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SUMMARY ARTICLE
A Primer on Pigmentation
David G. Greenhalgh, MD, FACS
There is at least a temporary loss of skin pigmentation with all but first-degree
burns. Commonly, pigment changes persist for months, and sometimes, permanent
changes in skin color add to the ultimate change in appearance that commonly affects
burn patients. There are many different treatment modalities for the treatment
of pigment changes, but most of them have little scientific basis and often lead to
disappointing results. The purpose of this review is to discuss the molecular and
cellular mechanisms of skin pigmentation, mechanisms of repigmentation after
burns, treatment options for dealing with pigmentation changes, and advice for
dealing with the sun after burn injury. (J Burn Care Res 2015;36:247–257)
There are significant pigmentation changes that occur
after a burn injury. Anyone who suffers from a seconddegree (partial-thickness) burn loses the outer most
layer of skin—the epidermis. Because the epidermis
contains our pigment, second-degree or deeper burns
that heal spontaneously are initially pink and unpigmented. The purpose of this review is to discuss what
determines the color of skin and how wounds regain
pigmentation. Treatment options for pigmentary
changes are also discussed. Another confusing issue is
how a burn survivor should deal with sun exposure.
Some burn patients have been told to totally avoid the
sun for a year or even for their lifetimes. Others are told
that sun exposure is acceptable if they use some type of
protection. What is the right approach? This review will
provide the reader with some of the concepts behind
managing repigmentation after burn injury.
PIGMENTATION
The color of our skin is determined by four pigments: melanin (brown/black), carotene (yellow),
oxygenated hemoglobin (red), and reduced hemoglobin
(blue).1 The main pigment, melanin, is found in the
bottom of the epidermis.2–6 Melanin gives skin the
From the Shriners Hospitals for Children Northern California,
Sacramento; Firefighters Regional Burn Center at University
of California, Davis; and Department of Surgery, University of
California, Davis.
Address correspondence to David G. Greenhalgh, MD, FACS, 2425
Stockton Blvd., Sacramento, California 95817. Email: david.
[email protected]
Copyright © 2014 by the American Burn Association
1559-047X/2015
DOI: 10.1097/BCR.0000000000000224
brown or black pigment that defines our skin color—
ranging from white to black. There are two types of
melanin produced—eumelanin (black-brown) and
pheomelanin (yellow-red), which explains the varied
colors of people. The other pigments play a lesser role
in skin color. Carotene, a byproduct of vitamin A,
is found in the dermis and epidermis and provides
yellow coloring. Eating too many carrots can lead to
an accentuation of the yellow color. Carotene is the
main pigment of feathers, whereas melanin dominates skin and hair pigment.6 Although the process
is influenced by skin perfusion, hemoglobin appears
either red if it is oxygenated (such as with blushing)
or blue when not oxygenated or reduced (such as
when people are cold). Pathologic processes may also
affect the color of skin. Because of shifts in dermal
blood supply, people often appear gray or green after
syncope. Yellow skin may be the result of too much
bilirubin (icterus) that occurs with biliary obstruction or cirrhosis. Hemosiderin and other products of
excess iron that are deposited in the tissues in chronic
venous stasis also lead to hyperpigmentation.5
The predominant pigment of skin and hair is
melanin. The biochemistry of melanin production
is well described but relatively complicated.2–4,6–8
The ultimate precursor is tyrosine, which undergoes hydroxylation by a copper-dependent
enzyme called tyrosinase (TYR) to produce β-3,4dihydroxyphenylalanine (DOPA), which then
leads to DOPAquinone. From DOPAquinone, the
pathway splits to synthesize either eumelanin or
pheomelanin. For the eumelanin pathway, DOPAchrome is created by spontaneous oxidation and then
two key enzymes DOPAchrome tautomerase (DCT,
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248 Greenhalgh
also known as tyrosine-related protein-2 [TYRP2])
and tyrosine-related protein-1 (TYRP1), which ultimately lead to the synthesis of eumelanin (­ Figure 1).
