NATURAL PHOTOTHERAPY

FLOW
Skin Vitiligo Psoriasis Phototherapy NEW PRODUCT

n Colour • Etiology • Etiology • History • A Window of Light

elanocytes and • Pathophysiology • Pathophysiology • Types of radiation • Composition
elanin • Current therapy • Current therapy from the sun • MOA
me Time • What is UV Light? • Directions for use
• Why UVB is Preferred • Published Studies
and How it works? • Advantages
• Photobiology in • Warnings
Vitiligo and Psoriasis? • Place in therapy
• Different • Summary
Phototherapies & • Conclusion
Comparison
• Gap in current
treatment
• There are so many different
shades of skin colour.
• Have you ever wondered why
others have lighter or darker
complexion than you?
Origin of cutaneous pigmentation
• Skin color determined by its content in pigments
– Melanins +++++,
– Oxygenated and reduced hemoglobin
– and Carotene

• Other factors
– epidermal thickness
– vascular supply
• What are Melanocytes?
– Melanocytes are special cells in our skin that
specialize in making a molecule called melanin.
• What is Melanin?
– Melanin is something called a pigment, which is the
molecule that gives our skin colour a darker shade.
 MELANIN
• What does melanin actually do?
– Melanin protects our skin from the damaging
Ultraviolet (UV) rays from the sun.
– Going sun tanning induces your body to produce
more melanin, which is why people who return from
tanning look darker.
– More melanin in the skin is the reason why people
who are darker usually do not get sunburned.
• In our skin, we all have around the same number of
melanocytes, which are the cells that produce melanin.
• However, the melanocytes in each of our bodies produce
different amounts of melanin.
– The more melanin you have in your skin, the darker
your skin colour will be.
Which has more melanocytes??

Which of these two men has more Melanin in his skin??

 MELANOCYTES

Black skin White skin

Similar number of melanocytes BUT melanin synthesis and melanocytes’

migration to the keratinocytes more significant for black skin
FITZPATRICK SKIN TYPES
DERMATOLOGIC
DISORDERS
Overview of the Diseases
Melasma

Lentigo
Hyperpigmenta
tion Iatrogenic
hyperpigmentatio Pregnancy mask
n

Post-acneic or
cicatricial
hyperpigmentatio
n

Hypopigmentati
on Vitiligo
Vitiligo
Vitiligo
 Hypopigmentation disorders
• Vitiligo

• High prevalence: 0.5 - 2% of the population

• Unknown etiology

• 3 major hypotheses, not exclusive of each other:

– immunologic factors
– oxidative stress
– sympathetic neurogenic disturbance
Vitiligo: Melanin Related Condition
• Vitiligo
– It is a skin condition that can manifest after birth at any
point in someone’s life(generally around 30 years).
– It leads to death or loss of function of the melanocytes in
the body, which leads to the inability to produce any more
melanin in the skin.
– Vitiligo is very visible on someone with a very dark
complexion due to the prevalence of white splotches of
skin.
VITILIGO

ÀAutoimmune disorder

ÀGenetic link

ÀAffects 0.5-8% of population

ÀDifficult to cure
Genetic Links
ÀPolygenic nature, multifactorial inheritance
ÀAutosomal and not linked to race or sex
ÀLinked to other autoimmune diseases

ÀWeakly heritable
Signs and Symptoms
Vitiligo lesions are characterized as follows:
• White or depigmented macules and patches
• Usually well demarcated
• Round, oval, or linear in shape
• Borders may be convex [1]
• Range from millimeters to centimeters in size
• Enlarge centrifugally over time at an unpredictable rate
Types of Vitiligo
Diagnosis
• Clinical findings, biopsy is occasionally needed for differentiating
vitiligo from other hypopigmenting or depigmenting disorders
• Microscopic examination of involved skin shows a complete absence
of melanocytes in association with a total loss of epidermal
pigmentation
LAB TESTS
• Thyroid panel consisting of thyroid-stimulating hormone (TSH), free
triiodothyronine (T3), and free thyroxine (T4) levels
• Antinuclear antibody
• Antithyroid peroxidase antibody
• CBC count with differential
VITILIGO PATHOPHYSIOLOGY
Treating Vitiligo
ÀLong and difficult process, rarely 100% effective on individual
ÀOften involves sunlight or ultraviolet light
ÀPhysical and chemical methods
ÀCosmetics
ÀDepigmentation
ÀPsychological counseling
Treatment of Vitiligo
Therapy Options-1
Therapy Options-2
Treatment Steps
Step 1 (Inhibiting Principle Mechanism
Depigmentation)
Corticosteroid/Tacrolimus/UV Immunosuppression and
B Preventing Immune activation
Step 2 (Promoting Principle Mechanism
Repigmentation)
UVB/Surgery Stimulating Melanogenesis,
Melanocyte Proliferation
Vitiligo Treatment Guidelines
Psoriasis
 PSORIASIS
 Erythematous lesions with loose, silvery-white scales
 Removing scale can induce punctate bleeding: Auspitz sign
 Papules can coalesce in pruritic patches / plaques
 Nails and joints may be affected

