Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
Methods of
Dermatological
Therapy
Ihab Younis , M.D.
Professor of Dermatology & Andrology
Benha Faculty of Medicine
CHAPTER 1 :
PHOTOTHERAPY IN DERMATOLOGY
The electromagnetic spectrum
Definition
It is a band of radiations arranged according to their wave lengths. The longest is radio waves
(used for radio and television transmission) and the shortest is the cosmic rays which are lethal to
humans but is prevented to reach the earth by the ozone layer. The arrangement of these
radiations according to their wavelength is as follows:
1- Radio waves
2- Microwave
3- Infrared rays
4- Visible light
5- Ultraviolet rays (UV)
6- X-rays
7- Gamma rays
8- Cosmic rays
Visible light
This is the portion of solar energy that the human eye detects as light. When scattered by a prism
it can be seen that it consists of 6 colors starting with red (longest wave length) and ending with
violet (shortest wave length). Indigo is no longer considered a part of visible light
The ultraviolet rays
The name means "beyond violet" (from Latin ultra="beyond"). The Sun emits ultraviolet
radiation in the UVA, UVB, and UVC bands, but because of absorption in the atmosphere's
ozone layer, 99% of the ultraviolet radiation that reaches the Earth's surface is UVA (some of the
UVC light is responsible for the generation of the ozone).
The range of UV wavelengths is often subdivided into UVA (380315 nm), also called Long
Wave or "blacklight" because it is invisible to human eye; UVB (315280 nm), also called
Medium Wave; and UVC (< 280 nm), also called Short Wave or "germicidal".
N.B. nm = nanometer = one billionth (1 x 10 -9) of a meter.
Health concerns of UV
1- Skin
UVA, UVB and UVC can all cause skin wrinkles and cancer. In general, UVA is the least
harmful as it penetrates deeper into the skin than UVB light, it is thought to be a prime cause of
wrinkles due to damage of collagen fibers but it does not cause immediate erythema and
sunburn. UVB is more responsible for skin cancer due to damage of DNA leading to mutations
and it causes immediate erythema and sunburn.
As a defense against UV radiation, the body tans when exposed to UV by producing melanin
which helps to block UV penetration. This will depend on skin type:
Type I - Always burns, never tans.
Type II - Burns easily, tans minimally.
Type III - Burns moderately, tans gradually to light brown.
Type IV - Burns minimally, always tans well to moderately brown.
Type V - Rarely burns, tans profusely to dark.
Type VI - Never burns, deeply pigmented.
2- Eye
High intensities of UVB light are hazardous to the eyes, and exposure can cause photokeratitis
and cataracts. Ordinary eyeglasses give some protection, and most plastic lenses give more
protection than glass lenses. Some plastic lens materials, such as polycarbonate, block most UV.
PUVA
Definition
PUVA is an acronym for P=Psoralen + UVA=Long wave ultraviolet rays (380315 nm).
History
Topical application of extracts, seeds, and parts of plants that contain
natural psoralens followed by exposure to sunlight has been used as a remedy for vitiligo for
thousands of years by the ancient Egyptians and Indians. In modern medicine, the first clinical
studies to treat vitilligo using topical and oral psoralens followed by sun exposure were
performed by Prof. Abdel Monem El Mofty of Cairo University in 1948. In 1974 it was shown
that orally administered 8-methoxypsoralen (MOP) and subsequent irradiation with artificial
UVA was a highly effective treatment for psoriasis.
Psoralens
Chemistry
Psoralens and many of its derivatives are naturally occurring tricyclic furocoumarins derived
from more than 30 plants e.g. ammimajus, lime, lemon, bergamot, parsley, celery, fig and cloves.
The derivative most widely used in photochemotherapy is 8-methoxypsoralen (8MOP,
methoxsalen, Ultrameladinine10mg/cap.) which is of plant origin. A synthetic form is trimethyl
psoralen (TMP, trioxsalen, Trisoralen5 mg tab) which is less phototoxic after oral administration
and is primarily used for the treatment of vitiligo.
Pharmacology
when taken by mouth, methoxsalen (8-MOP) is absorbed from the gastrointestinal tract.
Increased photosensitivity is present 1 hour after the dose, reaches a peak at about 2 hours and
disappears after about 8 hours. After oral administration the drug is metabolised in the liver by
hydroxylation and glucuronide formation and over 90% is excreted in the urine within 12 hours.
Individuals with a high clearance and low maximum serum concentration usually show reduced
sensitivity to PUVA. These patients i.e. those not responding to the usual dose may respond to
higher dose of psoralens or to the administration of the drug by other routes such as bath water
delivery. When applied locally 8-MOP rapidly penetrates the skin and can be detected in the
urine after 4 hours.
Mechanism of action
PUVA causes photoconjugation of psoralens to DNA and subsequent suppression of mitosis,
DNA synthesis and cell proliferation. It is also possible that PUVA may affect specific cells such
as lymphocytes or polymorphonuclear leucocytes which are believed to be involved in the
pathophysiology of psoriasis.
It is quite possible that immunological alterations are an essential component of the therapy. A
decrease in the percentage of circulating T-lymphocytes following PUVA treatment has been
reported.
The mechanism by which PUVA induces repigmentation in vitiligo remains unclear although the
following ways have been speculated.
1-By increasing the number of functional melanocytes as a result of mitosis or by activation of
dormant melanocytes in the epidermis and appendages especially hair follicles.
2-By inducing hypertrophy of melanocytes and an increased arborization of their dendrites.
3-By augmenting the development and melanization of melanosomes and increasing the transfer
of melanosomes to keratinocytes.
4-By stimulation of tyrosinase activity.
5-By enhancing the migration of activated melanocytes from skin appendages.
6-By generating a suppressor cell population which suppresses the stimulus for melanocyte
destruction during therapy.