If DOPAquinone acquires cysteines through a
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separate pathway, pheomelanin is produced. The
first reaction using tyrosinase is the rate-limiting step
for all melanogenesis. TYR, TYRP1, and TYRP2 are
essential for melanin production. A related pigment
Figure 1. The biochemical and cellular pathways of melanosome production in response to UV light. Ultraviolet (UV) light exposure to a keratinocyte that overcomes the protection of melanosomes (brown/black ovals) leads to DNA stress. Sunscreen and
protective clothing inhibit this reaction. DNA stress leads to proteins, such as p53, that assist with DNA repair and, at the same
time, lead to production of proopiomelanocortin (POMC). POMC is the precursor of α-MSH, which is secreted from the keratinocyte and binds to its receptor (MC1R). MC1R activation increases adenyl cyclase to produce cAMP. Epinephrine binding to
the β-adrenergic receptor (betaAR) also increases adenyl cyclase activity, whereas UV light activates bone matrix protein receptors
to inhibit the activation. Many other cytokines (described in the text) influence the activity of melanin synthesis. cAMP activity is
prolonged by inhibiting its breakdown through phosphodiesterase 4D3 inhibitors (PDEI4). cAMP then activates protein kinase
A (PKA) to phosphorylate CREB, which then binds to the CREB responsive element (CRE) to produce the main activator or
melanin production (MITF). Signaling through steel factor which binds to the receptor cKIT produces MAP kinases that in turn
phosphorylate MITF to produce tyrosinase (TYR), TYRP1 (or DCT), and TYRP2. Tyrosinase is the rate-limiting enzyme for converting tyrosine to DOPA and DOPAquinone. Dopaquinone can either take on cysteines to lead to the red pigment pheomelanin or
with the use of TYRP2 and TYRP1 produce the brown/black pigment eumelanin. Melanosomes start off as empty lysosome-like
structures (stage 1) that pick up either pigment at stage 2. The pigments are then concentrated into stage 3 and stage 4 melanosomes as they travel up actin filaments with the assistance of kinesin/myosin motors to the tip of dendrites. The keratinocyte has
special receptors called protease-activated receptor-2 (PAR2) that accept the melanosomes. The melanosomes are then transferred
to the keratinocyte by processes resembling phagocytosis. Once in the keratinocyte, the melanosomes are transferred to above the
nucleus to provide more protection from UV light—leading to a tan.
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“neuromelanin” is produced by dopaminergic neurons in the substantia nigra of the brain. These central nervous system cells are similar in origin to the
cells (melanocytes) producing pigment in the epidermis. Slight variations (polymorphisms) in the
structure of all of these proteins and enzymes lead
to the various colors of skin. Various defects in the
same molecules or their biochemical pathways lead
to all sorts of congenital pigment abnormalities, such
as albinism, that are well described in other reviews
(and will not be covered here).2–4,6–8
Specialized cells called “melanocytes” synthesize
melanin. These cells are derived from “melanoblasts”
that form in the second month of embryonic life.2,3
Melanocytes are derived from the neural crest of the
dorsal most point of the developing neural tube.
Melanoblasts then migrate to the dermis by 10 to 12
weeks and to the epidermis around 12 to 14 weeks
of gestation. Melanoblasts are directed by specific
receptors (especially the cKIT receptor) that recognize specific target ligands—“steel factor” to migrate
to their ultimate resting site in the skin. Once the
melanoblasts arrive at the skin (as early as 50 days
gestation), they differentiate into melanocytes. The
dermal melanocytes gradually decline in numbers,
whereas the epidermal melanocytes proliferate and
become established at the epidermal–dermal junction and start producing melanin by 4 months and
are well established by 6 months gestation. As people
age, their melanocyte numbers remain constant until
the fourth to fifth decades when their numbers gradually decrease.9
Melanin is stored in special cell organelles called
“melanosomes” that have a lysosome-like structure.
Melanosomes are included in a family of cell-specific organelles “lysosome-related organelles” that
contain acid-dependent hydrolases and lysosomalassociated membrane proteins.4 Included in the family of lysosome-related organelles are lytic granules
of cytotoxic T lymphocytes and natural killer cells,
major histocompatibility complex class II compartments seen in antigen-presenting cells, platelet-dense
granules, basophil granules, azurophil granules of
neutrophils and Weibel-Palade bodies of endothelial
cells.4 Melanosomes undergo four stages of development2–8 (Figure 1). They are assembled in the perinuclear region near Golgi stacks where they receive
all of the enzymes and structural proteins required to
make melanin. In Stage I, they are essentially empty
vacuoles that start to form intraluminal fibrils. In
Stage II, the intraluminal fibrils develop a meshwork
and they pick up tyrosinase and an essential structural protein—Pmell7. In Stage III, melanin is synthesized and deposited on the intraluminal fibrils.
Greenhalgh 249
Stage IV melanosomes are full of melanin and have
minimal tyrosinase activity. The structure and size of
melanosomes vary depending on whether they have
eumelanin (elliptical) or pheomelanin (round). The
melanocytes are then ready to distribute their melanosomes packages to the keratinocytes.
Melanocyte viability and melanin production are
regulated through several factors.2–4 Signals produced in response to inflammation have profound
effects on pigmentation, which may explain some of
the hyperpigmentation we see in burn patients.3,10
Endothelin-1, steel factor (also known as stem cell
factor), inflammatory mediators (prostaglandins
[PGE2, PGF2α] and leukotrienes), neurotrophins,
fibroblast growth factor-2 (basic fibroblast growth
factor), hepatic growth factor, granulocyte-macrophage colony stimulating factor, leukemia inhibitory factor, nitric oxide and catecholamines have all
been shown to influence melanocyte viability and
function. Melanin production is regulated through
the melanocortin-1 receptor (MC1R) (Figure 1).
