Hypertrophic scars/ Keloids

 

Salient features

 

 

·       Conventional scars are preceded by injury, immediate in onset, flat, and asymptomatic. Hypertrophic scars and kelolds are exuberant fibrous repair tissues after a cutaneous Injury.

 

·       Hypertrophic scars are raised and confined to the wound margin. Sometimes they improve spontaneously and tend to have a good response to treatment

 

·       Keloids extend beyond the wound margin, often with claw-like extensions and are delayed in onset. They seldom resolve spontaneously and response to treatment is often poor

 

Introduction

 

All wounds heal with some degree of scar formation, but the mechanisms that govern whether the result will be a fine thin scar, a prominent hypertrophic scar, or a tumor-like keloid remain unclear. The latter represent two forms of abnormal wound healing. Both are characterized by local fibroblast proliferation and excessive collagen production in response to cutaneous injury. However, their clinical, histopathologic features as well as proposed pathogenesesdiffer.

 

Epidemiology

 

There is a higher prevalence of keloids in African, African-American, Spanish and Asian populations, with an incidence ranging from 4–16%. Although the incidence of hypertrophic scars is probably higher than that of keloids, precise data are lacking. Neither entity has gender prevalence; they occur most commonly in those 10 to 30 years of age. Individuals in this age group are more frequently subjected to trauma and their rate of collagen synthesis is higher. Younger skin also possesses greater tension, as compared to older skin which has less elasticity and is more redundant.

 

Etiology

 

Proposed etiologic factors include: genetic predisposition; depth, type and location of the skin injury or wound; degree of tension; local infection or inflammation; and hormonal influences. There is often a familial tendency to develop hypertrophic scars and keloids and possibly an autosomal dominant mode of inheritance with incomplete clinical penetrance and variable expression. A range of skin injuries can lead to abnormal scarring, from lacerations, burns, surgical excisions and skin piercings to injections (vaccines, tattoo inks) and cutaneous inflammation skin disease (e.g. acne vulgaris, insect bites or infections). Moreover, tension is constantly transmitted to the skin from the underlying cartilaginous and bony skeleton, and skin tension can be aggravated by loss of tissue, as occurs with surgical excisions. In addition, hormonal influences have been proposed as an explanation for the appearance of keloids at or after puberty and their resolution following menopause, as well as reports of the onset or enlargement of keloids during pregnancy. There also is an apparent association with melanin pigment, as albino and vitiliginous skin do not form keloids. Lastly, some genetic disorders such as Goeminne syndrome and Bethlem myopathy in which spontaneous keloids are a characteristic feature. Keloid may also arise spontaneously, without history of injury, usually in presternal site.

 

Pathogenesis

 

In most studies, keloids and scars show the same biochemical and pathologic abnormalities. Keloids express increased levels of the gli-1 protein, an oncogene product also present in neoplasms such as basal cell carcinoma. Collagen synthesis and collagenase activity are increased in both keloids and hypertrophic scars. α1-Globulin (a collagenase inhibitor usually not present in normal scars) may contribute to increased collagen deposits. Hypertrophic scars have decreased levels of the profibrotic agent tumor necrosis factor. Within keloids, collagen synthesis by fibroblasts is markedly increased as is production of transforming growth factor (TGF)-β. TGF-β has been shown to play a pivotal role during the proliferative phase of wound healing. Expression of TGF-β1 or TGF-β2 leads to an increase in scarring, whereas expression of TGF-β3 is associated with a reduction in scarring. This has led to the introduction of therapies based upon the biologic effects of these different forms of TGF, e.g. injections of recombinant TGF-β3, injections of mannose-6-phosphate which inhibits TGF-β1 and TGF-β2 signaling. Carbon dioxide laser treatment reduces TGF- β1 levels in keloids.

 

Factors Associated with Keloids

 

Increased	Decreased
Transforming growth factor-β Platelet-derived growth factor Vascular endothelial growth factor Collagen Cytokines (e.g., IL-1, IL-6) Cyclooxygenase 2 Plasminogen activator inhibitor-1 Matrix metalloproteinase-2	SMAD proteins (e.g., SMAD7) Apoptosis

+

 

+Clinical Features

 

Although distinguishing a hypertrophic scar from a keloid clinically can sometimes be difficult, especially if the lesion is small or of recent onset, each has several characteristic features. Both keloids and hypertrophic scars have a smooth surface and are firm to palpation. The surface of keloids is usually smooth, but can be nodular and borders are often smooth, but can be irregular. The surface and borders of hypertrophic scars are always smooth and regular. Keloids and hypertrophic scars are often painful, hyperesthetic or pruritic and occasionally inhibit normal motion of adjacent tissues. Ulceration can occur. The color can vary from pink–purple (early lesions) to skin-colored to hypo- or hyper pigmented. While keloids may be more elevated above the skin surface than hypertrophic scars, the key difference is that keloids extend beyond the boundary of the original wound into adjacent normal skin, often with claw-like extensions resembling the pincers of a crab (in Greek, chelè means claw). In contrast, hypertrophic scars remain confined to the site of the original injury.

