In

Dermatology and Venereology

q3(1"
Sawsan Omran Hashim Am'

Fa u iy of od no
aa Un vors iy
KELOIDS : TRE ATME NT
E VAL UATI O N
Thesis
Submitted in partial fulfillment of Master Degree
cOnder Super vision of
Professor
Ahmed Abdul-fader Sa l em
Professor of Dermatology and Venereology
Faculty of od no
a a Un vors iy
Professor
Mona Anwa r El - Ha rra s
Professor of Dermatology and onoroooy
Fa u iy of od no
a a Un vors iy
Dr.
Amr Na zir Sa a da wi
Ass siani Professor of Dermatology and Venereology
Fa u iy of od no
a a Un vors iy
Fa u iy of od no
a a Un vors iy
2004
ACKNOWLEDGEMENT
Above all and first of all praise and thanks must be to ALLAH.
I would like to express my deepest gratitude to
Professor A hmed A bdul-Kader Salem, Professor of
Dermatology and Venereology, Faculty of Medicine, Zagazig
University, for his deep interest, sincere supervision, generous
assistance and continuous support during the progress of this work.
I am really grateful to Profossor ona Anwar E -Harras,
Professor of Dermatology and Venereology, Faculty of Medicine,
Zagazig University, for her kind advice, support, supervision and
sincere cooperation, in the accomplishment of this work.
| am honoured to express my deep thanks to
Dr. A mr Nazir Saadawi, Assistant Professor of Dermatology and
Venereology, Faculty of Medicine, Zagazig University, who helped
me and gave me much of his valuable experience and sincere
directions to complete this work.
LIST OF ABBREVIATION
a - SMA
a - smooth muscle actin
BFGF Basic fibroblast growth factor
CO
2
Carbon dioxide laser
CW Continues wave
ECU Extracellular matrix
EGF Epidermal growth factor
Er : YAG Erbium : YAG
FGF Fibroblast growth factor
FPDL Flash lamp pumped pulsed dye laser
HSC Hypertrophic scars
IFN - a Interferon - a
IFN - 13Interferon - [ 3
IFN - y Interferon - y
IGF 1 Insulin-like growth factor-1
KFs Keloid producing fibroblast
Nd : YAG Neodymium yttrium Aluminum Garnet
PDGF Platelets derived growth factor
TGF- beta I Transforming growth factor beta I
TGF-[3
Transforming growth factor
TRT Thermal relaxation time
CONTENTS
Page
Introduction and Aim of the Work - - - - - - - - - - - - - 1
Review of Literature - - - - - - - - - - - - - - - - - - - - - -
4
Chapter 1 : Keloids - - - - - - - - - - - - - - - - - - - - - - - - - - - - 4
- Historical background - - - - - - - - - - - - - - - - - - - - - - - - 4
- Epidemiological factors - - - - - - - - - - - - - - - - - - - - - - - 4
- Clinical features - - - - - - - - - - - - - - - - - - - - - - - - - - - - 5
- Histopatholology of keloids - - - - - - - - - - - - - - - - - - - - 7
- Physiology of wound healing - - - - - - - - - - - - - - - - - - 8
- Events in the process of wound healing - - - - - - - - - - - - 9
- Pathogenesis of keloids - - - - - - - - - - - - - - - - - - - - - - - 1 0
- The role of cytokines - - - - - - - - - - - - - - - - - - - - 15
- The role of mast cells - - - - - - - - - - - - - - - - - - - - 1 8
Chapter 2 : Treatment of keloids 1 9
1- Surgical therapy - - - - - - - - - - - - - - - - - - - - - - - - - - - 20
2- Physical therapy - - - - - - - - - - - - - - - - - - - - - - - - - - - 23
a- Laser in keloids - - - - - - - - - - - - - - - - - - - - - - - - 23
b- Radiation therapy - - - - - - - - - - - - - - - - - - - - - 41
c- Cryotherapy - - - - - - - - - - - - - - - - - - - - - - - - - - 42
d- Pressure therapy - - - - - - - - - - - - - - - - - - - - - - - 44
3 - Pharmacological therapy - - - - - - - - - - - - - - - - - - - - - 46
a- Intralesional corticosteroids - - - - - - - - - - - - - - - 46
b- Silicon gel - - - - - - - - - - - - - - - - - - - - - - - - - - - 49
c- Antihistamine - - - - - - - - - - - - - - - - - - - - - - - - - 50
d- 5-Flurouracil - - - - - - - - - - - - - - - - - - - - - - - - - 51
e- Calcium channel blockers - - - - - - - - - - - - - - - 53
4- Immunotherapy - - - - - - - - - - - - - - - - - - - - - - - - - - - 54
Patients and Methods - - - - - - - - - - - - - - - - - - - - -
56
Results - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
66
Discussion - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
82
Summary and Conclusion - - - - - - - - - - - - - - - - - -
89
References - - - - - - - - - - - - - - - - - - - - - - - - - - - -
92
Arabic Summary - - - - - - - - - - - - - - - - - - - - - - - -