There are seven melanocortin receptors but only
MC1R is involved in pigmentation. A related receptor, MC4R, is found in the hypothalamus and is
involved in energy metabolism.2 MC1R is found in
many species of animals and thus has an evolutionary role in the pigmentation of skin, hair, feathers,
and other ectodermal structures. MC1R is a seventransmembrane G-protein-coupled receptor that,
when bound, leads to activation of adenylyl cyclase
leading to cyclic adenosine monophosphate (cAMP)
production (Figure 1). cAMP then leads to phosphorylation of cAMP responsive-element-binding
protein transcription factor family members. cAMP
responsive-element-binding protein then binds on
to its response element (CRE) to produce microphthalmia transcription factor (MITF), which is pivotal
to the production of the many pigment enzymes and
differentiation factors. There are many (at least 30)
allelic variations in the structure of MITF that have
a profound influence on the variability in pigmentation in people.2–4
The two major agonists for MC1R are
α-melanocyte-stimulating hormone (α-MSH) and
adrenocorticotropic hormone (ACTH)2–8 (Figure 1). Both α-MSH and ACTH are derived from
proopiomelanocortin (POMC), which is produced
in the pituitary and also in the skin and especially
the hair follicles. As a side effect, adrenal insufficiency, which leads to increased ACTH, can lead
to increased pigmentation. POMC also is a precursor for β-endorphin; therefore, conceptually there
could be a link between pain signaling and pigmentation.11 α-MSH, however, is the main regulator
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250 Greenhalgh
of pigmentation. α-MSH has also been reported
to increase melanin production independently of
MC1R by blocking the inhibitor of tyrosinase [6(R)l-erythro-5,6,7,8-tetrahydrobiopterin (6BH4)]. There
is an inhibitor of MC1R transduced through the
Agouti (ASIP) gene, which produces “agouti signal
protein” that reduces the color of hair in mice and
pigmentation in people.2,4
Melanocytes reside in the bottom-most cell layer
of the epidermis (the basal layer) where they spread
out cellular “arms,” called “dendrites,” that distribute melanosomes to keratinocytes of the bottom
two layers of the epidermis2–8 (Figure 2). There are
several parallels for neurons and melanocytes. Both
cells, which are derived from the neural crest, have
the ability to create multiple dendrites to “communicate” to other cells. Neuron dendrites communicate to other neurons in the periphery and central
nervous center and melanocytes communicate to
their target cell, the keratinocyte. Each melanocyte
is associated with an “epidermal melanin unit” with
one melanocyte linking to roughly 40 keratinocytes
in the basal and suprabasal epidermal layers. The
mechanism of transfer of melanin to the keratinocytes has been extensively studied and again resembles protein transit in neurons.2–8 Melanosomes are
transferred on microtubules that are associated with
two microtubule-associated “motor proteins”—
kinesin and dynein. Kinesins attach melanosomes to
the microtubules and transfer them centrifugally to
the tips of the dendrites. Dyneins carry the empty
organelles centripetally back to the center of the cell.
Myosin-Va “captures” the melanosome on to the
actin of the microtubule and is required for delivery to the distal end of the dendrite. Other proteins
Rab27a and melanophilin participate in the transport process.2–4,12
The melanocyte transfer process depends on a
keratinocyte seven-transmembrane G-protein coupled receptor called “protease-activated receptor-2”
(PAR-2).2,12,13 PAR-2 increases phagocytosis of
melanosomes and ultraviolet (UV) light increases its
activity. The transfer occurs by several mechanisms:
exocytosis, cytophagocytosis, and fusion.7 Exocytosis
involves fusion of melanosomes with the melanocyte
cell membrane with ultimate release of melanosomes
into the intracellular space and phagocytosis by the
keratinocyte. Cytophagocytosis involves phagocytosis of the tip of the melanosome dendrite followed by
fusion to a lysosome, which releases melanosomes.
Fusion occurs when the melanocyte dendrite fuses
with the keratinocyte cell membrane to transfer
David Greenhalgh
Figure 2. Melanocytes (yellow) exist in the basal (bottom) layer of the epidermis and have multiple dendrites that transfer
melanosomes to sites above the nucleus of keratinocytes (grey) to protect their DNA from UV light.
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melanosomes. Finally, recent evidence demonstrates
that filopodia are used during the transfer of melanin.14 Melanin is then distributed in “caps” above
the nucleus of the keratinocytes, which protects the
nuclear DNA from UV light.
All people have a similar number of melanocytes
but pigmentation varies based on the number and
size of melanosomes distributed to the keratinocytes.