 

Most keloids appear within one year of an injury, although the intervening interval may be up to 24 years. Hypertrophic scars usually develop within a few weeks to months after wounding, and they frequently flatten spontaneously within 1 to 2 years. Keloids, on the other hand, do not regress over time. While both favor sites of increased wound tension such as the upper trunk, shoulder, mandible and upper outer arm, keloids can also develop in sites such as the earlobe, where there is minimal tension. In addition, keloids can form spontaneously, most often in the midchest region.

 

Differences between Keloids and Hypertrophic Scars

 

	Keloid	Hypertrophic Scar
Age	Especially third decade	Any
Preceded by injury Onset after injury	Not always Delayeda	Yes Immediate
Erythema Profile Symptomatic Growth beyond border of original wound	Varies Raised Yes Yes	Prominent Raised Yes No
Spontaneous regression	Rare	Occasional
Recurrence	Common	Rare
Distorted shape Treatment response	Common Poor	Rare Good

^aMay occur spontaneously.

 

 

Characteristics of hypertrophic scars and keloids

 

(A) Hypertrophic scar: This appears as a red, raised scar that does not extend beyond the boundaries of the original injury. They have nodular collagen deposits containing a-SMA producing myofibroblasts that are involved in scar contracture. Hypertrophic scars can regress with time. The main findings from studies on the role of TGF-b signaling and hypertrophic scarring are indicated.

 

(B) Keloid: This appears as a shiny and smooth protuberance ranging from pink to purple in color and extends beyond the boundaries of the original wound. Unlike hypertrophic scars, keloids do not have nodular collagen deposits, a-SMA-producing myofibroblast, do not undergo scar contracture, and do not regress with time. 

 

Pathology

 

In hypertrophic scars, there is an increase in both the number of fibroblasts and the density of collagen fibers within the dermis, both of which are oriented parallel to the skin surface. Keloids are characterized by the presence of whorls and nodules of strikingly thick, glassy, homogeneous collagen bundles that are composed of densely packed fibrils and oriented haphazardly throughout the dermis (keloidal collagen). Early on, there are abundant deposits of fibrillary collagen within the reticular dermis of keloids, while mature lesions often have the characteristic thick sclerotic collagen. In longstanding keloids, there may be a return to the earlier fibrillary pattern.

 

It is noteworthy that keloidal collagen may be absent in up to 45% of keloids. In scars with no detectable keloidal collagen, histologic features that favor a keloid include: no flattening of the epidermis; a lack of fibrosis within the papillary dermis; a tongue-like advancing edge as the scar tissue extends through the reticular dermis; a horizontal cellular fibrous band within the upper reticular dermis with a sharp demarcation from the normal-appearing papillary and reticular dermis; and prominent fascia-like fibrous bands in the deeper portion of the scar.

 

Shading indicates differences.

 

Diagnosis and differential diagnosis

Clinical diagnosis; biopsy not warranted unless there is clinical doubt, because this may induce new hypertrophic scarring. Differential diagnosis includes dermatofibroma, dermatofibrosar- coma protuberans, desmoid tumor, scar with sarcoidosis, and foreign-body granuloma.

 

Course and prognosis

Hypertrophic scars tend to regress in time becoming flatter and softer. Keloids, however, may continue to expand in size for decades.

 

Treatment

 

The management of keloids and hypertrophic scars continues to challenge clinicians, and there is no universally accepted treatment al­gorithm. Prevention remains the best strategy in predisposed patients, including avoidance of nonessential surgery in high-risk anatomic sites and attention to postsurgical wound care. There is limited evidence to support over-the-counter scar reduction products such as silicone cream and silicone gel sheeting and topical creams containing vitamin E. 

 

Intralesional glucocorticoid is the major first-line therapy for flattening hypertrophic scars and keloids. lntralesional injection of triamcinolone (10 to 20 mglmL) every month may reduce pruritus or sensitivity of lesion, as well as reduce its volume and flatten it. It works quite well in small hypertrophic scars but less well in kcloids. An alternative, especially for needle-averse individuals, is clobetasol propionate 0.05% cream under silicone dressing occlusion. Intralesional or topical corticosteroids may be combined with intralesional 5-fluorouracil.

 

Surgical revision of both hypertrophic scars and keloids must be undertaken with caution given the high recurrence rates. Surgery alone is generally not recommended for keloids, as they often recur as larger lesions. An exception to this may be keloids on the earlobes.

 

Cryosurgery has been used successfully and is often combined with intralesional triamcinolone. 

 

Pulsed dye laser therapy has become popular as a modality for postsurgical scar reduction and is associated with few side effects.

 

Due to theoretical concerns regarding carcinogenesis, radiotherapy is reserved primarily for treatment-resistant keloids. However, current postoperative protocols limit total exposure and vary from 12–16 Gy in 3–4 fractions to 20 Gy in 5 fractions, beginning within 24–48 hours following surgery.

 

Potential therapies based upon insights into pathogenesis include recombinant TGF-β3 (avotermin), human recombinant IL-10, and mannose-6-phosphate which is a potent inhibitor of TGF-β1 and TGF-β2 signaling.

 

 

Prevention

Individuals prone to hypertrophic scars or keloids should be advised to avoid cosmetic procedures such as ear piercing. Scars from bums tend to become hypertrophic and can be prevented by compression garments.