3
Methods of treatment
Methoxalen in the dose of 0.6 to 0.8 mg/kg body weight is administered orally followed by
whole body irradiation after 1-3 hours. Irradiation is done by exposure to UVA lamps. If PUVA
devices are not available, sunlight can be used in stead and this is called "PUVASOL" where the
patient takes 8-MOP capsules then gets exposed to the sun for a maximum period of 30 minutes
between 11 am - 2 pm when the sun is perpendicular to earth i.e. the time when maximum UVA
reaches the earth. Repeated exposures are necessary to clear PUVA responsive diseases, and as
pigmentation develops UVA doses have to be increased. The frequency of treatment is reduced
after a satisfactory clearing of the disease is achieved and the last UVA dose is used as a
maintenance dose. The duration of this maintenance phase and the frequency of treatment
depend on the disease being treated and its tendency to relapse.
Indications
1-Psoriasis: Two protocols are used:
USA protocol: The first treatment exposure dose is based on the skin typing. The patient is
exposed2-3times/week. Dose increments range from 0.5 - 1.5 J/cm2 depending on erythema
production and therapeutic response (A Joule is a unit of energy that equals 0.2389 calories).
European Protocol: The first treatment is administered after determination of the individual's
minimal erythema dose (MED) and accordingly, the initial UVA dose is the patient's MED. Four
treatments are given per week. Two treatments are given on consecutive days followed by a rest
on day 3 after which treatment is resumed for 2 days. Increments of dose are performed only
after the first four treatments if no more than a pink erythema has developed and range from 0.5
to 2 J/cm2 depending on the patient's ability to develop pigmentation.
Complete clearing is defined as eradication of 95% or more of the amount of psoriasis before
treatment. Improvement of skin lesions is usually seen by the fifth or sixth treatment. In patients
responding more slowly, an accelerated schedule of increments of UVA dosage should be
considered. Failure to achieve improvement by the 20th treatment is usually regarded as
treatment failure.
The number of exposures required for clearing varies from 15-25. The final clearance dose of
UVA radiation is about 5-20 J/cm2 depending upon the skin type.
Psoriasis of nails, palms and soles does not respond well to oral PUVA.
Most, but not all, patients relapse during the first few months after clearance if no maintenance
therapy is given. If maintenance PUVA treatment is given for 2-3 months and then stopped in
patients who are still clear, it has been shown that the majority of patients remain free of disease
for at least 6 - 12 months.
Determination of the minimal erythema dose (MED)
1-The patient wears a thick cotton shirt which has 10 small, vertical holes on its back.
2-The patient is given a 50 milli joule (mj) dose on the back while all the holes are opened, then
the first hole is closed and another 50 mj exposure is given. By that time the skin under the first
hole was exposed to 50 mj of UV while the skin under the second hole was exposed to 100 mj.
The second hole is closed and a third 50 mj exposure is given so the first hole was exposed to 50
mj, the second hole exposed to 100 mj and the third exposed to 150 mj. The procedure is
repeated in the same way (closing an hole and giving a dose) for all the holes. After 24-72 hours
the skin of the back is examined and the first skin area showing well-defined erythema is
determined and the amount of UV causing it is called "the minimal erythema dose".
Topical psoralens
A lotion containing 0.1 to 1% 8-MOP is used. Many clinicians allow 1 - 2 hours to elapse
between the topical application of the psoralen and UVA exposure, but reports have shown that
topical 8-MOP followed immediately by UVA irradiation can also clear psoriatic lesions. This
treatment is given 3-5 times weekly with UVA dose being gradually increased. Maintenance
doses may be needed.
4
The advantage of topical psoralen therapy is that systemic side effects can be avoided. But there
are certain disadvantages also: (1)Erythema and blisters are more common. (2) Intense irregular
pigmentation may be seen at the site of treated plaques.
Bath water delivery of psoralens
Patients soak for 15 minutes in a solution prepared by diluting 50ml of 8-MOP in 100 liters of
water and then quickly wipe dry. Immediately patients are given whole body irradiation with
UVA, the initial dose depending upon the skin type.
A study showed that patients on bath water 8 - MOP showed earlier and better response than a
group on oral 8MOP. Also, bath water delivery eliminates the disadvantages of topical
psoralens while keeping its advantages.
2- Vitiligo
Effective results may occur with either TMP or 8-MOP, TMP is the preferred drug of treatment
with sunlight as the UVA source. On an average, a course of treatment consists of at least 150
exposures of PUVA, and many patients improve significantly after about 50 exposures. However,
total repigmentation is only rarely achieved and some 30% of patients do not respond at all. In
these cases punch grafting can be done followed by PUVA or PUVASOL, with good response
after 3 - 6 months. Topical psoralen (8-MOP 0.1% or TMP 0.01%) therapy may also be tried in
cases with isolated lesions.
3-Cutaneous T-cell lymphoma (CTCL)
PUVA is dramatically effective in early stage disease when it induces complete and long lasting
remissions. The mode of action is the direct phototoxic destruction of the atypical cells in the
epidermis and dermis. The protocol for PUVA treatment in CTCL is essentially the same as in
psoriasis. In late stages of the disease PUVA improves quality of life and may prolong survival
when used in combination with more aggressive treatment modalities.
4-Atopic dermatitis
Most cases of atopic dermatitis improve with PUVA therapy. However, the number of treatments
needed to bring about remission may be more than that for psoriasis. Also there is a high and
early recurrence rate necessitating maintenance exposures. A combination of PUVA and topical
steroids may be more beneficial than PUVA alone.
5-Lichen planus
PUVA is an effective alternative for systemic steroids in generalized lichen planus. However,
lichen planus may be more resistant to treatment with PUVA than psoriasis. More exposures with
higher cumulative doses are needed for clearance. Relapse rate following PUVA is less than
following systemic steroids.
6-Cutaneous mastocytosis
PUVA treatment results in temporary involution of skin lesions with loss of Darier's sign, relief
of itching with improvement in the systemic symptoms.
Instructions for patients using PUVA
1-Do not apply any ointments or cosmetics before exposure.
2-Ideally, take the capsules two hours after a meal.
3-Cover male genitalia - this area must not be exposed to UVA.
4-Skin and eyes should be protected from sunlight for 12 hours after taking psoralen by applying
a sunscreen to all uncovered skin after treatment and by wearing ultraviolet protective sunglasses both indoors and outdoors until nightfall on the treatment day.
NB-UVB, similar to PUVA therapy, stimulates the dopa-negative, melanocytes in the outer hair
root sheaths to proliferate, produce melanin and migrate outward to adjacent depigmented skin
resulting in perifollicular repigmentation.
