Transcript PHOTOTHERAPY UV….Friend or Foe?

PHOTOTHERAPY
UPDATE 2009
Frederick C. Fehl, III MD
Dept of Dermatology
SCPMG San Diego
Disclosures
I have no known conflicts with any of the
products, medications or devices,
discussed in this lecture
I am receiving no honoraria
The Electromagnetic spectrum
Figure shows electromagnetic spectrum divided into the major regions:
UVA 400-320 (UVA I 400-340 and UVA II 340-320)
UVB 320-290
UVC 290-200
UV Spectrum
UVC (280-200nm)
– An arbitrary division was made between UVB and
UVC at 290nm because wavelengths shorter then
290nm do not reach the earth’s surface
– Absorbed by the ozone layer
– These wavelengths are absorbed by DNA, RNA and
proteins of cells and can be lethal to organisms
– Hence the term germicidal radiation
– Used in germicidal lamps that emit 254nm
UV Spectrum
UVB (280-320nm)
– Strongly erythemogenic (sunburn rays)
– Ordinary window glass filters out wavelengths
shorter then 320nm
– There is great variation of the erythemogenic
potential within the range:
For example 297nm is nearly 100 times more
erythemogenic then 313nm radiation even though
they are both in the UVB spectrum
UV Spectrum
UVA (320-400nm)
– Divided into two groups:
UVA1 (340-400nm) and
UVA2 (320-340nm)
– aka as “tanning rays” (tanning parlors emit)
– Not blocked by window glass unless…
– UVA radiation is more deeply penetrating (penetrates
to the deeper dermis whereas UVB is absorbed by
the epidermis
– This is why I often refer to it as the wrinkle rays
UV FACTS
Ultraviolet light is “light” we can not see…it’s
radiation!
Comprises 5% of terrestrial radiation
It spans the region of “light” from 400 to 100nm
UV is 7% more intense in the Southern
Hemisphere summer than Northern Hemisphere
summer
UVB comprises 5% of total UV compared to
95% for UVA…but UVB is more biologically
active!
UV FACTS
On a cloudy day…66% of UV gets to ground
(75% in the tropics)
In the tropics….a cloudy day get 75% to ground
Reflection off the ground is less than 10%
except for snow which can reflect 90%!
Choppy water more reflective than calm water
For every 1,000 feet in elevation, there can be
7% more UV
What about the Ozone depletion?
Red States vs. Blue States Summary
2008 Election Results
“Their may be more ozone depletion in Blue States then Red States”
Bush, Limbaugh et al
UV FACTS
UVB inflammation is a delayed effect:
– Develops 1-5 hrs after high dose
– Max effect at 24 hrs
– fades in 3 days
UVA inflammation is immediate
(immediate pigment darkening)
The UVA “tan” offers little protection
compared to UVB
UVA penetrates deep to dermis…UVB
affects epidermis
UV FACTS
UVB is considered more carcinogenic: AK, SCC
and BCC’s
UVA does have detrimental clinical effects ( e.g.,
flares autoimmune skin diseases such as lupus
etc, has been linked to melanoma)
UV can be our friend…Vitamin D, mood
elevation
UV is immunosuppressive!
70% of UV damage occurs before age 20!
Historical Aspects: Phototherapy
– Ancient times: Topical exposure to plants
containing psoralens + natural sunlight used
in Egypt and India to treat vitiligo
– 1925: Use of crude coal tar and UV radiation
was introduced by Goeckerman (Mayo Clinic);
became the standard therapy for psoriasis for
the next 50 years
– 1974: PUVA developed (oral regimen)
PUVA was quite effective for severe psoriasis
– 1970’s: broadband UVB also introduced
BB UVB IF given in doses that produce a slight
erythema could clear mild psoriasis
Mechanisms of Action of UVL
Reduction in skin proliferation (1st way):
– UVL is absorbed by chromophore
– The most important chromophore for UVB is DNA
– Pyrimidine dimers are formed
– These toxic photoproducts reduce DNA synthesis
Reduction in skin proliferation (2nd way):
– UVL induces the expression of p53 tumor
suppressor gene
– p53 causes cell cycle arrest and/or apoptosis
(cell death)
Mechanisms of Action of UVL
Immunosuppressive effects:
– Induces Interleukin 6 and 10 (sunburn sxs)
– Langerhans cells (antigen presenting cells)
are inhibited by UVL
– Keratinocytes release IL-1 and 6,
Prostaglandins E2 and TNF-α
Secretion of these compounds alters the
local immune response and may
contribute to suppression of disease
Action Spectrum
The effectiveness of clearing psoriasis
plotted against wavelength is defined as
the action spectrum of phototherapy
It is most desirable to use wavelengths (λ)
which are maximally therapeutic and
minimally erythemogenic
Action Spectrum
Studies in the early 1980’s demonstrated that 304 and
313nm had the optimal anti-psoriatic effect within the UVL
spectrum:
For wavelengths shorter then 295nm, no improvement in
psoriasis occurred (remember shorter λ’s are more
erythemogenic then therapeutic)
304nm
313nm
<295nm
Parrish, JA and Jaenicke, KF J Invest Dermatol 1981; 76: 359-362
Action Spectrum
The Philips Corp armed with the knowledge
regarding the action spectrum of psoriasis
develops a fluorescent lamp, TL 01, that emits the
optimal narrow band UVB frequency: 311-313nm
Differences:
broadband and narrowband UVB
NB UVB is much less erythemogenic then
BB UVB
– For example: 297nm is nearly 100 times more
erythemogenic then 313nm radiation even
though they are both in the UVB spectrum
Shown to be as effective as PUVA in the
treatment of psoriasis
Theoretically safer then BB UVB or PUVA
UVB Protocol
Pre-treatment Check List: UV Therapy
Review the patient’s history (Snapshot)?
