Scar Contractures, Hypertrophic Scars, and Keloids
Anthony E. Brissett, M.D., and David A. Sherris, M.D.
A scar contracture is the result of a contractile wound-healing process occurring in a scar that has already been re-epithelialized and adequately healed. Keloids and hypertrophic scars (HTSs) are fibrous tissue outgrowths that result from a derailment in the normal wound-healing process. The exact incidence of keloids and HTSs remains unknown. Beyond the common belief that trauma is the initiating event of keloid and hypertrophic scar formation, the remainder of the process remains uncertain. A combination of biochemical factors, skin tension, endocrinologic factors, and genetic factors are the likely culprits. Treatment begins by educating the patient about the etiology of the scarring process. All treatment protocols are individualized, but the standard approach to keloids and HTSs begins with corticosteroid injection followed by surgical excision, pressure dressings, and long-term follow-up.
KEYWORDS: Contracture, hypertrophic, keloid, scar
Keloids and hypertrophic scars (HTSs) are fibrous tissue outgrowths that result from a derailment in the normal wound-healing process. The first description of keloids dates back to approximately 1700 be in the ancient Egyptian writing of the Smith Papyrus documents.' Even today, African sculptures, drawings, and body scarification depict various patterns developing from hypertrophic scars that may indicate kinship, stature, or acts of bravery (Fig. 1).2 The term Cheloide was initially described by Alibert in the early 1800s. The root "Chele" is adopted from the Greeks and means "crab claw." This describes the keloid lateral outgrowths and crablike extensions into surrounding tissue}'4
Peacock et al. have provided us with the description of hypertrophic scars and keloids that is commonly used today. By their definition, an HTS is described as a fibrous tissue outgrowth with excessive scarring that re-mains within the confines of the wound (Fig. 2A). A keloid, on the other hand, is characterized by its ability to spread outside the boundaries of the original lesion (Fig. 2B). An additional form of abnormal wound healing is the scar contracture. By definition, a scar contracture is the result of a contractile wound-healing process occurring in a scar that has already been reepithelialized and adequately healed (Fig. 2C).6 Scar contractures typically appear as a fixed, rigid scar that con-tributes to both cosmetic and functional problems. It is imperative that the reconstructive surgeon differentiates among these three forms, as they require different treatment modalities.
The exact incidence of keloids and HTSs remains unknown. Numerous reports on the incidence of keloids in the Black population vary anywhere between 5 and 15%7-9 In a review of 175 cases of keloids from various races, Alhady and Sivanantharajah found that keloids were 15 times more likely to occur in darker-skinned individuals.
Although keloids can occur at any age, they are most likely to occur between the ages of 10 and 30 years. The incidence is equal in both men and women.11-13 The formation of keloids has been de-scribed to follow both an autosomal dominant and autosomal recessive transmission pattern.11,14,15 Keloid formation has not been associated with HLA-A or HLA-B antigens.76 There is an increased frequency in individuals with connective tissue disorder such as Ehlers-Danlos syndrome as well as Rubinstein-Tavbi disease and Scleroderma.17,15
The traditional approach to the normal wound-healing process consists of three phases: the inflammatory or exudative phase, the proliferative or granulation phase, and the wound contraction or remodeling phase. The inflammatory or exudative phase begins immediately upon injury and comprises the disruption of blood vessels leading to the influx of serum proteins, platelets, clotting factors, and collagen. Activated platelets release growth factors, fibrinogen, and fibronectin, which pro-mote cell migration into the wound.19,20 A rapid in-crease in fibroblast numbers and in epithelial cell mitoses as well as an increase in the synthesis of extra-cellular collagen and proteoglycan content characterizes the second phase. Reepithelialization intensifies during this stage.21 Wound contraction is characterized by a decrease in fibroblasts, macrophages, and wound vascularity. The contraction component in this phase is believed to be the result of myofibroblasts, which cause the wound to contract by 0.6 to 0.75 mm per day11,22 Contemporary thoughts describe primary, secondary, and tertiary stages of wound healing. In this model all aspects of wound repair occur simultaneously in differing degrees of intensity.Z3 A derailment in this process of wound healing contributes to keloid formation, scar contractures, and hypertrophic scarring.
Despite extensive research, the exact mechanism that results in an overly exuberant healing response re-mains elusive. Several theories have been proposed to assist in our understanding of this process. The central theme in the development of excessive scarring is trauma. However, reports of keloids developing spontaneously with no history of antecedent trauma exist;78 the inciting event may not have been recognized by the patient.
