LASER TREATMENT OF SCARRING SKIN DISORDERS: FOCUS OF MORPHEA Jasmina Kozarev, M.D.

Laser in medicine, vol I, issue 1, October 2012
LASER TREATMENT OF SCARRING SKIN DISORDERS: FOCUS
OF MORPHEA
Jasmina Kozarev, M.D.
Dermamedica Dr. Kozarev, Dermatology Laser Clinic, Sremska Mitrovica, Serbia
Corresponding authors address:
Jasmina Kozarev, MD, PhD
Dr Kozarev Dermamedica Laser Center
Vojvode Stepe bb, 22000 Sremska Mitrovica, Serbia
t. +381 22612122
f. +381 22 636303
e-mail: [email protected]
Web site: http//www.kozarevdermatology.com
Keywords: morphea, fractional laser, control wounding, immune response.
ABSTRACT
Introduction
Scar formation is an unfortunate consequence of many skin disorders. Morphea,
typically start with the insidious onset of firm, violaceous or erythematous plaques. The
plaques gradually enlarge with active, violaceous or erythematous borders and shiny,
white, firm centers. Atrophic, sclerotic and depressed scars are the eventual sequelae.
Numerous treatments have been tried, such as local corticosteroids, D-penicillamine,
intravenous penicillin, intralesional interferon gamma, plasmapheresis, PUVA therapy,
UVA1 phototherapy, PDL laser and in patients with severe disease, immunosuppressive
and vasoactive drugs. The aim of this study was to determine whether fractional Er:YAG
laser resurfacing of affected area would be effective in patients with localized
scleroderma. Because mast cells also elaborate a variety of cytokines, the presence of
mast cells following laser irradiation and accompanying tissue revascularization may
provide an explanation for the therapeutic outcome following microvasculature
destruction in terms of stimulating collagen remodeling.
Materials and methods
The cases are reported of five women patients presenting asymptomatic lesions:
on the trunk, mammary region, and tibial region. Previous conventional therapies had
failed. All patients had up to three similar cutaneous lesions. The lesions underwent
punch biopsy, and the histopathological findings confirmed the diagnosis of morphea.
Laboratory investigations showed no abnormalities. The treatment was performed once
monthly into three sessions with fractional ErYAG laser resurfacing (scanning device in
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Laser in medicine, vol I, issue 1, October 2012
turbo 4 mode, 10% of coverage, pulse width of 600 ms, fluence of 24J/cm2, and
frequency of 20 Hz), without any other specific local therapy. Clinical and dermoscopic
assessment of the lesions was performed before treatment, during follow-up and at
treatment end point. Patients evaluated the treatment pain level after each of the three
sessions.
Results
In all patients, the initial reactions to treatment consisted of erythema and
minimal swelling, slight burning sensation but no significant pain. The erythema lasted
between 2 and 10 days (mean, 4.6 days), and its severity was correlated with the initial
erythema level. In all patients clinical, digital photography and dermoscopic assessment
of the lesions before and at the treatment end point the therapy was highly effective. The
only side-effect was a transient hyperpigmentation of the treated lesions in the leg area,
with no systemic side effects observed during treatment. Also, blinded evaluation of
global images supported an improvement in skin texture in all treated sites.
Conclusion
Following treatment, patients achieved complete clinical remission of the lesions,
with a definitive improvement in the lesions' initial disfiguring features. Fractional
ablative photothermolysis appears to be effective, and the outcome is predictable.
Controlled trials are now necessary to confirm these preliminary results.
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Laser in medicine, vol I, issue 1, October 2012
Introduction
Morphea is a rare skin disease with yearly incidence rates of 25 per million (1).
Although rare, morphea is invariably scarring, and 10 percent of affected patients develop
functional disability as a result of the scars. It is a connective tissue disease limited to the
skin, the subcutaneous tissue or even the underlying muscle.
It is characterized by the appearance of single or of multiple sclerous patches with
an ivory center and surrounded by a violaceous ring, indicating an inflammatory activity.
Pigmentation disorders are sometimes present. It generally develops in three phases:
inflammatory, edematous and then atrophic. The depth of sclerosis is variable and can
reach the fascia and underlying muscle. The loss of sweat glands, hair follicles, and
melanocytes compromises the ability of skin, to resist mechanical trauma, and to protect
from UV radiation.
There are five forms of localized scleroderma: plaques, generalized morphea,
bullous morphea, linear morphea and morphea profunda.
