Professional Documents
Culture Documents
Supervised by
Prof Dr Raafat Riyad Gohar
Professor of General and Plastic Surgery
Faculty of Medicine, Cairo University
Prof Dr Mostafa Ahmed Abolsaoud
Professor of General and Plastic Surgery
Faculty of Medicine, Cairo University
Prof Dr Hamdy Mohamed Zawam
Professor of Oncology
Faculty of Medicine, Cairo University
Faculty of Medicine
Cairo University
2010
Skin Anatomy
Skin Anatomy
Introduction
The skin covers the entire external surface of the human body and
is the principal site of interaction with the surrounding world. It serves as
a protective barrier that prevents internal tissues from exposure to trauma,
ultraviolet radiation, temperature extremes, toxins, and bacteria. Other
important
functions
include
sensory
perception,
immunologic
Skin Anatomy
development. Teeth, hair, and hair follicles are formed by the epidermis
and dermis in concert, while fingernails and toenails are formed by the
epidermis alone. Hair follicles, sebaceous glands, sweat glands, apocrine
glands, and mammary glands are considered epidermal glands or
epidermal appendages, because they develop as downgrowths or
diverticula of the epidermis into the dermis ( Moore, 1998).
The definitive multi-layered skin is present at birth, but skin is a dynamic
organ that undergoes continuous changes throughout life as outer layers
are shed and replaced by inner layers. Skin also varies in thickness among
anatomic location, sex, and age of the individual. This varying thickness
primarily represents a difference in dermal thickness, as epidermal
thickness is rather constant throughout life and from one anatomic
location to another. Skin is thickest on the palms and soles of the feet (1.5
mm thick), while the thinnest skin is found on the eyelids and in the
postauricular region (0.05 mm thick). Male skin is characteristically
thicker than female skin in all anatomic locations. Children have
relatively thin skin, which progressively thickens until the fourth or fifth
decade of life when it begins to thin. This thinning is also primarily a
dermal change, with loss of elastic fibers, epithelial appendages, and
ground substance ( Burns, 2004 ).
-2-
Skin Anatomy
Epidermis
The epidermis contains no blood vessels and is entirely dependent
on the underlying dermis for nutrient delivery and waste disposal via
diffusion through the dermoepidermal junction. The epidermis is a
stratified squamous epithelium that consists primarily of keratinocytes in
progressive stages of differentiation from deeper to more superficial
layers. The named layers of the epidermis include the stratum
germinativum, stratum spinosum, stratum granulosum, and stratum
corneum. The stratum germinativum or the basal layer is immediately
superficial to the dermoepidermal junction. This single cell layer of
keratinocytes
is
attached
to
the
basement
membrane
via
hemidesmosomes.
As keratinocytes divide and differentiate, they move from this deeper
layer to the more superficial layers. Once they reach the stratum corneum,
they are fully differentiated keratinocytes devoid of nuclei and are
subsequently shed in the process of epidermal turnover. Cells of the
stratum corneum are the largest and most abundant of the epidermis. This
layer ranges in thickness from 15-100 or more cells depending on
anatomic location and is the primary protective barrier from the external
environment.
Melanocytes, derived from neural crest cells, primarily function to
produce a pigment, melanin, which absorbs radiant energy from the sun
and protects the skin from the harmful effects of ultraviolet radiation.
Melanin accumulates in organelles termed melanosomes that are
incorporated into dendrites anchoring the melanosome to the surrounding
-3-
Skin Anatomy
keratinocytes.
Ultimately,
the
melanosomes
are
transferred
via
2004).
-4-
Skin Anatomy
Dermis
The primary function of the dermis is to sustain and support the
epidermis. The dermis is a more complex structure and is composed of 2
layers, the more superficial papillary dermis and the deeper reticular
dermis. The papillary dermis is thinner, consisting of loose connective
tissue containing capillaries, elastic fibers, reticular fibers, and some
collagen. The reticular dermis consists of a thicker layer of dense
connective tissue containing larger blood vessels, closely interlaced
elastic fibers, and coarse bundles of collagen fibers arranged in layers
parallel to the surface.
The reticular layer also contains fibroblasts, mast cells, nerve endings,
lymphatics, and epidermal appendages. Surrounding the components of
the
dermis
is
the
gel-like
ground
substance,
composed
of
the
subcutaneous
Skin Anatomy
Dermoepidermal Junction
The dermoepidermal junction is an undulating basement membrane
that adheres the epidermis to the dermis. It is composed of 2 layers, the
lamina lucida and lamina densa. The lamina lucida is thinner and lies
directly beneath the basal layer of epidermal keratinocytes. The thicker
lamina densa is in direct contact with the underlying dermis. These
structures are the target of immunologic injury in bullouspemphigoid and
epidermolysisbullosa.
Dermal papillae from the papillary dermis contain a plexus of capillaries
and lymphatics oriented perpendicular to the skin surface. These
fingerlike projections are surrounded by similar projections of the
epidermis. This highly irregular junction greatly increases the surface
area over which oxygen, nutrients, and waste products are exchanged
between the dermis and the avascular epidermis ( Carlson, 1994 ) .
-6-
Skin Anatomy
Epidermal Appendages
Epidermal appendages are intradermal epithelial structures lined
with epithelial cells with the potential for division and differentiation.