Highly pigmented people have larger melanosomes
that are filled with more melanin and are found in
higher density than those of lighter pigmentation.
Darker pigmented people also have increased activity
of PAR-2, leading to more rapid transfer of melanosomes. The type of melanosomes, along with
their density, is determined genetically. As will be
described later, melanin production is also increased
in response to sun exposure. It is also interesting
to consider evolutionary theories of the development of different degrees of pigmentation in people.
One concept is that pigmentation is a compromise
between the need for sun exposure to complete the
final step in vitamin D synthesis and the need to protect the skin from the harmful effects of UV light.15,16
People who are chronically exposed to sun such as
at the equator have plenty of exposure for vitamin
D production but need more protection from UV
light—thus they have darkly pigmented skin. Those
people who have little sun exposure, especially those
people in the more northern or southern latitudes,
have evolved to produce less pigment to allow for
the limited sun exposure to produce vitamin D.
Thus, these people have pale skin that is at greater
risk for sun-related damage.
REPIGMENTATION BURN INJURY
Any burn that is partial-thickness or deeper destroys
the epidermis of the skin. Because melanin exists in
the lower levels of the epidermis, the pigment is lost.
Surprisingly, very little is written about the repigmentation process after injury.5,17–19 Much more is
published related to the repigmentation of vitiligo.
Partial-thickness burns heal by having the bottom layer of keratinocytes in the epidermis (called
the basal cell layer) migrate over the surface of the
wound. Migration from the wound edge can only
occur for about 1 inch, which explains why fullthickness wounds heal more by contraction and scar
formation than by re-epithelialization. In partialthickness wounds, however, the remaining dermis
contains hair follicles, oil, and sebaceous glands,
which contain the same epithelial cells (called keratinocytes) that migrate out of the follicle (or gland)
and spread over the dermis to resurface the area.
Greenhalgh 251
These “epithelial buds” spread over the wound to
create a new but unpigmented skin. The re-epithelialized skin has a new epithelial layer that protects
against water loss and thus is dry but pink due to the
loss of pigment and increased vascularity of freshly
“healed” skin.
There has been a debate about how melanocytes
migrate from the wound edge.5 Some have said that
melanocytes migrate along with the leading edge of
keratinocyte and then later synthesize melanin. Others say that there is a lag in melanocyte migration
that occurs after re-epithelialization. Chadwick et al
performed histologic studies of the healing of differing depth wounds (incisions, partial-thickness,
and full-thickness wounds) and followed melanocytes with special stains. They found that at 35 days
there was complete repopulation of melanocytes in
the basal layers of the epithelium of the partial-thickness wounds but not in the full-thickness wounds.
They concluded that there were different types of
repigmentation that occur in wounds—from migration from the wound edge and from skin adnexa. In
addition to the epidermis, melanocytes also exist in
hair follicles but their main role in uninjured skin is
to pigment hair.19 Melanocyte stem cells reside in the
“bulge” of the hair follicle, whereas mature melanocytes (but not stem cells) exist in the “bulb” or
bottom. The bulge is near the area of the sebaceous
gland and erector pili muscle of the hair follicle. Just
as for keratinocytes, melanocytes migrate from hair
follicles and other skin adnexa to repopulate the
new epithelium. Melanocyte migration to the lower
levels of the new epithelium or, at least, melanocyte
distribution of melanosomes to keratinocytes always
lags after re-epithelialization by weeks to months.
One will initially observe brown dots at the hair follicles that enlarge and gradually coalesce to form
new pigment (Figure 3). The reason for the delay
in pigmentation is not known. One could speculate,
however, that melanocytes first need to repopulate
the new skin, then synthesize melanin, and then distribute melanosomes to neighboring keratinocytes.
It is also conceivable that the first priority of new
keratinocytes is to set up a “barrier” before accepting
melanosomes. Later, after differentiation has started,
they will accept melanosomes to repigment freshly
healed skin.
The regulation of hair growth, type (straight or
curly), and color is highly regulated and influenced
by genetics.20,21 At least 150 genes influence the
type and color of hair. If one considers the multitude of hair colors and patterns of various animals
such as zebras and leopards, then it is clear that
the regulation of hair color is extremely important.
252 Greenhalgh
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Figure 3. Serial pictures of a thick split-thickness skin graft donor site that has re-epithelialized and shows the stages of repigmentation. (A) At 20 days after harvest, the donor sites have clear islands of pigmentation that correlate with hair follicles.
(B) At day 41, the donor site has various stages of repigmentation with some dark areas and pinker areas with clear pigmentation islands. There is an area of pigment loss that resulted from a sheer injury on the medial side of the donor site. (C) At 62
days after harvest, the donor site reveals marked hyperpigmentation that is associated with some hypertrophic scarring on the
lower edge. Delayed healing and possible excessive inflammation may have contributed to the hyperpigmentation. The series
of pictures demonstrate that there is little control in the extent of return of pigmentation.
