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Photodamaged skin is characterized as being wrinkled, yellowed, and sagging.

Mildly affected skin becomes irregularly pigmented, rough, and dry, with mild

wrinkles. Moderately affected skin becomes deeply wrinkled, sagging, thickened,

and leathery, with vascular lesions.

131 Largely irreversible, severely affected skin

can become deeply furrowed and permanently (and irregularly) pigmented, and may

manifest premalignant and malignant lesions.

131 Areas of the body most commonly

affected are the face, back of the neck, back of the arms and hands, the V-line of the

neck of women, and balding areas of the head of men.

Clinical Application of Photoaging

CASE 42-5

QUESTION 1: P.B. is a 38-year-old woman who has enjoyed many outdoor activities over the years. She

lives in a moderate climate, with hot, sunny summers and cold winters. She feels that she appears older than

other women her age because of wrinkling and color changes of her skin. Her facial color is somewhat

yellowish in appearance, and the fine wrinkles at the corners of her eyes and mouth have become more

obvious. She has noticed the formation of small brown spots mottling parts of her face, hands, and forearms.

P.B. has skin type III, a clear complexion, and skin that is sensitive to soaps, heavy cosmetics, and perfumes.

What nonprescription recommendations can you provide P.B. for treatment of her photoaged skin?

Many nonprescription agents known as cosmeceuticals, products marketed as

cosmetic products that contain biologically active ingredients, are targeted at

reducing visible signs of aged skin. These products include α-hydroxy acids, retinol,

ascorbic acid, hyaluronic acid, and lipoic acid. One particular product class widely

used is α-hydroxy acids and polyhydroxy acids. In normal concentrations (5%–17%),

they are included in many products to lessen the appearance of damage; however, in

high concentrations, they are used as facial skin peels because of their keratolytic

properties. They have been shown in studies to reduce skin roughness and

sallowness; however, minimal impact was seen on wrinkles.

131,134 Topical ascorbic

acid and lipoic acid have also been shown to improve skin texture and

wrinkles,

135–137 whereas a co-enzyme Q10 derivative (idebenone) may reduce skin

roughness and fine lines while increasing skin hydration.

138

In patients who choose to

use these products, it should be strongly recommended that they wear at least SPF 15

to 30 because they allow for greater absorption of UVR. These agents are not

regulated by the FDA and therefore do not have substantial evidence supporting their

effectiveness and can be very costly. Emphasis should be placed on protection from

the sun, using photoprotective strategies previously discussed.

CASE 42-5, QUESTION 2: Are there any prescription products that you would recommend to P.B. to

discuss with her physician?

There are several topical retinoids currently available that are derivatives of

vitamin A and are effective for the signs of photoaging (see Chapter 41, Psoriasis).

Tretinoin (all-trans-retinoic acid) is available as a cream (0.02%, 0.025%,

0.0375%, 0.05%, and 0.1%) or gel (0.01%, 0.025%, 0.04% [in microspheres],

0.08% [in microspheres], 0.1% [in microspheres]) and tazarotene (available as a

0.05 or 0.1% cream, 0.1% foam, and a 0.05% or 0.1% gel) are the only two topical

retinoids FDA approved for the treatment of photoaging. These agents are effective in

partially reversing some of the clinical and histologic changes of photoaging by

lessening fine wrinkles, mottled pigmentation, and the tactile roughness associated

with photoaged skin through mechanisms such as inhibition of metalloproteinase

expression.

139–142 Additional benefits of retinoid therapy include the formation of new

dermal collagen and vessels, reduction in the number and melanization of freckles,

resorption of degenerated connective tissue fibers, and treatment of premalignant and

malignant skin lesions.

143

In one of the initial trials, all subjects treated (100%)

demonstrated global improvement in the signs of photoaging, with 53% showing

moderate changes and the remainder having at least slight improvement. Of the

clinical parameters assessed, the most impressive improvements were found with

facial skin sallowness, with respondents developing a healthy, rosy glow.

140 These

agents are more potent than the retinoids found in over-the-counter products such as

retinyl esters, retinol, and retinaldehyde and therefore produce more profound

results.

CASE 42-5, QUESTION 3: Would P.B. be an appropriate candidate for therapy with a topical retinoid

product (e.g., tretinoin)?