These are important as a source of epithelial cells, which accomplish reepithelialization should the overlying epidermis be removed or destroyed
in situations such as partial thickness, burns, abrasions, or split-thickness
skin graft harvesting. Epidermal appendages include sebaceous glands,
-7-
Skin Anatomy
sweat glands, apocrine glands, mammary glands, and hair follicles. They
often are found deep within the dermis, and in the face may even lie in
the subcutaneous fat beneath the dermis. This accounts for the remarkable
ability of the face to re-epithelialize even the deepest cutaneous wounds
(Carlson M, 1994).
Sebaceous glands
Sebaceous glands, or holocrine glands, are found over the entire surface
of the body except the palms, soles, and dorsum of the feet. They are
largest and most concentrated in the face and scalp where they are the
sites of origin of acne. The normal function of sebaceous glands is to
produce and secrete sebum, a group of complex oils including
triglycerides and fatty acid breakdown products, wax esters, squalene,
cholesterol esters, and cholesterol. Sebum lubricates the skin to protect
against friction and makes it more impervious to moisture.
Sweat glands
Sweat glands, or eccrine glands, are found over the entire surface of the
body except the vermillion border of the lips, external ear canal, the nail
beds, labia minora, the glans penis, and the inner aspect of the prepuce.
They are most concentrated in the palms and soles and the axillae. Each
gland consists of a coiled secretoryintradermal portion that connects to
the epidermis via a relatively straight distal duct. The normal function of
the sweat gland is to produce sweat, which cools the body by
evaporation. The thermoregulatory center in the hypothalamus controls
sweat gland activity through sympathetic nerve fibers that innervate the
sweat glands. Sweat excretion is triggered when core body temperature
reaches or exceeds a set point.
-8-
Skin Anatomy
Apocrine glands
Apocrine glands are similar in structure but not identical to eccrine
glands. They are found in the axillae, in the anogenital region, and, as
modified glands, in the external ear canal (ceruminous glands), in the
eyelid (Moll's glands), and in the breast (mammary glands). They
produce odor and do not function prior to puberty, which means they
probably serve a vestigial function. The mammary gland is considered a
modified and highly specialized type of apocrine gland.
Hair follicles
Hair follicles are complex structures formed by the epidermis and dermis.
They are found over the entire surface of the body except the soles of the
feet, palms, glans penis, clitoris, labia minora, mucocutaneous junction,
and portions of the fingers and toes. Sebaceous glands often open into the
hair follicle rather than directly onto the skin surface, and the entire
complex is termed the pilosebaceous unit. Caucasian hair follicles are
oriented obliquely to the skin surface, whereas the hair follicles of black
persons are oriented almost parallel to the skin surface. Asian persons
have vertically oriented follicles that produce straight hairs. These
anatomic variations are an important consideration in avoiding alopecia
when making incisions in the scalp.
The base of the hair follicle, or hair bulb, lies deep within the dermis and,
in the face, may actually lie in the subcutaneous fat. This accounts for the
remarkable ability of the face to re-epithelialize even the deepest
cutaneous wounds. A band of smooth muscle, the arrectorpili, connects
the deep portion of the follicle to the superficial dermis. Contraction of
this muscle, under control of the sympathetic nervous system, causes the
-9-
Skin Anatomy
see fig ( 2 )
- 10 -
Skin Anatomy
- 11 -
Skin Anatomy
or
as
terminal
branches
of
muscular
vessels
(musculocutaneous perforators).
During their course to the skin, they travel within or adjacent to the
connective tissue framework and supply branches to each tissue with
which they come into close contact (bone, muscle, fascia, nerve, fat).
They emerge from the deep fascia in the vicinity of the intermuscular or
intramuscular septa or near tendons and travel toward the skin, where
they form extensive subdermal and dermal plexuses. The dermis contains
horizontally arranged superficial and deep plexuses, which are
interconnected via communicating vessels oriented perpendicular to the
skin surface. Cutaneous vessels ultimately anastomose with other
cutaneous vessels to form a continuous vascular network within the skin.
Clinically, this extensive horizontal network of vessels allows for random
skin flap survival.
In addition to the skin's natural heat conductivity and loss of heat from
the evaporation of sweat, convection from cutaneous vessels is a vital
component of thermoregulation. Cutaneous blood flow is 10-20 times
that required for essential oxygenation and metabolism, and large
- 12 -
Skin Anatomy
Lymphatics
Skin lymphatics parallel the blood supply and function to conserve
plasma proteins and scavenge foreign material, antigenic substances, and
bacteria. Blind-ended lymphatic capillaries arise within the interstitial
spaces of the dermal papillae. These unvalved superficial dermal vessels
drain into valved deep dermal and subdermal plexuses. These then
coalesce to form larger lymphatic channels, which course through
numerous filtering lymph nodes on their way to join the venous
circulation near the subclavian vein-internal jugular vein junction
bilaterally (Crockett, 1965 ).
Skin Innervation
Sensory perception is critically important in the avoidance of
pressure, mechanical or traumatic forces, and extremes of temperature.