Protocol of NB-UVB therapy
Psoralens are NOT usually used in NB-UVB therapy. Initially 70% of MED is given.
Subsequently if no erythema occurred, the dose is increased by 20%. If there is minimal
erythema the same dose is maintained. If there is well defined erythema the patient is postponed
until next visit, and the same dose is given and later increased by only 10%. If there is painful
erythema, edema or bullae, treatment is stopped until recovery then exposure is reduced to half
the starting dose and subsequently increased by 10% each visit. End point of treatment is
clearance of the disease.
Indications of NB-UVB
1-Vitiligo
Studies comparing NB-UVB to PUVA in the treatment of vitiligo show that NBUVB is as
effective or superior to PUVA. Repigmentation of over 75% of vitiliginous areas was achieved in
63%-67% of patients treated by NB-UVB compared to 46%-51% of patients treated by PUVA.
2-Psoriasis
When NB-UVB phototherapy and PUVA were compared, there was little overall difference in
efficacy.
3-Atopic dermatitis
NB-UVB seems to be an effective modality for the treatment of moderate-to-severe atopic
dermatitis and is favorably accepted by patients. It offers an effective alternative to steroids for
chronic severe atopic dermatitits.
4-Other indications
NB-UVB seems to be effective in patients with polymorphic light eruption, early stages of
cutaneous T-cell lymphoma, chronic urticaria, lichen planus, seborrheic dermatitis and
scleroderma.
Advantages of NB-UVB over PUVA
1- Safe use in children (the maximum duration allowed is 12 months) and pregnant women.
2- No need for post-treatment eye protection.
3-No drug induced nausea and no drug costs.
4-Exposure time is of that of PUVA which is more convenient for both the patient and the
dermatologist and less carcinogenic.
CHAPTER 2 :
7
LASERS IN DERMATOLOGY
The word laser is an acronym for Light Amplification by the Stimulated Emission of Radiation.
History
Maiman developed the first laser in 1960. It was a ruby laser, with a wavelength of 694 nm. It
is from this prototype that today's lasers are made. In 1964, Goldman and Wilson reported the
first cure of a basal cell carcinoma with ruby laser irradiation. Also, in 1964 the argon and
carbon dioxide lasers were developed. During the 1970s and 1980s the discovery of organic
dyes and heavy metals as active media led to the production of several new lasers.
How laser light is produced?
When atoms of a substance are exposed to a strong energy source (e.g. a strong light) they
become excited i.e. they gain different levels of energy. Atoms eventually return to their previous
energy level, upon returning to this level, the excess energy is released in the form of a photon
i.e. a particle of light.
A laser is a device that controls the way in which excited atoms release photons. In all types of
laser devices there is: 1) a source of intense flashes of light, 2) a lasing medium e.g. ruby, which
is exposed to intense light to get the atoms excited and 3) reflecting mirrors to amplify the light.
Fig. 1:
Laseratoms
light
Excited
production
In a laser device the lasing medium is found in a tube that has a highly reflective mirror at one
end and a partially reflective mirror at the other end. When the lasing medium is exposed to the
intense light, excited atoms are reflected by the highly reflective mirror so, they collide with each
other producing more photons (stimulated emission) then they are reflected by the partially
reflective mirror at the other end of the tube. Reflection between the two mirrors continues
permitting light to reflect back and forth, building up in each passage (light amplification) until
laser light is emitted out from the partially reflective mirror (Fig.1).
Properties of laser
1-It is coherent : an ordinary lamp will emit light waves in all directions but in lasers waves of
light are aligned with each other because they all have the same wave length (Figs.2&3).
2- It is collimated: i.e. the light beams travel parallel to each other (concentrated light waves).
These properties allow to deliver high-energy radiation of a specific wavelength to a small area.
Some important definitions
1-Irradiance (power density): It is the power per unit area incident on the skin during a single
pulse and is obtained by dividing the power output of the laser device by the diameter of the
laser beam.
2-Energy fluence (energy density):It is the amount of energy per unit area incident on the
skin for a specified length of time. It can be obtained by multiplying irradiance by the time of
exposure and dividing the product by the diameter of the laser beam. Increasing the fluence
increases the energy to which the skin is exposed (if beam diameter and exposure time are
constant).
3-Pulse duration: It is the length of time that the target tissue is exposed to laser irradiation.
4-A chromophore: It is a pigment that is able to absorb a specific wavelength e.g. pigmented
lesions can be treated with lasers that emit a specific wavelength of light that is absorbed by
melanin, the primary chromophore of pigmented lesions. The main chromophores of the skin are
hemoglobin and melanin.
5-Thermal relaxation time (TRT): It the time required for the targeted site to cool to one half of
the peak temperature it reached immediately after laser irradiation.
Classification of lasers used in dermatology
Laser type
Continuous-wave(CW): They emit a beam
that is at constant energy. They are used for
coagulation or vaporization of tissue.
Pulsed lasers:A laser which delivers its energy
in the form of a single pulse or a train of
pulses. The duration of a pulse is regarded to
be<0.25 seconds. The term Qualityswitched(Q-switched)refers to techniques in
which light is blocked from traversing the
laser cavity, then suddenly allowed to do so.
The result is storage of impressive energy in
the laser's excited state, suddenly released in a
short, high-intensity pulse.
Pulsed laser systems may be either longpulsed(LP)such as Pulsed dye laser (PDL)
with pulse durations ranging from 450ms to
40millisec, or very short-pulsed (5-100ns)
such as the Q-switched lasers
Pseudo-continuous wave lasers or quasicontinuous-wave (QCW) :They are pulsed
lasers that emit a beam in which the pulses are
so rapid that it appears to be virtually
continuous.They are also useful for
coagulation and vaporization of tissue.