– What disease is the MD treating?
– Does the patient have co-morbidities that may
make UV contraindicated?
Diseases Treated with UV
Psoriasis, psoriasis, and mostly psoriasis
Atopic Dermatitis
PMLE
Pruritus of renal failure
Pruritus of liver Disease (e.g., PBC)
Scleroderma
Idiopathic Pruritus of unknown etiology
CTCL
Vitiligo
Eosinophilic folliculitis of HIV
Winter Mood Affective Disorder
Pre-treatment Check List: UV Therapy
Review the patient’s history (Snapshot)?
– What disease is the MD treating?
– Does the patient have co-morbidities that may
make UV contraindicated?
UV AGRAVATED DISEASES
PMLE
SLE
DLE
SCLE
Solar Urticaria
Xeroderma Pigmentosa
Chronic Actinic Dermatitis
Cockayne’s Syndrome, Blooms
PCT
Dermatomyositis
Pemphigus
Actinic Reticuloid
Actinic LP
Pre-treatment Check List: UV Therapy
Review the Medications List:
– Are there any medications listed that are
photosensitizing?
– Will they be using any topical medications in
conjunction with their UV therapy?
Dovonex
Vectical
Tazorac
– Are they taking any oral agents to facilitate their
Rx?
Acitretin, Isotretinoin
Medications known to
cause photosensitivity
Every light box facility should
have a list such as this one to
cross check medications prior
to starting UVB
Examples include:
Zanolli et al textbook:
Phototherapy Treatment
Protocols (listed in KP
protocol)
Litt’s Drug Eruption Reference
Manual will also list
Pre-treatment Check List: UV Therapy
Labs:
– Did the MD order any pre-treatment labs?
Physical Exam:
– Do you agree with the MD’s Fitzpatrick skin type
assessment?
Orders:
– Do the orders make sense!
Right protocol for the disease
c/w published protocols
Broadband UVB vs. Narrow Band UVB
How do you do it?
What mj do you start at?
How much do you increase at each visit?
What happens if you miss a day, a week
or a month?
What happens if the patient sunburns?
Do you ask if the patient started any new
meds?
Dosing determination for UVB
Optimal done uses minimal erythema dose
determination (MED) for individual patients
by intricate phototesting
Not typical used by most Dermatologists
since it is time consuming and nurse
intensive
Most Dermatologists use schedules based
on the patients skin type
Example of MED determination NB UVB
UVB Treatment Protocol Using MED
Fitzpatrick Skin Type
Fitzpatrick
Skin Type
Response to Sun Exposure
Examples
I
Always burns, never tans
Fair skin and freckles,
blue eyed, Celts
II
Always sunburns, tans minimally
Fair skin, blond hair, blue
eyes, Scandinavian
III
Sometimes sunburns, tans moderately
Fair skin, brown hair,
brown eyes, unexposed
skin is white
IV
Seldom sunburns, tans easily
Light brown skin, dark
hair, brown eyes,
unexposed skin is tan;
Mediterranean, Hispanic
V
Rarely sunburn, tans profusely
Brown skin; Darker
Mediterranean, some
Asians, Pacific Islander,
Indian subcontinent
VI
Never sunburns, deeply pigmented
African Americans
Fitzpatrick Skin Type?
Fitzpatrick Skin Type I
Fitzpatrick Skin Type?
Fitzpatrick Skin Type II
Fitzpatrick Skin Type?