Numerous specialized structures are present in the skin to detect various
stimuli. As previously mentioned, Merkel cells of the epidermis detect
light touch. Meissner corpuscles also detect light touch. These are found
in the dermal papillae and are most concentrated in the fingertips. Pacini
corpuscles are found deep within the dermis or even in the subcutaneous
tissue. These structures are specialized to detect pressure.
- 13 -
Skin Anatomy
Pain is transmitted through naked nerve endings located in the basal layer
of the epidermis. Krause bulbs detect cold, whereas Raffini corpuscles
detect heat. Heat, cold, and proprioception also are located in the
superficial dermis. Cutaneous nerves follow the route of blood vessels to
the skin. The area supplied by a single spinal nerve, or single segment of
the spinal cord, is termed a dermatome. Adjacent dermatomes may
overlap considerably, of importance to note when performing field blocks
with local anesthesia ( Morris, 1997 ).
Surface Anatomy
Lines and creases are evident over major and minor joints. Skin
contraction produces wrinkles and creases that lie perpendicular to the
underlying muscular vector force. Relaxed skin tension lines (RSTL),
however, are formed during relaxation and often follow a different
direction than age and contracting wrinkles see fig (3). Relaxed skin
tension lines are created by the natural tension on the skin from
underlying structures ( Fongo, 1966 ).
- 14 -
Skin Anatomy
Fig ( 3 ) : Four main facial lines show the direction of relaxed skin tension lines.
Papillary ridges on the tips of the digits of the hands and feet and the
surface of palms and soles are often used for personal identification.
These are also known as friction ridges, since they assist in the ability to
grasp. They are formed during fetal development and are unique to each
individual, including identical twins. This distinct pattern does not change
with aging. Stratum mucosum composes the outer surface of the ridges
with underlying dermal papillae. Sweat pores are usually located at the
top of the ridges ( Ashbaugh, 1999 ).
- 15 -
Skin Anatomy
Skin Phototype
The amount of melanin pigment in the skin determines an
individual's skin color (skin phototype). Skin pigment can be inherited
genetically or acquired by various diseases. Hormonal changes during
pregnancy can also vary the amount of pigmentation.The Fitzpatrick
classification see table (1) is used to classify skin complexion and
response to ultraviolet exposure. This classification is based on a personal
history of sunburning and suntanning (Goldman et al., 2007 ). This
classification is used clinically for evaluation of facial skin pigmentation
before resurfacing procedures and is important for predicting outcomes
and adverse effects.
Table (1): Fitzpatrick Skin Classification (Fitzpatrick, 1988)
Type
Color
White
II
White
III
White
IV
Moderate Brown
Dark Brown
VI
Black
Skin Anatomy
- 17 -
Chapter II
Physiology of
Wound Healing
Introduction
Tremendous advancements have been made in understanding the
processes of wound healing. The cell types and the order in which they
appear in the wound have been established; many growth factors and
their functions have been elucidated ( Ueno et al., 2006 ). Despite the
advances in understanding the science of wound healing, many more
steps have yet to be discovered and elucidated. The frontier of this field
includes the prevention of hypertrophic and keloid scar formation and,
ultimately, any visual remnant of the wound.
An incision created by a scalpel, trauma resulting from a bullet, or tissue
death caused by a myocardial infarction all undergo a similar and
predictable reparative process. Understanding how the body repairs
damaged tissue and what factors influence the wound healing process
helps the surgeon ensure an acceptable outcome from surgery. Tissue
injury is common thread to every medical specialty. Wound healing in
any tissue follows a predictable sequence of events. A broad
understanding of the sequence of events, cells involved, relative time
table, and molecular signaling can allow for maximum optimization of
this important patient care issue. Although seemingly basic in concept,
advances in molecular science have allowed modern medicine to gain a
true appreciation of the complex interplay between the cells involved in
the phases of wound healing. As greater understanding of the growth
factors involved in wound healing emerges, future patient care may
- 18 -
damaged
from
the
- 19 -
wound
formation,
release
Wound healing and growth factors. Cells involved in wound healing. The cells
appearing in a wound are depicted in sequence from left to right, and the color bars
represent the range of days each cell type is in the wound.
- 20 -
Inflammatory phase
The inflammatory phase begins at the time of injury and lasts 2-4
days. The phase begins with hemostasis and formation of the platelet
plug. Platelets release platelet-derived growth factor (PDGF) and
transforming growth factor beta (TGF-b) from their alpha granules to
attract neutrophils and macrophages. Neutrophils scavenge for bacteria
and foreign debris. Macrophages are the most important mediators of
wound healing. Macrophages continue to emit growth factors to attract
fibroblasts and usher in the next phase of wound healing .
Proliferative phase
The proliferative phase begins on approximately day 3; it overlaps
with the inflammatory phase. The most important cell is the fibroblast.
Fibroblasts peak approximately day 7 from injury and are responsible for
initiating angiogenesis, epithelialization, and collagen formation.
Epithelialization is from the basement membrane if the basement
membrane remains intact (eg, first-degree burn). If the basement
membrane is not intact, the epithelialization is from the wound edges.
Fibroblasts produce mainly type III collagen during this phase.
Granulation tissue, formed in this phase, is particularly important in
wounds healing by secondary intention. When collagen synthesis and
breakdown become equal, the next phase of wound healing has begun.