1
INTRODUCTION AND AIM OF THE WORK
Keloids are human dermal fibroproliferative disorders occurring
following trauma, inflammation, surgery and burns and possibly
spontaneously (Horn, 2001).
A Family history of keloids is frequently elicited. In familial
cases, the exact mode of inheritance is unclear. Both autosomal
recessive and autosmal dominant patterns of inheritance are being
reported. A predisposition for keloids formation has been noted in
individuals with human leucocyte antigens (HLA) B 14, BW 1 6, and
blood group A (Tredget, 1997).
Clinically, keloids are defined as over growth of dense, fibrous
tissue following healing of the skin injury that extends beyond the
border of the original cutaneous insult (when identifiable), does not
regress spontaneously and tends to recur after excisions (English and
Shenefelt, 1999).
Histologically, keloids are characterized by haphazard deposition
of collagen fibers within the dermis, surrounded by a mucinous
extracellular matrixwith few macrophages and abundance of
eosinophils, mast cells, plasma cells and lymphocytes. The collagen
appears as thick hyalinized bands of eosinophilic nodules. These nodules
consist of a dense mass of fibroblasts within the collagen, encircled by
numerous small vessels (Horn, 2001).
The variety of treatment suggests that non is very satisfactory,
as the lesions are recurrent. The goal in managing keloids is four
folds. It includes restoration of the functional utility of the affected
anatomic part, relief of symptoms, enhanced cosmetics, and
prevention of recurrence. If keloids can be recognized early and
treated, resolution may be possible. The broad lines of treatment
include surgery, physical treatment, pharmacological therapy and
immunotherapy (Niessen et al., 1999).
Surgical excision of keloids has a high recurrence rate vary from
50to 100%. However, beneficial effects of surgical excision of
keloids has occurred with narrow-based (<1cm) pedunculated lesions
and when surgical procedures are combined with local flap to reduce
wound tension and adjunctive therapy. Such adjuncts include local
steroid therapy in the margin of the wound and monthly injections
there after (Lee et al., 2001).
Physical therapy includes ; laser therapy, radiation therapy
cryotherapy, and pressure therapy. Laser therapy is a developing
technique in the treatment of keloids. The laser beam seals blood vessels
up to 0.5mm., seals nerve endings and causes minimal necrosis of
surrounding tissue. The laser systems used in treatment of keloids are,
carbon dioxide laser, Argon laser, Neodymium Ytrium-Aluminum-
Garnet (Nd : YAG) laser and flash lamp pulsed dye laser. Radiation
therapy alone produces poor results, so surgical excision followed by
radiation therapy has been effective ( Manuskiatti et al., 2001).
2
Pharmacological therapy includes ; intralesional injection of
corticosteroids, silicone gel, antihistamine, 5- Flurouracil, and calcium
channel blockers. Intralasional injection of tramcinolone is used as a
first line of treatment modality. Corticosteroid injections alone will
improve but not eliminate keloids. Enhanced results may be achieved
when corticosteroids are combined with other treatment modalities.
Immunotherapy may have a role in the treatment of keloids,
Intralesional injection of interferon gamma (IFN-1) has been shown to
regulate collagen synthesis. The most dramatic results was achieved
when IFN- y was used after keloids excision (Shaffere et al. 2002).
The aim of this work was to search for a more satisfactory line
of treatment for keloids. Both intralesional steroid injection and
Nd:YAG laser were used for the treatment of keloids. Moreover,
a comparative clinical study between the results of both lines of
treatment was done.
3
RE VI E W O F L I TE RATURE
CHAPTE R I
K E L O I D S
Historical background :
Abnormal scaring was first described in the Smith Papyrus
between 2500and 3 000BC. In 1817, Alibert proposed the word
cheloide (Keloids) to differentiate these lesions from malignant
neoplasms. The word is derived from the Greek word chele, meaning
crab claws, referring to the manner in which these lesions grow
laterally into normal tissue (Yilmaz et al., 2000).
Epidemiological factors :
Keloids occur in individuals with a familial predisposition,
enlarge, and extend beyond the margins of the original wounds and
rarely regress. Keloids may develop even after the most minor of skin
wounds, such as insect bites or acne. The time lag between injury and
keloids formation is variable, though a majority tend to form within
the first year after initiating the skin wound. Furthermore, keloids
rarely regress with time (Tredget et al., 1997and Horn, 2001).
Patients with the highest incidence of keloids development are
between the ages of 10and 3 0years, although they occur in all age groups
and are rarely found in newborns or elderly (Appleton et al., 1996).
4
5
The exact prevalence of keloids is unknown. The male to female
ratio is approximately 1:1. Studies that report a higher female
incidence reflect greater cosmetic concern and more frequent ear lobe
piercing onu oba oi a , 1999
Cosnan oi a , 1996 in a review of three large series based on
clinical impression found an incidence between 4-5% and 16% in a
predominantly blacks. Blacks and Asians are affected more than
Caucasians, with comparable incidence ratios between 5:1 and 15:1.
There has been an estimated number of 3 00,000patients per year
treated in the United States na oi a , 2000
Clinical features:
Certain anatomical locations have an increased susceptibility to
keloid formation, although no body area is immune. The pre-sternal
area, upper back and posterior neck are the most susceptible regions of
the body Ur osio oi a , 1999 The ears, deltoid regions, anterior
chest and beard area are moderately susceptible to keloids formation.
On the other hand, keloids rarely develop on the palms, soles, penis,
scrotum or upper eyelids A sior and Handro, 2000 Mucous
membranes tend to be spared, but corneal keloids formation has been
reported (Urioste et al., 1999).
The keloids appear as broad, erythematous firm papules, nodules
or plaques with numerous telangiectasias and a shiny atrophic surface.
These extend in a claw-like fashion beyond the injury. Keloids tend to
have a more rope-like surface (Alster and Handrick, 2000).
p
Although, keloids are clinically different from hypertrophic scars,
there is often a gray area between both pathologies where the differential
diagnosis become difficult. The difference between them is quantitative
rather than qualitative (Table 1 ) (Alster and Handrick, 2000).
Table ( 1 ) : The difference between keloids and hypertrophic scars
( Sherris et al., 1 995 and Peled et al., 2000).
Clinical
characteristics
Hypertrophic scars
,
tieloids
Color - White, pink or red - Deep red or purple
Texture - Shiny, minimal markings - Shiny, no markings.
Morphology - Raised, firm within wound
borders.
- Raised, firm, extend beyond
wound borders.
Site - Usually occur on flexor
surfaces (Abdomen,
joints, etc).
- Presternal area, upper back
and posterior neck are the
most susceptible regions.
The ears,. deltoid region
and anterior chest are
moderately susceptible.
Response to
surgery
- I mprove with appropriate
surgery
- Often worsen by surgery
Histological
characteristics
- Few thick collagen fibers
- Scanty mucoid matrix
- Thick hyalinized collagen
- Mucoid matrix
- Nodular configuration
- Disorganized arrangement
6
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The relation between keloids and carcinogenicity is a site of
controversy. Hom, (2001) stated that keloids are regarded as benign
tumour with a zero carcinogenicity rate. On the other hand, Alster and
Handrick (2000), reported that alanine transaminase activity is
increased in keloids but not in hypertrophic scars. Because absent or
depressed alanine transaminase activity is a feature of malignant tumors,
this may be a reason that keloids are resistant to malignant degradation.
Histopathology of keloids :
Keloids are dense and sharply defined new growth of the
myofibroblasts and collagen in the dermis with a whorl like
arrangement of hyalinized bundles of collagenous fibers. The
spherical collagen bundles lie parallel to the epidermis but those
lower down interlace in all directions. The ribbon like bundles are
more compact and prominent. In older lesions there is a paucity of
elastic tissue. By pressure the keloids cause thining of the normal
papillary dermis and atrophy of the adjacent appendages which is
pushes aside. Mucopolysaccharides are increased and often there are
numerous mast cells (Haverstock, 2001).
Electron microscopy of keloids :
Electron microscopy and scanning electron microscopy
demonstrate the presence of fibroblasts and myolibroblasts and a
haphazard arrangement of collagen bundles. These tend to be dense
and homogenous, showing the net like arrangement of normal
7
collagen. The ground substance, as demonstrated by special stains, is
increased, with a fibrillar appearance instead of globular deposits
( Peled et al., 2000).
Physiology of wound healing :
Wound healing is a complexgroup of biochemical and cellular
events designed to achieve restoration of tissue integrity. A "partial
thickness" wound will heal rapidly by simple reepithelizatin while,
"full thickness wound" which extends to the dermis heal by primary or
secondary intention. The healing by "primary intention" occurs when
the wound is pulled together by sutures or adhesive so that the
epidermal edges are brought into-apposition ( Akasaka et al., 2001).
Delayed primary intention occurs if the wound is infected.
Closure should be delayed until it has been cleared by the natural
defense mechanisms, with appropriate antibacterial treatment. This
delayed closure reduces morbidity but does not affect or delay the
development of wound strength ( Beldon, 2000).
Healing by "secondary intention" occurs when there is a major
loss of skin. The wound may be allowed to heal from the base by the
formation of granulation tissue. In this process, there is deposition of
new collagen, but contraction of the wound is also important in
repairing the defect. This simple methods of wound management can
produce excellent cosmetic results, especially on concave surfaces
( Beldon, 2000).
8
Plasos of wound loa n
Classically there are three phases for normal wound healing :
Inflammatory, fibroblastic and the maturation phases (Peled et al.,
2000and Prathiba et al., 2001).
In the first "inflammatory phase", wounding is immediately
followed by classic inflammatory reaction. Capillaries dilate and pour-
out fluid into the wound, fibrin clots and seals the wound.
Biochemical substances are released that cause vasodilation and pain.
Inflammatory cells are mobilized and move into the wound area.
During this phase the epithelium grows across the sealed wound
(Prathiba et al., 2001).
In the second "fibroblastic phase", the main strength of the wound
is generated. Fibroblasts move into the fibrin clots and begin synthesizing
large amount of new collagen in structural framework. During this phase
the strength of wound rapidly increases (Peled et al., 2000).
In the third "maturation phase", the nodularity and redness of
the fibroblastic phase gradually soften and flatten. Biochemically,
there is ongoing simultaneous collagen synthesis and degradation.
There is continuing slow increase in wound strength up to a year
following injury (Peled et al., 2000and Prathiba et al., 2001).
Evonis n ilo ro oss of wound loa n
Platelets degranulation results in the release and activation of
potent cytokines, including transforming growth factor-(3 (TGF-(3),
9
epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-1), and
platelets derived growth factor (PDGF). These growth factors function in
the recruitment and activation of neutrophils, epithelial cells, endothelial
cells, macrophage, mast cells and fibroblasts. A prolonged inflammatory
phase results in increase in cytokines activity. An increased risk of scar
formation has been correlated with this exaggerated cytokine activation
(Ishiliara et al., 2000and Shang et al., 2001).
Granulation tissue formation and scar maturation require a
balance between matrixdegradation and collagen biosynthesis for
optimal wound healing (Niessen et al., 2001). Matrixdegradation is
coordinated through the action of collagenases, proteoglycogenases
and other proteases. As well antifibrotic factors are released and
include interferon - a (IFN-a), interferon-(l (IFN-P), and interferon -y
(IFN-y). These interferons inhibit fibroblast synthesis of collagen and
fibronectin and decrease fibroblast development (Niessen et al., 2001
and Shang et al., 2001).
Pathogenesis of keloids :
The basis for keloids formation has not been fully elucidated.
Although both an increased collagen synthesis and turnover is
observed, ultimately a disproportion at deposition of collagen has been
noted. Normal and elevated levels of type I and type III collagen have
been reported (Tredget et al., 1997; Naitoh et al., 2001): Keloids
derived fibroblasts produce increased amounts of collagen per cell in
comparison with normal fibroblasts. They appear to function
1 0
autonomously, demonstrating continued collagen synthesis in vitro in
the absence of any humoral substances ( L im et al., 2001).
A ten-fold increase in collagenase production has been shown
within keloids. Elevated levels of collagenase inhibitors such as
alpha-1 antitrypsin and alpha-2macroglobulin are present. As well as,
elevated levels of chondroitin 4-sulphate, which act to make collagen
fibers resistant to collagenase degradation, have been detected.
Slightly increased levels of IgG, 1gM and C3 have been reported,
while IgA and C4 levels remaining normal ( I shihara et al., 2000).
Alternations of growth factor levels in keloids have been reported.
Some of these agents promote collagen accumulation. One of the growth
factors is TGF-13 , which induce fibroblast, collagen, fibronectin and
proteoglycan ( Urioste et al., 1999 and S hang et al., 2001).
The difference between normal wound healing and with keloids
lie not only in length of time over which new collagen is formed, but
also in the arrangement of the newly formed collagen. In keloids, the
formation of new collagen following the inflammatory stage extends
much longer time than in normally healing wound. Even in the early
periods of fibroblastic phase, one can see that collagen fibers in the
granulation tissue are arranged in nodular pattern. The nodules
gradually increase in size and show thick, highly hyalinized bands of
collagen lying in a concentric arrangement
( Chin et al., 2000).
Immediately following wounding, platelet degranulation and
activation of the complement and clotting cascade form a fibrin clot
for haemostasis, which acts as a scaffold for wound repair ( L im et al.,
2001). Platelet degranulation is responsible for the release and
activation of an array of potent cytokines, including epidermal growth
factor (EGF), insulin like growth factor-1 (IGF-1), platelet derived
growth factor (PDGF), and transforming growth factor-13 (TGF-(3)
which function as chemotactic agents for the recruitment of
neutrophils, macrophages, epithelial cells, mast cells, endothelial cells,
and fibroblasts ( S hang et al., 2001 and Niessen et al., 2001).
Proliferation and differentiation of inflammatory cells are
required for phagocytosis, release of cytokines, and the formation of
granulation tissue. Prolongation of the inflammatory stage in large
wounds such as burn or following an infection exaggerates the
inflammatory phase of healing and hence increase the activity of
fibrogenic cytokines such as TGF-f3 and IGF-1, thus increasing the
risk of keloids development ( Boyce et al., 2001).
The transformation of a wound clot into granulation tissue
requires matrixdegradation and biosynthesis that are balanced to
achieve optimal wound healing. The degradation of extracellular
matrixis through the action of collagenase, proteoglycogenases, and
other proteases, which are released by mast cells, macrophages,
endothelial cells, and fibroblasts. Importantly, either excessive
synthesis of collagens, fibronectin, and proteoglycans by fibroblasts or
1 2
11111
deficient matrixdegradation and remodeling may lead to abnormal
lesions such as keloids and hypertrophic scars (Nirodi et al., 2000).
Histologically, keloids and hypertrophic scars differ from
normal skin by an increase in thickness of the epidermis and dermis,
lack of epithelial ridges, minimal amounts of distinct collagen fibers
and fiber bundles, and the presence of nodules (Tredget et al., 1997
and Beldon, 2000).
Immunohistochemical examination has revealed that
hypertrophic scars contain whorls of connective tissue in nodular
structures containing a-smooth muscle actin (a-SMA)-positive
fibroblasts with small blood vessels and fine, randomly oriented
collagen fibrils, whereas keloids have few if any a-SMA-positive
fibroblasts and large, thick collagen fibers (Tredget et al., 1997and
Beldon, 2000).
Although the predominant cell present in keloids and
hypertrophic scars is the fibroblast, Chin et al.;(2000) described a
four fold increase in the numbers of mast cells over those in normal
skin. Clinically the release of histamine by these cells likely
contributes to the common patient complaint of itchness. In addition,
the vasodilatory effect of histamine may promote erythema, and leakage
of plasma proteins into the regional tissues (Beer et al., 1998).
Comparisons of the rate of proliferation of fibroblasts form keloids or
hypertrophic scars and normal skin generally show no significant
1
difference, although several studies report a faster rate of proliferation
for normal cells (Beldon, 2000).
Excessive biosynthesis of extra cellular matrix(ECM) proteins
by fibroblasts has been proposed as one of the potential contributing
factors to the accumulation of excessive matrix. Using
propylhydroxylase activity as an indexof collagen synthesis, it has
been demonstrated that keloids have increased propyl hydroxylase
activity. However, other have used C proline to trace collagen
biosynthesis and found that keloids fibroblasts produced similar
quantities of collagen relative to normal controls ( L im et al., 2001).
Excessive matrixaccumulation can occur not only by increased
synthesis of ECM proteins but also by a reduction in matrix
degradation, either intracellularly or extrace'llularly. Intracellular
degradation of collagen by hypertrophic scars compared to patient-
matched normal skin fibroblasts using 02labeling was not
significantly different ( Peled et al., 2000). However, many
hypertrophic scars and keloids fibroblast cell stains have demonstrated
reduced mRNA for collagenase as well as net reductions in the ability to
digest soluble collagen commpared with their normal fibroblast pairs.
Other unique feature of keloids and hypertrophic scars
fibroblasts include a reduced ability of synthesize nitric oxide as an
important mediator of growth factor signaling, which likely functions
in wound healing through its antiproliferative and antimicrobial
14
1
15
effects It was found to be important in collagenase regulation also
( Cobbold, 2001 ).
Taken together, the undesirable physical properties of
hypertrophic scars and keloids appear not to be a simple matter of
excessive extracellular matrixprotein production. Activated
fibroblasts in hypertrophic scars and keloids are unable to degrade
collagen which may inhibit their ability to remodle the pre-existing,
randomly oriented collagen into a more uniform, organized matrix.
Increased verscian, a proteoglycan with long hydrophilic chondroitin
sulphate sugar chains, may contribute to tissue rigidity and bulk
through its propensity to attract water, interfering with the assembly
collagen fibrils into fibers and fiber bundles. Conversely, the smaller
proteoglycan, decorin, "decorates" the surface of collagen fibrils and
promtes the lateral association of fibrils to form smaller fibers and fiber
bundles as well as inhibits TGF-f3 activity ( Kossi and Laato, 2000).
The role of Cytokines or growth factors in
fibroproliferative disorders:
The release and activation of growth factors during the
inflammatory phase of healing are prerequisties for subsequent
processes, including angiogenesis, re-epithelization, recruitment and
proliferation. Angiogenesis is stimulated by endothelial chemo-
attractants and mitogens such as heparin, released by mast cells,
fibroblast growth factor (FGF) IL-8, released by neutrophils,
macrophages and kerationcytes and IGF-1, released by macrophages
(Niessen et al., 2001 and Ohtsura et al., 2000).
Wound reepithelization occurs following the migration of
epithelial cells from the wound margin and epidermal appendages
within the wound bed and has been shown to be enhanced by EGF,
TGF-a, vaccinia growth factor, and IGF-1 (Chodon et al., 2000).
Fibroblast recruitment, proliferation, and production of ECM are
influenced predominantly by the fibrogenic growth factors PDGF,
IGF-1, and TGF-13, as well as basic fibroblast growth factor (Ohtsura
et al., 2000). These fibrogenic growth factors upregulate ECM protein
production, increase the rate of proliferation and/or migration of
fibroblasts, and inhibit the production of proteases required to
maintain the balance between production and degradation. Of the
many fibrogenic growth factors that have been identified, three have
thus far been implicated in the development of hypertrophic scars and
keloids : TGf-13, PDGF, and IDGF-1 (Niessen et al., 2001).
Transforming growth factor-13 was initially isolated from human
platelets but has been shown to be produced at the wound site by
infiltrating lymphocytes, macrophages and fibroblasts (Niessen et al.,
2001). Many of the biologic actions of TGF-13 contribute to the normal
wound healing process and have been implicated in wide variety of
fibrotic disorders (Chodon et al., 2000). The release of TGF-13 by
platelets localizes it in the wound environment very soon after injury,
16
'IF
where it acts as a chemo-attractant for neutrophils, T-Iymphocytes,
monocytes, and fibroblasts ( S hang et al., 2001). In vivo, stimulation of
granulation tissue formation and enhanced connective tissue response
support the role of TGF-f3 in normal wound healing. However, the
prolonged and excessive presence of TGF-13 likely contributes to the
development of keloids and hypertrophic scars (Ghahary et al., 1995 ;
S hang et al., 2001).
Platelets derived growth factor is initially released into the wound
by platelets, with later production by infiltrating macrophages,
endothelial cells, epithelial cells and fibroblasts. In turn, PDGF also
functions as a chemo-attractant and mitogenic factor for fibroblasts
and endothelial cells. Although the abnormal persistence of PDGF has
not been correlated with the development of hypertrophic scars and
keloids, the ability of this cytokine to modulate the production of IGF-1
by fibroblasts and endothelial cells may indirectly contribute to
fibrosis ( Niessen et al., 2001).
The critical role that macrophages play in wound healing is based
partially on their release of growth factors, including IGF-1. Detailed
studies of cell growth control have divided growth factors into two
types: competency and progression. Competency factors such as PDGF
and FGF allow cells to enter the GI phase of the cell cycle, and
progression factors such as IGF-1 and EGF facilitate the progression of
PDGF- induced competent cells into the S phase of the cell cycle,
ultimately resulting in increased proliferation rate ( Beldon, 2000).
17
The role of mast cells in pathogenesis of keloids :
In most keloids, hypertrophic scars and surgical scars there are
approximately twice as many mast cells in apparently normal dermis
surrounding the scar as in the lesion itself oo oi a , 1996 It has
been previously suggested that mast cell number increase in connective
tissue as healing progresses, but there is some evidence to indicate that
mast cell number decrease in aging keloids. Finding mast cells in greater
number in dermis surrounding scars suggests ilai as the surgical scars
progress, their mast cell component approaches that of normal dermis
ananoio oi a , 1995 ; Ur osio oi a , 1999 and Havorsio , 2001
oor oi a 199S stated that, it would be valuable to quantify
mast cells in perilesional and entirely normal dermis from another skin
site to ascertain if any increase in dermal mast cells occur surrounding
scars even when lesional mast cells are not increased.
Mast cell numbers are not of value to distinguish between
keloids and hypertrophic scars histologically. The precise role of mast
cells in cutaneous scar reactions remains undetermined, but absolute
mast cell numbers may not accurately reflect tissue concentrations for
active mast cell products oor oi a 199S and K n, 2000
Clinically, the release of histamine by these cells likely to
contribute to the common patient complaint of itching. | n addition, the
vasodilator effect of histamine may promote erythema and leakage of
plasma proteins into the regional tissues K n, 2000
18
CHAPTER II
Treatment of keloids
Currently, treatment of keloids, remains time consuming and has
few consistently successful approaches. The result is that many
methods of care have been proposed but few regimens have been
standardized (Shaffer et al., 2002). The following scheme shows the
treatment modalities used in keloids (Porter, 2002) :
I- Surgical therapy
II- Physical therapy
A- Laser therapy
CO, laser
Ultrapulsed CO, laser
Argon laser
Argon-pumped dye laser
Flash lamp-pumped-pulsed dye laser (FPDL)
Neodymium-Yttrium-Aluminum-Garnet (Nd-YAG)
B- Radiation therapy
X-ray therapy
13-radiation therapy
C- Cryotherapy
D- Pressure therapy
III- Pharmacological therapy
Intralesional injection of corticosteroids
Silicon gel
Antihistamine
5-flurouracil
Calcium channel blockers (verapamil)
IV- Immunotherapy
19
| - Sur a iloray
Surgical excision of keloids is the most long-standing form of
treatment (Gloster, 2000).
Recurrence rates for simple surgical excision of keloids alone
vary from 50% to 80%. Surgery has been largely relegated to a second
line therapy for lesions unresponsive to other treatments and large
lesions requiring debulking before the use of other modalities
( Kuwahara and Rasberry, 2000).
Several surgical approaches are available. Care must be taken to
remove all sources of residual inflammation, including trapped hair
follicles, epithelial cysts, and sinus tracts, which may act as potential
sources of fibrogenic growth stimuli (Lee et al, 2001). Surgical
reconstruction should be designed to minimize tissue trauma and
wound tension while avoiding dead space, haematoma formation and
infection (Field, 2001).
Reorientation of scars to parallel lines of skin tension are vital
(Field, 2001). If the surrounding tissue is not under excessive tension,
smaller keloids may be excised and closed primarily. If primary
closure is not possible and asking graft is necessary, full-thickness
excision of the keloids retaining a rim to which the skin graft is
attached, is thought to decrease recurrence (Haverstock, 2001). The
ri m is thought to act as a splint to decrease the central tensile forces. A
full thickness graft that permits primary closure of the donor site is
preferred to a split thickness graft that leaves an open donor site,
because the donor site has a lower incidence of abnormal scar
1
formation ( S haffer et al., 2002). As well, a full thickness graft may
provide a sufficient micro vasculature to allow for anastomosis with
the host micro vasculature, thus resulting in decreased angiogenesis
and fibroblast proliferation ( Urioste et al, 1999).
Contracted scars may benefit from the use of z-plasty or
w-plasty, in which the contractile bands of the keloid are served and
rearranged. This must be performed with great caution because of the
risk of generating new keloids ( Haverstoke, 2001).
Excisional surgery of keloids, in the absence of adjunctive therapy,
results in 45-100% recurrence rates ( Berman and Bieley 1996).
Excisional surgery combined with intraoperative and
postoperative intradermal corticosteroids injections are the most
common mode of therapy for the treatment of keloids. Recurrence
rates following excisional surgery combined with corticosteroids
range from 0-100% but the majority of studies report < 50%
recurrence. The concentration of postoperative triamcinolone
acetonide was vary from 10to 40mg/ml ( Porter, 2002).
The use of pressure as a surgical adjunct for treating ear lobule
keloids most commonly occurring after ear piercing resulted in no
recurrences in several studies with small number of patients. Button
compression therapy, using two shirt buttons sutured together to
sandwitch the ear lobe after excision of the keloids and sutured
together led to no recurrence at 8months to 4 years, after the buttons
were left in situ from 3 weeks to 6 months ( Horn, 2001).
21
Excisional surgery of keloids followed by radiation give
excellent results. In a study of 124 keloid patients underwent surgery
followed by post operative x-ray radiation (600rad/day for three
consecutive days), and were followed up at 6 and 24 months. Good to
excellent results were obtained in 92% at 24 months (Hom, 2001).
Excisional surgery combined with preoperative hyaluronidase
solution (150U in 1 ml of sodium chloride solution) followed by
external radiation of 720-1080rad in 8-12fractions had 0%
recurrence. In general, reports of surgery with adjunctive radiation
therapy included large numbers of keloid patients, long follow-up
periods, and obtained more favorable results than radiation therapy
alone ( Porter, 2002).
Injection of IFN-a 2b into the surgical excision site immediately
following keloids excision limited keloids recurrence only in the areas
injected. Berman and Bieley ( 1996), have used 1FN-a 2b for treating
keloids after surgical excision in 11 patients with 12head and neck
keloids. 10million units mixed with 1mm of diluent with injections of
0.1 ml per linear cm of excised tissue (up to 5cm) was injected into
the suture line after surgical excision of the keloids. Patients had a
repeat injection at the same site and same concentration at one week.
One patient (8.3 %) had recurrence. This patient had only one-half of
her excision site injected. Follow up ranged from 3 to 3 1 months with
an average of 14.7months. Most of these referral patients had a
history of prior recurrence following initial surgical excision ( Niessen
et al., 2001).

