Normal wounds have stop signals that halt the repair process when the dermal defect is closed

and
epithelialization is complete. When these signals are absent or ineffective, the repair process may
continue unabated and cause excessive scar formation.

The underlying molecular mechanisms leading to excessive repair are not yet known. Profibrotic
cytokine overexpression has been implicated.115,116 A lack of programmed cell death, apoptosis, at
the conclusion of repair with continued presence of activated fibroblasts secreting ECM components
has also been implicated.

To minimize visible scar on skin, elective incisions are least noticeable when they are placed parallel to
the natural lines of skin tension (Langer's lines). This placement has two advantages: the scar is
parallel or within a natural skin crease, which camouflages the scar, and this location places the least
amount of tension on the wound.

Wound tension widens the scar. Sharply defined and well-aligned wound edges that are
approximated without tension heal with the least amount of scar.
Scar formation is the ultimate outcome of wound
repair in children and adults.

Scars (also called cicatrices) are macroscopic fibrous tissue that visibly replaces normal skin
after injury. There is a wide spectrum of skin scarring postwounding, including scarless fetal wound
healing, fine-line (normal) scars, stretched (widespread) scars, atrophic (depressed) scars, scar
contractures, hypertrophic scars, and keloids.
Postsurgical scar assessment is fundamental for a complete functional evaluation and as an
outcome measure. The Vancouver Scar Scale is the most widely used rating scale for scars but the
Patient and Observer Scar Assessment Scale is recognized as the most comprehensive tool, taking
into account the important aspect of the patients perspective. Recently, a new scale, called the Stony
Brook Scar Evaluation Scale, has been proposed.

NORMAL WOUND HEALING

MECHANISME OF SCAR FORMATION

 Inflammation, fibroplasia, formation of granulation
tissue, and scar maturation

Acute inflammatory response

Fibroblasts proliferation
Synthesizing collagen and fibrin

Fibroblasts Myofibroblasts
Collagen deposition, wound contraction

Scar formation

Epithelialmesenchymal interactions probably continuously regulate skin integrity and

homeostasis. In addition, over 612 months, the acellular matrix is actively remodeled from a
mainly type III collagen backbone to one predominantly composed of type I collagen. This process is
carried out by matrix metalloproteinases that are secreted by epidermal cells, endothelial cells,
fibroblasts, and the macrophages remaining in the scar, and it strengthens the repaired tissue.
However, the tissue never regains the properties of uninjured skin.

Fibroblasts at the wound site originating from surrounding tissues as well as supplied in the
form of marrow-derived blood-borne cells are recognized as the primary drivers of scar formation.
Platelets, macrophages, T lymphocytes, mast cells, Langerhans cells, and keratinocytes are
directly and indirectly involved in the activation of fibroblasts, which in turn produce excess
ECM. Dermal scarring can result in loss of function, movement restriction, and disfigurement. The
mechanism of scar formation involves inflammation, fibroplasia, formation of granulation tissue,
and scar maturation. In response to tissue injury, the acute inflammatory response is followed by
the proliferation of fibroblasts, which are cells responsible for synthesizing various tissue
components, including collagen and fibrin. During the acute inflammatory phase, circulating
progenitor cells migrate to injured tissue. Rapid cellular proliferation occurs, which ultimately results
in the formation of new blood vessels and epithelium. Fibroblasts then differentiate into
myofibroblasts, which are the cells responsible for collagen deposition and wound contraction.
Scar formation ultimately results from excess accumulation of an unorganized ECM.

Sensory nerves, including nonmyelinated C fibers and delta fibers, traverse all cutaneous layers,
including the epidermis. These fibers run parallel to capillaries coursing around follicular
complexes. A higher density of nerve fiber is associated with scar tissue. Unlike diabetic tissues,
hypertrophic scar has excessive neuropeptide activity. In addition, proinflammatory substance P
concentration is greater in the hypertrophic scar samples when compared with normal uninjured
skin. High substance P and low neutral endopeptidase activity in scar tissue is believed to
induce an exuberant neuroinflammatory response contributing to scar formation.

HYPERTHROPYC SCAR

Constitutively active proliferative phase

Unique to humans (do not occur in animals)

Have not overgrown the original wound boundaries but are instead raised

Self-limited type of over healing can regress with time

Most common: joint surfaces(extremities), sternum, neck.

The pathophysiology of hypertrophic scar formation involves a constitutively active proliferative

phase of wound healing. The scar tissue has a unique structural makeup that is highly vascular,
with inflammatory cells and fibroblasts contributing to an abundant and disorganized matrix
structure. The net result is that the original skin defect is replaced by a nonfunctional mass of tissue.

Beyond these observations, investigations into the pathophysiology of the disease have been limited
by the absence of a practical animal model and have relied upon the use of human pathological
specimens. These studies are problematic in that such specimens represent the terminal stages of
the scarring process and may not contain the initiating factors that originally led to the
development of the disease.

While animal models have provided some insight into the genetics and pathogenesis of cutaneous
fibrosis, it is unclear how closely the process of hypertrophic scarring in these models resembles
that seen in humans. Specifically, it is unknown whether the same factors that initiate
hypertrophic scarring in these species are involved in human disease.