Beyond the common belief that trauma is the initiating event the remainder of the process remains uncertain. A combination of biochemical factors, tension, and endocrinologic factors are likely culprits.
Platelet-derived growth factor (PDGF) is believed to be essential in wound repair. PDGF is the principal mitogen in the serum for mesenchymally de-rived cells and is the first growth factor shown to be chemotactic for neutrophils, monocytes, fibroblasts, and smooth muscle.24 It has also been shown that PDGF has a beneficial effect in models of impaired wound heaung.24-28 Although these studies evaluated PDGF in situations of poor healing, one can begin to speculate about the effect of PDGF on the development of an excessive extracellular matrix.
Transforming growth factor B (TGF-B) is critical to normal wound healing but may also contribute to keloid formation.29-32 Peltonen et al. described an in-crease in fibroblasts as well as type I and VI collagen in active keloids. Moreover, TGF-Bl mRNA and protein were detected in an area active in type I and VI collagen expression. Peltonen et al. concluded that an initial step in keloid fibrotic reactions involves the expression of the TGF-B1 gene by neovascular endothelial cells, thus activating the adjacent fibroblast to produce markedly elevated levels of TGF-Bl as well as type I and VI collagen.33
Mechanical tension and strain on wound edges is one of the most important known extrinsic factors linked to the development of HTSs and keloids.6,22,29 Increased mechanical tension within the wound may translate to changes in phenotypic expression of fibroblasts. Keloids and HTSs are more common in wounds closed under tension. Anatomic sites under exceptional skin tension such as the shoulder and presternal area develop keloids and HTSs at increased rates. Scars that traverse the relaxed skin tension lines at right angles are subject to constant tension as a result of contraction of the underlying musculature and may become hypertrophic. Pierced earlobes, however, are also common sites for keloid formation, despite minimal tension on the wound, possibly due to chronic chemical irritation from the posts or irritation from inserting and removing the earrings.
Keloids have a tendency to enlarge during puberty and pregnancy and may resolve at the time of menopause. It has also been reported that keloid fibroblast have increased androgen binding when compared when normal fibroblasts.
The time between the onset of trauma to the development of scar can vary. Both forms typically develop within 1 to 3 months following trauma, although keloid formation may occur up to 1 year later." The majority of keloids and HTSs are asymptomatic. Most patients will be referred for cosmetic or functional concerns, but some patients may complain of pruritus. This symptom can be explained by an overabundance of mast cells as well as increased histamine levels found within keloid tissue and may increase in intensity during times of active keloid growth.
Apart from the extension of keloid tissue beyond the confines of the original scar, the appearance of keloids and HTSs is similar. In the Caucasian population, they often appear as a raised, firm, reddened tissue outgrowth that has a tendency to pallor over time. In more darkly pigmented individuals, these lesions are uniformly hyperpigmented with little if any color change over time.
The most common location for the development of keloids in the head and neck is the earlobe. In a retrospective review of head and neck keloids over 15 years, Lindsey and Davis found that 55% (111/202) of the keloids occurred on the earlobe. Of these cases, 110 developed following ear piercing. The next most likely area included the deltoids and trapezius (43/202), followed by the sternal notch (15/202), and then the postauricular area (11/202). Keloids of the chin, fore-head, lateral face, and neck were relatively uncommon (Table 1). In this review, there were no cases of keloids that occurred within the midface or around the upper or lower eyelids.'s
Malignant transformation of keloids has been re-ported in several poorly documented cases.36 Because the presentation of keloids may be similar to that of cutaneous malignancies or dermatofibroma sarcoma protuberans, histopathologic confirmation may be necessary to exclude malignancy.
As previously indicated, it is imperative for the head and neck surgeon to properly identify the type of scar as a wound contracture, hypertrophic scar, or keloid as this information will dictate the most effective form of treatment. A scar contracture can be identified by its restrictive nature as well as its confinement to the area of trauma and its lack of fibrous tissue outgrowths. Keloids and HTSs, on the otherhand, all have some degree of fibrous outgrowth. HTSs remain with the confines of the wound and typically decrease in size over time as op-posed to keloids, which may have phases of quiescence followed by reactivation and enlargement.