Topical retinoid therapy is most effective for patients 50 to 70 years of age with

moderate-to-severe photoaging and for prophylactic use in patients undergoing the

initial changes of photoaging.

139 Recently, P.B. has noticed some of the skin changes

consistent with early photoaging and would be a good candidate for prophylactic

therapy with topical tretinoin. Treatment may improve her sallow skin color and

lessen the mottling on her face and forearms and fine wrinkles at the corners of her

eyes and mouth, as well as prevent worsening of the photoaging process that she is

experiencing.

CASE 42-5, QUESTION 4: P.B.’s physician calls you asking for dosing recommendations for tretinoin. What

advice do you provide?

Because both the beneficial and adverse effects of topical retinoid therapy are

dose dependent, the underlying goal is to provide the maximal benefit by using the

highest concentration that causes minimal skin irritation. Considering P.B.’s skin

sensitivity to soaps, cosmetics, and perfumes, her skin is likely to be irritated easily

by topical therapy; therefore, it would be best to initiate therapy with the lowest

strength (e.g., tretinoin 0.025% cream or tazarotene 0.05% cream). These agents are

usually applied every night at bedtime, but in some instances, they are applied

initially on an every-other-night basis until the skin accommodates to the irritant

effects. The likelihood of irritation depends on the type of vehicle more than the

concentration of the agent.

143 The cream or the microsphere gel formulations cause

the least skin irritation and would be preferred for initiating therapy for P.B. The

microsphere gel formulation is preferred for patients with persistent acne or for those

with focal actinic lesions. Younger patients often prefer the gel because it leaves no

residue and is compatible with most cosmetics. The solution and gel may be better

tolerated in older patients with oily, thick, pigmented skin.

CASE 42-5, QUESTION 5: You are now dispensing tretinoin cream 0.025% to P.B. What patient counseling

should P.B. be given?

Before applying the cream to her face at bedtime, P.B. should wash her face

gently, using her fingertips and mild soap, then pat her skin dry with a towel. If gentle

washing with her fingers does not remove the dry, peeling skin, a washcloth can be

used gently on the face. The treated stratum corneum is fragile, and erosions could

occur if P.B. is not careful when washing. After waiting about 15 minutes, she should

apply a pea-sized amount of cream to her forehead and spread the cream evenly over

her entire face. Care should be exercised while applying the cream to the areas

adjacent to the eyes and mouth because tretinoin can cause irritation and burning of

mucous membranes.

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Skin irritation can be expected to start in the first 3 to 5 days of therapy and,

hopefully, will subside in 1 to 3 months. Irritation can manifest as erythema, peeling,

burning, and stinging. If P.B. experiences excessive irritation, she can reinitiate the

regimen on a slower timeline by applying the cream on an every-other-night or everythird-night basis for the first 2 weeks to reduce skin irritation, or she can also apply a

topical corticosteroid product such as hydrocortisone 1% cream. Once she begins to

tolerate the therapy, her frequency of applications and strength of cream should be

titrated to cause mild scaling with only occasional mild erythema. A thicker film of

cream can be applied to photodamaged areas. After 9 to 12 months of therapy, she

can begin maintenance therapy, which consists of application two or three nights a

week indefinitely.

Because these agents can dry the skin, P.B. should be counseled to use

moisturizers during the day to help decrease the dryness and irritation of the skin.

Nighttime application of moisturizers should be discouraged when topical tretinoin is

being used because the moisturizers can cause a pH incompatibility with the cream

and possibly dilute the concentration of tretinoin. With a thinning of the stratum

corneum, P.B.’s skin may be more susceptible to the effects of UVR. For this reason,

as well as to prevent further actinic damage, P.B. should begin prophylactic daytime

application of a sunscreen. Considering her skin type (III) and early photoaging

changes, a sunscreen with an SPF of at least 30 would be appropriate. P.B. should be

counseled not to become discouraged by any apparent lack of response; her skin

damage is mild, her response to therapy will be gradual, and part of the goal of

therapy is to prevent further damage. Her wrinkles may actually appear to worsen

early in therapy owing to an initial buildup of the stratum corneum. P.B. should avoid

facial saunas and irritating soaps and cosmetics. Retinoids are recognized as being

teratogenic, and although risk is more highly associated with oral forms more

commonly used for acne, use should generally be avoided in any patients who are

pregnant or planning to become pregnant.

