Hypertrophic scars are common complications of burn injury and other soft tissue injuries. Excessive extracellular matrix combined with inadequate remodeling of scar tissue results in an aesthetically and functionally unsatisfactory, painful, pruritic scar that can impair function. Treatment options are available to rehabilitation practitioners, but none are entirely satisfactory. An interdisciplinary clinical program is necessary for best outcomes. Challenges to be met by the rehabilitation community include research into the quantification of burn scar measurement, the effects of mechanical forces on wound healing and scar management, and the best combination of surgical, pharmacologic, and therapy interventions to maximize outcome from reconstructive procedures.
Hypertrophic burn scars are the most common complication of burn injury. Although the worldwide prevalence of hypertrophic scars is not known, it is estimated that up to 1 million burn injuries occur annually in the United States. This may represent a small portion of the worldwide burden of burns and scarring as the incidence of burn injury is much higher in underdeveloped countries. Hypertrophic scars may be seen after other soft tissue injuries, including surgical incisions, compound fractures, or other wounds.
In a 10-year review of burn injury admissions in North America, approximately 95% of patients survived their hospital stays. This impressive survival rate means that a great number of patients bear the life-long burden of hypertrophic scars.
Stages of wound healing and the wound healing spectrum
Under normal circumstances wound healing progresses in an orderly fashion. Normal wound healing may be divided in to inflammatory, proliferative, and remodeling phases. In the inflammatory phase, the injury and resultant cellular debris initiate platelet aggregation and the migration of leukocytes and macrophages to the wound site. The clot that develops to create a seal of the wound serves as a matrix for promoting further cellular migration into the wound bed.
Approximately 3 days after the initial injury, at the start of the proliferative phase, other cell types are activated to enter the wound such as fibroblasts and vascular cells. After approximately 5 days after injury, epidermal cells begin to proliferate and migrate over the surface of the wound and the provisional matrix below.
Through the remodeling phase over the course of the following weeks and even months, further changes occur in the wound as the collagen deposition by local fibroblasts changes to have a predominance of type 1 over type 3 collagen and the vascular structures mature.
The desirable result of normal wound healing is replacement of the initial hemostatic clot with skin that approximates the aesthetic, mechanical, and functional properties of the preinjury tissue. Changes in the steps of normal wound healing may result in either a “hypoplastic” or chronic nonhealing wound or the hypertrophic “over-healed” wound.
Many clinicians are familiar with the “under-healed” chronic wound. Impediments to normal wound healing may include intrinsic metabolic abnormalities such as vascular diseases or diabetes. The nonhealing chronic wound may be exacerbated by extrinsic biologic factors such as the presence of bioburden as well as extrinsic mechanical factors such as excessive pressure in patients with impaired sensation, sensorium, or motor function.
The opposite end of the wound healing spectrum are the dermatoproliferative disorders: hypertrophic and keloid scarring. Hypertrophic scars differ clinically from keloid scars in that hypertrophic scars are described as developing within the margins of the original injury, whereas keloid scars may extend beyond the original injury. Hypertrophic scars are described as raised from the surrounding skin. They are painful, pruritic, and contractile. A comparison of the spectrum of clinical outcomes in wound healing is made in Table 1 .
| Result | Chronic Nonhealing Wound Ulcer | Normal Healing | Dermatoproliferative Disorders |
|---|---|---|---|
| Clinical Characteristics | Exudating, nonepithelialized | Epithelialized, approximates preinjury functional properties, and is aesthetically and mechanically acceptable | Epithelialized, increased volume, erythema, contracture, pruritus, chronic dynamic process of inflammation and fibrosis |
| Factors | Inadequate substrates, excessive mechanical forces, excessive moisture, bioburden | Appropriate substrates, vascularity, minimization of mechanical forces and bioburden, moist wound-healing environment | Prolonged inflammatory wound healing phase, activated transforming growth factor-beta signaling |
Risk factors for development of hypertrophic scars
Although there have been advances in developing technology to predict healing in burn wounds, there are no reliable tools presently available to predict which wounds will develop in to hypertrophic burn scars. Clinical experience suggests that patients whom have darker pigmented skin are more likely to develop a dermatoproliferative disorder. Also, adolescents are thought to have a higher likelihood of developing a hypertrophic scar than adults. The best clinical predictor for the development of hypertrophic burn scars is a prolonged inflammatory wound healing phase. This would usually correspond with a wound that has not epithelialized and continues to exudate for more than 3 weeks.