As with most things in medicine and life, "an ounce of prevention is worth a pound of cure." This old adage certainly applies to all scars. The avoidance of scar contractures starts with careful planning of the surgical incision. Incisions that are placed parallel to relaxed skin tension lines or that may have irregular angles are more likely to heal in a satisfactory manner without functional or cosmetic problems. Additional strategies and techniques useful in preventing scar contractures were published in the mid-1960s and have led to the wide-spread use of pressure, positioning, splints, and rangeof-motion (ROM) exercises in an attempt to prevent the development of scar contractures 3739 The exact mechanism of splints is unclear. Linares et al. described a form-fitting neck splint and face mask utilized to de-crease the formation of scar contractures in patients with significant burns to the face and neck.40
Despite the surgeon's best efforts, scar contracture undoubtedly occurs. In most cases, surgical intervention results in significant improvement but should not be undertaken until the wound-healing phase has been completed, between 6 and 12 months.
Z-plasties, multiple Z-plasties, and local flap re-construction are often necessary to adequately release scar contracture.6 Webbing of the medial canthus, oral commissure, and neck are especially amenable to single or multiple Z-plasty reconstruction. It is important to utilize pressure and ROM exercises to prevent contracture development following revision. In addition, the use of triamcinolone acetonide (10 mg/ml; Kenalog 10, Westward-Squib, Buffalo, NY) intralesional injection
Table 1 Common Locations for the Development of Keloids
98B, 10W, 3A
110 Piercing, IT
30T 101, 2S, 1 BT
8T, 4ST, 31
3B, 1W, 1A
3T 11, 1 S
There was a total of 202 patients: 154 Blacks, 44 Whites, and 4 Asians. A total of 31 recurrences were re-ported. T indicates trauma; I, insect bite or sting, S, surgical trauma; BT, blunt trauma.34 Modified from Lindsey and Davis, Archives of Otolaryngology, 1997.
Hypertrophic Scars and Keloids
Although a plethora of treatments exists for HTSs and keloids, no single treatment has been particularly successful, and results are moderately successful at best. The treatment of HTSs and keloids begins with appropriate surgical planning and gentle handling of the soft tissue. Incisions should be oriented along the lines of relaxed skin tension to minimize tension, dead space should be eliminated, and suture should be minimized to reduce foreign body reaction. Favorable suture material has been studied extensively and remains controversial. In general, suture materials stimulate an inflammatory response. Foreign body reaction in the wound is more extensive with the absorbable compared with non-absorbable sutures, multifilamentous compared with monofilamentous sutures, and inflexible and superficially implanted sutures.41 Treatment begins by educating the patient about the etiology of the scarring process. It has been our experience that these patients are in search of a panacea, of which there is none. All protocols are individualized, but the standard approach to keloids and HTSs begins with corticosteroid injection followed by surgical excision and pressure dressings. Al-though the remainder of this article deals with individual treatments, to obtain the best outcome a combination approach is mandatory.
The use of intralesional as well as topical corticosteroid has enjoyed extensive coverage in the literature and is the mainstay of the treatment of HTSs and keloids.6,21,42-44 The success of corticosteroids on reducing scar formation stems from its ability to decrease fibroblast proliferation, collagen synthesis, and glycosaminoglycan synthesis as well as suppress inflammatory mediators.6,21 In a developing keloid or HTS treatment is begun with direct, serial, intralesional injections. Triamcinolone acetonide (10 mg/ml; Kenalog 10, Westward-Squib, Buffalo, NY) is injected intralesionally with a 25- or 27-gauge needle at 4- to 6-week intervals. Injections are discontinued when the scar is stable, when surgical intervention is imminent, or if side effects develop. The steroid solution must be injected directly into the lesion. Extravasation into the surrounding normal tissue may result in tissue atrophy, hypopigmentation, and telangectasia.
The treatment of preexisting keloids begins with three, monthly, intralesional injections of triamcinolone acetonide (40 mg/ml; Kenalog 40, Westward-Squib, Buffalo, NY) mixed with equal parts of 2% lidocaine 1:100,000 epinephrine (Table 2). Although the effectiveness of intralesional corticosteroids prior to excision is debatable, this regime is critical for several reasons. First, rare forms of keloids and HTSs are extremely responsive to intralesional injections alone. Second, al-though mixed with anesthetic, these injections can cause a burning sensation, patients need to be aware of the level of discomfort because of the necessity of postexcisional injections. Finally, because the treatment demands close long-term follow-up, pretreatment compliance is important to assess.