144

BURN INJURIES

Incidence, Prevalence, and Epidemiology

Approximately 486,000 Americans are treated for burns annually.

145 Although

admission for and mortality from burn injuries continues to decline, the total number

of emergency department visits remains elevated, with over 40,000 individuals

requiring hospitalization; burns cause an overall yearly mortality of over 3,200.

146

With the development of multidisciplinary burn centers and a better understanding of

the pathophysiology of the burn wound, survival of patients with second- and thirddegree burns has improved by 5 to 6 times during the last three decades.

147 Data from

the 2015 National Burn Repository Annual Report reviewed the combined data set of

acute burn admissions for the time period between 2005 and 2014.

147 Key findings

included the following:

Over 68% of the burn patients were men. The mean age for all cases was 32

years old. Children under the age of 5 years accounted for 19% of the cases,

whereas patients age 60 or older represented 13% of the cases.

The two most commonly reported etiologies were fire/flame and scalds, and

accounted for almost 8 out of 10 reported. Scald injuries were most prevalent in

children under 5, whereas fire/flame injuries dominated the remaining age

categories.

More than 75% of the reported total burn sizes were less than 10% of total body

surface area (TBSA), with a mortality rate of 0.6%. The mortality rate for all

cases was 3.2% and 5.7% for fire/flame injuries.

Seventy-three percent of the burn injuries, with known places of occurrence, were

reported to have occurred in the home. Seventy-two percent of cases with known

circumstances of injury were identified as accident, nonwork-related.

Burn injuries range from relatively minor, superficial injuries to severe, extensive

skin loss resulting from contact with hot solids and liquids, steam, chemical agents,

electricity, or other physical agents, such as UVR or infrared radiation. Burn injuries

occur in 8 to 12% of all reported abuse cases involving children who come to the

attention of healthcare professionals.

148 Teenagers and adults between 17 and 30

years of age most commonly are involved in accidents with flammable liquids, but

the mortality associated with clothing ignition continues to decrease as a result of the

use of flame-retardant forms of fabric in clothing. Both income and income disparity

by country are associated with higher rates of burn-related deaths.

149

Complications such as fluid and electrolyte imbalances, metabolic derangements,

respiratory failure, sepsis, scarring, and functional impairment are the primary causes

of hospitalization for these cases. Most burns, however, are minor and can be

managed in an ambulatory environment, provided the burned patient is evaluated

carefully, the severity of the burn is assessed accurately, and proper and continuous

follow-up care is ensured.

The number of serious burns is decreasing in the United States because of better

prevention (smoke detectors, water temperature regulations, and decreased smoking),

and the advances in acute burn wound management have contributed to this decline as

well, including its pharmacotherapy, with topical antimicrobial therapy, early

excision or enzymatic debridement of devitalized tissue, and skin grafting or

substitutes.

150,151

Etiology

ZONES OF INJURY

The skin functions as a protective barrier of the underlying organ systems from

trauma, temperature variations, harmful penetrations, moisture, humidity, radiation,

and invasion by microorganisms (see Fig. 39-1 in Chapter 39, Dermatology and

Drug-Induced Skin Disorders). It also is involved with carbohydrate, protein, fat, and

vitamin D metabolism, produces secretions that lubricate the skin, is involved with

the immune response, and provides the body with the sense of touch.

Burn wounds caused by thermal injury can be described by varying zones of

injury.

152 The most peripheral area of injury is the zone of hyperemia. The tissue in

this area is characterized by inflammatory changes with minimal tissue damage. The

zone of stasis is the next area of injury, extending inward from the zone of hyperemia.

This area involves ischemic, damaged tissue, with blood vessels only partially

thrombosed. The damaged endothelial linings of blood vessels within this zone of

injury may trigger further thrombosis, resulting in further ischemia, cell death, and

deepening of the burn wound. This process of further injury can occur 24 to 48 hours

after the initial injury. Drying of the burn wound or infection can cause deepening of

the burn wound by preventing re-establishment of circulation to injured tissue. The

central-most area, or the zone of coagulation, is characterized by thrombotic vessels

and necrotic tissue. This area absorbs the most thermal energy, resulting in the

greatest tissue damage. Minor burns may involve only the most peripheral zones of

injury, whereas severe burns encompass all three zones of injury.