Melanocytes give hair its color, but the melanocytes
of hair follicles are different than in skin. Hair follicle melanocytes are larger and have longer dendrites than in epidermis.20 They also produce larger
melanosomes—thus explaining why skin pigment
is often lighter than hair color (such as a Caucasian
person with black hair). This fact also explains why
hair turns gray, although skin pigment does not
change color. In addition, “hair” melanocytes only
synthesize melanin during the anagen phase of hair
follicle life cycle. Delayed skin repigmentation could
be related to these cellular differences. It is conceivable that melanocytes need to “reprogram” from a
“hair pigmenting” to “skin pigmenting” phenotype
during the re-epithelialization and repigmentation
of wounds. Another possibility is that the hair follicle involved in resurfacing the wound must enter
anagen before initiating melanin synthesis. Anagen could be delayed because of the hair follicle’s
re-epithelialization activities.
The deeper the wound, the slower the repigmentation process and very deep wounds may never regain
pigment. The entire repigmentation process often
takes over a year to be completed. During this time,
sun exposure may alter the extent of pigmentation—
this is why burn patients are advised to be careful with
sun exposure during the repigmentation phase. Too
much exposure may lead to darker skin than the surrounding areas. Although most people advocate being
careful with sun exposure, one burn group suggested
that sun exposure might improve outcomes.22
Unfortunately, we do not have much control over
the extent of repigmentation; therefore, there is
often a color difference in the healed burn wound.
The deeper the burn, the more difficult it is to get a
good color match. Influencing the extent of the final
pigmentation is difficult. Some patients have lighter
areas while others have darker areas. For obvious reasons, light-colored people have fewer problems with
color differences than darker-pigmented people.
Because the re-epithelialized wound has no pigment,
those patients with little pigment have less contrast
in color difference. Darkly pigmented people have
marked contrasts between normally pigmented skin
and the unpigmented wound. Therefore, a darkly
pigmented person with minimal hypertrophic scarring still has a very noticeable color contrast which
can lead to significant quality of life issues.
Inflammation influences pigmentation, therefore
infection or delayed healing, which increases cytokine expression, can lead to excessive pigmentation.
One way to reduce hyperpigmentation is to limit the
extent of sun exposure until repigmentation is complete. Unfortunately, his concept is often carried to
the extreme. Patients may be told that they should
never go out in the sun during repigmentation, and
some have reported to me that they were told never to
go in the sun for the rest of their lives. Such extremes
are counter to our major goal in burn care, which is
to have a burn survivor return to as normal activity
as possible. Patients and caregivers should use common sense when dealing with the sun. More caution
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should be used during the early stages of healing—
such as keeping areas covered or using adequate sun
block. Patients should avoid prolonged exposure
and minimize going outside during peak sun hours
(10:00 to 4:00). Eventually, they should return to
normal activities, and like all people (burn or not),
they should be careful with sun exposure. Questions
arise as to whether burn patients are at increased risk
for sun-related skin cancers than uninjured people?
This question has not really been investigated, but
currently, there is no evidence of increased risk for
skin cancer from sun exposure. The risk for developing Marjolin’s ulcers is related to chronic nonhealing
wounds, not sun exposure.
TREATMENT OF HYPOPIGMENTATION
The options for treating pigmentation changes are
limited.23,24 Currently, the main way to repigment
areas that lack color is to create a new wound—
usually with dermabrasion—and then place a new
graft at the site.23,24 Skin grafts carry pigments
to the new site. One can even completely excise
the hypopigmented area and place a new graft,
but that is an extreme treatment. Some surgeons
have reported applying epithelial autografts after
dermabrasion with improved pigmentation.25 The
application of noncultured epithelial cells has had
mixed results by other surgeons.26 People will also
tattoo hypopigmented areas, but it is hard to get
a good color match and tattoos tend to fade with
time. One can also use sun tan lotions that “create
instant tans,” but they are obviously temporary. A
novel approach that is in its infancy is to use agonists that augment the UV signaling pathway but
avoid the risks of UV exposure.27 The concept is
to use activators of the α-MSH receptor (MC1R)
(Figure 2). These “analogs” of α-MSH have been
developed and are often more potent than α-MSH
itself. Other strategies target other sites in the UV
signaling pathway.27 Drugs that increase cAMP
(adenylate cyclase activators or phosphodiesterase
inhibitors) are being tested as agents that increase
pigmentation. One must wonder, however, whether
manipulating such universal signaling agent is
worth the potential side effects. Finally, investigation into the pharmacologic manipulation of the
key pigmentation transcription factor (MITF) is
underway.27 Studies of these novel pharmacologic
agents are in their infancy.