Mast cells and fibrocytes, circulating bone marrow-derived progenitor cells that differentiate
into fibroblasts, are proposed to promote tissue fibrosis, especially in burn patients. Both cell
types are present in hypertrophic scar tissue and secrete profibrotic cytokines. Mast cell
histamine enhances collagen production in fibroblasts and is elevated in the plasma of patients
developing hypertrophic scar.
The keratinocytes regulatory role in this scenario has gained more interest in the past years.
By secreting various factors, keratinocytes stimulate migration, proliferation, and matrix
remodeling in a paracrine and autocrine way. Increased collagen production was found in
normal fibroblasts co-cultured with hypertrophic scar-derived keratinocytes.

Hypertrophic scar fibroblasts produce more connective tissue growth factor (CTGF/CCN2) after TGF-
stimulation. CTGF stimulates chemotaxis, proliferation, MMP expression and ECM production.
The proteoglycan decorin binds TGF-and regulates collagen fibrillogenesis by downregulating TGF-
production.

In contrast to normal dermal fibroblasts, hypertrophic scar-derived fibroblasts secrete less

decorin and probably contribute thereby to sustained TGF- activity.

A distinct histological difference between keloids and hypertrophic scars is the predominance of
myofibroblasts in hypertrophic scar tissue.

Controversial findings exist concerning the persistence of fibroblasts after accomplished healing.
Programmed cell death is thought to underlie myofibroblast disappearance after wound closure.
Whether fibroblast resistance to apoptosis leads to excessive scarring is still unknown.

KELOID
Keloid scarring, also known as keloid disease, is a locally aggressive benign fibroproliferative scar
that continually grows beyond the confines of the original wound and invades into surrounding
healthy skin. Unlike hypertrophic scars which stay within the boundaries of the original wounds and
usually regress spontaneously, keloids grow beyond the boundaries of the original wounds and
rarely regress. These pathological scars are not only aesthetically displeasing, but can also be both
painful and functionally disabling, causing patients both physical and psychological distress.
There is a strong genetic predisposition to keloid disease.

First, keloids are more common in ethnicities with darker pigmented skins and have been
reported to be 515 times more prevalent in blacks than in whites. Familial heritability and
prevalence in twins also support the concept of the genetic susceptibility to keloid scarring. The
major pathways involved in keloid disease include apoptosis, mitogen-activated protein kinase,
TGF-, IL-6, and plasminogen activator inhibitor-1.

Hypertrophic Scar Keloid

Scar grows within its Scar grows more than its
boundaries boundaries
Widened scar, hyper / hypo Red appearance, muscle,
pigmented rigid
Not painfull or itchy Itchy and painfull
Proximal flexor, joints Ear lobules, chest, deltoid,
Can regress with time. face
Cannot regress with time.

Sudjatmiko G. Penyembuhan luka normal. Dalam: Petunjuk Praktis Ilmu Bedah Plastik Rekonstruksi. Edisi ketiga. Yayasan Khazanah
Kebajikan. Jakarta: 2011.
 No clear histologic difference between hypertrophic scar and
keloid has been demonstrated.
Hypertrophic scars and keloids are both fibroproliferative
disorders of wound repair with excess healing.
Both fibroblasts have an upregulation of collagen synthesis,
deposition, and accumulation.
It may be that keloid fibroblasts respond to a greater degree than do
hypertrophic scar fibroblasts to the signals stimulating scar formation.

Lorenz HP, and Longaker MT. Wound Healing: Repair Biology and Wound and Scar Treatment. In: Mathes SJ and Hentz VR. Plastic
Surgery. Saunders. 2005. p219-22
Before antiscarring therapy is instituted, an accurate description and classification of the scar type
are useful. This assists with assessment of the outcome after late follow-up. A clinically based scar
classification scheme has been proposed by the International Advisory Panel on Scar Management,
which is composed of plastic surgeons, burn surgeons, and dermatologists (Table 15.6). Consistent
and accurate diagnosis of scar types is essential for optimal management and useful literature
interpretation.
Many treatment modalities have been developed for the prevention and management of
hypertrophic scarring and keloids. Many of the techniques have well documented and time-proven
clinical use, but few have been supported by randomized, prospective studies.

Therapies

This inherent problem makes choosing the best treatment modality difficult on the basis of objective
scientific evidence. Therefore, most modalities are applied on the basis of the treating physicians
personal biases and experiences. Scar therapies, with their respective advantages and disadvantages,
are listed in Table 15.7.
Fig. 15.8 Scar management algorithm. (Reproduced from Mustoe TA, Cooter RD, Gold MH,
etal.International clinical recommendations on scar management. Plast Reconstr Surg 2002; 110: 560
571, with permission.)