- 21 -
Remodeling phase
Increased collagen production and breakdown continue for 6
months to 1 year after injury. The initial type III collagen is replaced by
type I collagen until a type I:type II ratio of 4:1 is reached, which is equal
to normal skin. Also, fibroblasts differentiate into myofibroblasts, causing
tissue contraction during this phase of wound healing. Collagen
reorganizes along lines of tension and crosslinks, giving added strength.
Strength eventually approaches 80% of the strength of uninjured tissue.
Vascularity decreases, producing a less hyperemic and more cosmetically
appealing wound as this phase progresses.
The timetable for wound healing can be quite variable. Chronic wounds
can stall in the inflammatory phase because of poor perfusion, poor
nutrition, or a myriad of other factors causing excessive buildup of
exudates in the wound base. These wounds tend to remain unhealed
unless active and aggressive means are undertaken to correct the
underlying comorbidities while providing proper wound care.
- 23 -
Local cytokines
Growth factors represent the intercellular signaling that orchestrates the
complex sequence of cell migration, division, differentiation, and protein
expression during wound healing. The 8 major families of growth factors
are expressed in varying levels by the cells involved with healing.
Table ( 2 ): Growth Factors
Growth
Production
Known Effects
1.
Platelets,
Epidermal
macrophages
Factor
Growth
Factor
(EGF)
applied topically.
2.
Platelets,
TGF-a:
Mitogenic
Transformi
macrophages,
ng Growth
lymphocytes,
Factor
hepatocytes
and
promotes
chemotactic
for
chemoattraction
of
inflammatory cells.
TGF-b3 (antagonist to TGF-b1 and b2): Has
been found in high levels in fetal scarless
wound healing and has promoted scarless
healing in adults experimentally when TGF-b1
and TGF-b2 are suppressed.
3. Vascular
Endothelial cells
Endothelial
Growth
Factor
- 24 -
(VEGF)
4.
Macrophages,
Fibroblast
mast
Growth
lymphocytes
5. Platelet-
Platelets,
Derived
macrophages, and
Growth
endothelial cells
synthesis.
6.
Macrophages,
IL-1:
Interleukins
keratinocytes,
neutrophils,
endothelial cells,
lymphocytes,
IL-4:
fibroblasts,
differentiation. Induces
osteoblasts,
proteoglycan synthesis.
cells,
Promotes
T-
angiogenesis,
granulation,
and
Factor
(FGF)
Factor
(PDGF)
basophils,
mast
cells
IL-8:
Proinflammatory,
chemotactic
fibroblasts,
and
Activates
Chemotactic
for
for
fibroblast
collagen
and
neutrophils
and
fibroblasts.
7. Colony-
Stromal
cells,
Stimulating
fibroblasts,
Factors
endothelial cells,
lymphocytes
8.
Fibroblasts
Keratinocyt
e
Stimulates
keratinocyte
growth
factor
- 25 -
migration,
Wound optimization
Creating conditions that allow for proper wound healing can make
all the difference in various wounds, from an inconspicuous wound after
plastic surgery to an amputation or even death in a patient with severe
vascular disease or burn. When approaching an injured patient, the
following list can guide the thought process of the physician or caretaker
in optimizing healing conditions.
Perfusion: Tissues cannot heal without the cells, oxygen, and nutrients
that the cardiovascular system delivers ( Jonsson et al., 1991 ). This is
particularly important in the wound healing of patients with diabetes or
paraplegia, patients who smoke, and patients who have been exposed to
radiation. Patients with severe vascular disease may experience enhanced
wound healing via increased perfusion after a vascular bypass or related
procedure. Patients who smoke should cease smoking immediately in the
event of major surgery or injury. Nicotine causes severe vasoconstriction,
and the toxins in cigarette smoke can greatly decrease the ability of
tissues to heal. Paraplegics and diabetics with neuropathy must cease all
substance abuse and be continually educated and reinforced on the need
for pressure relief to avoid pressure ulcers. In the event of pressure sore
discovery, absolute pressure relief to increase perfusion is paramount.
- 28 -
- 29 -
Chapter III
Complications of
Wound Healing
Prevention of Complications
Preoperative evaluation
Surgical complications must be anticipated and addressed as soon as surgical
treatment is determined to be necessary, usually during the preoperative
consultation. Appropriate patient selection involves the detection of both
physical and psychiatric conditions, which may interfere with a desirable
outcome.
Medical risk factors are identified during the initial patient encounter. An
effective strategy is to combine the use of a questionnaire form, which may
be reviewed by the physician, and direct questioning to clarify and confirm
identified risks See fig (6).
Risk factors for intraoperative and postoperative bleeding include both
medication use (eg, aspirin, warfarin, herbal remedies, vitamins) and active
medical problems (eg, blood dyscrasias, liver or kidney disease). Allergies to
medications, anesthetics, topical antibiotics, latex, and bandage adhesives
need to be ascertained. Immunosuppression, whether related to underlying
disease or secondary to medication, should be recognized. Tobacco and
- 30 -
Figure ( 7 ):
Ecchymosis on the neck
due to tracking of blood in
naturally occurring tissue
planes.
Figure ( 8 ):
Periorbital ecchymosis
- 33 -
Figure ( 9 ):
Extensive ecchymosis in a
patient on anticoagulant
medication.