Burn wound depths are described as superficial, partial thickness, or full thickness. Superficial burns, such as sunburn can be expected to heal spontaneously in approximately 10 days without a significant risk of hypertrophic scarring. Superficial partial-thickness burns such as a typical household scald injury result in blistering, painful wounds that should be expected to epithelialize within approximately 2 weeks provided no complications arise in the wound healing process. The risk of developing hypertrophic burn scars from superficial partial-thickness buns is low, but not zero.
Deep partial-thickness burns have less blistering than superficial partial-thickness burns, are painful, and may take up to 3 weeks or longer to epithelialize. The risk of scarring with deep partial-thickness burns is significant. Full-thickness burns destroy the epidermis and dermis and result in burn wounds that may be less painful than partial-thickness burns and typically have limited exudate but may present with necrotic eschar. The risk of hypertrophic scarring from full-thickness burns is high.
Different anatomic regions seem to have different risks for the development of hypertrophic scars. For example, it is unusual to observe the development of hypertrophic scars on the scalp, eyelid, or palm of the hand.
Risk factors for development of hypertrophic scars
Although there have been advances in developing technology to predict healing in burn wounds, there are no reliable tools presently available to predict which wounds will develop in to hypertrophic burn scars. Clinical experience suggests that patients whom have darker pigmented skin are more likely to develop a dermatoproliferative disorder. Also, adolescents are thought to have a higher likelihood of developing a hypertrophic scar than adults. The best clinical predictor for the development of hypertrophic burn scars is a prolonged inflammatory wound healing phase. This would usually correspond with a wound that has not epithelialized and continues to exudate for more than 3 weeks.
Burn wound depths are described as superficial, partial thickness, or full thickness. Superficial burns, such as sunburn can be expected to heal spontaneously in approximately 10 days without a significant risk of hypertrophic scarring. Superficial partial-thickness burns such as a typical household scald injury result in blistering, painful wounds that should be expected to epithelialize within approximately 2 weeks provided no complications arise in the wound healing process. The risk of developing hypertrophic burn scars from superficial partial-thickness buns is low, but not zero.
Deep partial-thickness burns have less blistering than superficial partial-thickness burns, are painful, and may take up to 3 weeks or longer to epithelialize. The risk of scarring with deep partial-thickness burns is significant. Full-thickness burns destroy the epidermis and dermis and result in burn wounds that may be less painful than partial-thickness burns and typically have limited exudate but may present with necrotic eschar. The risk of hypertrophic scarring from full-thickness burns is high.
Different anatomic regions seem to have different risks for the development of hypertrophic scars. For example, it is unusual to observe the development of hypertrophic scars on the scalp, eyelid, or palm of the hand.
Cellular signals and pathways in hypertrophic scarring
Several cellular signals are implicated as having an important role in the development of hypertrophic scars. One signal thought to be of particular importance is transforming growth factor-beta (TGF-β). This protein is part of a large family including bone morphogenic proteins and activins. TGF-β exists in both latent and activated forms. TGF-β acts through a signaling pathway mediated by the SMAD proteins. The net effect of activated TGF-β interacting with the TGF-β receptor and activation of the SMAD pathway in fibroblasts appears to be an increase in production of extracellular matrix and signals leading to cellular proliferation. Over time, some cells can develop autocrine TGF-β positive feedback loops that can lead to a self-propagating cycle of excessive extracellular matrix production and cell proliferation.
Hypertrophic scars are dynamic and express different histologic appearances, cellular signals, and molecular characteristics depending on the stage of development. This may result in conflicting descriptions of the microscopic hypertrophic scar environment.
Excessive extracellular matrix formation does not account for all of the clinical characteristics of hypertrophic scars. Overall, an imbalance between too much matrix formation and inadequate matrix remodeling is thought to exist as the overall milieu in hypertrophic scarring. Cellular signaling between keratinocytes and fibroblasts is an important component of this process and there is some evidence that keratinocyte signals such as stratifin may activate matrix metalloproteinases that would have an important effect on scar fibroblasts in reorganizing extracellular matrix proteins. Multiple other cell types, including mast cells and bone-marrow–derived mesenchymal stem cells, are also present in the hypertrophic scar and are likely significant in clinical characteristics of the hypertrophic scarring phenotype.