One should also know that there is no melanin in
the palms or soles of the feet; therefore, skin grafts
harvested from all areas except for the palm or sole
will leave a pigmented graft in those areas. Some
Greenhalgh 253
surgeons advocate that palm grafts be harvested
from the sole of the foot to avoid pigmentation,
but the quality of that skin is poor. Other sources
of full-thickness, while leaving pigment, have much
better qualities in texture and flexibility. Another
interesting finding is that autologous composite skins that are placed on patients do not have
melanocytes and thus usually have no pigment or
islands of pigments that are probably the result of
isolated melanocytes remaining in the wounds.28
Even 4:1 meshed autografts carry melanocytes that
lead to a relatively uniform color. It is also important to know that when grafting the face, skin
harvested from below the clavicle is yellower than
skin from above the clavicles. Skin harvested from
below leads to obviously darker and yellower grafts
that persist for life. Skin harvested from above, the
scalp, for instance, matches the color of the rest of
the face well.
TREATMENT OF HYPERPIGMENTATION
For an unknown reason, skin grafts often become
darker than the surrounding skin. Studies in mice
suggest skin grafts have increased melanocyte numbers and increased melanocyte activity.29 The treatment of hyperpigmentation has received more
investigation than for hypopigmentation. The main
strategy is to inhibit the enzymes of melanogenesis.30
The most well-known therapy is to inhibit tyrosinase
activity with hydroquinone creams. Dark skin can
be lightened using creams containing hydroquinone
creams, but the extent and uniformity of lightening
is not controlled and the results are often disappointing. There are other inhibitors of tyrosinase that are
well described in an excellent review.30 These targets
for hyperpigmentation treatment include other key
enzymes such as TYRP-1 and TYRP-2. MITF activity may also be manipulated to reduce pigmentation
(as opposed to increasing pigmentation as described
above).30 Finally, lasers are increasingly being used
to reduce pigmentation in burn patients.31 Research
into the control of pigmentation after burns would
significantly benefit burn survivors.
TANNING
It is well known that sun exposure increases pigmentation, a process called “tanning.” Skin can be
damaged by all wavelengths of light, from infrared
to UV. Of the light striking the surface of the earth,
56% is infrared light (wavelength 780–5000 nm),
39% visible light (wavelength 400–780 nm) and 5%
UV light.32 The greatest concern for skin damage,
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254 Greenhalgh
however, comes from UV light. How UV light
affects tissues is complicated.27,32–34 There are three
types of UV wavelength that reach the ground. UV
C light (UVC: wavelength 190–280 nm) is filtered
by the ozone layer in the stratosphere and is usually
not a major problem. UV B light (UVB: wavelength
280–320 nm) is the main source of concern in the
skin. UV A (UVA: wavelength 320–400 nm) is the
third type to reach the surface and it also injures
skin. The ratio of UVA to UVB light is 20:1. Because
UVA light has a longer wavelength, it is not affected
as much by altitude, latitude, or atmospheric conditions as UVB light. UVA light is also not filtered by
regular glass and penetrates farther into the skin.
UV light will lead to erythema that is well known
as “sunburn.” UVA light has 1000-fold less erythema-inducing effects compared with UVB light.
Within seconds of exposure, UVA and visible light
will lead to “immediate pigment darkening” that
is caused by photo-oxidation of existing melanin
stores. At higher UVA levels, “persistent pigment
darkening” will be found within 2 to 24 hr, which
is also caused by photo-oxidation of melanin. UVB
light will produce erythema (redness), “sunburn,”
as early as 4 hr and peaks after 8 to 24 hr of exposure. It also causes photochemical damage to DNA
and is thus involved in “photoaging” (thinning,
wrinkling, sagging, and other changes due to sun
exposure). All forms of light (especially UVB light)
cause “delayed tanning” by increasing melanocyte
numbers, enhancing tyrosinase activity, and stimulating melanin production. This “delayed tanning”
starts 2 to 3 days after exposure, peaks at 3 weeks
and does not return to the original color until 8 to
10 months later. No tanning occurs unless there is
erythema in the skin. In addition to tanning, UVB
light exposure increases skin mitotic activity to
cause a doubling of thickness of the dermis and epidermis. UVA light does contribute to photoaging,
and it is a likely contributor to the development of
skin cancers. UVB light is also tied to the formation of skin cancers, although the relationship is not
clear because it seems that UVB light increases the
chances of one type of skin cancer (squamous cell)
and may not be as great a factor in inducing other
types (basal cell and melanoma). Evidence now
indicates that visible light along with infrared light
also injures the skin.35 UVB light does have a beneficial effect—it stimulates vitamin D synthesis in the
epidermis. Only a small area needs to be exposed,
and only 5% of the light needed to produce redness
is needed for Vitamin D production.