Bleeding Complications
Figure ( 10 ):
Early hematoma under full-thickness
skin graft repair
- 35 -
Figure ( 11 ):
Expression of early hematoma
Figure ( 12 ):
Expression of the hematoma in this
patient did not require takedown of
the graft
Seroma, a collection of serous fluid under the suture line, may occur
in areas of extensive undermining or dead space. Seromas may be drained to
alleviate pain and tension on the wound by using a large-bore needle and
syringe to withdraw the fluid. See figure (13) ( Leese et al., 2000 ) ( Waner
et al., 1993 ).
- 36 -
Infection
The postoperative wound infection rate in skin surgery is low.
Reported rates are 0.7-2.29%. Most skin surgical procedures fall into either
the clean category or the clean-contaminated category in the classification
scheme, which predicts the infection rate as a function of wound
contamination.
acutely infected wounds that are generally not encountered in skin surgery.
- 37 -
- 38 -
Suture
Reactions
and
Contact
Dermatitis
and
Hypersensitivity
Suture reactions
Sutures are foreign bodies; as such, they cause a local,
immunologically mediated tissue response, clinically evident as erythema. .
The longer the sutures are in, the more reactivity occurs. The larger the
caliber of the suture, the more reactivity; the increase of one suture size
results in a 2- to 3-fold increase in tissue reactivity. Synthetic or wire sutures
are much less reactive than natural sutures (eg, silk, cotton, catgut); a
monofilament suture is less reactive than a braided suture.
Suture tracking results from the sutures being tied too tightly or being
left in place too long. Puncture scars on either side of the wound connected
by a linear scar in the area where sutures were placed give a railroad track
appearance ( See Fig 14 ).
Figure ( 14 ):
Typical railroad track
appearance of suture
tracking caused by sutures
that were tied too tightly.
- 39 -
chlorhexidine
has
been
reported
but
is
rare.Delayed-type
hypersensitivity has been reported with the use of topical lidocaine ( Marks,
1982 ).
wound
has
minimal
tensile
- 40 -
strength,
and,
although
Necrosis
Necrosis of tissue occurs secondary to tissue ischemia. Any condition
that results in a decrease of oxygenated blood flow to the wound has the
potential to cause necrosis. Damage to tissue during surgery is the most
common cause. Excessive tension on wound edges, excessive suturing and
- 41 -
- 42 -
Other complications
Milia are essentially tiny epidermal inclusion cysts. they may appear
after excisional surgery at the suture line because of implantation of
epidermal components into the dermis ( Mandy, 1986).
Telangiectases may appear after surgery around the sutured area, and
they are often associated with wound tension or a personal tendency.
Pruritus within scars is a relatively common occurrence ( Field et al.,
2000).
- 43 -
Chapter IV
Defintion &
Historical
Background
- 44 -
Figure ( 15 ):
Keloid
Figure ( 16 ):
Hypertrophic Scar
- 45 -
ChapterV
Epidemiology ,
Etiology & Genetics
ingrown
hairs,
melanocyte-stimulating
hormone
and
- 46 -
the scar had developed even at a younger age. A possible explanation for
the greater incidence in the younger age group could be their increased
predisposition to trauma because of their adventurous habit, apart from
the subtle difference in the healing property. Keloids may follow wounds
from diverse aetiology.
The most important risk factor for the development of abnormal scars,
such as keloids, is a wound healing by secondary intention, especially if
healing time is greater than 3 weeks ( Newsome et al., 2003). Sharquie
and Al-Dhalimi found spontaneous keloids in about one-third (34%) of
their Iraqi patients ( Sharquie and Al-Dhalimi, 2003 ).A proportion of
our patients gave no history of trauma; in such patients some trivial,
unnoticed or overlooked injury such as insect bite or razor cut had been
the precursor of such keloids. Other uncommon injuries include
circumcision
(especially females),
feet
burning
for
post-febrile
Genetic predisposition
Some
evidence
supports
relationship
between
genetic
- 48 -
Chapter VI
Pathophysiology
Pathophysiology
Pathophysiology
Keloids are dermal fibrotic lesions that are a variation of the
normal wound healing process. They usually occur during the healing of
a deep skin wound. Hypertrophic scars and keloids are both included in
the spectrum of fibroproliferative disorders. These abnormal scars result
from the loss of the control mechanisms that normally regulate the fine
balance of tissue repair and regeneration.
The excessive proliferation of normal tissue healing processes results in
both hypertrophic scars and keloids. The production of extracellular
matrix proteins, collagen, elastin, and proteoglycans presumably is due to
a prolonged inflammatory process in the wound. Hypertrophic scars are
raised, erythematous, fibrotic lesions that usually remain confined within
the borders of the original wound. These scars occur within months of the
initial trauma and have a tendency to remain stable or regress with time.
Keloid formation can occur within a year after injury, and keloids enlarge
well beyond the original scar margin. The most frequently involved sites
of keloids are areas of the body that are constantly subjected to high skin
tension. Wounds on the anterior chest, shoulders, flexor surfaces of the
extremities (eg, deltoid region), and anterior neck and wounds that cross
skin tension lines are more susceptible to abnormal scar formation.
