Widened and Hypertrophic Scar Healing

"You were advised his flesh was capable of wounds and scars."

—William Shakespeare, Henry IV

Much of art and literature depicts violence and wounding as part of the human condition. To wound, and to be wounded, is to be human. Moreover, while many societies perceive prominent scars as disfiguring, some primitive societies use scarification for beautification or ornamentation. For the surgeon, a scar may be the only trademark of the surgical procedure performed, as FitzGibbon has stated, "By your scars you will judged." ^[12]

In reviewing the origin of the terms cicatrix and scar, the term cicatrix is interesting in itself. Originally, it was the Greek word eschara, meaning a fireplace. These fireplaces were situated in the middle of the house, and, around them, the main domestic activities took place. Because of these activities, and because mischievous children gathered around them, injuries and subsequent scars were so frequent that the name of the cause came to be that of the effect. The use of the word was passed to Italy along the lines of commerce and became cicatrix. From Italy, it moved to France as the word eschare, which now means a crust covering an ulcer. In the British Isles, eschare mingled with the Saxon word scaur, much resembling eschare in pronunciation and meaning.

In the Middle Ages, the word cicatrix had wide significance and included any unnatural white mark on the skin; scleroderma, morphea, and "white spot" disease would all fall under the same term. Even white spots, leukonychia, so often seen on toenails, were included under the term cicatrix. ^[13]

Because abnormal scar formation is unique to humans, animal model research contributions have been limited to our understanding and the treatment of keloids and hypertrophic scars. The wide range of suggested etiologies for abnormal wound healing and the wide range of proposed treatments of abnormal scarring indicate that our understanding of these processes is incomplete.

For excellent patient education resources, visit eMedicineHealth's Skin Conditions and Beauty Center. Also, see eMedicineHealth's patient education articles Suture Care, Wound Care, and Removing Stitches.

Frequency

Hypertrophic scars are more common than keloids. Hypertrophic scars may occur in persons of any age or at any site, and they tend to spontaneously regress. In general, hypertrophic scars are more responsive to treatment. While keloids occur most frequently in patients of color, they may occur in persons of any race with a proven tendency to keloid formation. Keloids are 5-15 times more common in darker pigmented people than in white people. ^[14] This predilection for formation in people with certain skin colors is not observed with hypertrophic scars.

Keloids are more prevalent in persons aged 10-30 years, while hypertrophic scars occur in persons of any age. In general, the risk for either type of abnormal scar diminishes with age. ^[15] Furthermore, the propensity for keloid formation can be familial, genetically transmitted as an autosomal dominant or recessive trait. ^{[16, 17, 18]}

Widened scars can occur in persons of any age. Widened scar formation occurs with no predilection to sex or ethnicity. No inheritance pattern is associated with the risk for scar widening. Widened scars are most commonly found to involve the arms, legs, and abdomen. Suntanning can contribute to scar widening through attenuation of the tissues.

Abnormal scar formation is unique to humans, and, as such, animal model research has not produced much significant information to further the understanding and treatment of keloids and hypertrophic scars. Despite numerous studies, no uniformly accepted theory or explanation indicates which factor initiates keloid or hypertrophic scar formation.

Several genetic and environmental causes have been implicated in the etiology of keloid and hypertrophic scars. In both keloid and hypertrophic scar formation, an excessive accumulation of collagen from increased collagen synthesis or decreased collagen degradation occurs. ^{[19, 20]} Proposed causes for abnormal scar formation have one thing in common: inflammation. Almost all abnormal scars are associated with inflammation, such as the inflammation that occurs with foreign body reaction, bacterial infection, tattoos, burns, injections, bites, vaccinations, trauma, surgery, or infection.

