted in the skin mainly by keratinocytes in response to UVR. The UV-induced expression of this hormone is controlled by the tumor suppressor p53, and absence of functional p53 attenuates the tanning response. Activation of the melanocortin receptor leads to increased intracellular cyclic adenosine 5′-monophosphate (cAMP) and protein kinase A activation, resulting in an increased transcription of the microphthalmia-associated transcription factor (MITF), which stimulates melanogenesis. Since the precursor of α-MSH, proopiomelanocortin produced by keratinocytes, is also the precursor of β-endorphins, UVR may result in not only increased pigmentation but also in increased β-endorphin production in the skin, an effect that has been hypothesized to promote sun-seeking behaviors and even mediate addiction to tanning. The Fitzpatrick classification of human skin phototypes is based on the efficiency of the epidermal-melanin unit, which usually can be ascertained by asking an individual two questions: (1) Do you burn after sun exposure? (2) Do you tan after sun exposure? The answers to these questions permit division of the population into six skin types, varying from type I (always burn, never tan) to type VI (never burn, always tan) (Table 57-1).