The most important risk factor for the development of abnormal scars
such as keloids is a wound healing by secondary intention, especially if
healing time is greater than 3 weeks. Wounds subjected to a prolonged
inflammation, whether due to a foreign body, infection, burn, or
inadequate wound closure, are at risk of abnormal scar formation. Areas
- 49 -
Pathophysiology
- 50 -
Pathophysiology
- 51 -
Pathophysiology
- 52 -
Chapter VII
Clinical
Presentation
Clinical Presentation
Clinical Presentation
Keloids appear as firm, mildly tender or pruritic, bosselated, welldemarcated tumours occurring more frequently on shoulders, chest, neck,
upper arms, earlobes and cheeks. Keloids are variable in size from 2 to 3
mm papules to large pendulous tumours. Shapes vary from evenly
contoured symmetric protrusions with regular margins to irregular clawlike projections. The colour of keloid is also variable, mildly
erythematous in new lesions while dull red or more pale in older lesions.
Keloids may occur on eyelids, genitalia, palms, soles, cornea or mucous
membranes rarely.
Keloids develop rapidly over weeks or months following trauma or other
precipitating factors. The lesions may continue to grow or remain stable
for long periods of time. Sometimes, keloids may undergo central
suppurative necrosis. This change is thought to be due to ischemic
necrosis from vascular compromise secondary to keloid overgrowth.
Dark skinned individuals are more susceptible to keloid formation,
especially on the face. Growth of keloid may be stimulated by pregnancy.
Surgically resected keloid is followed by regrowth of a larger tumour and
if skin graft has been used, keloid may occur in donor site as well.
- 53 -
Clinical Presentation
- 54 -
Clinical Presentation
Histology
Keloids
have
normal
epidermal
layer;
abundant
There are four histologic features that are consistently found in keloid
specimens that are deemed pathognomonic for their diagnosis. They are
1) the presence of keloidal hyalinized collagen.
2) a tonguelike advancing edge underneath normal-appearing epidermis
and papillary dermis.
3) horizontal cellular fibrous bands in the upper reticular dermis.
4) prominent fascialike fibrous bands. ( Lee et al., 2004 ).
- 55 -
Clinical Presentation
Metabolic activity
Keloidal scars have higher levels of adenosine triphosphate and
fibroblasts than hypertrophic scars. There is a higher density of
fibroblasts in both types of scars but keloidal scars have a higher
expression of proliferating cell nuclear antigen. This may explain the
tendency of keloidal scars to grow beyond the boundary of the original
injury or trauma.
Other differences
Antinuclear
antibodies
against
fibroblasts,
epithelial
and
endothelial cells have been found in patients with keloids but not in
hypertrophic scars.
Differential diagnosis
Keloids can be differentiated from hypertrophic scars, as described
earlier. Hypertrophic scars remain within the boundary of initial injury.
They are not claw-like and often regress spontaneously.
Keloids can be distinguished histologically from dermatofibrosarcoma
protuberans, clinical picture of which may be similar to keloids.
Allergic contact dermatitis secondary to gold earrings may produce
keloidal lesions on the earlobes but histopathologic study of these lesions
shows a dense infiltration of lymphocytes and formation of lymphoid
follicles rather than dense collagen tissue.
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Clinical Presentation
HYPERTROPHIC SCARS
KELOIDS
rgery
skin color
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Clinical Presentation
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Chapter VIII
Prevention &
Modalities of
Treatment
Prevention
The most important factor in hypertrophic scar and keloid
formation is prevention. Avoiding all unnecessary wounds, especially in
keloid-prone patients, remains an obvious but imperfect solution ( Slemp
et al., 2006 ). All surgical wounds should be closed with minimal tension,
incisions should not cross joint spaces, midchest incisions should be
avoided, and incisions should follow skin creases whenever possible
( Slemp et al., 2006 )( Rudolph, 1987 )( Lanza et al., 1992 ). Especially
in head and neck surgery, the esthetic subunits of the face must be
considered for incision sites (Baisch et al., 2006 ). An atraumatic
operation technique should be used, followed by efficient hemostasis, and
wound closure should include eversion of the wound edges. It is also
crucial to properly debride contaminated wounds and limit foreign bodies
in the form of polyfilamentous sutures ( Slemp et al., 2006 ). Particularly
in the face, subcutaneous sutures should be used only when necessary.
Furthermore, wound healing and the esthetic outcome of scar formation
can be improved with massage or greasing ointments ( Baisch et al.,
2006 ).
2.
Contractubex cream or
3.
4.
5.
Treatment
Surgery for Keloids
Simple total excision of a keloid stimulates additional collagen
synthesis, thus sometimes prompting quick recurrence of a keloid even
larger than the initial one. For this reason, intra-marginal surgical
excision of keloid tissue is recommended in order not to stimulate
additional collagen synthesis. Surgical excision of a keloid alone is
associated with a high recurrence rate. Thus, surgical therapy should be
combined with adjuvant treatment such as pressure, corticosteroids, and
radiotherapy. Kauh and colleagues demonstrated that surgical excision
combined with steroid injection into the wound bed causes downregulation of type I collagen gene expression without compromising
wound healing. If intralesional steroids are used post-op eratively, we
recommend leaving the sutures 3 to 5 days longer to prevent wound
dehiscence. Never the less, surgical therapy for the treatment of keloids
has been relegated mainly to second-line therapy for lesions unresponsive
to steroids or pressure ( Rockwell et al., 1989 ).