II- Physical therapy

This includes,
A- Laser therapy.
B- Radiation therapy either x-ray or [ 3 - radiation.
C- Cryotherapy.
D- Pressure.
A- Laser in keloidS
The word laser is an acronym for Light Amplification by
Stimulated Emission of Radiation.
Laser radiation properties :
Laser light has several unique properties making it different from
standard light e.g. sunlight.
Monochromaticity :
Monochromaticity means that laser light from a given source is
all of one wavelength. Whereas standard light is polychromatic, often
covering the entire visible spectrum. This property is important for
targeting of specific chromophores in the skin, such as
oxyhaemoglobin, melanin, tattoo ink and water where each has a
characteristic absorption spectrum.
23
Coherence :
Coherence means that the waves of energy are in phase with each
other, both in space and time.
Collimation:
Collimation means that the laser beam component waves are
highly parallel, producing a narrow beam allowing them to be
propagated for long distances with minimal convergence or
divergence and focused into very small spot sizes.
These previous three properties of laser light allow high-energy
radiation of a specific wavelength to be delivered to a small area.
The wavelengths of lasers used in dermatology can range from
ultraviolet (100nm) through the visible range into the infrared
(10.600nm).
L aser construction :
A laser consists essentially of a power source, a lasing medium,
a resonating cavity and delivery system. It is necessary to supply
energy into a lasing medium to elevate electrons to an excited state
and produce a population inversion ( L anigan, 2000).
The lasing medium will determine the characteristics of the laser
light emitted. The lasing medium can be solid (e.g. crystals such as
ruby), liquid (e.g. rhodamine dye) or gaseous (e.g. carbon dioxide).
24
The resonating cavity contains the lasing material and has mirrors at
either end to reflect back released photons (Urioste et al., 1999).
The light emerging from a laser cavity can be delivered to tissue
either via an optical fiber or using an articulating arm with mirrors to
deflect the beam. The hand piece delivers the laser beam onto the skin
(Connell and Harland, 2000).
Laser beam can be delivered as a continuous, pulsed or pseudo-
continuous beam. Continuos wave lasers, e.g. carbon dioxide and
argon lasers, produce a steady beam of radiation although this can be
mechanically shuttered into pulses of light. The pulses thus produced
are usually tens milliseconds or longer. Pulsed lasers, e.g., flash lamp
pumped pulsed dye lasers, emit a single pulse or a train of pulses.
Extremely short pulses of light can be delivered by Q. switched as Q.
switched Nd : YAG laser (Alster and Handrick, 2000).
Laser light interaction with tissue :
Laser light when it interacts with tissue can be reflected,
scattered, transmitted or absorbed. The important effect
therapeutically is absorption. The absorbing molecule within tissue,
which in the skin could be haemoglobin, melanin, collagen or water, is
termed the chromophore (Porter, 2002).
The penetration of light into skin is governed by the
combination of absorption and scattering. In general, as the
wavelength of light increases the penetration into skin also increases.
The outcome of laser-tissue interactions can be grouped as follows :
photothermal, photochemical plasma induced ablation, photo-ablation
and photodisruption. By far the most important interaction in
dermatology is photothermal (Shaffer et al., 2002).
Phototheremal interactions :
In phototheremal laser interactions, the absorbed photons are
converted to heat. The local increase in temperature is the most
significant influencing factor. The effect of heat on biological tissue
depends on the duration and the peak value of tissue temperature
achieved. The effect of heating can be seen as coagulation, which can
proceed to necrosis and vaporization, resulting in tissue ablation and
carbonization (Lanigan, 2000).
As tissue is heated, structural changes occur in complex
molecules such as proteins, DNA and RNA. These structural changes
result in impairment of function (denaturation). In addition to
denaturations there is grosser structural disorder with enlargement of
molecules termed coagulation. Denaturation and coagulation generally
proceed as tissue temperature rises above 60C (Porter, 2002).
Thermal coagulation causes cell necrosis. Heating tissue above
100C causes evaporation of water and vaporization of tissue. Tissue
vaporization is used therapeutically in resurfacing lasers such as the
CO, laser ( Driscoll, 2001).
26