Laser source
CO2
Wavelength
10,600 nm
Argon
488-514nm
585-600 nm
Diode
800 nm
Q-switched ruby
694 nm
Q-switched alexandrite
755 nm
LP neodymium: yttriumaluminumgarnet(Nd:YAG)
1064 nm
Erbium:YAG
2490 nm
CO2 (pulsed)
532 nm
Copper vapor/bromide
510-578 nm
577-585 nm
Krypton
568 nm
10,600 nm
The intense pulsed light (IPL) source is not a laser because it emits noncoherent light within a
wavelength of 500 to 1200nm. Filters are used to eliminate shorter wavelengths, thereby
concentrating light energy so that improved dermal penetration is achieved. Light is delivered as
a series of single-, double-, or triple-pulse sequences with pulse durations of 2 to 25 milliseconds
9
and delays between pulses ranging from 10 to 500 milliseconds. The main advantage of IPL is
the relatively cheaper price(less than 50% of laser machines).
Laser light interactions with tissue
1-Photothermolysis interactions:This is determined by the theory of selective photothermolysis,
introduced by Anderson and Parrish in 1983, that 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. To limit the amount of thermal energy deposited within the
skin, the exposure duration of the tissue to light (pulse duration) must be shorter than the
chromophore's thermal relaxation time (TRT). For example in treating vascular lesions if the
pulse durations are much longer than the calculated TRT this will allow thermal diffusion from
the vessel, damaging the surrounding tissue leading to scarring. Therefore, laser parameters
(wavelength, pulse duration, and fluence) should be tailored for specific cutaneous applications
to effect maximal target destruction with minimal collateral thermal damage.
2-Photomechanical interactions: Extremely rapid thermal expansion can lead to mechanical
waves and subsequent photomechanical destruction of organelles, membranes, and cells.
3-Photochemical interactions:Photochemical interactions of interest to dermatologists include
photobiologic responses to UV radiation and photodynamic therapy of skin diseases(Chapter 3).
Although all 3 types of laser effects can occur, photothermal and photomechanical reactions are
most commonly observed in current cutaneous laser surgery practice.
Indications of lasers in dermatology
I-Hair reduction (Photoepilation)
Treatment with laser devices will permanently reduce the total number of hairs in the treated area
but it will not result in a permanent removal of all hair.
Indications of hair removal
1-Hirsutism: Male-patterned terminal hair growth in a woman.
2-Hypertrichosis: Congenital or drug-induced increase in hair growth.
3-Pseudofolliculitis:A foreign body inflammatory reaction affecting persons with curly hair.
4- Hair growth from a grafted donor site.
Devices used
The chromophore targetted for photoepilation is the melanin found in the matrix and shaft of hair
follicles. That is why photoepilation is not effective for white hair.
.The 755-nm wavelength emitted by the alexandrite laser (the most popular) penetrates more
deeply into the dermis and is less likely to be absorbed by epidermal melanin, theoretically
making it safer to use with patients of darker skin. Results of alexandrite laser demonstrated a
20% to 56% reduction of hair growth 6 months after a single session. The 20-millisecond pulse
duration resulted in fewer and less severe side effects. Several treatment sessions using low
fluences may be required to effect satisfactory results.
.The longer wavelength (800- to 810-nm) emitted by the diode laser is sufficiently absorbed by
melanin to make it effective for hair removal, yet less absorbed than that of the ruby or
alexandrite, thus, making it potentially safer for individuals with darker skin phototypes. A study
showed hair regrowth ranging from 47% to 66% 6 months after 2 treatments with diode laser.
.The deeply penetrating 1064-nm wavelength of the LP Nd:YAG (and NOT the older Qswitched Nd:YAG)laser may provide certain advantages over the aforementioned laser systems,
10
particularly when treating patients with darker skin. The closer approximation of their pulse
durations to the thermal relaxation time of the hair follicle allows adequate heating of the
targeted follicle to effect its destruction. One year after therapy, a greater than 50% hair reduction
was still present in 40% in patients who had 5 sessions of treatment.
.IPL sources can also be used to effect hair reduction. By using a series of filters, a specific
wavelength may be selected to suit an individual skin type and color. Studies reported
approximately 50% to 60% reduction in hair counts 12 weeks after a single treatment. Multiple
(3 or 4) treatment sessions have been shown to result in approximately 75% hair reduction after at
least 6 months follow up. Side effects and complications of IPL treatment are similar to those
seen after laser-assisted hair removal.
Pretreatment Instructions
1. Before treatment, patients are advised to avoid tanning (not to increase melanin around hair
follicle). Broad-spectrum (UVA/UVB) sunscreens with SPF 15 or higher should be used.
2. No plucking, waxing, or electrolysis should be done.
3. The site to be treated may be shaved one to two days prior to laser treatment.
4. A prophylactic (protective) oral antiviral medication may be started the day prior to treatment
to suppress the possibility of developing a herpes simplex infection in the treatment area. An
oral antibiotic may be prescribed if the nasal or perianal skin is to be treated.
Procedure
1. The treatment can be performed with or without topical anesthesia (e.g.lidocaine cream),
depending on the patient's comfort level. The pain response varies with the individual, with
the area being treated and with the energy level of the treatment. Accordingly, anesthesia
must be tailored to each patient.
2. The laser is applied to the target area at the fluence level predetermined by patch testing.
3. The patient, the doctor and everyone in the room must wear protective eyewear during the
laser procedure.
Postoperative care
1. After treatment, most patients have a mild sunburn-type sensation that fades in 2-3 hours.
Moisturizers and/or cool compresses can help during this time.
2. Small blisters can be treated with a topical antibiotic applied 3 times daily until they resolve.
3. A sunblock should be used for as long as 6 weeks after treatment.
4. Treated sites should be washed with gentle soap (e.g. Dove) and water twice a day. Ejection
of hair shafts (i.e.clearing out) occurs in the first 10-14 days. The hair that re-grows tends to
be lighter and finer in texture.
Follow-up care
Three treatments (range, 2-6 sessions) are usually needed to achieve the desired effects. The
timing of treatments is important because hair should be treated during the anagen phase. This
phase is short (6-12 wk) for hair on the face (70% of hairs are anagen and 30% are telogen), so
treatments are spaced a month apart. On the trunk, limbs and pubic area the anagen phase lasts
12-16wk (30% of hairs are anagen and 70% are telogen), and 2-month spacing is best.
Complications
1-Hyperpigmentation is the most common complication and usually resolves within 6 months
without treatment.
2-Pain, some erythema and minor edema can persist for 2-3 days after facial treatment and
longer in other areas (e.g.1 wk on the trunk).