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Pressure
The use of pressure to treat keloids was initially described in
1835,50 although compression therapy was not popularized until the
1970s, when physicians noted that pressure stockings used on lower
extremity burns resulted in scars that matured more rapidly, with less
erythema and thickness. The compression phenomenon is not well
understood, but theories include the following:
(1) a decrease in blood flow with a resultant decrease in a2macroglobulin and a subsequent increase in collagenase-mediated
collagen breakdown, normally inhibited by a2-macroglobulin.
(2) hypoxia leading to fibroblast degeneration and collagen
degradation.
(3) lower levels of chondroitin 4-sulfate, with a subsequent increase
in collagen degradation.
(4) decreased scar hydration, resulting in mast cell stabilization and
a subsequent decrease in neo-vascularization and matrix production.
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Figure ( 21 ):
compression garment
for the forearm
clips are in common use for patients with ear lobe keloids. Pressure
therapy should be started immediately after reepithelialization of the
wound, and patients should wear these pressure devices for continuous 8
to 24 hours a day for the first 6 months of scar healing. The success rate
depends largely on patient compliance ( English and Shenefilt, 1999 ).
Fig ( 22 ):
Compression garment for the face
Radiation
Debeurmann and Gougerot first described the use of X-rays for the
treatment of keloids in 1906. Later evidence showed that radiation
therapy alone is inadequate for the treatment of keloids; therefore,
Cosman and colleagues introduced the use of post-excision radiation
therapy as an adjunct to surgical excision. The reported efficacy rate
varied between.
65% and 99% compared with excision alone. It is suggested that radiation
directly affects fibroblast proliferation by inducing apoptosis. The total
dose recommended for the treatment of keloids varies from 15 to 20 Gy
fractionated over five to six treatments. The main drawback of radiation
therapy, aside from hyperpigmentation, is the risk of radiation-induced
malignancy, although only a few cases have been described, and large
treatment cohorts with extensive follow-up have provided no evidence to
substantiate the risk of carcinogenesis. Nevertheless, radiation therapy is
contraindicated in children, as well as in areas of high carcinogenic
potential, namely the breast and thyroid ( Malaker et al., 2004 ).
Laser Therapy
Many laser types, including the carbon dioxide laser and the pulsed
dye laser (PDL), have been tested for treatment of hypertrophic scars and
keloids, with varied results. The carbon dioxide laser, which is commonly
used for skin resurfacing, has not been proven to be more effective in
- 65 -
treating problem scars than are other methods. The PDL is considered to
be the criterion standard for vascular lesions, such as port wine stains,
initial hemangiomas, and facial telangiectasias. Additionally, this laser
type is often successfully used for non-vascular indications, such as
keloids or hypertrophic scars. Currently, the PDL wavelengths 585 and
595 nm are most frequently used for therapeutic purposes. Alster reported
an average improvement of 57% after the first treatment and 83% after
the second treatment with PDL for hypertrophic surgical and traumatic
scars. In addition to a reduction in erythema, flatening, a clear reduction
in itching and pain, and optimization of the skin texture have been
observed. The entire scar in each patient was exposed to PDL at a
wavelength of 585 nm, a pulse duration of 0.45 ms, and a fluence of 6.5
to 7.25 J/cm2. Recent biochemical studies suggest that 585-nm PDL
treatment alters signaling pathways to favor collagen degradation and
fibroblast apoptosis. In contrast to the above-cited results, Chan and
colleagues failed to show any clinical improvement using PDL for
hypertrophic scars. In 27 hypertrophic scars, one side of each of which
was treated (585 nm, 78 J/cm2, 2.5 ms, 5 mm), the authors documented
no superiority of the treated half after three to six treatments regarding
thickness and elasticity, although pain and touch sensitivity were far
better on the treated side. Several reports have shown a trend toward
better clinical improvement using low to moderate fluences, although
laser therapy has not shown a clear advantage over cold scalpel excision,
especially in keloids (See fig 24)( Norris, 1999 ).
- 66 -
Figure ( 24 ): Ear keloid treated with catbon dioxide laser pre and immediately post
Corticosteroids
Intralesional corticosteroid injections have become a mainstay in the
treatment of hypertrophic scar and keloids, alone or in combination with
other therapeutic procedures. Corticosteroid application can soften and
flatten keloids but cannot narrow hypertrophic scars or eliminate keloids.