Three different laser sources are now available to be involved in morphea
treatment protocol: vascular-specific pulsed dye laser (PDL) to reduce hyperemia,
ablative fractional lasers to improve texture and pliability of the atrophic scar, and
intense pulsed light (IPL) to correct scar dyschromia.
Depending upon the constellation of patient symptoms and functional deficits,
treatment of the morphea scar involves a number of modalities. Surgical incision or
excision of the scar may be necessary, and defects are reconstructed with biologic skin
substitutes, split- and full-thickness skin grafts, tissue rearrangement, tissue-expanded or
pedicled
flaps,
and
even
free
tissue
transfer.
Fractional laser resurfacing, first introduced in 2005 has been largely utilized for
cosmetic indications, such as treatment of scars, photoaging, fine lines of the mouth and
eyelids, and abnormal pigmentation. Ablative fractional Er-YAG laser beam targets
intracellular water, leading to vaporization of tissue and denaturation of surrounding
extracellular proteins. Fractional resurfacing is theoretically attractive in the management
of morphea scars, because microscopic columns of abnormal dermis are vaporized or
coagulated, which in turn stimulate collagen production and remodeling. These
microscopic treatment zones (MTZs) produce by scanning fractional laser mode are 250
micrometers in diameter and 10 to 20% of coverage up to 200 micrometers in depth,
leaving a significant amount of epidermis and dermis intact, to assist in rapid and
controlled wound healing. Deeper, safe penetration with these ablative lasers may be
possible by using turbo mode. This provides greater flexibility of Er:YAG laser fractional
treatments. It allows fractional treatments to be accomplished from the keratinous layer to
depths the practitioner deems necessary for the clinical application at hand.
In comparison to full-surface ablative skin resurfacing, the fractionated very short
pulse Er:YAG laser treatment provides very rapid reepithelization, with limited adverse
side effects and reduces patient downtime to 4 days or less. Several recent reports have
demonstrated the clinical value of fractional resurfacing in atrophic scar treatment, with
dramatic results observed even in very old scars (2).
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Laser in medicine, vol I, issue 1, October 2012
Material and method
This was a retrospective study conducted at the Dr Kozarev Dermatology Laser
Clinic in Serbia between March 2010 and March 2012. The patients included had to
exhibit localized scleroderma in an inflammatory or atrophic phase (excluding those with
linear morphea, generalized morphea, morphea profunda and systemic scleroderma) that
had been active for at least one year despite high potency dermocorticosteroids or
immunomodulators applied for more than two months.
Five female patients aged between 34 and 67 years with biopsy-proven localized
scleroderma (morphea) were studied. All patients had evidence of previous therapy non
response with localization as asymptomatic lesions: on the trunk, mammary region, in the
anterior tibial region of the right leg, and posterior tibial region. All patients had up to
three similar cutaneous lesions. An active localized scleroderma was defined clinically by
the inflammatory character of the peripheral border and by the extent of the central
induration and confirmed histologically in all cases.
The laboratory tests performed including a full blood count, urinalysis and liver
function test, antinuclear antibody titre, C-reactive protein, erythrocyte sedimentation rate
and additional tests for a range of antibodies: Hepatitic B and C antibodies, toxoplasma
antibodies, anticentromere, anti-Sc 70, anti-dsDNA, and anti-RNP.
In each patient the condition had previously failed to respond to potent topical
corticosteroids, imiquimod cream, and/or PUVA bath photochemotherapy.
Patients were required to discontinue all therapy at least two months before study
initiation.
The most affected sclerotic plaque of each patient was judged at baseline and then
every 4 weeks during treatment. Sclerotic plaques were assessed by a clinical skin score
(3). The clinical skin score assesses the degree of thickening and induration by palpation
of the most affected part of the morphea plaque on an analogue scale graded from 10
(severe sclerosis, hard like a pressing hard wood) to 0 (normal skin elasticity with
folding).
In each patient all plaques was treated and the non affected skin on the
contralateral side of the body were used as a control are which was scored at baseline and
after therapy.
Dermoscopic assessment of the lesions was performed before treatment, during
follow-up and at treatment end point.
Patients evaluated the treatment pain level after each of the three sessions using VAS
score. A patient is asked to indicate his/her perceived pain intensity (most commonly)
along a 100 mm horizontal line, and this rating is then measured from the left edge (4).
The patient data are summarized in Table 1.