Extensive, well-demarcated erythematous

plaques
PATHOPHYSILOGY PSORIASIS
What drug therapies are used in treatment?
Topical therapies Systemic therapies
 Corticosteroids  Methotrexate
 Vitamin D analogues  Cyclosporine A
 Topical retinoids  Oral vitamin A derivatives
 Calcineurin inhibitors Biological therapies
 Salicylic acid  Adalimumab
 Anthralin  Etanercept
 Coal tar  Golimumab
 PHOTOTHERAPY  Infliximab
 Secukinumab
Psoriasis Treatment Guidelines
PHOTOTHERAPY
History of Phototherapy
As early as 3,500 years ago, the Egyptians recognized that sunlight can be used to
treat Vitiligo

1896 - Niels Ryberg Finsen (father of modern phototherapy) developed the

“Finsen Lamp” treatment for Lupus Vulgaris

1923 - William Henry Goeckrman - artificial BB-UVB + topical coal tar for psoriasis

1974 - John Pareish developed 8-MOP + UVA - leading to PUVA therapy

1984 - Van Weelden, Baart de la Faille, Young and van der Leun demonstrated
clinical efficacy of NB-UVB, ushering the NB-UVB era

2013 - Revolutionary photochemistry. Development of a molecular composition

that selectively filters sunlight to deliver NB- UVB therapy!
Types of radiation from the sun
• Electromagnetic(EM) energy from the sun comes to Earth in the form of radiation. The
term "radiation" simply denotes the fact that the energy travels as rays.

• The sun emits all kinds of rays: cosmic rays, gamma rays, x-rays, ultraviolet rays(UV),
infrared rays(IR), microwaves, short radio waves(SRW) and long radio waves(LRW).
What is UV Light?
• Light is essential for life on earth.
• UV is part of the EM spectrum between
visible light and X-ray.
• Approximately 10% of the sun power is
emitted in the UV range.
• UVA (400-320nm), UVB (320-280nm),
UVC (280-100nm).
• Shorter wavelength = higher energy
• High energy UVC mostly absorbed by the
ozone layer
Why UVB is better?
How does Phototherapy/UVB work in
Psoriasis?
How does Phototherapy work in Vitiligo?
Same as Tanning Process

EFFECT
Types of Phototherapy
• PUVA/PUVASOL (Psoralen Ultra Violet A band therapy/PUVA with Sunlight)
• Narrow band UVB (Narrow Band Ultra Violet B Band therapy)
• BB UVB (Broad Band Ultra Violet B Band therapy)
• Photodynamic therapy
• Excimer laser
• UV light Targeted phototherapy
• Monochromatic light machines
• Low-level lasers
PUVA/PUVASOL
• Topical PUVA: With PUVA, a person either soaks in a bath or
applies a lotion containing psoralen, which makes the skin more
receptive to the UV light treatment that follows.

• Oral PUVA: With oral PUVA, a person takes pills containing

psoralen before phototherapy. This form of treatment may be
especially helpful for very thick plaques.

• PUVASOL is advised for those patients who cannot visit the

hospital for phototherapy.
• PUVA is more intensive and has more side effects than broadband
or narrowband UVB, and is usually only resorted to when
treatment with the others have been unsuccessful.
• The major photochemical effect is damage to DNA.
Problems with Psoralens
Eye problems:
• Because Psoralens bind to the proteins in the lens , there is further risk for cataract
evolution under PUVA therapy.
• In addition , damage to the retina could also be possible due to the photo-oxidative
reactivity of psoralens passing through the retinal vessels.
• Therefore, eye protection has to be worn for at least 12 hours after PUVA