Selective photothermolysis :
The theory of selective photothermolysis suggests that selective
tissue absorption of laser light leads to selective destruction of the
absorbing tissue. Skin lesions can, therefore, be treated with a laser
emitting a wavelength corresponding to the absorption peak of the
chromophore contained in the lesion ( Brissett and Sherris, 2001 ).
The mechanism of selective thermolysis is based upon the
thermal relaxation time of the tissue to be irradiated. Thermal
relaxation time is defined as the time required for an object to
decrease its temperature by 50% after being exposed to laser energy
without increasing the temperature of the surrounding tissue ( Brissett
and Sherris, 2001 ). Table (2) shows the classification of sun reactive
skin type ( Fitzpatrick, 1 999).
Table ( 2): Fitzpatrick's classification of sun-reactive skin types
( Fitzpatrick, 1 999).
Skin type Colour Reaction to first summer exposure
I White Always burns, never tans
II White Usually burns, tans with difficulty
III White Some times mild burns, tans average
IV Moderate brown Rarely burns, tans with ease
V Dark brown Very rarely burns, tans very easily
VI Black No burns, tans very easily
27

<-<

Clinical lasers used in treatment of keloids
Carbon dioxide laser (CO2)
The carbon dioxide laser was one of the first laser to be used in
keloids management. In 1982, the continuous wave CO, laser was
successfully employed in the excision of keloids. Its advantage were
attributed to its non traumatic and anti-inflammatory properties
(Urisote et al., 1999).
The carbon dioxide laser emits a continuous wave invisible
beam of 10.600nm, which is in the mid infrared or heat part of the
electromagnetic spectrum. The Co, laser is a gas laser that uses a
mixture of carbon dioxide, nitrogen, and helium as the lasing medium.
Excitation of the lasing medium is most commonly achieved by high
voltage electrical current. To obtain adequate energy transfer, an
intermediary nitrogen atom is first excited with the energy
subsequently transferred to carbon dioxide atoms. After the carbon
dioxide atom decays with the emission of infrared energy, the
molecule is brought down to the ground state through collisions with
the helium atom (Shaffer et al., 2002).
The mid-infrared photons produced by the Co, laser cannot be
transmitted through conventional fiber optics. Articulated arms direct
laser energy from the laser cavity to the desired location through a
series of hollow, rigid tubes with reflecting mirrors at each
connection. The arms can be attached to micromanipulators and
28
iipmmewimm
microscopes, expanding the utility of laser. The hand piece at the end
of the articulated arm contains a lens that focuses the beam to various
spot size of 0.1 to 2.0mm. The hand piece is held from the skin
surface, so that the spot size is small, it is said to be focused. When
focused, the laser imports much energy to a small area, thereby
allowing it to be used as a cutting tool. If, in contrast, the spot size is
made larger by increasing the distance of the focal point from the skin,
the laser beam is said to be defocused. This reduces the power density
allowing ablation of the superficial skin without damage to the deeper
structures (Driscoll, 2000).
There is nonselective absorption of the laser light by
intracellular and extracellular water producing thermal tissue damage
to a depth of 0.6mm. Any tissue with high water content will absorb
the Co-, laser energy and will vaporize as the water reaches boiling
point. Care must be taken to protect surrounding tissues from this heat
(Manuskiatti et al., 2001).
A retrospective study by orr s n 1991, evaluating the
effectiveness of the continuous wave Co, laser as a primary modality
in the treatment of keloids concluded that laser excision of keloids
with healing by secondary intent alone failed to suppress keloid
growths and recurrence. These findings have been supported by
studies performed by Afo bor oi a , 1996 ; lrli and Arndi
(1997) as they reported that higher recurrence rates were observed
29
1
after laser excision of keloids using continuous wave
CO, laser.
It is common practice at present to reserve Co, laser keloids
excision to special situations such as the debulking of large keloids
before initiation of another treatment modality ( Yilmaz et al., 2000).
Surgical removal of keloids with the Co
o
laser alone has reported
recurrence rates of 3 7.5-92%, but when combined with postoperative
corticosteroids and hyaluronidase (40mg/ml of triamcinolone
acetonide and 150mg of hyaluronidase), the recurrence at one or more
years follow up was 16% ( Berman and Bieley, 1996).
I n ( 1994) G old, stated in a study that silicone gel sheeting was
topically applied post operatively after eight keliods were removed by
a carbon dioxide laser, 12.5% had recurrence at 12week, compared
with a 3 7.5% recurrence of keloids excised by carbon dioxide lasers
without postoperative treatment with silicone gel sheeting.
High energy, pulsed CO, laser de-epithelialization of keloids
and hypertrophic scars followed by immediately by 585-nm pulsed dye
laser irradiation has been shown to provide excellent clinical results. One
or two passes of the CO, laser are performed at 500mJ energy/pulse and
5W of power using a 3 mm collimated hand piece to de-epithelialize
and produce collagen shrinkage within keloids. A 585- nm pulsed dye
laser is then used at an energy density of 6.5.1/cm
2
to deliver non
3 0

overlapping 5to 7mm pulses over the de-epithelialized keloids

(Driscoll, 2001).
U irau sod Co
2
asor
Modification in laser technology have produced two groups of
Co, lasers. The first are high-energy, short pulsed Co, lasers that
produce individual, high energy pulses (up to 500mJ) with pulse
durations of less than 900microseconds (p.^). The second group are
scanned continuous wave Co, lasers, which use a computer controlled
optico-mechanical scanner to direct a focused, continuous wave laser
beam in a special pattern, resulting in less than milliseconds (ms)
tissue exposure time (Lanigan, 2000).
Bernstien et al. (1998), evaluated the high energy short pulsed
Co, laser and the scanned Co, laser in the treatment of 24 post surgical
keloidal scars. Scar improvement was evaluated by photographic
analysis of all cases before and after treatment. A11 24 keloids had
greater than 50% improvement, with 20of the 24 showing a greater
than 75% improvement. They concluded that the short pulsed and
scanned Co, lasers appear to be very effective in the surgical
managements of keloids.
The continuous-wave effect of carbon dioxide laser produced
unwanted scarring by thermal damage to the dermis. By mechanically
"pulsing" the beam to short burst that approached the thermal
relaxation time (TRT) of the skin (about 700msec), destruction
3 1
VOW
without scarring can be achieved. Pulse durations of 250msec to one
sec are delivered by ultrapulsed carbon dioxide laser. This allows
thermal destruction of the epidermis and papillary dermis without
thermal diffusion to the surrounding tissue ( D riscoll, 2001). Outcome
is improved by using the ultrapulsed laser in conjunction with an
optomechanical scanner. This scanner provides uniform ablation of
the epidermis and papillary dermis by rapidly moving the beam across
the targeted area allowing little or no diffusion to surrounding tissue.
The zone of thermal damage produced by the ultrapulsed laser is less
than 100iLtm, as opposed to the 400j..tm produced by continuous-wave
carbon dioxide laser ( Manuskiatti et al., 2001).
I n their study L upton and Alster ( 2002), stated a variety of
lasers can be used to treat scars and keloids effectively. It is of
paramount importance that the type of scar be probably classified on
initial examination so that the most appropriate method of treatment
can be chosen. They concluded that the 585-11111 pulsed dye laser is the
most appropriate system for treating hypertrophic scars, keloids,
erythematous scars, and striae. The PDL carries a low risk of side
effects and complications when operated and appropriate treatment
parameters and time intervals. Atrophic scars are best treated with
ablative CO, and Er : YAG lasers.
A serum-free in vitro model was used to determine the effect of
combined carbon dioxide (CO") and erbium (Er) : YAG laser irradiation
on keloid-producing fibroblasts (KFs) from two distinct facial sites.
32
TGF-beta I and bFGF play an integral part in wound healing and were
assayed using this model. At 48hours after seeding, 20% of each well
was exposed to 1.7J/pulse of Er: YAG laser energy and CO, delivered
at 3 or 5W and at a duty cycle of 25%, 50% or 100% using a
quantitative enzyme-linked immunosorbent assay. The results showed
that laser treated ear lobule KFs demonstrated decreased TGF-beta 1
production when compared with preauricular KFs. Statistical
significance (P < 0.005) was seen in the 3 -w CO2 25% duty cycle ; a
trend was seen in the 3 -w CO, 50% duty cycle (P < 0.08). Preauricular
KFs secreted increased bFGF when compared with lobule KFs.
Significance was seen in the 3 -w CO, 25% and 50% duty cycles
(P < 0.05). Laser treated preauricular KFs had increased bFGF
secretion when compared with non laser treated preauricular KFs in the
3 -w CO
2
25%, 50% and 100% duty cycles (Chong et al., 2001).
In Happak et al. (1996) study ; 13 hypertrophic scars and
keloids were studied and he stated that keloids recurred after an initial
improvement. The attempts to remove hypertrophic scars did not bring
the desired results.
In a prospective analysis, Stern and Lucente (1989), noted no
significant advantage to excision of ear lobule keloids with the CO,
laser versus simple excision with a scalpel. In this study, 23 keloids
were excised by laser and only 4 by scalple. The authors used a 20-w
CO, laser at an average intensity of 12w. Adjuvant treatment with a
series of triamcinolone injections were administrated only when the
3 3
first sign of recurrence was noted. Results were unsatisfactory with an
overall 70% recurrence rate.
Argon laser :
The argon laser emits blue-green light at sixdifferent wave-
lengths ranging form 457to 514 nm with 80% of the energy being
contained in the 488- and 514 nm peaks with a skin penetration of one
to 2mm (Lanigan, 2000).
The argon laser was one of the first lasers used in the treatment
of keloids. It was thought to work by coagulation of the capillary
plexus leading to an area of local anoxia. With the production of lactic
acid by glycolysis, pH decreases, and as a result collagenases are
released. The resulting increase in collagenases will cause increased
collagenolysis (Yilmaz et al., 2000).
Although absorption is selective, the subsequent tissue effects
may or may not be equally selective depending on the pulse duration
of the laser exposure. If the duration is long, the laser energy absorbed
by haemoglobin and melanin produces heat, which non-specifically
damages surrounding dermal and epidermal structures. The degree of
damage produced by the laser on the skin depends on power density,
measurement specified by power output, spot size, and duration of
exposure. Very short exposures may limit non-specific damage to
adjacent structures maximizing the potential selectivity of the device.
However, currently available argon lasers have pulse exposures
3 4
4IPilP
greater than that required for a truly specific tissue effect (Spicer and
Goldberg, 1996).
Henning et al., (1986) failed to show overall improvement in 13
keloids treated with the argon laser. Apfelberg et al., (1989), found
similar results as they reported a recurrence rate varied from 45to 93 %.
Argon-pumped dye laser:
The argon-pumped dye laser contains fluorescent organic dye as
the active medium with an argon laser as a power source.
A rhodamine 6 G may be used to emit a wide range of wavelengths,
from 488to 63 8-nm. The argon pumped dye laser emit a continuous-
wave beam that can be mechanically shuttered to produce pulse
durations of 20msec (Lanigan, 2000).
Flash lamp-pumped pulsed dye laser (FPDL):
The FPDL, unlike the argon-pumped dye laser, uses a high-
power flash lamp to produce a true pulsed beam. The active medium
of the FPDL is a rhodamine dye that produces yellow light. Much of
the original FPDL research was done on yellow light at a wavelength
of 577-nm. This wavelength coincides with the longest absorption
peak wavelength of oxyhaemoglobin. At 577-nm the FPDL penetrates
the skin to a depth 0.5mm, 2mm below the dermoepidermal junction.
Penetration can be further increased to 1.2mm if the wavelength is
changed to 585-nm (Connell and Harland, 2000).
3 5
Over the past ten years great studies have been made with use of the
585-nm vascular-specific flash lamp-pumped pulsed dye laser in the
treatment of hypertrophic scars and keloids. The first study demonstrating
a success in scar treatment come from Alster and Colleagues in 1 993 .
They treated keloids at 6.5-7.5J/cm
2
with a 5mm spot or 6-6.75J/cm
2
with a 7mm spot and repeated at 6 to 8weekly intervals depending on
clinical response.
Alster's work became confirmed by Dierick et al. ( 1 995), who
treated 15patients with keloids and obtained an average improvement
of 77%. After an average of 1.8treatments. Goldman and
Fitzpatrick ( 1 995), also treated 48patients with similar laser
parameters. Keloids less than one year old did better than those more
than one year. Similar results were also seen by Alster and
McMeekin 1 996. Combination of CO2
and FPDL in treatment of
keloids have also shown additional benefit of the compared to CO,
laser alone (Alster, 1 997 ).
Using the principle of selective photothermolysis, Paq uet et al.,
( 2001 ) concluded that using the 585-nm pulsed dye laser, for the
treatment of keloids, yielded only minimal effects if any, on the erythema
of keloids. While Manuskiatti et al. ( 2001 ), reported that, the clinical
improvement of keloids after PDL treatment demonstrated no statistically
significant fluence dependence in the study, but a trend toward better
response with lower fluences was seen. In addition, multiple treatments
sessions were suggested for achieving greater response.
3 7
For persistent keloids and scars combination of intralesional
corticosteroids injections and laser therapy may be necessary
(Porter, 2002).
It is not known how the PDL improves the appearance of
keloids but some theories about microvascular damage may affect
collagen or collagenase activity within keloids. Thermal damage to
abnormal collagen within keloids and mast cell alterations after laser
irradiation may also be of importance (Shaffer et al., 2002).
To assess the efficacy of the 585-nm pulsed dye laser on the
appearance of keloids ; Paquet et al. (2001), studied eleven patients
with skin phototypes II-IV and keloids were treated with 585-nm
pulsed dye laser. After one to three treatments sessions, clinical
assessments of the scars were performed in combination with
remittance spectroscopy measurements of the redness and melanin
pigmentation. A group of nine keloids covered by silicon gel sheeting
served as control group and data were compared statistically. They
found that during laser treatments, a desecrate decrease in redness of
the scars was clinically reported. However, this improvement was not
confirmed by the objective spectrophotometric data. No side effects,
specially hyperpigmentation were disclosed. The keloids redness was
not improved in the control group.
The successful use of the 585-nm pulsed dye laser for the
treatment of hypertrophic scars has been well established over the past
decade. Although five years ago this treatment option might have been
considered as available choice only after all other methods failed. It is
now generally recognized as an excellent first line treatment option.
Early scar treatment with pulsed dye laser irradiation effectively
prevents scar formation or worsening and yields a better and more
prolonged clinical improvement. The concomitant use of
corticosteroids, 5-flurouracil, or other treatments is proving to be of
particular importance in reducing scar bulk and symptoms of more
proliferative scars A sior and Handr, 2000
A sior and W ans 1995 , treated sixteen adult patients who
developed keloidal or hypertrophic sternotomy scars after cardiac
surgery, one-half of their keloids treated by a 585-nm flash lamp-
pumped pulsed dye laser with pulse duration of 450microseconds,
spot size of 5mm, and fluences of 6.5-7.25J/cm
2
(mean, 7.0J/cm
2
).
The two treatments (which occurred 6-8weeks apart) resulted in
statistically significant improvement of keloids symptoms including
pruritus and erythema, decreased scar height and improved skin
surface texture in the laser treated portion compared with the untreated
sites at 6 months post-therapy.
It was found that, a 585-nm flash lamp pumped pulsed dye laser
is preferred for the treatment of hypertrophic scars and keloids. C2
laser vaporization of scars that are proliferative, such as hypertrophic
scars and keloids, is not advised due to the high rate of recurrence or
worsening A sior, 1997
3 8