3-Blistering, herpes simplex outbreaks, and bacterial infections are uncommon.
4-Temporary skin lightening, especially in darker skin types, or in patients with a recent tan, may
be seen.
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treatment of Becker's nevus. Unfortunately, laser treatment has yielded disappointing results
characterized by partial response and recurrence.
Epidermal Nevi
Laser therapy is an attractive alternative for extensive epidermal nevi in which other surgical
methods would result in unacceptable cosmetic results. The flashlamp-pumped pulsed dye laser
and CW lasers may be useful in the inflammatory linear verrucous epidermal nevus.
Nevus of Ota, Ito, and Mongolian spot
The Q-switched ruby laser became the treatment of choice in the early 1990s. Now satisfactory
results can also be obtained with the Q-switched Nd:YAG and Q-switched alexandrite lasers.
Treatment fluences range from 5 to 10 J/cm2 depending on location and number of treatments,
which can exceed 10 for extensive and resistant lesions.
Melasma
Since it is most predominant in facial distribution, melasma can be safely treated with a number
of pigment-specific and ablative lasers e.g. Q-switched ruby laser and IPL. However, recurrence
is the rule, and retreatment on a regular basis is necessary; given the expense and risk for side
effects, laser treatment of melasma cannot be generally recommended.
Other lesions
Postinflammatory pigmentation treatment by lasers has been disappointing so far. The trauma
induced by a laser can itself evoke a hyperpigmentation response in susceptible individuals.
Treatment of dark infraorbital circles with the Q-switched ruby laser has been moderately
successful.
Successful treatment for drug-induced induced hyperpigmentation by Q-switched ruby or
alexandrite has been reported.
IPL therapy of lesions with evidence of deep pigment such as melasma and Becker's nevi has
been less successful.
3-Tattoos
The mechanism of tattoo ink removal by selective photothermolysis probably involves a
combination of transepidermal elimination, physical alteration of ink granules, transport by
phagocytic cells or lymphatics, and possibly an alteration of the dermal stroma.
For optimal pigment removal, the choice of laser is based on the absorption spectra of the ink
colors present within the tattoo.
Cosmetically, the best results are obtained when treating blue-black, amateur tattoos, which are
produced with carbon-based pigment such as India ink. Using the Q-switched ruby laser at
settings of 410 J/cm 2 (5-mm or 6.5-mm spot size), these tattoos clear without scarring after
four to six treatment sessions, spaced 3 to 4 weeks apart.
In contrast, professional tattoos often contain multiple pigment types (black, blue, green, red,
yellow, orange, purple, etc.), typically deposited in a dense band in the papillary and upper
reticular dermis. While some professional tattoos will clear, treatment response can be difficult to
predict, especially for tattoos featuring bright colors.
Blue, black, and green tattoos are responsive to Q-switched ruby (694 nm) or Q-switched
alexandrite (755 nm) treatment. Both lasers produce significant but transient hypopigmentation
in darker skin types. The 1064-nm Q-switched Nd:YAG laser is better tolerated by darkly
pigmented skin, and is probably the laser of choice for most black tattoos.
Yellow and orange pigments absorb minimally at any of the commercially-available laser
wavelengths, making these colors notoriously difficult to remove. The Q-switched Nd:YAG laser
or PDL the optimal treatment for these colors.
Green tattoos often resist laser lightening for unclear reasons that may relate to the chemical
composition of the ink itself (e.g. copper or chromium content).
The most common side effect of laser-assisted tattoo removal is transient pigmentary alteration.
Hypopigmentation is more frequently seen after Q-switched ruby laser irradiation and, therefore,
should not be used when treating patients with darker skin. Hyperpigmentation is usually mild
and transient, and can be treated with topical bleaching agents. A more serious complication of
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treatment involves a systemic allergic or localized granulomatous tissue reaction to tattoo ink
particles. Atrophic scars have also been reported.
III-Vascular lesions
Vascular-specific laser systems target intravascular oxyhemoglobin to effect destruction of
various congenital and acquired vascular lesions.
Devices used
Port wine stain
PDL is used to attain deeper penetration and faster treatment. PDL is used in long wavelengths
(585 to 600 nm) and large spot sizes (7 to 10 mm). As a result of reduced HbO 2 absorption at
these long wavelengths, somewhat higher fluences are used to achieve adequate vessel damage,
typically 8 to 12 J/cm2 and pulsewidths of 1 to 10 msec .
A study used an IPL with 550-nm (for red to pink PWSs) or 515-nm (for purple PWSs) cutoff
filters, pulsewidths of 2.5 to 5.0 msec, and high fluences of up to 60 J/cm2 , and observed
minimal adverse effects comparable to those seen with standard PDL treatment.
Capillary hemangiomas
PDL 585 nm; 5 to 7 mm spot; 0.45 msec pulsewidth; 5 to 10 J/cm2 fluence is the most effective
After a mean of 2.5 treatments, 96.6 % of hemangiomas showed no further growth, with 13.8
percent showing total regression and 14.9 percent showing marked regression.
Deep hemangiomas respond to penetrating infrared lasers such as the 1064-nm Nd:YAG.
IPL sources have also been reported for treatment of deeper hemangiomas.
Telangiectases, leg venulectases and spider nevi
Most vessels will clear using relatively low fluences, and more than two sessions per treatment
area are seldom required. PDL (585nm; 450 s or 600 nm; 1.5 msec ) provide reliable clearance,
leaving purpura that typically fades over 1 to 2 weeks.Additional effective systems include the
Nd:YAG
Lesions Featuring Prominent Vasculature
The PDL is also the first line treatment for hypertrophic scars and keloids. Significant clinical
improvement in hypertrophic scars is usually noted after 1 or 2 PDL treatments; however, a
greater response may be achieved after multiple treatment sessions using lower energy densities.
Initially, the PDL was used to target the vascular component of scars to reduce or eliminate
persistent erythema. Scar flattening and improved pliability proved to be an incidental finding..
Keloids and very thick or proliferative hypertrophic scars may require additional laser treatments
or the simultaneous use of intralesional corticosteroid or 5-fluorouracil injections to enhance
clinical results.