• Studies have not shown an increased incidence of cataracts under eye protection, so
this preventive measure seems to achieve the desired effect.
Continued..
• Phototoxic reactions are delayed, with an erythema reaction peaking 48 to 72 hours after
irradiation. Therefore, accurate UVA dosimetry is distinctly required for PUVA therapy as over
dosage can easily lead to skin necrosis.
• Sometimes, the patient's extremities (in particular the lower extremities) arc exposed to higher
doses than the trunk.
• Early side effects: Oral PUVA is generally well tolerated; however, a number of potentially
serious side effects exists :
• Phototoxic reactions : a prodromal state with general malaise and itch precedes the rash.
• GI symptoms (ie, nausea and vomitus) are not uncommon but can often be improved by intake
of 8-MOP with some food , especially milk.
Continued..
• Rarely, increase in transaminase levels in the liver, and, thus liver function tests should routinely be
performed before starting oral PUVA.
• Late side effects: PUVA in the long term leads to a photoaged skin pattern with elastosis,
poikiloderma, and lentigines.
• Of concern is the induction of Non Melanoma Skin Cancers , which is proven and occurs in more
than 25% of PUVA-treated patients.
• Whether melanoma can be induced by PUVA has not been clarified.
All patients who received several course of oral PUVA should enter a long-term-follow up program
for at least 25 years
Targeted phototherapy
• Targeted therapy may either use broadband UVB, NB-UVB Excimer(308) laser or light
beams, NB-UVB (311 nm), or UVA1.
• Concentrated phototherapy
• Focused phototherapy
• Microphototherapy
Excimer laser
• Uses Xe Cl2 gas
• 308 nm wavelength
• Previously used in cardiology and ophthalmology
• Delivery system may be fibre optic/water guided
• Very quick delivery
• Initial reports claimed response with in 1-3 exposures in psoriasis and vitiligo
• works in resistant lesions and scars
• Very expensive-Rs10 to 15 lac
• Huge machine-over 120 kgs
• High maintenance cost
• Frequent replacement of Xe CL2 gas
• Frequent breakdown of fibre optic cables
• Not effective in peripheral vitiligo
UV-B PHOTOTHERAPY
• BB-UVB: Fluorescent lamps are used.
• Wavelengths <300 nm are implicated in causing non melanoma skin
cancers and inducing erythema.
• NB-UVB: 308-313 nm wavelength
• Philips TL-10 lamp with an emission spectrum (311-312 nm).
• 5-10 fold less potent than BBUVB for erythema induction, hyperplasia,
edema and Langerhans cell depletion from the skin.
• More suppressive effect than BBUVB.
• Adv:NB-UVB schedules can be tailored according to patient skin type
and local experience
• Disadv
– The bulbs/tubes need to be replaced after 1000hrs
– Many don’t do so as each tubes cost around Rs. 100,000/-
Monochromatic excimerlight (IPL) machines
• Excilite( 304 nm), Pxlite( 308 nm)
• Use monochromatic light (intense pulse light)
• LARGE TREATMENT SURFACE: 36*14 cm
• more reasonable in cost
• Easier maintenance
• In a pilot study of 37 patients, Thirty-five patients (95%)
showed signs of repigmentation within first 8 treatments.
COMPARISON
Type PUVA BB-UVB NB-UVB Excimer Laser

Wavelength 320–400 290–320 310–313 308

Range (nm)
Lesion size Large Large Small-Localized Small-Localized
lesion (TPT) lesion

Treatment 2-3/Weekly 2-3/Weekly 2-3/Weekly Alternative

Sessions days
Exposure of Yes Yes No No
uninvolved
areas
Side effects High low low low
Cost + + ++ +++
Efficacy Comparison
Gap in current treatment
COMPLAINCE AND DROP OUTS
• Requires visit to a medical clinic (home therapy about 5%)
• 2-3 visits per week for several months (50- 90 sessions)
COST CONCERNS
• Significant time and cost commitment (Rs.2000/session)
• High maintenance cost with Excimer laser
• REPLACEMENT Costs
SAFETY CONCERNS
• While safer then BB-UVB, NB-UVB lamps emit significant harmful non-therapeutic
UVB
• Difficult for children with conventional Phototherapy
• Slow response with conventional Phototherapy
• Not effective in Acral vitiligo
A Window of Light

• Revolutionary photochemistry (PhotocilTM) developed allows delivery of NB-UVB from natural

sunlight while filtering non- therapeutic UVB and UVA

• Combines two novel molecules into a topical cream producing a “topical band pass filter”
Presilux
• Composition: Not a Drug(Registered as Cosmetic Product)
• NO ACTIVE PHARMACEUTICAL INGREDIENT

• Non active important ingredients: diethylamino hydroxybenzoil hexyl benzoate(DHHB) and

alpha-glucosyl hesperidin(α-GH) (a glucosylated derivative of a natural plant flavonoid).
 How does PRESILUXTM work?
• Combines two novel molecules into a topical cream producing a “topical band pass filter”. Which
allows delivery of NB-UVB from natural sunlight while filtering non-therapeutic UVB and UVA.
In Vitiligo
In Psoriasis
Treatment plan
USAGE DIRECTIONS