Neodymium-Yttrium-Aluminum-Garnet (Nd:YAG) laser:

The Nd: YAG is a solid state laser containing a crystal of
Yttrium-Aluminum-Garnet (YAG) doped with neodymium (Nd) ions.
The primary wavelength of this laser is in the near infrared at 1064 nm
with a pulse duration of 10nsec (Lanigan, 2000). The Nd : YAG lasers
produce continuos wave (CW) or pulsed (Q-switched) radiation. The
Q-switched laser produces high fluence infrared light with pulse
duration of 10-20ns and has repetition rates (.10Hz). By insertion of a
frequency doubling crystal into the laser beam the wavelength is halved
to green light at 53 2-nm (Landthaler and Hohenleutner, 1997).
The penetration is advantageous in the treatment of dermal
lesions but fraught with complications in other due to the deeper
thermal injury. In addition the energy tends to scatter more than CO-,
laser (Lanigan, 2000).
The Nd : YAG laser energy is delivered to the skin by flexible
fiber optics. The distal end of the fiber is coupled to a focusing hand
piece. Solid sapphire crystal probes fixed to the end of the fiber have
expanded the versatility of Nd:YAG laser. These contact fibers serve
as thermal scalpels that can incise tissues haemostatically. The
Q-switched Nd:YAG lasers deliver nanosecond pulses that result in
less depth of penetration and subsequently, less complications of
scarring and hypopigmentation (Ries and Speyer, 1996).
3 9
Because of the extensive penetration of the Nd:YAG laser into
the skin it can not be used to ablate superficial skin lesions but used to
treat large haemangiomas, thick nodular portwine stains and highly
vascular tumour as Kaposi' s sarcoma due to powerful coagulation and
haemostatic effects. Common warts and planter warts can be
coagulated by means of Nd:YAG laser ( Pfau et al., 1994).
The Nd:YAG laser seems to be suitable for tissue welding
because it can destroy tissue by heat without direct contact, bleeding
or smoke. Laser welding may have advantages over suturing because
it provide better cosmetic results ( S picer and G oldberg, 1996).
The Nd:YAG laser has been shown to exert an effect on collagen
metabolism. Collagen production was shown to be selectively inhibited
by a direct photobiological effect while DNA replication and cell
viability of fibroblasts were unchanged ( Yilmaz et al., 2000).
I n their study Berman and Flores (1998a), concluded that
radiation therapy, using various protocols, has been a safe and
efficacious modality in reducing recurrence. The CO2, Nd: YAG, and
Argon lasers have been used as destructive modalities for the
treatment of proliferative scarring. The pulsed dye laser offers
symptomatic improvement and reduces the erythema associated with
these scars.
40
B- Radiation Therapy :
X-ray therapy :
Cosman et al. ( 1996), found that the most advantageous time
for radiation to prevent recurrence of keloids was early postoperative.
The mechanism of radiotherapy involves the destruction of
proliferative fibroblasts and neovascular bed.
Total doses range between 1500and 2000rads. The treatment
begins immediately after surgery; several repeated doses may follow
for few days. Radiation therapy alone is not recommended because it
is poorly effective with recurrence rate between 50% and 100%
( Porter, 2002).
Postoperative interstitial radiotherapy with iridium 192has been
employed in multiple studies, with a dose variation from 14 to 20Gy,
at a point from 2.5to 5mm to the wire. Keloid recurrence rates ranged
from 20% to 3 6.8%. Advantages to this treatment include easy
application, irradiation of limited volume, and comparable efficacy to
external radiotherapy. The most important side effect of radiation
therapy is malignancy. For this reason many clinicians reserve
radiotherapy for keloids resistant to any other modalities ( D evita 2001).
41
-P
=IA
'
oia-rad ai on Sironi un-9S
Beta-radiation alone was effective in the eradication of
symptoms (55%), while the results in the reduction of size were poor.
Pre-operative radiation was found to be of no advantage. Excision
followed by radiation therapy is a useful and effective methods of
keloid eradication. No malignant transformation occurred Kunar
oi a , 1994
C- Cryotherapy :
Tlo therapeutic effect of cryotherapy are related to direct cell
damage as well as changes in micro-circulation provoked by freezing.
These extremely low temperatures cause vascular damage and blood
stasis within the keloids tissue lead to cell anoxia. As blood flow
becomes more and more sluggish, white thrombi form, occluding the
lumens of the smaller vessels and leading to tissue necrosis and
sloughing. Keloids that have a greater blood flow by Doppler and
those that are more erythematous, respond better to cryotherapy
Porior, 2002
During each treatment session, the entire lesion should be
treated with two to three freeze thaw cycles of 3 0seconds each. The
healing process lasts about a month. At that time the patient can be
evaluated for further treatment. The age of the lesion is an important
factor in predicting the success of the treatment regardless of the
patient' s age. The younger keloids seem to respond better to
cryosurgery than the older ones do. Generally two to 10sessions,
separated by 3 0days are required Ur osio oi a , 1999
Cryotherapy alone has resulted in complete keloids flattening in
51% to 74% of patients treated, but when used in combination with
intralesional steroids, 84% response rate was seen with follow-up
periods up to 1-5years En sl and Slonofo i, 1999
The efficacy of intralesional cryosurgery in treatment of large,
bulky keloids unresponsive to intralesional steroids, was evaluated by
Guia and Kunar 2001 , they found that, 7out of 12patients
showed more than 75% flattening. Depigmentation was observed
along the tracks of the needles in all the patients, which improved
during follow up due to pigment spread from the normally pigmented
areas inbetween.
Jaros oi a 1999 , stated that cryosurgery has used as a simple
and effective method prior to intralesional steroids injections to
facilitate the injection. This step may work by inducing tissue oedema
with subsequent cellular and collagen disruption. The liquid nitrogen
is applied very briefly for 5-15seconds until the skin frosts. After 10-
15minutes the keloids are then injected until the skin begins to
blanch. This technique allows better dispersal of the steroids
preparation through out the keloidal tissue, and it minimizes its
deposition into the subcutaneous or surrounding normal tissue.
43