Immature hypertrophic scars (red)

Once excessive scarring is identified, the International Advisory Panel on Scar Management consensus
initial management is silicone gel sheeting, steroid injection, and localized pressure therapy (Fig.
15.8). It can be difficult to predict whether immature hypertrophic scars (red, slightly raised) will
regress or progress. When erythema persists for more than 1 month, the risk of progression to
linear hypertrophic scar increases, and appropriate therapy should be started.
Linear hypertrophic scars (red, slightly raised)

Treatment options include the application of pressure garments or topical silicone sheets, 585-nm
pulsed-dye laser therapy, and re-excision. The last option is most useful in cases of excess scar due
to wound infection or dehiscence. If the original wound was closed following the basic tenets described
and healed otherwise uneventfully, re-excision with primary closure is not likely to result in an
improved scar. Recurrence of hypertrophic scar is high in these circumstances, and therefore most
plastic surgeons do not treat hypertrophic scar with excision and primary closure unless they plan
adjuvant therapy. Silicone gel has proven benefit from randomized, controlled trials and is a
recommended first-line therapy. Concurrent steroid injections are helpful for pruritic or resistant scars.
Pressure therapy can be added when feasible. Pulsed-dye laser (585 and 595 nm) treatment of
hypertrophic scars is another alternative. Light energy from the pulsed-dye laser is absorbed by
intravasal hemoglobin leading to coagulation, vessel obstruction, and tissue hypoxia with necrosis. As a
consequence, new collagen synthesis, collagen fiber realignment, and remodeling are the molecular
bases for the effects seen after pulsed-dye laser treatment.

Widespread burn hypertrophic scars (red, raised)

Extensive surface-area burn hypertrophic scars may best be treated at burn centers when
feasible. Multimodality therapies are generally used; these include silicone gel sheeting, custom-
fitted pressure garments, and physical therapy alone or with massage, electrical stimulation, or
ultrasound. Steroid injection of especially difficult areas is sometimes necessary. Laser treatment can
be useful. Surgical treatment with Z-plasty, excision and grafting, and flap reconstruction is frequently
required.

Minor keloids (red, raised)

No uniformly successful treatment for keloid scar exists. Excision and primary closure invariably result in
recurrence. Therefore, additional therapy is necessary, and its efficacy depends on the timing of the
patients presentation. Steroid injection directly into the keloid has the most benefit early in the
keloid course. Steroid has been shown to decrease collagen gene expression. Mixed with 2% plain
lidocaine in a 50 : 50 ratio, triamcinolone acetonide 10 mg/mL is commonly used initially; if no
response occurs, 40 mg/mL concentration is attempted. Silicone gel sheeting should be used
concurrently. Patients presenting with mature keloid lesions of months to years in duration that are
slowly changing respond poorly to steroid injection and silicone sheeting. Surgical excision with
adjuvant therapy including intralesional steroids, silicone sheeting, and pressure therapy is a
reasonable treatment alternative. Careful follow-up is necessary to prevent recurrence. A short
course of low-dose radiation therapy to the keloid excision site immediately after excision has been
shown to reduce the rate of recurrence.

Major keloids (dark, raised)

Major keloids are difficult to treat effectively, and many are resistant to any treatment. Surgical therapy
with all adjunctive therapies described before may still fail and result in recurrence. Radiation therapy is
generally used in this group, provided the patient is not young and accepts the possible risk of late
cancer formation. Before surgery is performed with postoperative adjuvant therapy, patients should
be counseled about the high rate of recurrence with the risk that the next keloid will be larger and
more difficult to control. As recommended by the International Advisory Panel on Scar Management,
these patients may best be treated by clinicians with a special interest in keloid treatment.

The first step toward treatment of excessive scarring is early recognition and institution of therapy after
surgery or trauma. Meticulous tissue handling, suturing, and wound management with efforts to
prevent infection are mandatory. Sun protection to reduce scar hyperpigmentation is essential. Patients
who are at increased risk of excessive scarring benefit from preventive techniques, which include
silicone gel sheeting or ointments, hypoallergenic microporous tape, and concurrent intralesional
steroid injection.

Silicone gel sheeting is widely used for hypertrophic scar and keloid treatment. Silicone gel sheeting
has a 20-plus-year history with several randomized, controlled trials that support its safe and effective
use. It is painless and thus useful for children. Proposed mechanisms of action for scar reduction
include improved hydration and occlusion, increased temperature elevation of 1C (or less) that can
affect collagenase kinetics, and change in the adhesion molecule expression of the lymphocytic
infiltrate. When treatment with silicone gel sheeting is not feasible (e.g., scar location on the face,
scalp, or neck), silicone oil-based creams are an alternative. For example, silicone-based creams are
frequently used on cleft lip repair scars, hypertrophic scars after burns, or hand injury without
allergic or other untoward reaction to date.
Microporous hypoallergenic tape can relieve tension across wounds and minimize the excessive scar
risk from shearing. Although there are no prospective, controlled studies to support its use, tape is
routinely used and recommended by many authors. The tape is applied for a few weeks after
surgery.

In patients who are at extremely high risk, such as after excision of keloid or hypertrophic scar,
concurrent intralesional steroid injections can be given prophylactically, followed by monthly
injections as necessary. Success rates, measured by no recurrence, are reported up to 92% for keloids
and 95% for hypertrophic scars at a mean follow-up of 30.5 months.