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EXTENT OF INJURY

Rule of Nines

Total body surface area (TBSA) is used to assess the size of burns of the skin. The

burned surface area is calculated as a percentage of TBSA to determine burn size. In

adults, the rule of nines is used to approximate the percentage of burned surface area.

Burn severity is proportional to the percent of TBSA involvement and depth of the

wound. The percent of TBSA for adults can be estimated by using the “rule of nines,”

in which each arm constitutes 9% of the TBSA, the head 9%, each leg 18%, the front

and back of the torso 18% each, and the genitalia 1%.

153 For children younger than 10

years of age, the percent TBSA must be adjusted because their bodies have different

proportions. Variations of the Lund and Browder chart have been used for this

purpose.

154 At birth, the infant’s head constitutes about 19% of the TBSA. For each

additional year of age, the head decreases by about 1%, and the BSA of the legs

increases by about 1% of the patient’s TBSA, so a quick estimation of the size of a

burn can be made.

Classification of Wounds

Burn wounds also are classified according to the depth of tissue damage.

Determining the depth of the burn wound can be difficult during the first 24 to 48

hours because of the presence of edema and continued tissue ischemia and infection,

both of which can cause deepening of the wound. In addition, the depth of destruction

can vary within the same burn, and skin surface characteristics may not match

underlying tissue damage, making assessment of the burn wound difficult.

152

First-Degree Burns (Superficial-Thickness Burn)

First-degree burns result from injury to the superficial cells of the epidermis; a

common example is a mild sunburn. The burned skin does not form blisters, but it

does become erythematous and mildly painful. This superficial-thickness burn heals

within 3 to 4 days without scarring.

Second-Degree Burns (Partial-Thickness to Superficial Burn)

Second-degree burns may be superficial or deep, depending on the depth of dermal

involvement. Superficial second-degree burns involve the epidermis and the upper

layer of the dermis. The burn surface often is erythematous, blistered, weeping,

painful, and very sensitive to stimuli. The erythema blanches with pressure, and the

hair follicles, sweat, and sebaceous glands are spared. Superficial second-degree

burns heal spontaneously within 3 weeks with little, if any, scarring. Deep seconddegree burns involve the deeper elements of the dermis and may be difficult to

distinguish from third-degree burns. The burn surface is pale, feels indurated or

boggy, and does not blanch with pressure. This wound is less painful than more

superficial wounds; some areas may be insensitive to stimuli. Healing occurs slowly

over the course of about 35 days with eschar formation and possible severe scarring

and permanent loss of hair follicles and sweat and sebaceous glands.

Third-Degree Burns (Partial-Thickness to Deep Burn)

Third-degree burns entail complete destruction of the full thickness of the skin,

including all skin elements. The wound may appear pearly white, gray, or brown and

is dry and inelastic. Pain is sensed only when deep pressure is applied. If the wound

is small, healing over the course of several months can occur by epithelial migration

from the margins of the injury, with scar and contracture formation. Third-degree

burns are repaired by excision and grafting, or excision and primary closure to

prevent contractures of the skin.

155

Fourth-Degree Burns (Full-Thickness Burn)

Fourth-degree burns are similar to third-degree burns except that devitalized tissue

extends into the subcutaneous tissue, fascia, and bone. These burns are blackened in

appearance; they are dry and generally painless because of destruction of nerve

endings and are at great risk for infection.

COMPLICATIONS OF SEVERE BURN WOUNDS

Fluid Loss

In severe burns, release of vasoactive mediators and capillary injury cause

sequestration of large amounts of body fluid, plasma, and electrolytes in

extravascular compartments, resulting in edema both locally and throughout the entire

body. This redistribution of fluid is compounded by the loss of large amounts of

fluid, electrolytes, and protein into the open wound. The cumulative effect is a

marked decrease in blood volume, a fall in cardiac output, and decreased tissue and

organ perfusion. During the first 24 to 48 hours after a severe burn injury, adequate

fluid must be given to replace fluid lost from the vascular space to prevent shock and,

possibly, multiple-organ failure and death.

156