A study by van den Broek et al found a prolonged decrease in inflammatory gene expression in patients who developed hypertrophic scars, as well as an extended increase in expression of extracellular matrix-related genes, in contrast to patients who developed normotrophic scars. The study, using biopsies of five patients who developed hypertrophic scarring and six patients who developed normotrophic scarring, also found a prolonged, albeit delayed, type 2 activated macrophage infiltration in hypertrophic scar tissue. ^[21]

A prospective study by Correia-Sá et al found that compared with patients who developed normal scars after body contouring surgery, those who developed hypertrophic scars following the procedure had, prior to surgery, higher eosinophil and basophil counts and greater C-reactive protein levels, as well as vitamin D plasma levels of almost 50% less. The investigators suggested that the latter finding is important because of vitamin D’s apparent anti-inflammatory effect. ^[22]  However, further investigation is needed into the possible use of vitamin D (oral or topical) in the prevention of hypertrophic scars.

Skin tension is frequently implicated in hypertrophic scar formation. Abnormal scar healing commonly involves areas of high skin tension, such as the anterior chest, shoulders, and upper back. ^{[23, 24, 25]} Other factors implicated in the etiology of abnormal scar formation include wound infection or anoxia, a prolonged inflammatory response, and wound orientation different from the relaxed skin tension lines.

Keloid formation has a genetic basis, as demonstrated by its predilection for persons of certain races and in certain families. Because keloids tend to demonstrate accelerated growth during puberty or pregnancy and tend to resolve with menopause, hormones (both androgen and estrogen) have been implicated in keloid formation. Other hormones linked to keloid formation include thyroid hormone alterations and melanocyte-stimulating hormones. ^{[26, 27]}

Immunologic alterations have been demonstrated in abnormal scars. Specifically, irregular immunoglobulin and complement levels, increased transforming growth factor-beta, and mast cells have been found in abnormal scars. ^{[28, 29, 30, 31]} Additionally, decreased tumor necrosis factor and interleukin 1 levels have been found in these abnormal scars. ^{[32, 33]}

Widened scars result from excess tension perpendicular to the wound edges during the healing process. Scar widening usually occurs within the first 6 months of injury.

Normal wound healing requires a balance of catabolic and anabolic activities. Although multiple factors are involved in abnormal scar formation, studies indicate that keloid and hypertrophic scars result from increased collagen production (anabolic) and decreased collagen degradation (catabolic). Cohen demonstrated that levels of the collagen-related enzyme prolyl hydroxylase are elevated in keloid-affected skin compared with normal skin. ^[19] Prolyl hydroxylase is required for the hydroxylation of proline during collagen synthesis, suggesting that collagen overproduction occurs with keloids.

Collagen production is elevated in keloid biopsy samples and in cultured fibroblasts derived from keloids. ^{[34, 35]} Additional studies show that increased collagen production by cultured fibroblasts derived from keloids persists throughout their in vitro life span; they do not revert to normal after transfer of the lesion to culture. ^[36] No significant differences in DNA content or cellularity are found when keloid dermis is compared with normal dermis. This suggests that each fibroblast is producing more collagen rather than an increase occurring in the number of fibroblasts producing a normal amount of collagen. In keloid formation, excessive collagen production by fibroblasts may be due to the wound environment.

Contrary to the increased collagen production theory, keloids and hypertrophic scars may also result from a decrease in collagen degradation. levels of the collagenase inhibitor alpha-2 macroglobulin have been shown to be decreased in keloid lesions. ^[37]

Widened scar formation is thought to result from wound edge separation with tension perpendicular to the healing skin wound. A state of tension exists naturally in skin; wounded skin gapes and becomes elliptical rather than round. Although Dupuytren first noted this property of skin, Langer received most of the credit. ^[25] Langer studied the direction of these ellipses by stabbing a round-tipped awl into hundreds of cadavers. When a wound is closed opposite to the lines of tension, the chance of widened scar formation is increased.

Upon clinical examination, keloids and hypertrophic scars are raised above the skin level. Hypertrophic scars are self-limited; they hypertrophy within the confines of the wound. Initially, hypertrophic scars can be raised, red, pruritic, and even painful; however, over time, they become pale and flat. Hypertrophic scars appear worse at 2 weeks to 2 months.