The pain caused by application of liquid nitrogen; although

generally not sever, is a drawback for some patients, especially when
the keloids to be treated are fairly large. A certain degree of atrophy
and hypopigmentation is also inevitable with this approach. The
hypopigmantation is due to sensitivity of melanocytes to low
temperatures and is fairly permanent. This characteristic makes
cryotherapy less desirable in dark patients Porior, 2002
D-Prossuro iloray
The mechanism by which pressure alters keloids include a
decrease in blood flow with resultant decrease in alpha-macroglobulin,
lower level of chondroitin sulphate with subsequent increase in collagen
degradation, decreased scar hydration resulting in mast call stabilization
and subsequent decrease in neovascularization and extracellular matrix
production or excessive hypoxia resulting in fibroblast degeneration and
collagen degradation Asior and Wosi, 1997
The pressure exerted must exceed the inherent capillary pressure
of 24mm Hg, and the treatment should be maintained day and night
for 6 to 12months. Daily discontinuation of pressure should not
exceed 3 0minutes. Materials used include compression wraps (carbon
bandage), tubular support bandages (Jobskin), presized garments
(Jobst), adhesive plasters, pressure earrings and self-adhering
polyurethane sponges Ur osio oi a , 1999
44
Russell et al. (2001), assessed 3 0patients, between 1989and
1999, who had been fitted with pressure devices made from zimmer
splints. There was a 50% or greater reduction in the size of each
keloid when assessed at one year. Zimmer splints are cheap, readily
available, easily moulded to fit the patients and can be decorated so
that they can be worn as earrings.
I I I - Pharmacological therapy
Many pharmacological agents have been used in the treatment
of keloids, these agents include:
a- Intralesional injection of corticosteroids.
Hansen (1956), was the first to use hydrocortisone injections at
the site of lesions for the treatment of keloids with success. Conway
et al. ( 1 960), reported the use of decadron, a cortisone analogue with
success. In 1 963 , Murray advocated injecting steroids into the
excised scar wound edges at the time of surgery to prevent recurrence.
Ketchum et al. ( 1 966), reported the successful intralesinoal
treatment of patients with triamcinolone. The triamcinolone is now a
mainstay of keloid therapy.
Berman and Bieley ( 1 996), reported a response rate between
50% to 100% to triamcinolone acetonide injection (10to 40mg/m1),
when used alone, with recurrence rate of 9% to 50% in 5years.
Dexamethasone-21 phosphate (1 mg/ml) may be used with a response
rate of 76.5%. When combined with surgery, the recurrence rate in
the majority of studies falls below 50% ( Berman and Bieley 1 996).
Although the various guidelines exist for preparation, dosage,
and administration, one approach employs varying concentrations (10,
20, 3 0, and 40mg/ml) in different lesions or areas of the same lesion
46
47
to establish the minimal effective dosage for subsequent treatments,
usually at 3 - to 4- weeks intervals ( Tredget et al., 1997).
Frequent initial injections (once to thrice weekly) were found to
be more efficacious with decreasing frequency (weekly to monthly)
during a period of stabilization and resolution of keloids. The addition
of the pulsed dye laser treatments simultaneous with injection therapy
was found to be most effective ( Fitzpatrick, 1999).
Enhanced results may be achieved when corticosteroids are
combined with other treatment modalities (i.e., Laser or cryosurgery).
Injections need to be administered at intervals of 4 to 6 weeks for
several months or until the keloid is flattened ( S haffer et al., 2002).
Various delivery systems exist including spring or CO,-
powered devices, but most commonly Luer-lok syringes with 25to 3 0
gauge needles are used to place the injections 0.5cm apart and into
the bulk of the lesion ( Tredget et al., 1997 and Horn, 2001).
Intralesional injection of triamcinolene acetonide for the
treatment of keloid is painful, and lidocaine-mixed preparations are
much the same. The speed of injection is an important determinant of
pain in intralesional therapy. The injection should be extremely slow
and lidocaine should be added for sensitive patients ( O no, 1999).
The effect of corticosteroids may be explained in part by
interruption of the inflammatory response. The specific mechanism of
action of corticosteroids is related to both suppression of collagen
synthesis and to the release of collagenase inhibition resulting in
collagen catabolism ( L arrabee et al., 1990).
Chowdri et al. ( 1999), stated that corticosteroids appear to act
by inhibiting fibroblast growth and inhibiting alpha 2-macrogobulin
resulting is collagen degradation. The corticosteroid suspensions are
injected directly into the scar. Corticosteroid injections will improve
but will not eliminate a keloid ( Horn, 2001).
A common complication of corticosteroid injections is pain at
the site of injection, which can be averted by topical anesthesia and/or
regional injections of local anesthetic around the keloids to be
injected. Other adverse side effects include scar or subcutaneous tissue
atrophy, telangiectasia, necrosis, ulceration and Cushingoid habitus.
Local pigmentation and atrophy can be minimized by confining the
injection to the dermal region of the keloid and maintaining the steroid
concentrations below 5mg/m1 ( O no, 1999). A systemic response to
coricosteroids is uncommon and can be avoided by timing injections
greater than every 4 weeks ( Tredget et al., 1997 and S haffer, 2002).
L ahiri et al., ( 2001), used combination of cryotherapy and
intralesional injection of triamcinolone acetonide to treat keloids. The
method consisted of steroid injection followed by cryotherapy
followed by further steroid injection. They found that the initial
steroid injection is probably better absorbed during the thawing phase
following cryotherapy. The oedema that occurred after thawing
increased the volume of the lesion so that further steroid injection was
48
possible, and that was probably responsible for the greater effect that
they have observed. After cleaning the area, triamcinolone acetonide
at a concentration of 10mg/ml was injected into the keloids.
Cryotherapy is applied for 1 and 2.5minutes. Once the frozen tissue
thaws, a further injection of triamcinolone was administrated to blanch
then to edematous and hyperaemic tissue, for better and longer lasting
action. This cycle was repeated every 4-6 weeks as necessary.
1)- Silicone gel:
Silicone gel was used by Qu nn oi a 19S5 , as a line of topical
therapy for keloids. They found that the gel softened and reduced
keloids in a shorter period of time than pressure therapy. Sawada and
Sono 1992 , used silicone cream in the treatment of keloids with
occlusion. They named this process hydration and occlusion.
Gold (1994), used silicone gel sheets topically on keloids with
success. The silicone oil has been used as silicone cream or silicone
gel in the treatment of keloids. Topical application of silicone gel to
keloids for at least 12hours daily for about months has been showed
to be effective Do ory and son 1994
Suoia oi a , 2000 , evaluated the efficacy of treatment with
topical silicone gel sheet for keloids, by comparing it with simple film
occlusion. They found that occlusion with silicone gel sheet or plastic
film induced hydration of the skin surface which was followed by an
initial quick and later slow process of dehydration when the skin was
49
exposed to the ambient atmosphere. The magnitude of the increase in
hydration induced by silicon gel sheet was always smaller than of the
plastic film occlusion and, unlike the latter treatment, hydration
become less with repetition of silicone gel sheet treatment.
The mechanism of action is still unclear, however hydration and
occlusion are found to play an important role by increasing the
temperature of the scar 1 or 2F of the body temperature thereby
enhancing the activity of collagenase ( Berman and Belly, 1996).
Chin et al. (2000), found elevated level of metalloproteinases in
wound fluid collected under occlusive dressing. In normal wound
healing, the proteinases are important in degrading the extracellular
matrixand thus in controlling scar formation. The most common side
effect of silicon gel is contact dermatitis ( Tredget et al., 1997).
In their study, D e O liverira et al., ( 2001), concluded that,
silicone and non-silicone gel dressings are equally effective in the
treatment of keloids and hypertophic scars.
c- Antihistamine therapy:
Antihistamines have been used in keloids treatment to stabilize
mast cells and reduce histamine level ( Urioste et al., 1999).
Venugopal et al. ( 1999), investigated the effect of avil
(pheniramine maleate) on fibroblasts cultured from abnormal scars in
comparison to normal skin. They observed a decrease in the
proliferation rate in cells from normal skin (3 9%), hypertrophic scars
51
(44%) keloids (63 %). They also reported a decrease in the rate of DNA
synthesis in cells from normal skin (50%), hypertrophic scars (55%)
and keloids (63 %) treated with 8mg avil (72h). The rate of decrease in
collagen synthesis in normal skin (44%), hypertrophic scar (74 %) and
keloids fibroblast (73 %) correlated with change in DNA synthesis.
d- 5- tbrouracil therapy :
Five-flurouracil, a pyrimidine analogue with antimetabolite
activity, it was investigated as an adjunct to glaucoma filtering
surgery, a procedure in which inhibition of wound healing is desirable
to achieve surgical success. This drug has been ' shown to inhibit
fibroblast to reduce postoperative scaring by decreasing fibroblast
proliferation. The safety and efficacy of this agent in surgery was
demonstrated in long term follow-up with a multi-center study of
5-flurouracil ( Fitzpatrick, 1 999).
In 1 989, Fitzpatrik began clinical investigation of the use of
intralesional injections of 5--flurouracil for treatment and prevention
of hypertrophic scars and keloids and he concluded that the use of
5-flurouracil intralesionally for treatment of hypertrophic scars and
keloids appears to be both effective and safe.
Uppal et al. ( 2001 ), evaluated the effects of a single dose of
5-flurouracil on keloids and the possibility of altering the
pathophysiology of keloids using a single application of 5-flurouracil
solution for 5minutes after extra lesional excision. They found a
perceived improvement in conditions for those treated with
5-flurouracil, compared to the control specimens with a significant
reduction in all the markers assayed.
The injection of 5-flurouracil was performed as frequently as
3 times per week, and as the keloids began to respond, the injection
was reduced to twice per week, once per week, and then every other
week with occasional injections given at 1 to 6 months apart. The total
dose per treatment ranged from 2mg to 50mg. Intralesional injection
of 5-flurouracil in combination with 1% xylocaine in the same syringe
were tried to decrease the pain of injection. Xylocaine mixtures were
found to be ineffective in alleviating pain, as the pain is caused by the
injection procedure itself F i air , 1999
Some patients with erythematous scars and keloids have
received pulsed dye laser with 5-flurouracil injections. These laser
treatments were generally done at 4 to 8week intervals. When laser
treatments and 5- flurouracil treatments were done at the same
treatment session, the laser treatment was usually performed first.
Laser treatments were added once the keloids had begun to respond to
injection therapy and soften and be no longer symptomatic. The added
value of the laser was to eliminate erythema and to improve the
texture of the keloids and scar. In keloids that had failed to respond to
intralesional kenalog, intralesional 5-flurouracil plus kenalog was
injected, 16 treatments being performed over the first 8months and 4
treatments over the following 6 months. During the last year of
52
i t
1111111

