phototherapy update 2009 frederick c. fehl, iii md dept of dermatology scpmg san diego
TRANSCRIPT
PHOTOTHERAPYPHOTOTHERAPYUPDATE 2009UPDATE 2009
Frederick C. Fehl, III MDFrederick C. Fehl, III MD
Dept of DermatologyDept of Dermatology
SCPMG San DiegoSCPMG San Diego
DisclosuresDisclosures
I have no known conflicts with any of the I have no known conflicts with any of the products, medications or devices, products, medications or devices, discussed in this lecturediscussed in this lecture
I am receiving no honorariaI am receiving no honoraria
Figure shows electromagnetic spectrum divided into the major regions:
UVA 400-320 (UVA I 400-340 and UVA II 340-320)UVA 400-320 (UVA I 400-340 and UVA II 340-320)UVB 320-290UVB 320-290UVC 290-200UVC 290-200
The Electromagnetic spectrum
UV SpectrumUV Spectrum
UVC (280-200nm)UVC (280-200nm)– An arbitrary division was made between UVB and An arbitrary division was made between UVB and
UVC at 290nm because wavelengths shorter then UVC at 290nm because wavelengths shorter then 290nm do not reach the earth’s surface290nm do not reach the earth’s surface
– Absorbed by the ozone layerAbsorbed by the ozone layer– These wavelengths are absorbed by DNA, RNA and These wavelengths are absorbed by DNA, RNA and
proteins of cells and can be lethal to organismsproteins of cells and can be lethal to organisms– Hence the term germicidal radiationHence the term germicidal radiation– Used in germicidal lamps that emit 254nmUsed in germicidal lamps that emit 254nm
UV SpectrumUV Spectrum
UVB (280-320nm)UVB (280-320nm)– Strongly erythemogenic (sunburn rays)Strongly erythemogenic (sunburn rays)– Ordinary window glass filters out wavelengths Ordinary window glass filters out wavelengths
shorter then 320nmshorter then 320nm– There is great variation of the erythemogenic There is great variation of the erythemogenic
potential within the range:potential within the range:For example 297nm is nearly For example 297nm is nearly 100 times100 times more more erythemogenic then erythemogenic then 313nm313nm radiation even though radiation even though they are both in the UVB spectrumthey are both in the UVB spectrum
UV SpectrumUV Spectrum
UVA (320-400nm)UVA (320-400nm)– Divided into two groups:Divided into two groups:
UVA1 (340-400nm) andUVA1 (340-400nm) andUVA2 (320-340nm)UVA2 (320-340nm)
– aka as “tanning rays” (tanning parlors emit)aka as “tanning rays” (tanning parlors emit)– Not blocked by window glass unless…Not blocked by window glass unless…– UVA radiation is more deeply penetrating (penetrates UVA radiation is more deeply penetrating (penetrates
to the deeper dermis whereas UVB is absorbed by to the deeper dermis whereas UVB is absorbed by the epidermisthe epidermis
– This is why I often refer to it as the This is why I often refer to it as the wrinkle rayswrinkle rays
UV FACTSUV FACTS
Ultraviolet light is “light” we can not see…it’s Ultraviolet light is “light” we can not see…it’s radiation!radiation!
Comprises 5% of terrestrial radiationComprises 5% of terrestrial radiation
It spans the region of “light” from 400 to 100nmIt spans the region of “light” from 400 to 100nm
UV is 7% more intense in the Southern UV is 7% more intense in the Southern Hemisphere summer than Northern Hemisphere Hemisphere summer than Northern Hemisphere summersummer
UVB comprises 5% of total UV compared to UVB comprises 5% of total UV compared to 95% for UVA…but UVB is more biologically 95% for UVA…but UVB is more biologically active!active!
UV FACTSUV FACTS
On a cloudy day…66% of UV gets to ground On a cloudy day…66% of UV gets to ground (75% in the tropics)(75% in the tropics)
In the tropics….a cloudy day get 75% to groundIn the tropics….a cloudy day get 75% to ground
Reflection off the ground is less than 10% Reflection off the ground is less than 10% except for snow which can reflect 90%!except for snow which can reflect 90%!
Choppy water more reflective than calm waterChoppy water more reflective than calm water
For every 1,000 feet in elevation, there can be For every 1,000 feet in elevation, there can be 7% more UV7% more UV
What about the Ozone depletion?What about the Ozone depletion?
Red States vs. Blue States Summary2008 Election Results
“Their may be more ozone depletion in Blue States then Red States” Bush, Limbaugh et al
UV FACTSUV FACTSUVB inflammation is a delayed effect:UVB inflammation is a delayed effect:– Develops 1-5 hrs after high dose Develops 1-5 hrs after high dose – Max effect at 24 hrs Max effect at 24 hrs – fades in 3 daysfades in 3 days
UVA inflammation is immediate UVA inflammation is immediate (immediate pigment darkening)(immediate pigment darkening)
The UVA “tan” offers little protection The UVA “tan” offers little protection compared to UVBcompared to UVB
UVA penetrates deep to dermis…UVB UVA penetrates deep to dermis…UVB affects epidermisaffects epidermis
UV FACTSUV FACTS
UVB is considered more carcinogenic: AK, SCC UVB is considered more carcinogenic: AK, SCC and BCC’s and BCC’s
UVA does have detrimental clinical effects ( e.g., UVA does have detrimental clinical effects ( e.g., flares autoimmune skin diseases such as lupus flares autoimmune skin diseases such as lupus etc, has been linked to melanoma)etc, has been linked to melanoma)
UV can be our friend…Vitamin D, mood UV can be our friend…Vitamin D, mood elevationelevation
UV is immunosuppressive!UV is immunosuppressive!