Intralesional corticosteroid injection decreases fibroblast proliferation,
collagen synthesis, and glycosaminoglycan synthesis and suppresses proinflammatory mediators. We recommend beginning with direct serial
intralesional corticosteroid injections in an already- developing keloid or
hypertrophic scar. The most commonly used drug for steroid injection is
triamcinolone acetonide (TA) at a dose of 5 to10 mg/mL, which should
be injected with a 25- to 27-gauge needle into the upper dermis of a
- 67 -
Intralesional injection of the pyrimidine analog 5-fluorouracil (5FU) has been investigated for the regression of keloids and hypertrophic
scars. 5-FU targets rapidly proliferating fibroblasts in dermal wounds
responsible for excessive collagen production. 5-FU has been shown to
be effective in the treatment of hypertrophic scars, whereas studies of
intralesional 5-FU application have provided mixed results in keloids.3
The injection can be painful, and purpura and ulcers have been
documented. 5-FU can also be combined with corticosteroids; Fitzpatrick
was the first to report improved efficacy and less painful injections by
mixing corticosteroids (triamcinolone acetonide) with 5-FU. Apikian and
Goodman found that the combination of 5-FU with corticosteroids has
- 68 -
Imiquimod 5% Cream
Onion Extract
Allium cepa, or onion extract, is found in numerous scar treatment
products.83 This botanical ingredient exhibited anti-inflammatory,
bacteriostatic, and collagen down-regulatory properties86 and improves
collagen organization in a rabbit ear model, but three major clinical
studies in the United States evaluating the effects of onion extract on
human wound healing showed no evidence that this extract could be
- 69 -
Interferons
Interferons are cytokines secreted by T-helper cells that, apart from
other functions, suppress fibrosis. All interferon isoforms (a, b, g) have
been shown to reduce collagen and extracellular matrix production while
increasing collagenase level but have been applied only experimentally
and predominantly in small numbers of patients. Furthermore, the use of
interferons is also associated with severe side effects, including fever,
chills, night sweats, fatigue, myalgia, and headache.
Immunotherapy
Immune modulators and antibody therapies are new in the context
of problem scars. Commercial drugs like tacrolimus and sirolimus are
known to affect cytokine activation, TNF-a, interferons, and interleukins, with wide-ranging effects on inflammation and cell-cycle
regulation. Topically used, these drugs may suppress fibroblast activity
and increase the apoptosis rate in keloids.84 Anti-TGF-b antibody
application use in animal models decreased scar hypertrophy and
collagen contraction.90 Further molecular investigations will yield more
specific, probably gene-based, therapies that are designed not only to
treat, but also to prevent problem scars. ( Dolore et al., 2009 )
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Chapter IX
Electron Beam
Irradiation
Keloid
Irradiation of keloids which was first described in the early 1900s
by Freund is a well-accepted procedure. It can reduce the recurrence
rates to 333% according to the literature without any complications. The
main resrvation against this modality, the carcinogenic effect, has not
definitely been proven in a single case. The radiation protocols used in
the clinical setting include X-ray therapy, afterloading brachytherapy
with iridium-192 (192Ir) wires, electrons from linear accelerator, and
stron- tium-90-yttrium-90 (90Sr-90Y) contact brachytherapy. All
techniques are applied with varying dose and fractionation schedules (
Ingeborg et al., 2005 ).
Between 1988 and 2000, 378 cases of keloids were treated by Ogawa,
and 147 keloids in 129 patients were selected for this study. Keloids that
occurred at a different site in the same patient and keloids that recurred
later at the same site were deemed to be different keloids. Those keloids
were surgically removed, and the patients were treated postoperatively
with 15-Gy electron beam irradiation and followed for more than 18
months. The therapeutic outcomes were evaluated. Statistical analysis
was performed using Fishers exact probability test or chi-square test.
Recurrence occurred in two sites on 14 earlobes (14.3 percent), in two
sites on 12 necks (16.7 percent), in 22 sites on 51 anterior chest walls
(43.1 per- cent), in 13 sites in 33 scapular regions (39.4 percent), in four
sites on 15 upper limbs (26.7 percent), in four sites in 11 suprapubic
regions (36.4 percent), and in one site on 11 lower limbs (9.1 percent).
The overall recurrence rate was 32.7 percent. Analysis of the therapeutic
outcomes showed that the recurrence rates in the sites with high stretch
tension, such as the chest wall, and the scapular and suprapubic regions
were statistically higher than in sites without high tension, such as the
neck, earlobes, and lower limbs (41.1 percent versus 13.5 percent, p =
- 72 -
0.0017). The results suggested that keloid sites with a high risk of
recurrence should be treated with escalated radition doses and posttreatment self-management ( Ogawa et al., 2003 ).
Researchers in Japan reported postoperative irradiation with a low megavoltage (4MeV) electron beam. Keloid sites were irradiated within 1 or 2
days after surgery for three consecutive days. The advantages of the use
of an electron beam are that the peak of dose is delivered to the layer of
the occurrence of keloid, and the depth of penetration of radiation is
limited, without appreciable effect on deeper structures.
External radiation following excision, often combined with other
therapies, has been associated with recurrence rates of less than 10%
(Berman and Bieley, 1996 ).
a total dose of 1500 cGy at 500 cGy per fraction starting within one week
after excision and at intervals of 96 hours. The success rate was 84%
(21/25) (Sun, 1993 ).
Chronic skin and soft tissue reactions may involve skin depigmentation,
some dryness and thinning of the skin and sometimes sensitivity loss;
however, these reactions have to be seen in the context of various
previous treatments and the post-surgical repair processes. In summary,
not all possible treatment side effects can be addressed to radiotherapy,
- 75 -
and quite often the surgical and other non-surgical therapies produce their
own pattern of side effects that cannot attributed to radiotherapy
( Seegenscmiedt et al., 2008 ).
- 76 -
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