Melanosomes are placed above the cell nucleus
and act as barriers to harmful UV light. It makes
sense that melanin is in the epidermis because this
outer layer protects the underlying tissues from
harmful light. Melanin, strategically located above
the nucleus, absorbs the harmful UV light before
it reaches the nucleus (and thus the DNA) to protect the skin. Exposure stimulates the melanocyte
to produce hormones (in a simplified version—
POMC a precursor of α-MSH) to stimulate melanocyte growth and melanin production (Figure 1).
Melanin also neutralizes reactive oxygen species
that cause damage to DNA. It absorbs, scatters,
photo-oxidizes, and scavenges these reactive free
radicals. It was once believed that darker pigmentation offered protection from light damage but
darker skin is also damaged from UV light. Pheomelanin is a little more active as an antioxidant
than eumelanin but they are both effective. Tanning does increase the “sun protection factor (SPF)
of skin by 3.”32
SUN PROTECTION
The main reason for sun protection is to reduce
skin cancers. Skin cancer affects over two million
people in the United States annually.36,37 Despite the
high risk of skin cancer, a recent National Ambulatory Medical Care Survey revealed that using sunscreen was mentioned by primary care doctors to
only 0.07% of patients during their visits.38 Dermatologists recorded the mention of sunblock in only
1.6% of their patient visits.39 The U.S. Preventive
Services Task Force found that there was sufficient
evidence to support sun protective counseling for
fair-skinned patients between the ages of 10 and 24
yr, but failed to find evidence to support counseling
in patients greater than 24 years of age.36 An editorial in response to these reports suggested that there
is clear evidence to support sunblock use in Australia and that performing evidence-based studies to
prove efficacy is an extremely difficult proposition.39
It is extremely difficult to perform any evidencebased studies for any treatment in burns; therefore,
it would seem ludicrous to wait for evidence before
suggesting the use of sunblock in burn patients. In
my experience, however, the discussion of sunblock
use with burn patients is prevalent in clinics managing burn patients.
Sun protection strategies can be divided into environmental, physical, and chemical. The environmental protection strategies follow common sense.4,32–34
Approximately 50% of the total daily solar UV dose
reaches the ground between noon and 3:00 pm.
Therefore, it is recommended that people at risk
(such as burn patients) avoid direct exposure during
Journal of Burn Care & Research
Volume 36, Number 2
those hours or as the American Academy of Dermatology suggests—between 10:00 am and 4:00 pm.40
Ozone absorbs large amounts of UVB and UVC
light but little or no UVA or visible light. The loss
of the ozone layer is a major concern for increasing
skin cancer risks. Elevation above sea level also influences the extent of UV exposure. For every 300 m
in elevation, there is an increase in UV light exposure
of 4% near sea level that increases to 8% to 10% in
the higher elevations (such as for skiers). For every
degree of change in latitude, there is a 3% increase in
UV exposure so that the highest risk is at high elevations near the equator.41 Some other interesting facts
are that fog, haze, or clouds can reduce UV exposure
by 10% to 90% but sunburns still occur. Snow, sand,
and metal can reflect up to 90% of UV light. Sea
water can reflect up to 15% but pool water does not
reflect much light. UV light will penetrate around
1 m into water so swimmers are at risk. Shade is an
obvious environmental protector from sunlight, but
there is less protection from a beach umbrella than
dense foliage.
The main physical sun protection is from photoprotective clothing. There is a large variation in the
protective effects of clothing. A light-colored cotton shirt provides only a SPF of 10. It is reported
that one third of summer clothing had an UV protection factor (UPF—a measure of total UVA and
UVB light blocked) of 12 to 15.4,33 In Australia and
New Zealand where skin cancers are very prevalent, there is a standard that clothing must have a
UPF of at least 15. In Europe, there are also standards to keep clothing at a UPF of 40. There is no
sun protection standard for clothing in the United
States. The characteristics of the clothing influence
the extent of sun protection.32,33 Loose fitting, dry
clothing with tightly woven, thicker, darker, and
unbleached fabrics offer more protection. Denim,
wool, and synthetic fabrics or those treated with an
UV absorber are also safer. Loosely woven, lighter
colored (bleached), and thinner fabrics have less
protection from the sun. There is less UV light protection from cotton, linen, acetate, and rayon clothing than other materials. Wet clothing provides less
protection by allowing light to pass through the
gaps in the threads. There are specially manufactured clothes designed to reduce sun exposure and
laundry additives that absorb UV light. How much
more effective they are than carefully chosen “regular” clothes is not known. Wide brim hats provide
mild protection to the face and neck. A hat with a
brim greater than 7.5 cm wide increases the SPF of
the nose 7, cheeks 3, chin 2, and neck 5. The protection is less for smaller brimmed hats.32
Greenhalgh 255
Chemical protection is offered by topical sunscreens which are divided into inorganic and
organic forms. Inorganic sunscreens include zinc
oxide and titanium dioxide. These agents both
reflect and absorb UV and visible light. Zinc oxide
has been found to be more effective than titanium
dioxide. The inorganic sunscreens are effective but
they are less cosmetically acceptable because they
are obviously white on the skin. Organic sunscreens
absorb UV radiation and are divided into UVB
absorbers, UVA absorbers, and broadband absorbers (absorbing UVA and UVB light). UVB absorbers have been available for many years, but recent
evidence suggests that UVA light is also involved in
the development of skin cancers. Therefore, there
are currently sunscreens that absorb both UVA
and UVB light. The effectiveness of sunscreens is
measured by the SPF.33 SPF is defined by the sun
radiation dose (mainly UVB) required to produce
the minimum erythemal dose (MED – the threshold
dose that can produce sunburn) after application of
2 mg/cm2 of sunscreen divided by the dose producing
1 MED on unprotected skin. Therefore, an SPF of 2
absorbs 50% of UV radiation; SPF 8 absorbs 87.5%,
SPF 16 absorbs 93.6%, and SPF 32 absorbs 96.9%.