On the basis of the success of the PDL in treating hypertrophic scars, several investigators
evaluated its use for the treatment of striae. PDL produced improvement in skin surface
appearance and increased dermal elastin in striae. The optimal treatment fluence was determined
to be 3 J/cm2 using a 10-mm spot size.
Because of the increase in capillary loops in verruca vulgaris, the pulsed dye laser was used for
the treatment of these viral lesions. Despite initial enthusiastic reports, it is now clear that this
treatment is based mainly on nonspecific thermal destruction, but remains a good alternative
treatment for lesions resistant to liquid nitrogen.
Similarly, the increase of capillaries in the papillary tips seen in psoriasis has led to the use of the
PDL to treat plaque-type psoriasis, with positive results in several studies.
IV-Cutaneous laser resurfacing
Indications
1-Severely photodamaged facial skin.
2-Facial rhytides (wrinkles)
14
15
16
CHAPTER 3 :
PHOTODYNAMIC THERAPY(PDT)IN DERMATOLOGY
Definition
Photodynamic therapy (PDT) is a treatment modality involving administration of a
photosensitizing compound (a sensitizer) that accumulates in the target cells followed by
selective irradiation of the lesion with visible light. The drug and light are individually non-toxic,
but their combination destroys tissues.
Because the photosensitizer is preferentially absorbed by hyperproliferative tissue and the light
source is directly targeted on the lesional tissue, PDT destroys cells, with minimum damage to
adjacent healthy structures.
History
Oscar Raab, a German medical student first reported the death of Paramecium caudatum (a
protozoan) after light exposure in the presence of acridine orange in the year 1900. His professor,
von Tappeiner, coined the term "photodynamic" to describe oxygen-consuming chemical
reactions in vivo . Von Tappeiner and Jesionek (a dermatologist), in 1904, used topical eosin and
visible light to treat skin tumors, condyloma lata and lupus vulgaris.
Mechanisms of action
1-Direct cytotoxicity
After the application of aminolevulinic acid (ALA) or methylaminolevulinate (MAL) to human
skin, they are transformed into porphyrins which accumulate mostly in sebaceous glands and the
epidermis. Neoplastic cells accumulate more porphyrins than normal cells. Following light
activation, porphyrins are excited to a higher energy triplet state, which can generate reactive
oxygen species, such as singlet oxygen or free radicals. Porphyrins derived from ALA are mainly
localized in the vicinity of mitochondria, which can lead to apoptosis or necrosis of malignant
cells upon light exposure.
2-Vascular injury
Vascular injury is important in tumor destruction mediated by PDT. Vascular endothelial damage
leads to platelet and polymorphonuclear leucocyte activation that releases pro-aggregatory
agents. These events result in arteriolar constriction, venular thrombosis and blood flow stasis
causing indirect tumor cell necrosis from nutritional deprivation.
3-Inflammatory response
Degradation of phospholipids occurring after photo-oxidative damage of cell membrane and
impairment of vascular functions results in the release of various inflammatory mediators e.g.
IL-1, IL-2 and TNF. This leads to accumulation of immune effector cells like macrophages and
neutrophils. Degranulation of neutrophils and release of toxic oxygen radicals, lysosomal
enzymes and chemotactic agents contribute to the destruction of the tumor tissue and sustain the
damage by attracting further immune cells. Establishment of immunological response against the
treated malignancy leads to generation of tumor-specific immune cells that appear to be directed
against both strongly and poorly immunogenic cancer types.
4-Other mechanisms
For the treatment of acne, preferential targeting of sebaceous glands and P. acnes reduction are
believed to be the main mechanisms involved. The exact mechanisms involved in ALA PDT for
the treatment of photoaging are not well known, but increased collagen synthesis has been
demonstrated following ALA PDT.
The sensitizers
1-Aminolevulinic acid (ALA) (Levulan solution): Limitations of topical ALA are that it is an
unstable hydrophilic molecule, has poor penetration depth and consequent requirement of long
17
application times, has low tissue selectivity and may cause porphyrin to accumulate in distant
sites.
2-Methylaminolevulinate (MAL) (Metvix cream): Its advantages are that it is a stable lipophilic
molecule, has greater and faster penetration as well as a greater selectivity for neoplastic cells
and shows no systemic uptake.
Light sources
1-Lasers
The purpose of lasers in PDT is to initiate photochemical reactions in contradistinction to their
photothermal or photomechanical effects, as are seen in other dermatologic uses. Almost any
laser with an output wavelength within the visible spectrum (400-800 nm) may be used to
activate ALA and MAL.
Laser PDT has many advantages. First, the monochromaticity of lasers provides maximum
effectiveness if the wavelength of the laser corresponds with the peak absorption of the
photosensitizer. Second, lasers can produce high irradiance to minimize the therapeutic exposure
time. On the other hand, lasers are relatively expensive and they require special maintenance.
2- Noncoherent light sources
In the treatment of large skin lesions, noncoherent light sources are superior to laser systems
because of their large illumination fields. Other advantages of noncoherent light sources are their
low cost, smaller size, and ready availability. Additionally, polychromatic light sources allow the
use of different photosensitizers with different absorption maxima. Given the right dose of drug
and light, noncoherent light sources appear to be as effective as laser sources.
In current dermatologic use, the most widely accepted application of ALA PDT is with blue light
(Blu-U device) for the treatment of actinic keratoses.
MAL PDT involves exposure to 37 J/cm2 or 75 J/cm2 of red light using the Aktilite or the
Curelight device, respectively.
Indications
1- Actinic keratoses(AKs)
ALA is to be applied weekly on AKs only, followed 14-18 hours later by 10 J/cm2 of blue light
exposure using the Blu-U device. However, in clinical practice, most physicians are currently
using shorter (30-90 min) incubation times. In one study, 73%of patients had a complete
response with all lesions at week 12.
For the treatment of AK with MAL, the cream is applied on lesions following skin preparation.
Skin preparation consists of removal of the crusts or hyperkeratotic portion of the AK with a
curette, which probably enhances MAL penetration. MAL is then applied under occlusion for a
period of 3 hours, followed by exposure to 37 J/cm2 or 75 J/cm2 of red light using the Aktilite or
the Curelight device, respectively.