An alternative to injection is the use of topical steroids. Because of their relatively poor tissue absorption through intact or sutured skin, topical steroids help to prevent abnormal scar development in relatively superficial lesions only, such as those occurring from dermabrasion.6.45 The use of 1% hydrocortisone or Flurandrenolide-impregnated tape can prevent or decrease abnormal scarring with these superficial-type wounds.
Druit first described surgical excision of keloid tissue in 1844.46 Although surgical excision is the most long-standing, simplest, and only definitive way of removing keloid tissue, its effectiveness as a single mode of treatment is limited and sometimes futile. Recurrence rates following surgical excision alone approach over 80%. Some authors have reported rates as high as 100%, with the vast majority of keloids redeveloping within the first 2 years following excision.47'4s Almost every aspect of surgical excision has been debated, including type of instrument used to make the incision, total versus subtotal excision, healing by secondary intention versus primary closure, as well as suture type. Gentle handling of tissues, minimal use of cautery, judicious use of suture material, removal of residual inflammatory tissue, and the reorientation of scars within the lines of minimal tension are generally accepted as necessary components.
Table 2 KeloidTreatment Protocols
Time Treatment Regimen
0 . Injection 7: Equal parts triamcinolone acetonide, 40 mg/mL, and 2% lidocaine with 1:100,000 epinephrine
1 month . Injection 2: Same as injection 1
1 month . Injection 3: Same as injection 1
1 month . Surgical excision of keloid and injection 4: triamcinolone acetonide, 10 mg/mL
5-7 days . Suture removal-application of silicone gel sheeting or pressure dressing
1-3 weeks . Injection 5:1 part triamcinolone acetonide, 40 mg/mL, to 3 parts 1% lidocaine with 1:100,000 epinephrine
4-6 weeks . Injection 6: Same as injection 5; begin tapering gel sheeting
4-6 weeks . Injection 7: Same as injection 5
4-12 weeks . Continue injections as needed to prevent recurrence, consider pressure dressing at signs of recurrence
Each time given is counted from the previous step of the protocol., Modified from Sherris et al. Otolaryngol Din North Am, 1995.
The use of a CO2 laser versus cold steel for excision of keloids has not been shown to reduce the rate of recurrence when used as a single treatment modality.49s0 Leaving a rim of tissue behind following excision has shown to result in decreased recurrence and may offer some advantages. Engrav et al. reported an improved outcome with intramarginal versus extramarginal excision.51 As indicated previously, surgical excision alone is likely to result in recurrence, and therefore intralesional corticosteroids are recommended following excision. These injections are continued every 4 to 6 weeks for 6 months. Patients are followed every 3 months for a minimum of 2 years.
The use of pressure to treat keloids was initially de-scribed in 1835.21 It was not until the 1960s that the use of pressure in both the prevention and treatment of keloids, HTSs, and scar contracture became popularized by physicians treating burn victims at the Shriners Hospital.
Some of the explanations proposed include a decrease in blood flow with a resultant decrease in alpha2-macroglobulin and a subsequent increase in collagenase-mediated collagen breakdown, normally inhibited by alpha2-macroglobulin.
Lower levels of chondroitin 4-sulfate, with a subsequent increase in collagen degradation.
Decreased scar hydration, resulting in mast cell stabilization and subsequent decrease in neovascularization and extracellular matrix production.
Excessive hypoxia, resulting in fibroblast degeneration and collagen degradation.
The use of pressure in the head and neck is limited due to vital structures and irregular contours. The area most amenable to the use of pressure dressings is the ear lobe. An ear press, which is a modification of a pressure clip described by Agrawal et al., is used for the treatment of patients with ear lobe keloids.S2 Pressure application is begun immediately following reepithelialization of the wound. Patients should wear these clips continuously for the first several weeks, removing them only for hygienic purposes, and then slowly taper their use over several months. Patient compliance is a major factor with the use of pressure clips. The modification to the original design of the ear press is its ability to accommodate silicone gel sheeting (Fig. 3A, B).
Perkins and Walis first described the use of silicone gel sheeting for the treatment of scars in burn patients in 1982.53 Since that time, several articles have been published documenting improved appearance of scars following the application of a semi-occlusive silicone gel sheet.54,55 Silicone gel sheeting is fabricated from cross-linked silicone polymers of a 3.5-mm thickness.21 The exact mechanism of action of silicone gel sheeting is unclear. It has been postulated that the occlusive nature of gel sheeting decreases evaporative water loss and thus improves hydration. It is believed that hydration results in decreased capillary activity, a decrease in inflammatory and mitogenic mediators, and a decline in collagen synthesis.21 There is evidence that the use of nonsilicone gel sheeting produces similar improvements in scar appearance, indicating that occlusion exclusive of silicone contributes to improvement.