treatment, 4 sessions of pulsed dye laser were performed at
6.25J/cm
2
. Complete flattening of keloids and hypertrophic scars was
achieved with this treatment regimen F i air , 1999
o- Ca un lanno b o ors voraan
Calcium channel blockers (verapamil) or calmodulin inhibitors
(trifluoperazine) have been injected into keloids that failed to respond
to corticosteroids in attempt to activate collagenase synthesis n the
lesions through the alterations in fibroblast morphology that are known
to induce collagenase gene transcription (Tredget et al., 1997).
Lawrence (1996), treated 45ear lobe keloids with excision
followed by injections of intralesional verapamil (0.5to 2.0ml, 2.5
mg/ml) for one month and pressure earrings for 6 months. Twenty-two
keloids (55%) showed no evidence of recurrence at follow up (range 6-
28months). There were no significant difference in recurrence rates
related to sex, age, keloid size, keloid age or number of verapamil
injections received. The author found beneficial effects in ilroo of five
patients treated with calcium channel blockers with few if any side
effects with a maximal intralesional injection of 2m1 (2.5mg/ml).
5
I V-I mmunotherapy
Preliminary studies have shown that immuotherapy may have a
role in the treatment of keloids. In 1990, Gransio n oi a examined
the effect of Intralesional injection of IFN-y in a dose of 10[Ig to
20011g twice weekly for 4 weeks. A significant reduction in the keloid
size was noted. Histologically, INF-y treated keloids showed a
decreased or absence of collagen nodules. A decrease in mast cell was
noted. Overall intralesional injection of INF-y is well tolerated.
However injection tend to be painful and a flu-like syndrome
characterized by headache, diffuse myalgia, and low grade fever
(3 7.5C) have been observed, lasting 6 to 48hours after an injection.
P iio oi a 1994 , studied the effect of INF-y on the clinical and
biological evolution of keloids. They observed that the size of the lesion
was reduced after intralesional injection of 1NF-y. ornan and F oros
199Sb noted lower rate of keloids recurrence in sites treated with
postoperative INF-7,1) in comparison with keloids treated with excision
alone. These findings were supported by Conojo- r oi a , 199S
Interferons (INF-a, INF-13 , INF-y) inhibit types | and III
collagen synthesis by dermal and synovial fibroblasts and type 11
collagen synthesis by chondrocyte in a dose doondoni fasl on Tl s
inhibition occurs through a reduction in cellular mRNA Ur osio oi
a , 1999
54
Recombinant human IF-1 has been shown to down regulate
collagen synthesis and may be useful in the treatment of diseases
characterized by collagen over production. The most dramatic result
was achieved when IF gamma was used after keloid excision, therefore
IF gamma may be a useful adjunct to surgical excision of keloids to
prevent the recurrences ( Yilmaz et al., 2000 ; Edwards, 2001 ).
55
PATIENTS AND METHODS
Patients :
This study was carried out in Dermatology and Venereology
Department, Faculty of Medicine, Zagazig University Hospitals. This
study involved twenty patients had keloids on various locations on
their body including back, chest, ear lobules, face, forearm, mastoid
region and deltoid region. Cases included in this study had skin types
III-V. These patients were 8males and 12females. Their ages ranged
from 10to 3 8years (mean 24 years).
Full history was taken from each case including: personal
history, present history, family history, history of surgery, history of
trauma or history of previous treatment. Full clinical and
dermatological examination was done. All patients were photographed
before, during and after treatments.
Patients were selected to fulfill the following criteria:
No history of hepatitis infection.
Patients who had previously received others forms of treatment
were excluded from this study.
No contraindication for laser therapy in (group B) such as;
patients with photosensitivity, or those taking photosensitizer drugs.
Pregnant females were excluded.
56
191111111111111P
Aaraius
- Laser
- Dermojet
Lasor aaraius
Patients were treated by Q-Switched Nd: YAG (Paragon Elite
Medical laser) manufactured by lynton laser Ltd, with Rainbow wave
length extension accessory (585nm) from Lindow House, Beeech
Lane, Wilmslow, Cheshire SK95ER United Kingdom.
Dornojoi
Dermojet (leur-lok syringe with 25-3 0guage needle), it is a
MADAJTXL, o 11919xLU from MADA MEDICAL Company,
Carlstadt, New Jersey, USA.
oilods
Tlo iwoniy ai onis lad o o ds woro ass f od nio iwo
rous
Grou A
Included 10patients, they were treated with intralesional
injection of triamcinolone acetonide.
Grou
Included 10patients, they were treated with laser therapy of
wave length 585nm.
57
All patients of both groups were examined locally for: colour,
texture, morphology, number, site and size keloids and skin type.
G roup ( A):
Patients were treated with intralesional injection of
triamcinolone acetonide using dermojet. Preoperative photograph for
all patients were taken before treatment. They were injected with
concentration 20mg/ml. Injection was placed 0.5cm apart into the
bulk of the lesions with two weeks interval between each sitting and
for a period of 6 months.
The patients were examined regularly for pain, ulceration,
cushinoid habitus, local pigmentation and atrophy.
Post injection photographs were taken for all patients.
Patients who failed to respond to injection after 6 months were
directed to another modality of treatment.
E valuation of patients:
The degree of improvement of the patients were evaluated as
follows:
Patients were asked to give their subjective assessment of their
clinical response to injection.
Photographs were taken for each patient to assess improvement.
58
Assessment of keloids was made pretreatment, at 2weeks
interval during the period of treatment, then 4 weeks interval after
treatment and then follow up for 6 months after therapy.
The assessment included site, number and depended on palpation
of keloids as follow:
0: nil excellent response
1: minimal good response
2: moderate weak response
3 : No changes No response
Group B : Laser therapy
I- Patient selection:
The patients had realistic expectation of the treatment and were
fully awared that most dermatological lesions required several laser
sessions to obtain the desired clinical outcome and that each treatment
session is accompanied by discomfort and prolonged healing time.
II- Preoperative management:-
Before laser therapy all patients were subjected to the following:
Preoperative information sheets.
Informed consent reviewed and signed.
59
Patients were prepared with retinoic acid 0.05% for 2to 3 weeks
preoperative to improve wound healing.
Application of low dose of steroid cream reduces the intense
irritation induced by retinoic acid.
Sun block protection is essential in reducing the retinoic acid
photosensitivity.
EMLA cream (anesthetic cream) was applied half hour before
laser procedure.
EMLA cream was removed with wet gauze immediately before
laser surgery.
Doctors and patients wore safety glasses.
III - Operating procedure :
Laser was applied to small tested area as test spots. We used
different energy density, the excellent results were obtained at 11.3 J/cm
2
.
Examination of tested area was done two weeks later before starting
treatment sessions.
In this study laser parameters used were: wave length 585nm,
repetition rate 10HZ, spot size 1.5mm and fluences 11.3 Jim'.
Number of treatment:
The number of treatment needed was dependent on the size of
keloids. In general 2to 6 sessions (mean 4) were needed to treat
60
61
keloids in order to obtain the desired degree of flattening and colour
lightening.
The treated keloids were evaluated 4 weeks post operatively.
Then another laser treatment could be delivered depending on the
clinical results.
I V- Postoperative management:
Laser irradiation of keloids produced an immediate purpuric
tissue reactions that took 7to 10days to resolve.
Ice pack was applied for 10to 15minutes each hour.
Antibiotic or healing cream was used (Fucidic acid cream)
The patient was instructed that the lased area was kept dry and
avoid sun exposure to the lased area.
All area treated by laser should be protected by sun-screen.
Showers were permitted but prolonged bathing was not advised.
Re evaluation of the patient was done 4 weeks later for the
second session.
V- Evaluation of patients:
The degree of improvement of the patients was evaluated by:
Patients were asked to give their subjective assessment of their
clinical response to laser therapy.
Photography were taken for each patient to assess any
improvement.
Any complication was recorded.
Assessments of the keloids were made pretreatment, at 4 weeks
during treatment and at 8weeks after therapy for 6 months after the
end of therapy.
The assessment included, site, number, and palpation
(Consistency) of keloids.
The palpation of keloids was made as follow:
0: nil excellent response
1: minimal good response
2: moderate poor response
3 : No change No response
Statistical Analysis
The following statistical methods used for analysis of results in
the present study (Dean et al., 1994).
A- Descriptive study :
* Data were summarized using :
1- The arithmetic mean ( X) as an average describing the central
tendency of observations
Mean (X) =

W her e:
X = individual data
n = number of individual data
2- The standard deviation (SD) as a measure of dispersion of the
results around the mean
Standard deviation (SD) =

Ex
2 (/X)
2

n 1
3 - Qualitative variables represent as number and percentage
63
- Conar son of noans
1- Tlo siudoni's i iosi for onar son of noans of iwo
ndoondoni rous
, -,
W her e:
X
|
,X2 Tlo mean of the first and second groups
respectively.
SD
|
, SD2= The standard deviation of the first and second
groups respectively
n number of observation in each group.
The results of the " t " value was then checked using student "t"
table at degree of freedom df = n
1
+n22
C- Cl -squarod iosi
2

Used to find the association between the row and column
variables.

2
0 E)
2
=
W her e:
o = observed value.
df= (r-1) (c-1)
64
Siudoni's i test
SDj
2
+
SD;
n, n,
Row total X column total
E = Expected value
Grand total
cif = degree of freedom
r = row
c = column
Level of significance :
P value > 0.05
< 0.05
< 0.001
Non significance
Significant
Highly significant
65
RESULTS
The results of the present work are shown in tables 3 to 11 and
figures 1 to 8.
The study included 20patients. Out of these patients, 12were
females (60%) and 8were males (40%) (table 3 ).
Table (3 ) shows sexdistribution between the two groups ; in
group (A) 5patients were males (50%) and 5patients were females
(50%). In group (B) males represented 3 0% of cases (3 patients) and
females represented 70% of cases (7patients).
In group (A) the age range was from 10to 3 4 years (mean
20.3 13 .2). In group (B) the age range was from 12to 3 8years
( mean 23 .9 12.5) with no statistical significant difference between
the two groups (P > 0.05) (table 4).
The commonest sites involved were, in order of frequency, the
back 8patients (40%), the chest 4 patients (20%), ear lobules
3 patients (15%), the face 2patients (10%), the forearm one patient
(5%), one patient (5%) in the mastoid region and one patient in the
right deltoid region (5%) (table 5).
The most common cause was trauma in 10patients (50%),
followed by burns in 4 patients (20%), post infection in 2patients
(10%), while in four patients (20%) the cause was not known (table 5).
66
In both groups ; 3 0% of the keloids were small, while 50% of
keloids in group (A) and 40% in group (B) had medium sized keloids.
The large keloids represented 20% of group (A) compared to 3 0% in
group (B) (table 6). The difference was statistically insignificant.
I n group ( A), the response to intralesional steroid injection was
shown in table (8) ; all patients get subjective significant symptomatic
relief. Seven patients out of ten showed excellent response (70%)
(grade 0) (fig. 1, 3 ), while 2patients (20%) showed good response
(grade 1) (fig 4) and one patient (10%) had no response (grade 3 ) to
intralesional steroid injection (fig. 5).
Three patients out of the seven who achieved excellent response,
had excellent response after three injections, two patients after four
injections, one patient after two injections and one patient after five
injections (table 7).
It was found that all the small sized lesions (3 patients), three
out of five medium sized lesions (60%) and one out of the two large
lesions had achieved excellent response to intralesional injections
(table 7).
I n group ( B), excellent response (grade 0) was achieved in 5
patients (50%), good response (grade 1) in 3 patients (3 0%) and no
response (grade 3 , 4) in 2patients (20%) (table 8, 9and figs. 2, 6, 7, 8).
The three patients with small sized lesions showed excellent
response to laser therapy (100%), while in the four medium sized
67
lesions ; 2patients (50%) had achieved excellent response and 2
patients (50%) showed good response. In the large sized lesions, one
patient had good response with no response in two patients (table 8).
Regarding the maximum number of laser sessions needed to
achieve excellent response, one patient had achieved excellent
response after three sessions, one patient after four sessions, two
patients after five sessions and one patient after 6 sessions (table 8).
Regarding excellent response, there is no statistical significant
difference between both groups (table 9).
Local complication of treatment in group (A) included infection
in two patients (20%), dermal atrophy in one patient (10%) and
hypopigmentation in one patient (10%). However, hypopigmentation
recovered completely in two months, while dermal atrophy persisted
for one year after completion of treatment (table 10).
In group (B), local complications included scales in one patient,
swelling in two patients and pain in one patient. All these side effects
respond to medical treatment (table 11).
68
q111111K
Tab o So d sir bui on of ilo siud od ai onis
Sex Grou A Grou
o No.
a os 5 50 0
Fona os 5 50 7 70
Toia 10 100 10 100
Cl squaro
2
0.83
P value = 0.3 6 NS
Tab o 4 A o d sir bui on of ilo siud od rous
Grous t SD
Ean o of a o n
years
T P
Group (A) 20.3 13 .2
10-3 4 0.62 > 0.05
NS
Group (B) 23 .9 12 5 12-3 8
S Non significant
69
Table ( 5) : Aetiology and distribution of the keloids.
S io of os on o Aoi o o a fa iors
Trauna urn | nfo i on Un nown
a S 4 2 -
2
Closi siorna 4 2 1 - 1
Ear obu os
-
--
Fa o l n 2 1 -|
Foroarn 1 - 1 - -
asio d ro on 1 - - - 1
Do io d ro on 1 - 1 -
' '
Table ( 6) : S ize of the keloids in both groups.
S ize of keloids G roup A G roup B
No.
cyo
No.
0/0
S mall ( 0-5 cm
2
)3 3 0 0
Medium ( 5-15 cm
2
)5 50 4 40
L arge ( > 15 cm
2
)2 20 3 0
Toia 10 100 10 100
P value = 0.85NS
Chi square (X
2
) = 0.3 1
Tab o 7 Eosonso of o o ds io nira os ona ori osioro d
njo i on rou A ro ard n ilo s o of o o ds
and nunbor of njo i ons
S o of os on
E o oni rosonso unbor of njo i ons
o No. of patients No. of injections
Sna 0-5 n
2
3 100 1 2
2
3
od un 5-15 n
2
3 60 1 3
4
Lar o > 15 n
2
1 50 1 5
Chi square (X
2
) = 1.9
P value = 0.3 8NS
71
Tab o S Eosonso of o o ds io asor iloray rou
ro ard n is s o and nunbor of soss ons
S o of o o ds
E o oni rosonso Good rosonso o rosonso
No. of patients Lasor soss ons
No
% No. of patients No. of sessions
No `V.No ' V . ,
1
Sna 0-5 n' 0 0 0 0
3 100 1 4
1 5
1 5
od un 5-15 n
2
1
-
50 0 0
50 1 6
Lar o > 15 r
2
1 3 3 .3 2 66.7
0 0 0 0
Tab o 9 Conar son boiwoon boil rous ro ard n rosonso
Tyo
E o oni rosonso Good rosonso o rosonso
o

