Continuing Education Activity

Hypertrophic scarring represents an undesirable variant in the wound healing process. In hypertrophic scars, excess connective tissue is deposited in the area of the original tissue wound. This activity reviews the evaluation and management of hypertrophic scarring and highlights the role of the interprofessional team in the recognition and management of this condition.

Objectives:

• Describe the recommended management of Hypertrophic scarring.
• Outline the typical presentation for a patient with Hypertrophic scarring.
• Review the pathophysiology of Hypertrophic scarring.
• Explain the interprofessional team strategies for improving care coordination and communication regarding the management of patients with Hypertrophic scarring.

Introduction

Hypertrophic scarring represents an undesirable variant in the wound healing process. Another variant of wound healing, the keloid scar, is often used interchangeably with hypertrophic scarring, but this is incorrect. The excess connective tissue deposited in hypertrophic scarring is restricted to the area within the original wound. The excess connective tissue deposited in the keloid, however, extends beyond the area of the original wound. This article will review both of these entities in detail.[1][2][3][4]

Etiology

A variety of risk factors are linked to both hypertrophic scars and keloids. A very important, common, risk factor in clinical practice is tension on the wound. Hypertrophic scars and keloid scars often develop on areas of the body that undergo the most skin tension. These include the back, chest, and upper arms, or the occurrence of any scar over a bony or soft-tissue prominence. In contrast, hypertrophic scars rarely develop in areas with little skin tension such as the upper eyelids. In patients prone to keloid development, however, keloid can develop with any scar.[5][6][7][8]

Certain systemic factors can increase the risk of hypertrophic scars. One study showed that hypertension is associated with increased keloid severity. Another systemic risk factor is inflammation. Systemic inflammation is seen after burn injuries further increasing the risk of developing hypertrophic scars and keloids for up to 1 year.

Multiple episodes of trauma to the same area are also a risk factor for hypertrophic scarring and keloid scars. One example is the use of earrings. Each time a person puts on or takes off the earing there can be some amount of trauma to the area. The site of ear piercings is a common area for the development of keloids, and there is an unclear association with nickel or other metals commonly used in ear jewelry. Burn wounds are prone to hypertrophic scarring, especially if they affect the deeper dermis (second and third-degree burns). One study found that hypertrophic scarring was much more likely in burn wounds that took three weeks or more to heal. Infection is another risk factor for hypertrophic and keloid scars. In addition, genetics can play a role in hypertrophic scars or keloids. Certain single-nucleotide polymorphisms are associated with keloid scars in persons of Japanese descent.[9]

Epidemiology

Adolescents and pregnant women may be more likely to form hypertrophic scars. People with darker skin complexions are about 15% more likely to develop keloid scars, and the lowest incidence of hypertrophic scars is in persons with albinism. It is estimated that 70% of deep (full thickness), burn injuries result in hypertrophic scars.

Pathophysiology

Although there is a defined clinical distinction between hypertrophic scars and keloid scars, these two disorders may lie within a spectrum of the same pathophysiologic process. The precise mechanisms distinguishing the two remain elusive. Wound healing is divided into three phases (inflammatory, proliferative, remodeling). The scar is formed in the last phase (remodeling phase).

There are increased numbers of myofibroblasts in hypertrophic scars. Transforming growth factor-beta (TGF-beta) stimulates differentiation of both local and bone fibroblasts into myofibroblasts, which then creates tension on the wound. It is hypothesized that existing tension on a wound may exacerbate this pathway, creating a vicious cycle. Certain pro-inflammatory mediators are unregulated in keloid scars. These include tumor necrosis factor-alpha, interleukin-1 alpha, interleukin-1 beta, and interleukin-6. Some experts believe that these mediators are more prominent in response to trauma in patients predisposed to hypertrophic and keloid scarring.

Burn wounds can be divided into superficial (partial thickness) and deep (full thickness). The majority of partial-thickness burn wounds heal without hypertrophic scarring. Deep wounds stimulate dermal fibroblasts to produce collagen and inflammatory mediators like transforming growth factor-beta 1 (TGF-beta1). TGF-beta1 further stimulates fibroblasts to deposit elastin and collagen, potentially leading to increased deposition in wounds predisposed to hypertrophic scarring. Over-expression of TGF-beta has been implicated in keloid scarring also, though the expression levels in hypertrophic scars and keloid scars remains a matter of ongoing investigation. [9].

Histopathology

The distinction between hypertrophic scars and keloid scars can be seen histologically. Both hypertrophic scars and keloids show thick bundles of collagen on histopathology. Hypertrophic scars show the deposition of collagen type III fibers that are arranged parallel to the epidermis. Keloid scars show haphazard sheets of type-1 and type-2 collagen with random directional orientation. This is sometimes termed “keloid collagen,” and tends to be much more histologically disorganized. There also tend to be more blood vessels and neo-capillary ingrowth histologically in keloid scars than in hypertrophic scars.