The application of silicone gel sheeting should begin as soon as reepithelialization has occurred. Daily application for a minimum of 12 hours is recommended and is tapered over a 1-month period. The exact duration that imparts maximum benefit is unknown and re-quires further investigation. If keloids or HTSs begin to reoccur, corticosteroid injection as well as the application of gel sheeting should be resumed. In children, the use of a silicone cream is recommended due to ease of application.
Debeurman and Gougerot first described the use of X-ray for the treatment of keloids in 1906.58 The use of radiation therapy is controversial because of the risk of secondary malignancy, although only a few cases have been described.59-61 Timing, duration, dose, and therapeutic effect remain controversial. Benefit may be de-rived from the destruction of proliferating fibroblasts. The total dose recommended for the treatment of keloids varies from 1500 to 2000 rads fractionated over 7 to 10 days.
The success of radiotherapy (RT) alone for the treatment of keloids is poor, with a reported recurrence of 50 to 100%.62 In 1961, Cosman et al. introduced the concept of postexcision radiation therapy, with promising results.63 Since that time, multiple studies have re-ported success rates of >80% with the use of RT following scar excision.64,6s Recurrences typically developed within 1 to 3 years. The use of interstitial RT with iridium-192 implanted into the wound site following scar excision has been described with recurrence rates ranging from 20 to 40%.21,66,67 The proposed advantages of interstitial implants include ease of application, irradiation of a limited volume, and comparable efficacy to external beam therapy.21
The most common sequelae following RT is hyperpigmentation. Due to the reported risk of malignancy following radiation, the use of postexcision RT should be reserved for use in only the most functionally debilitated patients. RT is contraindicated in children as well as in areas of high potential carcinogenesis such as the breast and thyroid tissue.
The use of interferon (INF) -alpha, -beta, and -gamma for the treatment of keloids down-regulates the production of types I, II, and III collagen.68.69 The resultant down-regulation develops secondary to decreased mRNA.21,70 Larrabee et al. evaluated the effects of intralesional IFN-gamma in a dose of 0.01 mg or 0.1 mg injected weekly over a 10-week interval.68 They found some degree of shrinkage in all keloids following injection, with 5 of 10 patients enjoying over a 50% response, whereas the other 5 patients received less than a 50% response. Only one patient had a complete response with no evidence of recurrence at 18 weeks. Similar findings were reported by Granstein et al.
Berman and Flores reported on 124 patients treated with excision only (n = 43), excision and intralesional steroid injection (n = 64), or excision followed by intralesional injection of IFN-alpha-2b (n = 16). They reported a significant difference in the rate of keloid recurrence with the IFN-alpha-2b (19%) versus excision alone (51%) or with postexcisional corticosteroid injections (58%).72
The most common reported adverse clinical effects include fever, chills, night sweats, fatigue, myalgia, and headache. Laboratory abnormalities include reversible granulocytopenia, elevation of hepatic transaminase, and serum triglycerides. These adverse effects occur in a dose-dependent fashion.
As we begin to understand the mechanism responsible for abnormal wound healing, additional treatment modalities are being introduced. Many cases are anecdotal. Some novel studies that have had positive results show promise for the future.73,74
Gassner et al. reported a statically significant improvement in the appearance of scars when the forehead was paralyzed with botulinum toxin.74 The authors hypothesized that temporary paralysis of the underlying musculature surrounding the wound resulted in de-creased wound tension and improved appearance as a result. Although initial results appear promising, further investigation into this treatment modality is needed.
Numerous additional interventions have been at-tempted, including colchicine,75 beta-aminocaproic acid, d-penicillamine,76 topical vitamin A and E,77 as well as zinc-impregnated cloth.78 Although all these interventions address specific mechanisms within the healing process, they have not resulted in dramatic improvements in wound appearance or the treatment of keloids 21
The development of scar contractures, hypertrophic scars, and keloids is a frustrating problem for both patients and physicians. The exact etiology and pathogenesis remains equivocal, and the current treatment options are only marginally successful. Appropriate planning of incisions and gentle handling of tissue is imperative to prevent this problem. Combinations of treatment modalities are most successful. Additional re-search into both normal and abnormal wound healing is warranted to achieve a better understanding of these processes.
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