Check for weather condition Apply Presilux Apply the SPF 300 sunscreen and cover the non affected area

Proceed outside Expose skin to direct daylight for 20-30 minutes Return inside.
Directions for use
• Apply as needed

• Apply Presilux cream to affected skin area(s) in accordance with your doctor's instructions

• Allow affected area(s) of skin to receive exposure to daylight preferably between 10am to 2pm
following application of Photocil cream

• Use accompanying dosimeter or mobile app in accordance with your doctor's instructions to
monitor sun exposure
USE
• Indicated for vitiligo and psoriasis

• Allows penetration of therapeutic radiation while filtering out most non-therapeutic radiation
from daylight and artificial light
Novel topical cream delivers safe and effective sunlight therapy for Vitiligo by selectively filtering damaging ultraviolet
radiation

Andy Goren MD, Antonio Salafia MBBS, John McCoy PhD, Sharon Keene MD, Torello Lotti MD. Dermatologic Therapy (In Press)

• 2 vitiligo studies completed over 60 patients

• 11.25 week average, 3 sessions per week
• 28% patients showed 70% repigmentation
• 28% patients showed 50% repigmentation
• Similar efficacy to artificial light therapy
• No adverse events (excluding slight erythema
Novel topical cream delivers safe and effective alternative to traditional psoriasis phototherapy

Andy Goren MD, Antonio Salafia MBBS, John McCoy PhD, Sharon Keene MD, Torello Lotti MD. Dermatologic Therapy (In Press)

• A double-blind placebo-controlled study on 15 psoriasis patients

• Patients were instructed to apply approximately 2 mg/cm2 of cream
• Average treatment time was 32 minutes (average of 38 sessions)
• 43% of treatment group patients showed complete clearance
• Remainders experienced minimum 50% lesion clearance
• None of the patients in placebo arm experienced >20% clearance.
• No adverse events (excluding slight erythema)
Advantages
• Photocil cream opens a new window in dermatological phototherapy

• Alternative to artificial light phototherapy

• Patients can receive therapy at their convenience and at an affordable cost per treatment

• It help to ensure higher patient compliance with the treatment

• Can be combined with other forms of therapy as well

Warnings
• For external use only

• When using this product do not get into eyes

• Stop use and ask doctor if condition worsens or symptoms do not improve after more than 7 days

• Keep out of reach of children.

• If swallowed, get medical help or contact a Poison Control Center right away
PRESILUX PLACE IN THERAPY
Vitiligo Treatment Guidelines
Psoriasis Treatment Guidelines
How should a clinician choose between topical
and systemic drug therapy?
 Determine disease severity
 Measure affected body surface area
 ≤3%: mild
 3%-10%: moderate
 ≥10% or serious adverse affect on QOL: severe
 Determine the location of lesions
 Consider affect on QOL
 Mild disease: topical therapies
 Moderate-to-severe disease: systemic and topical therapies;
biologics if systemic fail / can’t be used
What is the role of phototherapy?
 when disease substantially affects QOL
 Efficacious and cost-effective
 Not immunosuppressive like systemic drugs
 Affects Langerhans cells directly, cytokines indirectly
 Don’t use with photosensitive disorders
Is there a role for combination drug therapy
and phototherapy?
 Improves efficacy and decreases toxicity of a potentially hazardous combination agent

Phototherapy can be combined with:

 Anthralin or coal tar
 MTX
 Retinoids
 Biological therapies
Summary
• Sun emits abundance of ultraviolet rays.
• UVB is the most bioactive in humans.
• NB-UVB induces melanocyte migration and differentiation.
• NB-UVB radiation to systemically suppress the major components of cell mediated immune
function is thus likely to be linked to its beneficial effect in several inflammatory skin diseases
including psoriasis.
• PUVA is more intensive and has more side effects than broadband or narrowband UVB.
• Significant time and cost commitment with artificial phototherapy.
• Revolutionary photochemistry developed allows delivery of NB-UVB from natural sunlight while
filtering non- therapeutic UVB and UVA.
Conclusion
• Sunlight has been recognized for eons as a therapy for Vitiligo

• Attempting to “capture” the sun’s therapeutic properties led to the development of artificial UV
light sources

• Artificial light sources have inherit limitations in the daily lives of humans

• Revolutionary photochemistry (Presilux) harnesses the power of natural sunlight for NB-UVB
therapy opening a new window in phototherapy
References
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