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Table 1: Characteristics of patients with morphea treated with fractional Er:YAG laser
Age/sex
Duration
of disease
Number
of lesions
34/F
1.5 years
3
Duration of
previous
therapy
(months)
3
37/F
42/F
47/F
67/F
9 months
2 years
1 year
8 months
3
2
2
1
4
2
6
4
Previous therapy
procedure
Local
corticosteroides
PUVA
Imiquimod
Local corticoides
PUVA
Laser treatment was initiated with ErYAG fractional laser. Fractional laser
treatment was started at least two months after discontinuation of the
dermocorticosteroids, immunomodulators like imiquimod or other intralesional or light
based therapy procedures. The treatment was performed once monthly into three
sessions with fractional ErYAG laser resurfacing. (Dynamis SP, Fotona, SLO). A
commercially available chill air cooling system (Zimmer Cryo 6 Unit, Germany) has
been used to control pain and discomfort associated with procedure. During the
procedure F- runner scanning device allowed precise
control of ablation used in turbo 4 mode, 10% of coverage, pulse width of 600 ms,
fluence of 24J/cm2, and frequency of 20 Hz), without any other specific local therapy.
Results
Fractional ErYAG laser treatment was well tolerated, with slight stinging
phenomena during laser procedure. In all patients, the initial reactions to treatment
consisted of erythema and minimal swelling in the treated areas; the patients reported a
burning sensation but no significant pain. The erythema lasted between 2 and 10 days
(mean, 4.6 days), and its severity was correlated with the initial erythema level.
In all patients sclerosis regressed greatly, skin score markedly decreased and
dermoscopy findings objectively showed a reduction of amount of cicatrisation, skin
hardness and dischromia. At the end of the follow up period number of hair follicule in
the treated zone increased greatly.
In all patients clinical, digital photography and dermoscopic assessment of the lesions
before and at the treatment end point the therapy was highly effective.
The only side-effect was a transient hyperpigmentation of the treated lesions in the leg
area, with no systemic side effects observed during treatment. Also, blinded evaluation of
global images supported an improvement in skin texture in all treated sites.
Laser treated control contralateral sites did not show any visible changes seen in
the control biopsy. All patients evaluated therapy subjectively as effective and well
tolerable and discomfort and personal dissatisfaction associated with the disease
significantly decreased during therapy.
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Finally, we did not observe recurrence or worsening of the disease within a follow-up of
up to a year after treatment.
Discussion
Localized scleroderma is characterized by collagen accumulation and excessive
sclerosis of the skin. The cause of this disease is unknown, collagen metabolism
abnormalities are involved in the physiopathology of scleroderma, related in particular to
the reduced synthesis of matrix metalloproteinases.
On the basis of new insights into the key role of effector T cells in scleroderma, in
particular Th-17, T-cell directed therapies are expected to have promising effects (5).
The major complaints are tightness and itching and the disease is often
complicated by contractures and cosmetic disfigurement. Numerous treatments have been
tried, such as local corticosteroids, D-penicillamine, intravenous penicillin, intralesional
interferon gamma, plasmapheresis, oral PUVA therapy or PUVA-bath
photochemotherapy, UVA1 phototherapy and, in patients with severe disease,
immunosuppressive and vasoactive drugs (6, 7).
However, treatments have had only limited success or have caused considerable
side-effects. Topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) is
an experimental therapeutic approach, which is based on photosensitization of abnormal
tissue by ALA-induced porphyrins and subsequent irradiation with red light, thus
inducing cell injury via generation of singlet oxygen and other free radicals (8).
Eisen and Alster showed positive clinical effect after 585nm pulse dye laser
irradiation of hypertrophic scars and improvement if the sclerotic morphea plaques (9).
To our knowledge, there have been no reports in the literature on the use of
fractional Er;YAG laser in the treatment of morphea plaque. This small case study
demonstrates an efficacy of ablative Er;YAG fractional laser treatment in localized
scleroderma resistant to high potency topical corticosteroids, imiquimod and PUVA
therapy with a very high response rate. The response to laser based treatment seems to be
positive.
High potent corticosteroids and immunosuppressive agents are effective in the
early inflammatory phase. If no response is seen after 8 weeks, therapy may be changed
to lesion limited-phototherapy (NB-UVB, BB-UVA, UVA1, or topical psoralen and
UVA). We do not have data supporting efficacy of topical steroids, as the most
commonly utilized therapy for active limited plaque morphea. There is no indication for
topical steroids in the burnt-out phase of morphea (10).