History and Physical

Hypertrophic scarring presents as an area of increased induration and often dyspigmentation over the site of a wound, especially in areas of increased wound tension. Keloids present as marked hypertrophy of dermal tissue and they often feature dyspigmentation. As mentioned above, keloid scars extend beyond the margin of the original wound, as this is the defining feature to distinguish them clinically from hypertrophic scars. Hypertrophic scars and keloid scars also differ in the time it takes for them to develop, especially after burn injury. Hypertrophic scars develop in 1 to 2 months after injury, whereas, keloids develop months to years after the initial injury.

Hypertrophic scars and keloids often cause irritation, pruritus, and even neuropathic pain. Severe hypertrophic scars or keloids over a large area can cause contractures that may be disabling.

Evaluation

The diagnosis is usually made clinically. However, if a hypertrophic scar or keloid continues to worsen or change a biopsy may be necessary. Hypertrophic scars remain within the boundaries defined by the original defect/wound. Keloid scars extend beyond the original wound. There is a theoretical increased risk of malignant transformation in keloid scars not seen as frequently in hypertrophic scars [10]

Treatment / Management

Reducing tension on the wound with good surgical technique is an important aspect of prevention of hypertrophic scars during surgery. Patients who are known to form hypertrophic scars or keloids should avoid elective surgical procedures.[11][12][13]

Once the hypertrophic scar or keloid scar has formed there are a variety of treatment modalities that may be used. Corticosteroid injection is a mainstay of therapy for hypertrophic scars. Surgical excision may be used to treat hypertrophic scars or keloid scars. However, in the case of keloid scars, surgical excision should not be used alone but rather in combination with another modality such as corticosteroid injection or radiotherapy. Radiotherapy has been shown to treat and prevent keloid scars. Laser therapy including long-pulsed Nd:YAG laser or pulsed dye laser have proven benefit in treating hypertrophic scars. These lasers target blood vessels and therefore are very helpful in reducing the color changes seen in hypertrophic scars. Cryotherapy may be used to treat hypertrophic or keloid scars. Although one would assume that a destructive treatment such as cryotherapy would induce scars, experts believe that a different collection of inflammatory mediators are released in response to cold injury compared to other types of injury such as burn injury. 5-Fluorouracil has successfully treated and prevented keloids.

The treatment of burn wounds and the prevention of hypertrophic and keloid scars after burn injury represents a daunting challenge for clinicians. As mentioned above, burn wounds can be divided into superficial (partial thickness) and deep (full thickness). The majority of partial-thickness burn wounds heal without hypertrophic scarring. Most experts opt to manage deep wounds by excising the burned area and placing a split-thickness autograft. Laser therapy is often used to treat hypertrophic scars caused by burns. Laser therapy not only improves the color of the hypertrophic scar but can reduce the height of the scar and tension on the scar. Laser therapy can also relieve symptoms such as pain and pruritus. Traditionally, compression therapy was used in the management of burn wounds, but a meta-analysis found that compression therapy did not show efficacy in altering the progression of hypertrophic scars. In addition, good nutrition and vitamin supplementation are recommended for burn patients or those with chronic wounds. Like many other disorders in dermatology and medicine, the future of burn wound management may lie in targeting specific molecular pathways. These include therapies directed at WNT/beta-catenin pathway, the TGF-beta pathway, the Notch pathway, the Sonic hedgehog pathway and the RAS/MEK/ERK pathway.

Differential Diagnosis

Although most hypertrophic and keloids scars are diagnosed clinically, a biopsy may be necessary, especially if one of these lesions continues to grow or change. There are a few entities to keep in mind that may mimic a hypertrophic scar or keloid clinically and/or histologically. These include, but are not limited to: sarcoma, dermatofibrosarcoma protuberans, dermatofibroma, nodular scleroderma, and infectious processes such as a lobomycosis.

Enhancing Healthcare Team Outcomes

The actual treatment of hypertrophic scarring is done by a plastic surgeon and/or a dermatologist. Once the hypertrophic scar or keloid scar has formed there are a variety of treatment modalities that may be used. Corticosteroid injection is a mainstay of therapy for hypertrophic scars, as is silicone sheeting, or various other topical preparations. Surgical excision may be used to treat hypertrophic scars or keloid scars, though this carries the risk of recurrence of the hypertrophic scar or keloid (much more common in the latter). Cryotherapy and laser therapy, including long-pulsed Nd:YAG laser or pulsed dye laser, have proven benefit in treating hypertrophic scars. These lasers target blood vessels and therefore are very helpful in reducing the color changes seen in hypertrophic scars.  Despite the plethora of treatments, the results of most treatments are suboptimal; this is a challenging condition to treat. [14][15] There is no one treatment better than the other and all have the potential to worsen the scar. Like many other disorders in dermatology and medicine, the future of hypertrophic scars treatment may lie in targeting specific molecular pathways. These include therapies directed at WNT/beta-catenin pathway, the TGF-beta pathway, the Notch pathway, the Sonic hedgehog pathway, and the RAS/MEK/ERK pathway.