Fitzpatrick Skin Type III
Fitzpatrick Skin Type?
Fitzpatrick Skin Type IV
Fitzpatrick Skin Type?
Fitzpatrick Skin Type V & Type III
Fitzpatrick Skin Type?
Fitzpatrick Skin Type VI
Initial NB UVB Dosing
based on Fitzpatrick Skin Type
Fitzpatrick Skin Type
Tanning Response
Initial NB UVB Dose
I
Always burns, never tans
100 mJ
II
Usually burn, tans with
difficulty
220 mJ
III
Sometimes mild burn, tan
average
260 mJ
IV
Rarely burns, tans with
ease
330 mJ
V
Very rarely burns, tans
very easily
350 mJ
VI
No burn, tans very easily
400 mJ
Kaiser Protocol dated 10/15/07
UVB Phototherapy for Psoriasis
Ideally 3X a week (Dr. Koo recommends
up to 5X a week)
Combination therapy is ideal!
Calicipotriene + UVB 2X/week = UVB
3X/week
Tazarotene 3X/week added to UVB
requires less than ¼ of UVB to achieve
50% PASI
Goeckerman, Anthralin, Keratolytics
Current Kaiser Recommendations regarding
Dose Escalation based on Skin Type for NB
UVB
Skin
Type
Interval
Increase
Estimated Dose Goal
Maximum Dose
(not to exceed)
I
15mJ
520 mJ
2000mJ
II
25mJ
880 mJ
2000mJ
III
40mJ
1040 mJ
3000mJ
IV
45mJ
1320 mJ
3000mJ
V
60mJ
1400 mJ
5000mJ
VI
65mJ
1600 mJ
5000mJ
Key Safety Points
Type of box:
– NB vs. BB
– For clinics with multiple boxes
even if same light system
we assign a pt to a particular box
they always use that box even if they have to wait!
Remember units matter:
– 800 milljoules vs. 800 Joules
…….Burn Unit!!!
Two different boxes with two different input metrics
Not all UV light is Equal
Minimal Erythema Dose MED for Skin Type III
MED
3J/ cm UVA
30 mJ/cm UVB
Broad band
200-300 mJ UVB
Narrowband
20-30 mins sunlight
NYC in Summer
Noontime
Key Safety Points
Physicians should order the UVB in
Health Connect using the units that you
will enter into the box (i.e., avoid unit
conversion issues: how many
millijoules = a joule?)
my order
I then add my smartphrase .FFUVB
These units should correspond to
what YOU input into that pt’s light box
NB UVB Protocols
Remember different diseases use different
protocols
– Vitiligo protocol quite different then psoriasis
– Atopic dermatitis protocol different then
psoriasis (e.g., much lower max dose)
Remember the Kaiser Permanente protocol
is a quite conservative NB UVB protocol for
the treatment of psoriasis imho 
When in doubt whether the protocol is
appropriate for the disease being treated
ask the ordering MD to verify!
Thank You!
Vitiligo NB UVB Protocol
Treatment frequency is typically twice weekly
Start at all patients at 200 mJ/ cm2
Incremental Dosing
– If skin was pink the previous night and:
Pink now: Skip treatment & notify the MD
Not Pink now: Treat at same dose
– If skin was not pink the previous night:
Increase by 50 mJ/cm2
Maximum dose is 500-800 mJ /cm2
Missed Treatments of NBUVB for Vitiligo:
4-7 days
8-14 days
15-21 days
100% (same as last dose)
decrease dose by 50%
start over
Fig. 134.5 Narrowband phototherapy for vitiligo.
Before treatment
after 10 mos of NB UVB twice weekly
© 2003 Elsevier - Bolognia, Jorizzo and Rapini: Dermatology - www.dermtext.com
What’s New in Phototherapy
Narrow Band UVB 311
UVA – 1
Photodynamic Therapy
– Blue Light
– Red Light
Excimer Laser
New Lasers
UV FACTS
UV is a discrete, oscillating
electromagnetic pulse of energy, E (joules,
J) and a wavelength, lambda (nanometres,
nm, 10 -9th m), travelling through space at
velocity, c (3x10 8th m/s), such that
E=hc/lambda, where h= 6.63 X 10 -34th
J/s (Planck’s Constanat).
Common Terms
Watt (W) = Unit of power
Energy (Joules) = Power (W) x time (sec)
– Joule (J) = Unit of energy
– 1000 Millijoules (mJ) = 1 Joule
Fluence (Dose) = Energy delivered to a
unit area (J/cm2 )
Irradiance = Power delivered to a unit area
(W/m2)