o
Sioro d 7 70 2 20 1 10
Lasor 5 50 3 3 0 2 20
Chi square (X
2
) = 0.87
P value = 0.64 NS
Tab o 10 Con ai ons of nira os ona njo i ons
Con ai ons Patients
No. %
Infection 2 20
Dermal atrophy 1 10
Hypopigmentation 1 10
Cushingoid features 0 0
Tab o ( 1 1 ) : Con ai ons of asor iloray
Con ai ons Pai onis
o
Blisters 0 0
Scales 1 10
Swelling 2 20
Pain 1 10
Oozing 0 0
73
A oforo iroainoni Afior ono njo i on iwo woo s
6
E o oni roso ui on afior iwo njo i ons four woo s
F 1 Fona o ai oni lad fa a o o d on r li loo iroaiod w il
iwo niraosona ori osioro d njo i ons slowod o o oni
rosonso
A oforo iroainoni Afior ilroo asor soss ons
C Afior four asor soss ons
F 2 Tlo rov ous ai oni n f 1 w il o o d on ofi loo
iroaiod w il asor iloray slowod o o oni rosonso
75
T 11IMP
E o oni roso ui on afior ilroo njo i ons 6 woo s
F a o ai oni w il anior or losi wa ood iroaiod
nira os ona ori osioro d njo i ons slowod o o oni
rosonso
76
<
A oforo iroainoni Afior iwo njo i ons 4 woo s
C Good roso ui on afior ilroo njo i ons 6 woo s
F 4 Fona o ai oni w il o o d n ilo do io d ro on iroaiod w il
ilroo nira os ona or osioro d njo i ons slowod ood
rosonso
7 7
A oforo iroainoni Afior o ovon njo i ons 22 woo s
4
C Afior sur a ronova
F 5 Fona o ai oni w il oar obu o o o d iroaiod w il o ovon
nira os ona ori osioro d njo i ons w il no rosonso ilon
lan od io sur a ronova
7S
A oforo iroainoni
Afior f vo asor soss ons
F 6 Fona o ai oni lad o o d on ilo ba iroaiod w il f vo asor
soss ons slowod ood rosonso
79
Afior four asor soss ons
C Good roso ui on afior s asor soss ons
F 7 Fona o ai oni lad siorna o o d iroaiod w il s asor
soss ons slowod ood rosonso
80
A oforo iroainoni
A oforo iroainoni
| nnod aio y afior asor soss on
F S a o ai oni lad o o d on ilo ba iroaiod w il s asor
soss ons and no rosonso
S1
DISCUSSION
Many treatment modalities have been advocated for the treatment
of keloids but non have been universally successful. Pressure therapy is
effective for the prevention of scar hypertrophy, and is useful even for
established keloids ( Sherris et al., 1 995 and Niessen et al., 1 999).
Cryotherapy is associated with hypertrophy and discolouration, and
needs technical experience ( Gupta and Kumar 2001 ). The use of
radiation in the treatment of keloids is well established but its hazards
such as atrophy, lack of growth and increased incidence of malignancy
li mit its role ( Perez and Brady, 2002).
Surgery alone has a high recurrence rate. It has been
recommended as a second line therapy for lesions that do not respond
to steroids and pressure, and large lesions requiring debulking
( Lawrance 1 996 ; Hom 2001 ; Porter 2002).
The aim of this work was to evaluate and compare the efficacy
of intralesional steroids injection and laser therapy for treatment of
keloids. Twenty patients participated in the present study. They were
classified into two groups, ten patients (group A) were treated with
intralesional steroid injection and ten patients (group B) were treated
with laser therapy.
As regards intralesional steroids injection (group A), all the
patients in this group achieved symptomatic relief. The same results
were reported by Conway and Siar , 1960 , Ho andor, 1961 ;
Koi lun oi a , 1966 , o a oi a , 19S7 , Tan 1992 and
Clowdr oi a , 1999
One of the first studies to report results of triamcinolone
acetonide injection found that 88% of keloids injected with steroids
regressed to varying degrees within 3 to 5days after injection
Koi lun oi a , 1966 , while Clowdr oi a , 1999 , found
complete response in 91.9% of keloids with no recurrence.
In the present study excellent response was achieved in 70% of
cases, good response in two patients (20%) and no response in one
patient (10%). Clowdr oi a 1999 , found in their study that the
maximum number of injections needed to get complete response was 4
in 15patients, 5in 3 4 patients and 6 in 9patients.
On the other hand, Lal r oi a , 2001 , stated a mean of 4.23
sessions per patient to get a complete or almost complete resolution in
12 patients (28%). In this study the maximum nunbor of injections
needed to get complete response was as follow, two injections n ono
83
patient, three injections in three patients, four injections in two patients
and five injections in one patient (mean = 2.7injections per patient).
In this work, no statistical significant difference in response to
intralesional steroid therapy regarding the size of keloids was observed.
This result was supported by Chowdri et al. ( 1999), who mentioned no
statistical significant difference in response to intralesional injection
regarding the size of keloids. On the other hand L ayton et al. ( 1994),
stated that, grossly palpable keloids measuring more than 6 mm in depth
showed no response to steroids therapy, and lesions less than 6 mm
depth on the back flattened significantly more with steroids therapy than
those on the chest.
In the present study, the treatment complications to intralesional
steriods injection were; infection in two patients (20%), dermal
atrophy in one patient (10%), and hypo pigmentation in one patient
(10%). Chowdri et al. ( 1999), found that local complication of the
treatment included; infection in 3 .44% of cases, dermal atrophy in
1.72% and hypopigmentation in 1.72%. However in this work it was
observed that hypopigmentation recovered completely in 9months,
while dermal atrophy persisted for one year after completion of
treatment. Also, L ahiri et al. ( 2001), reported hypopigmentation
84
along subcutaneous veins following intralesional triamcinolone
injection.
In this study, laser therapy (group B), it was found that 50%
(5patients) had achieved excellent response, 3 0% (3 patients) showed
good response and 20% (two patients) showed no response to laser
therapy. In those patients who achieved excellent response, one
patient showed excellent response after 3 laser sessions, one patient
after 4 sessions, two patients after 5sessions and one patient after 6
laser sessions.
These results came in agreement with that of Hondorson oi a
19S4 , wlo noiod on oio rosonso in 55% of patients. Also A sior
and Wosi 1997 , rooriod 57% to 83 % improvement in keloids after
one or two treatment sessions using 585nm flash lamp pulsed dye
laser and later confirmed this finding in a second study of sternotomy
scars.
Tl s result was supported by Asior and Handr 2000 , who
reported 80% clinical improvement after two pulsed-dye laser
treatment. They concluded that more fibrotic or proliferative keloids
typically require additional sessions to obtain the desired degree of
improvement.
85
This finding also came in accordance with Paquet et al. ( 2001),
who assessed the efficacy of the 585-nm pulsed dye laser on the
appearance of keloids and reported that after one to three treatment
sessions, a discrete decrease in redness of the keloids was clinically
reported. However this improvement was not confirmed by the
objective spectrophotometric data. On the other hand L upton and
Alster ( 2002), stated that the 585-nm pulsed dye laser is the most
appropriate system for treating keloids, hypertrophic scars and striae.
Also, Manuskiatti et al. ( 2001), found a significant
improvement in scar height, erythema, and palpation in all laser
treated keloids using the 585-nm pulsed dye laser. There was no
significant difference in treatment outcomes versus the fluence of
laser (3 , 5and 7J/cm
2
), although there was a trend for lower fluences
to show more improvement. Objective clinical improvement was seen
as early as week sixteen, after more than two treatment were given.
Multiple treatment more than two sessions appeared to provide a
greater percentage of scar resolution.
On the other hand, Paquet et al. ( 2001), reported that the
585-nm pulsed dye laser yields only minimal effects on erythema of
keloids, while Connell and Harland ( 2000), reported that erythema
improved by 40% in their study using Nd: YAG laser.
86
Regarding the size of keloids, this study showed no statistical
significant difference in response to laser therapy. However, three
patients with small keloids (0-5cm' ) had complete response, while
non of the three patients with large keloids (> 15cm' ) showed
complete response. The same results were reported by S lo and
andorloofi 199S , who found that, the smaller the size of the
keloid, the better the response to laser therapy with no statistical
significant difference.
These results came in agreement with Conno and Har and
2000 , who reported that ; keloids have been treated in many ways
with varying success. A wide variety of treatments indicated that no
treatment has been shown to be markedly superior

to the others. A
pilot study was undertaken using 585-nm pulsed dye laser and
intralesional steroid injection. In this study they found that 75% and
60% improvement in patients treated with intralesional steroid and
laser respectively. They also concluded that pretreatment with pulsed
dye laser facilitated steroid injection by making the keloid oedematous
and therefore softer. In addition combination of both modalities is
summative.
As regards side effects and complications observed after laser
treatment of keloids, scales were seen in 10% (1/10) of patients,
87
swelling in 20% (2/10) of patients, and pain in 10% (1/10) of patients.
No blisters, Oozing or hypopigmentation were detected in this study.
This goes with Rosenberg and Gregory (1996), who reported that
minimal or no hypo pigmentation could occur.
On the other hand, Shaffer et al. (2002), in their study reported
that hypopigmentation was recorded in 5% of cases who received
combined modality in the form of laser therapy and intralesional
corticosteroid injection.
In the present study, the results of both groups were comparable
with no statistical significant difference. These results may be
attributed to many reasons. First of all the number of the treated
patients (10for intralesional injection and 10for laser treatment) are
low and cannot be used for statistical data. Secondly, patients were
treated by rainbow arm of Nd : YAG laser with 585-nm wavelength
and 1.5spot size and this is not the actual pulsed dye laser because we
cannot have free hand in manipulating the parameters of this laser as it
is adjusted as such, so it cannot be used for statistical analysis also.
Thirdly, the number of the patients of the study must include other
type of treatment modalities as pressure, cryotherapy, and new laser
system.
88
q||||||P
SUMMARY AND CONCLUSION
Many treatment modalities have been used for the treatment of
keloids such as, surgery, physical therapy, pharmacological therapy
and immunotherapy.
The present study was done to evaluate the efficacy of
intralesional steroid injection and laser in the treatment of keloids.
Moreover a comparison was made between intralesional steroid
injection and laser therapy.
Twenty patients participated in this study, 8males and 12
females, their age ranged from 10to 3 8years. These 20patients had
been divided into two groups : (A) and (B) each composed of 10
patients.
In group (A) the patients were treated using the intralesional
injection of traimcinolone acetonide (20mg/m1) by dermojet every 2
weeks between each sitting and for a period of 6 months.
In group (B) the patients were treated using Q-switched Nd:
YAG laser with wave length 585-nm, repetition rate 10Hz, spot size
1.5mm and fluences 11.3J/cm'. The number of sessions were from 2
to 6 sessions with one month interval between each session to allow
time for maximal healing.
89
Results of treatment showed complete response in 70%, partial
response in 20% and no response in 10% of cases in group (A), 3
patients out of the 7who achieved excellent response, had excellent
response after 3 injections, 2patients after 4 injections, one patient
after 2injections and one patient after 5injections. Group (B) showed
50% excellent response, 3 0% partial response and no response in 20%
of cases. Regarding the number of laser sessions needed to achieve
excellent response ; one patient had achieved excellent response after
3 sessions, one patient after 4 sessions, 2patients after 5sessions and
one patient after 6 sessions. No statistical significant difference was
found between both groups.
In both groups, the size of keloids have no statistical significant
difference in affecting the response to treatment and the number of
treatment sessions needed to achieve complete response is variable.
The treatment complications in both groups are temporary and
resolved by the end of follow-up period.
In conclusion, there is no classic and unique solution for curing
all cases of keloids. A cheap, safe and available treatment must be
tried for patients and what is suitable for some patients are not suitable
for others. Intralesional steroids, pressure therapy, cryotherapy,
surgery and laser treatments all are available measures that can be
90
used separately or in combination with each other for treatment of our
patients. Our recommendations for future studies are :
Examination of a large number of patients to have a statistical
results.
Evaluation of more than one line of treatment together to get the
high beneficial results for our keloidal patients.
New laser apparatus will have the way for more new era of
treatment.
9
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