Note that after an SPF of 30, there is little increase
in effectiveness in sunscreens at higher SPFs. There
is no standard way to measure effectiveness of UVA
radiation blockade. Australia and New Zealand
do use standards to claim that a product provides
“broad spectrum” protection. An 8-μm layer must
not transmit more than 10% or a 20-μm layer must
not transmit more than 1% of radiation between
320 and 360 nm (part of UVA light). Others test
products as to whether they induce skin darkening
or not.
There are other forms of photoprotection that will
not be covered in detail. There are topical antioxidants such as vitamin C, vitamin E, beta carotene,
and many more. These agents have low SPFs so they
tend to be added to sunscreens. There are also systemic antioxidants that have been described. There
are excellent reviews that are available that describe
the many agents.32–34
So what are the guidelines that should be given to
patients recovering from their burns? I propose that
burn patients follow the guidelines that all people
should follow to protect themselves from photoaging and skin cancers (Table 1). In addition, patients
should be extra cautious with exposing those burns
that are regaining their pigment to improve the ultimate color match. Once pigment has stabilized, burn
survivors should follow the recommendations of all
people. The American Academy of Dermatology
Journal of Burn Care & Research
March/April 2015
256 Greenhalgh
Table 1. Recommendations for sun exposure for burn
patients
•
•
•
•
•
•
•
•
While outdoor activities are acceptable, extra caution with
sun exposure should be used until repigmentation has
stabilized (approximately 1 year after injury).
Seek shade and avoid sun between 10:00 am and 4:00 pm.
Wear protective clothing, including wide-brimmed hats.
Beware of water, snow, and sand reflecting light.
Avoid tanning beds.
Everyone should use sunscreens irrespective of their skin
color.
° Use SPF 30 or more.
° Use broad spectrum (covers UVA and UVB) sunscreens.
° Use water-resistant sunscreens.
° One ounce of sunscreen (a shot glass) is the amount
needed to cover exposed areas in an adult.
° Wait 15 min for the sunscreen to absorb in the skin.
° Reapply sunscreen every 2 hr or after swimming or
excessive sweating.
All children younger than 6 months of age should not be
exposed to sun.
Because of loss of sweat glands, patients with extensive
skin grafting should be careful with being exposed to
excessive heat while in the sun.
recommends the following to reduce UV light
exposure:40
•• Seek shade and avoid sun between 10:00 am
and 4:00 pm.
•• Wear protective clothing, including widebrimmed hats.
•• Beware of water, snow, and sand reflecting
light.
•• Avoid tanning beds.
•• Everyone should use sunscreens irrespective of
their skin color.
•• Use SPF 30 or more.
•• Use broad spectrum (covers UVA and UVB)
sunscreens.
•• Use water-resistant sunscreens.
•• One ounce of sunscreen (a shot glass) is the
amount needed to cover exposed areas in an
adult.
•• Wait 15 min for the sunscreen to absorb in
the skin.
•• Reapply sunscreen every 2 hr or after swimming or excessive sweating.
In addition, the American Academy of Pediatrics recommends that all children younger than 6
months should be kept out from the sun whenever
possible.37 Children older than 6 months should
follow the same recommendations as those mentioned above for adults. They also remind us that
80% of the lifetime sun exposure takes place before
the age of 18 years. The goal for any recovering burn
survivor is to regain as much function and activity as
possible. Going outside is important for all people.
Burn survivors should not avoid such activities but,
instead, use common sense when exposed to sun.
The survivor should be extra cautious when the
wounds are regaining pigment. Otherwise, using
the guidelines that apply to all people for sensible
exposure to the sun is the best recommendation.
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