Clinical characteristics and measurement of hypertrophic scars
Hypertrophic burn scars develop during the remodeling phase of wound healing, typically in the first few months of injury. During this time, the volume increases and the scars become contractile and erythematous. However, after several months, the scars may show spontaneous regression without complete resolution to normal skin. Fig. 1 shows a hypertrophic scar on the shoulder of a patient 20 months after original injury. This patient was injured with scalding water at 13-months-old.
Although hypertrophic burn scars may show regression, there is significant heterogeneity in the volume, erythema, and pigmentation within a single scar, as shown in Fig. 2 . In this case, the photograph was taken 21 months after deep partial-thickness flame burns. The peripheral margins of the scars have regressed in volume and erythema; however, the texture and volume of the scars in the left flank and arm are significantly abnormal compared with the surrounding skin.
The description of hypertrophic burn scars therefore poses a challenge to the rehabilitation practitioner. There are several clinical tools used to try to describe hypertrophic scars. The Vancouver Scar Scale (VSS) is a clinician rating scale that includes items to describe vascularity, height, pliability, and pigmentation in a scar. With the Patient and Observer Scar Assessment Scale, an observer rates the scar on vascularity, thickness, relief, pliability, surface area, and pliability while a patient assesses color, stiffness, thickness, relief, and itching. The Manchester Scale assesses color as compared with surrounding normal skin for appearance, contour, texture, size, number, and characteristics of the margins or borders of the scar. Overall, the VSS is probably the most widely used and applicable to the burn scar patient.
However, there are several limitations in using the VSS. In a large scar, such as the one in Fig. 2 , it can be unclear which area of the scar the VSS is being used to rate. Also, because it is a subjective rating scale, it may not accurately describe characteristics such as volume.
An ideal measurement tool for the description of a hypertrophic burn scar would be valid, reliable, sensitive to change over time, and include characteristics such as volume, viscoelastic properties, and color.
The viscoelastic or biomechanical properties of skin and scar may be measured with a device known as a Cutometer (Courage + Khazaka electronic GmbH, Köln, Germany). These devices measure deformation in the skin or scar by the application of a vacuum chamber and measurement of laser light reflectance. With a known vacuum force and quantifiable deformation in the skin or scar, calculations may be made for descriptors of the viscoelastic properties of the skin or scar. Although the Cutometer has been shown to be a reliable tool in the quantification of burn scars, there is likely a ceiling effect seen in very hard, nonpliable scars.
The color of a scar, which is a combination of the pigmentation as well as the vascularity, may be measured with a device known as a Mexameter (Courage + Khazaka electronic GmbH, Köln, Germany). This device characterizes the color of a scar by the wavelengths of light absorbed by melanin and hemoglobin. This instrument has promising qualities for use in quantifying hypertrophic scars, but has not been shown to well discriminate between normotrophic scars and hypertrophic scars. The limitations in discriminating between normotrophic and hypertrophic scars, as well as differences in opinion of the value in including color as an essential outcome for burn scars, may limit the utility of the Mexameter as a preferred measurement tool for the quantification of scar properties.
The volume of a scar may be approximated by measurement of thickness through transcutaneous ultrasound. Thickness of skin or scar may be quantified by measuring the distance between the different echogenic properties of tissue within skin and scar compared with subcutaneous fat or other tissues. So far, transcutaneous ultrasound appears to be the best quantitative tool available to discriminate between normal skin, normotrophic scars, and hypertrophic scars. However, because of the small area measured, a true measurement of total scar volume is not currently possible with this device.
Like the VSS, each of these instruments is limited in the degree of scarring measured. For example, the apertures of the measurement devices for the Cutometer and transcutaneous ultrasound may be 1 cm in diameter or less. As such, for scars with significant heterogeneity, such as in Fig. 2 , a technique for repeating measurements of the same region of scar needs to be devised.
The need for clinically relevant measurement tools to describe hypertrophic scars is important outside of burns rehabilitation because hypertrophic scars may be seen in other inflammatory traumatic conditions. The hypertrophic scars seen in Fig. 3 are the result of a complex ankle fracture and delayed wound healing. Despite the significant difference in primary injury, the scars share several characteristics with the burn scars illustrated in Fig. 2 .