2- Basal cell carcinoma (BCC)
Only MAL has been studied for the treatment of BCC. Both the Curelight and the Aktilite
devices have been used in these studies. In all these studies, a gentle curettage was performed to
remove crusts before MAL application.
Studies show histological cure rates at 3 months to be 85% for superficial BCC and 75% for
nodular BCC with a recurrence rate of 18% after two years. The cosmetic outcome has been
shown to be superior to surgery or cryotherapy.
3-Acne vulgaris
ALA PDT is currently used off-label for the treatment of acne. A short incubation time of 30-60
minutes is used followed by light exposure, mostly from a Blu-U or an IPL. Significant clinical
improvement and a decrease in sebum production and sebaceous gland size have been shown
posttreatment
4-Bowen disease
Both ALA and MAL have been shown to induce good clinical responses in Bowen disease.
Bowen disease might be one of the best clinical indications for PDT because the lesions often are
large and the surgical approach may result in extensive scarring.
18
5- Kaposi's sarcoma
Studies to date have shown that response rates with PDT are equal to those with other therapeutic
modalities in Kaposi's sarcoma.
6-Skin metastases
The conclusion from various studies is that PDT is helpful to palliate initial small metastases of
breast cancer but is not suitable for the management of advanced or inflammatory carcinoma due
to low response rate and complications.
7-Other applications
ALA and MAL PDT with the Blu-U or IPL devices have been used for the treatment of
photoaging. Also, though no controlled studies have been done, topical 10% ALA ointment
applied for 5 hours followed by irradiation with 25 J/cm2 from an incoherent light source showed
clearing of chronic plaque psoriasis. Hirsutism responded to PDT with the advantage that hair
follicle damage was highly selective and did not damage the adjacent dermis.
Side effects
1. A burning sensation is observed during light exposure after ALA or MAL application. This
sensation usually decreases rapidly once the light source is paused or exposure is terminated.
2. A phototoxic reaction on AKs and BCC is characterized by erythema, edema, crusting,
vesiculation, or erosion occurs in most patients. This is considered a normal and desirable
reaction to achieve clearance of these lesions. It lasts only a few days but sometimes can last
7-10 days.
3. Hyperpigmentation is sometimes seen after PDT. It tends to fade over a few months.
Hypopigmentation at treated sites has also been reported.
4. Cases of allergic contact dermatitis and urticaria to MAL have been reported.
Precautions
1. Sun exposure on the treated lesion sites and peripheral skin should be avoided for at least 48
hours following topical application of ALA and MAL.
2. Direct eye contact with ALA or MAL should be avoided.
Contraindications
1. Persons with porphyria, cutaneous hypersensitivity or allergy to porphyrins.
2. Children less than 8 years old.
19
CHAPTER 4:
ELECTROSURGERY IN DERMATOLOGY
Definition
A surgical procedure that uses high frequency energy to cauterize, coagulate or cut soft tissue.
N.B.Electrosurgery is often incorrectly referred to as electrocautery. Although electrocautery is a
form of electrosurgery, in electrocautery, the electrode tip, rather than human tissue, serves as the
source of electrical resistance. In electrocautery, the electrode tip becomes hot and can cause a
burn in tissue.
History
Egyptians 3000 years ago used heat to treat tumors. In 1889 Sir Henry Thopson built the first
electrosurgery unit. In 1926 Cushing and Bovie built a device that provided hemostatic and
cutting effects.
Devices used
Modern devices (e.g. Hyfrecator and Surgetrone) use frequencies more than 50 000 Hz.
Frequencies less than that cause neuro-motor excitability causing repeated muscular contractions
which may lead to tetany.
Mechanism of action
Electrosurgical equipment converts domestic alternating current into high frequency alternating
current. When this current meets the high resistance of the skin, it produces heat. If the heat is
delivered as intermittent pulses, desiccation/fulguration will result while continuous delivery
raises intracellular water above the boiling point causing cell membrane rupture to produce a
cutting effect.
Effects of electrosurgery on tissues
1.Electrodesiccation (Fig.4)
In electrodesiccation, an active electrode touches or is inserted into the skin to produce tissue
destruction. The current is of high-frequency, high-voltage, low-amperage and damped
(a damped current is a current whose amplitude of oscillation decreases with time, eventually
going to zero).
2.Fulguration (Fig.4)
In fulguration, the electrode is held away from the skin to produce a sparking at the skin surface
and more shallow tissue destruction.The current is of very high voltage, very high frequency,and
very low amperage that is highly damped.
20
3.Electrocoagulation
Electrocoagulation is ideal for clotting small blood vessels (less than 2 to 3 mm in diameter) in
deep and superficial surgery. Usually, a 2- to 5-mm metallic sphere at the end of a treatment
electrode is the optimal tip for hemostasis of small vessels. These electrode tips can be directly
applied to the relatively dry surface of a surgical bed that has been momentarily compressed. The
current used is similar to electrodessication but the voltage, frequency, and current damping are
all smaller, while amperage is higher.
4.Electrosection
In electrosection, the electrode is used to cut tissue. An electrode tip in the shape of a fine needle,
wire loop, diamond, ellipse, or triangle is advanced slowly through the tissue, causing a steam
envelope to advance around the tip and producing a smooth cutting effect with little sense of
pressure against the tissue by the operator. A high-voltage, low-amperage, high-frequency
undamped current is used.
Indications for electrosurgery
Lesions
1-warts 2-Condylomata 3-Molluscum contagiosum
4-Skin tags5- Seborrheic keratosis 6-Actinic keratosis
7-Pyogenic granulomas
8-Nevi
9-Cherry nevi
10-Spider Nevi 11-Telangiectasias
12-Basal cell carcinoma
Technique used
Dessication or fulgration
Coagulation or section
Section
Coagul. or dessication or fulgration
Coagulation
Section or dessication or fulgration
Steps of electrosurgery
1-Local anesthesia : Injectable anesthesia is administered, 10 minutes at least, before most
electrosurgical techniques. The use of local anesthetic with epinephrine further reduces blood
loss, but the use of epinephrine at the tips of digits and the nose should be avoided. Anesthesia
may not be necessary for electrosurgery for small lesions. Some of the anesthetics available are
given in the next table.