Because, spontaneous remissions of localized scleroderma are mentioned,
treatment protocols are targeted at the active phase, stabilizing the size of current lesions
and preventing the occurrence of new lesions. Possible outcomes of the inflammatory
localized scleroderma lesions are scars which, although they can be treated in a number
of ways, may have a negative psychological impact on social life and relationships.
A 67-year-old woman presented with slightly erythematous, sclerotic patch with
an ivory center on her left brest in March 2010 (Fig. 1A). The same area after two laser
sessions and after a year in the end of the follow up period (Fig. 2A).
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Fig 1a
Fig 2a
A 47-year-old woman presented with slightly 24 cm long and 14 cm wide
atrophic morphea plaque in May 2010 (Fig. 3A). The same area after three laser sessions
and after a year in the end of the follow up period (Fig. 4A).
Fig 3a
Fig 4a
Role of matrix metalloproteinases and decreasing process of collagen degradation
is in the middle of the hypotheses concerns abnormalities of the collagen metabolism of
the external matrix by an increase in the production of type I and III collagen.
The molecular impact of Er;YAG laser resurfacing on photodamaged or inflamed
skin is evident. It had been clear that laser resurfacing eliminates much of the damaged
collagen, and they demonstrated that it replaces the damaged fibers with what appeared to
be a better matrix.
Cutaneous wound healing is the interaction of a series of complex processes that
lead to renovation, reconstruction, and a proportional restoration of the damaged skin’s
elasticity.
The profile of gene and protein alterations represents a well-organized and highly
reproducible wound healing response. Epidermal resurfacing with the Er:YAG laser has
impact on the dermal matrix via substantial dermal changes. Clinical effectiveness of
laser skin resurfacing is based on the induction of synthesis of new collagen and other
components of extracellular matrix. The goal of Er:YAG fractional laser treatment is
transition from inflammatory to proliferative phase of tissue repair.
In inflammatory phase, the principle cell is macrophage, which is responsible for
degradation of damaged tissue (wound debridement). These cells stimulate influx and
proliferation of fibroblasts by production of cytokines (11).
In proliferative or fibroplastic phase myofibroblasts participate in active
production of extracellular matrix components including collagen I and III (12).
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We believe repetitive irradiation of human skin with Er:YAG laser could be a potentially
useful method for modulation of chronic inflammatory response.
The mechanisms of action of fractional ablative laser in the morphea treatment
could be induction of collagenase activity, which need to be investigated.
Whitby and Ferguson studied the distribution of growth factors in healing fetal
wounds. They found platelet derived growth factor (PDGF) in fetal, neonatal and adult
wounds, but transforming growth factor beta and basic fibroblast growth factor (bFGF)
were not detected in the fetal wounds. They conclude that it may be possible to
manipulate the adult wound to produce more fetal-like, scarless wound healing by
therapeutically altering the levels of growth substances and their inhibitors (13).
Another extracellular matrix glycoprotein tenascin is synthesized by fibroblasts
that is present during embryogenesis but only sparsely distributed in adult’s dermal
papilla. In the in healing wounds this protein is re-expressed, in the regenerating
connective tissue area (14).
Can we produce control wounding by using fractional ablative procedures?
A number of experimental studies have suggested that mast cell degranulation
may induce inflammatory response, fibroblast proliferation and collagen remodeling,
which constitute the key steps of the wound healing process. Changes in the total mast
cell number and percentage of degranulation were assessed during the inflammatory
phase of repair (15).
Pincherito et al. demonstrated that CO2 laser wounds are associated with greater
levels of mast cell degranulation than scalpel wounds (16).
Because mast cells also elaborate a variety of cytokines, the presence of mast cells
following laser irradiation and accompanying tissue revascularization may provide an
explanation for the therapeutic outcome following microvasculature destruction in terms
of stimulating collagen remodeling.
Conclusion
Despite great advances, at present there is no “magic bullet” that can be used in
the management of morphea plaque. Following treatment, patients achieved complete
clinical remission of the lesions, with a great improvement in the lesions' initial
disfiguring features.
On the basis of the present results, fractional ablative photothermolysis appears to
be effective, and the outcome is predictable.
Prospective, double-blind placebo-controlled trials with larger numbers of patients are
now necessary to confirm these preliminary results.
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Conflict of Interests
The authors report no conflict of interest and have not received any funding for research,
education, or consulting from any laser companies.
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