Keloid scars can be differentiated from hypertrophic scars by their spread beyond the original wound. Keloid scars tend to remain red, pruritic, and painful for many months to years until menopause. Patients usually have a personal or familial history of keloid formation.

Different from hypertrophic and keloid scars, widened scars are flat and sometimes depressed. With adequate wound maturation, these wounds fade to the pigment of the surrounding uninjured skin. Widened scars are not usually red or pruritic.

The most common presenting concern of patients with abnormal scars is disfigurement. However, some patients experience other symptoms in association with their abnormal scar, such as pain, pruritus, and loss of motion from contracture. These other symptoms can be indications for surgical correction of the scar. Determining what type of abnormal scar the patient has is important for treatment planning.

Widened scar formation is thought to result from wound edge separation with tension perpendicular to the healing skin wound. The risks of widened and hypertrophic scarring are increased in the areas of the body where tension across the skin is greater. A state of tension exists naturally in skin; wounded skin gapes and becomes elliptical instead of round.

While an anatomy professor in Vienna, Austria at Saint Joseph's Academy, Langer wrote about the structure of joints, blood vessels, and lymphatics. However, he is best remembered for his lines (ie, Langer lines). Langer showed that the ellipses, which he called spaltbarkeit, meaning cleavage, occurred along the lines of tension. He used an ingenious technique to demonstrate this concept. He incised around a circular template and noted that the outer skin retracted in varying degrees in different areas of the body. The direction of the wound retraction coincided with his cleavage lines.

The Langer diagrams were developed from cadavers in a uniform position, with their extremities in extension as they were in rigor mortis. Langer discovered that his lines changed depending on the position of the cadaver. For instance, the longitudinal orientation of a wound in the antecubital fossa changes to transverse when the elbow is relaxed versus when it is in a semiflexed position. Furthermore, Langer found that wound tension was greater in certain areas, such as the sternum, abdomen, and extremities. ^[37]

Later, Kocher recognized the surgical importance of Langer's tension lines and advised that surgical incisions follow these lines. ^[38] However, Langer, an anatomy professor, did not intend for his lines to be used as guidelines for incisions. Later, Borges argued that Langer's lines represented lines of cleavage in cadavers and not lines of relaxed skin tension for live humans. ^[39] Furthermore, the facial musculature of a cadaver is often not relaxed; some display a wide-eyed stare or wide-open mouth. Accordingly, Langer's lines are quite different from the relaxed skin tension lines of the face. These lines were described by Borges in 1962, and they are probably the most well-accepted guideline for incisions of the face. ^[40]

The relaxed skin tension lines follow furrows formed when the skin is relaxed. Unlike wrinkles, they are not visible features of the skin. They are merely derived from the furrows produced by pinching on the skin. These furrows are produced most easily with pinching perpendicular to the lines. When the skin is pinched oblique to the relaxed skin tension lines, an S-shaped pattern is created. Fewer and higher furrows are created if skin is pinched parallel to the lines. ^[40] Closing incisions opposite to the relaxed skin tension lines can increase the risk of widened or hypertrophic scar formation because this places more tension across the wound.

A potential relative contraindication to keloid scar revision surgery exists because of the risk of worsening the scar. Sometimes, when keloids recur after excision, they become larger than the original. The risk of worsening a keloid scar appears to be increased if the scar does not respond to or improve with steroid injections.

The risk of revision surgery may not be worth the potential benefit for hypertrophic scars in certain anatomic locations because of the risk for recurrence.

The risk of recurrence for widened scar revision is increased in patients with attenuated skin, especially in patients with certain skin conditions such as Ehlers-Danlos syndrome or progeria, patients of advanced age, or patients with suntanned skin. Also, if the scar is over an implant such as abdominal mesh or a breast implant, the risk of implant infection, deflation, or exposure from dehiscence may outweigh the benefit of the procedure.

Because of the risk of attenuated tissues incapable of retaining sutures and consequent recurrence, scar revision should be withheld until maturity of the scar. Scar maturation usually takes 12 months.