2-Warts and tumors are destroyed by dessication or fulguration then curetted and the base is
cauterized to stop bleeding.
3-Wound care: wounds heal by secondary intention and may be cleansed daily and then covered
with petrolatum or antibiotic ointment. These ointments promote a moist environment for new
tissue growth and have been proven safe and effective. The wound may then be covered with
typical adhesive bandages.
Local infiltration anesthetics available in Egypt
Anesthetic
(Trade Name)
Lidocaine
(Xylocaine)
Lidocaine with
epinephrine
Concentration
for infiltration
2%
2% with
epinephrine
1:100,000
Mepivacaine
2% with
with
levonoradrenaline
levonoradrenaline
1:20,000*
Onset
(Minutes)
<2
Duration
(Hours)
0.5-1
<2
2-6
3-5
2-6
Transmission of
infection
Pacemaker problems
Eye injury
Prevention
-Avoid preparing the skin with alcohol, or let it dry thoroughly.
-Do not use ethyl chloride as a topical anesthetic.
-Make sure the patient is not grasping or touching metal parts of the
treatment table.
-The operator should not make or break contact with the patient during
the delivery of the current.
Use a smoke evacuator with the intake nozzle held within 2 cm of the
operative area.
Investigate risk of arrhythmia with the patient's specific pacemaker.
-Use special care when performing electrosurgery near the eye.
-Do not let the active tip of your electrosurgical device get close to the
eye because the spark can arc to the globe and cause damage.
22
CHAPTER 5 :
CRYOSURGERY IN DERMATOLOGY
Definition
It is the destruction of skin lesions by freezing.
History
The earliest freezing agent used in the treatment of skin diseases was the salt-ice mixture (boiling
point -20C) advocated by Arnott in 1851. By 1913, the clinical effectiveness of liquid air and
solid carbon dioxide (CO2 snow) was well known. CO2 snow is little used now but the most
commonly used cryogen( freezing agent) is liquid nitrogen ( boiling point -196C).
Equipment
Liquid nitrogen is cheap and easily available and may be stored in the office in 5 or 10 liter tanks
for approximately 10 days. Cotton swabs have been used to administer the nitrogen, but they are
capable of transmitting virus particles. It is now recommended that liquid nitrogen be
administered with a direct spray or contact probe with an autoclavable tip. Nitrous oxide
cryoprobes are also available. The gas is easily obtained because of its use in anesthetics; this
refrigerant is probably less appropriate than liquid nitrogen for treating malignancy.
Mechanism of Action
Temperatures of -25C to -50C can be achieved within 30 seconds if a sufficient amount of
liquid nitrogen is applied by spray or probe. Generally, destruction of benign lesions requires
temperatures of -20C to -30C. Effective removal of malignant tissue often requires
temperatures of -40C to -50C. Irreversible damage in treated tissue occurs because of
intracellular ice formation. The degree of damage depends on the rate of cooling and the
minimum temperature achieved. Inflammation with bulla formation develops during 24 hours
after treatment, further contributing to destruction of the lesion through immunologically
mediated mechanisms.
Slow thaw times and repeat freeze-thaw cycles produce more tissue injury than a single freeze
and thaw. Usually, several minutes are allowed between repeat freeze-thaw cycles. Repeat
freeze-thaw cycles generally are employed only in the treatment of malignancy.
Continuous freezing at one location for more than 30 seconds after an adequate freeze ball is
achieved around the target area can result in disruption of the collagen matrix of the skin and
possible scarring.
Technique of cryosurgery
1-The nozzle of the spray gun is positioned 1 to 1.5 cm from the skin
surface and aimed at the center of the target lesion.
2-Liquid nitrogen is sprayed until an ice field (or ice ball) encompasses
the lesion with a suitable margin. The margin size depends primarily on
the thickness of the lesion and whether the lesion is benign or
malignant. Margins for most benign lesions can extend as little as 1 to 2
mm beyond the visible pathologic border. Premalignant lesions need
margins of 2 to 3 mm, while malignant lesions require margins
of 5: mm
Fig.6
Technique of
of clinically normal skin to ensure adequate removal. These margin sizes
allow
cryosyrgery
Enough depth of freeze to ensure temperatures of -50C to a depth of 4 to 5 mm.
3-Liquid nitrogen spray flow is maintained to keep the target field frozen for an adequate time.
This time may vary from 5 to 30 seconds beyond the initial time for formation of the ice field. If
more than one freeze-thaw cycle is required for lesion destruction, complete thawing should be
allowed before the next cycle (usually two to three minutes).
23
Type
Freeze
time
(seconds)
Margin
(mm)
Number of
treatment
sessions
Interval
between
treatment
sessions
(weeks)
Actinic keratosis
5
1
1
Common warts
10
2
3
4
Cutaneous horn
10 to 15
2
1
Hypertrophic scar
20
2
1
Keloid
20 to 30
2
3
8
Pyogenic granuloma
15
<1
1
Skin tags
5
2
1
Solar lentigo
5
<1
1
Dermatofibroma
20 to 30
2
2
8
For basal and squamous cell carcinomas: two 30-second freeze-thaw cycles should be employed .
Complications
Acute
Bleeding at the freeze site.
Blister formation.
Edema.
Headache (after treatment of facial lesions).
Pain.
Protracted or permanent
Hair and hair follicle loss.
Hypopigmentation.
Protracted but temporary
Alteration of sensation(the nerves are superficial on the lateral aspects of the digits,the angle
of the jaw, and the ulnar fossa of the elbow. Cryosurgery should be avoided in these areas to
prevent nerve damage).
Hyperpigmentation (in people with darker complexions).
Hypertrophic scarring.
Milia.
Contraindications to Cryosurgery
Absolute contraindications
Lesions for which a biopsy for pathology is
required
Lesion located in an area with
compromised circulation
Melanoma
Proven sensitivity or adverse reaction to
cryosurgery
Relative contraindications
Cold urticaria
Collagen or autoimmune disease
Heavily pigmented skin
Lesions located in pretibial areas, eyelid
margins, nasolabial fold, ala nasi, and hairbearing areas
Multiple myeloma
Raynaud's phenomena
24