70% of UV damage occurs before age 20!70% of UV damage occurs before age 20!
Historical Aspects: PhototherapyHistorical Aspects: Phototherapy– Ancient times: Ancient times: Topical exposure to plants Topical exposure to plants
containing psoralens + natural sunlight used containing psoralens + natural sunlight used in Egypt and India to treat vitiligoin Egypt and India to treat vitiligo
– 1925: 1925: Use of crude coal tar and UV radiation Use of crude coal tar and UV radiation was introduced by Goeckerman (Mayo Clinic); was introduced by Goeckerman (Mayo Clinic); became the standard therapy for psoriasis for became the standard therapy for psoriasis for the next 50 yearsthe next 50 years
– 1974: 1974: PUVA developed (oral regimen)PUVA developed (oral regimen)PUVA was quite effective for severe psoriasisPUVA was quite effective for severe psoriasis
– 1970’s: 1970’s: broadband UVB also introduced broadband UVB also introduced BB UVB BB UVB IFIF given in doses that produce a slight given in doses that produce a slight erythemaerythema could clear mild psoriasis could clear mild psoriasis
Mechanisms of ActionMechanisms of Action of UVL of UVL
Reduction in skin proliferation (1st way):Reduction in skin proliferation (1st way):– UVL is absorbed by chromophoreUVL is absorbed by chromophore– The most important chromophore for UVB is DNAThe most important chromophore for UVB is DNA– Pyrimidine dimers are formedPyrimidine dimers are formed– These toxic photoproducts reduce DNA synthesisThese toxic photoproducts reduce DNA synthesis
Reduction in skin proliferation (2nd way):Reduction in skin proliferation (2nd way):– UVL induces the expression of p53 tumor suppressor UVL induces the expression of p53 tumor suppressor
genegene– p53 causes cell cycle arrest and/or apoptosis (cell death)p53 causes cell cycle arrest and/or apoptosis (cell death)
Mechanisms of ActionMechanisms of Action of UVL of UVL
Immunosuppressive effects:Immunosuppressive effects:– Induces Interleukin 6 and 10 (sunburn sxs)Induces Interleukin 6 and 10 (sunburn sxs)– Langerhans cells (antigen presenting cells) Langerhans cells (antigen presenting cells)
are inhibited by UVLare inhibited by UVL– Keratinocytes release IL-1 and 6, Keratinocytes release IL-1 and 6,
Prostaglandins E2 and TNF-Prostaglandins E2 and TNF-αα
Secretion of these compounds alters the Secretion of these compounds alters the local immune response and may local immune response and may contribute to suppression of diseasecontribute to suppression of disease
Action SpectrumAction Spectrum
The effectiveness of clearing psoriasis The effectiveness of clearing psoriasis plotted against wavelength is defined as plotted against wavelength is defined as the action spectrum of phototherapythe action spectrum of phototherapy
It is most desirable to use wavelengths (It is most desirable to use wavelengths (λλ) ) which are maximally therapeutic and which are maximally therapeutic and minimally erythemogenic minimally erythemogenic
Action SpectrumAction SpectrumStudies in the early 1980’s demonstrated that 304 and Studies in the early 1980’s demonstrated that 304 and 313nm had the optimal anti-psoriatic effect within the UVL 313nm had the optimal anti-psoriatic effect within the UVL spectrum:spectrum:
For wavelengths shorter then 295nm, no improvement in For wavelengths shorter then 295nm, no improvement in psoriasis occurred (remember shorter psoriasis occurred (remember shorter λλ’s are more ’s are more erythemogenic then therapeutic)erythemogenic then therapeutic)
304nm
313nm
Parrish, JA and Jaenicke, KF J Invest Dermatol 1981; 76: 359-362
<295nm
Action SpectrumAction SpectrumThe Philips Corp armed with the knowledge The Philips Corp armed with the knowledge regarding the action spectrum of psoriasis regarding the action spectrum of psoriasis develops a fluorescent lamp, TL 01, that emits the develops a fluorescent lamp, TL 01, that emits the optimal narrow band UVB frequency: 311-313nmoptimal narrow band UVB frequency: 311-313nm
Differences: Differences: broadband and narrowband UVBbroadband and narrowband UVB
NB UVB is much less erythemogenic then NB UVB is much less erythemogenic then BB UVBBB UVB– For example: 297nm is nearly For example: 297nm is nearly 100 times100 times more more
erythemogenic then erythemogenic then 313nm313nm radiation even radiation even though they are both in the UVB spectrumthough they are both in the UVB spectrum
Shown to be as effective as PUVA in the Shown to be as effective as PUVA in the treatment of psoriasistreatment of psoriasis
Theoretically safer then BB UVB or PUVATheoretically safer then BB UVB or PUVA
Pre-treatment Check List: UV TherapyPre-treatment Check List: UV TherapyReview the patient’s history (Snapshot)?Review the patient’s history (Snapshot)?– What disease is the MD treating?What disease is the MD treating?– Does the patient have co-morbidities that may Does the patient have co-morbidities that may
make UV contraindicated?make UV contraindicated?
Diseases Treated with UV Diseases Treated with UV
Psoriasis, psoriasis, and mostly psoriasisPsoriasis, psoriasis, and mostly psoriasisAtopic DermatitisAtopic DermatitisPMLEPMLEPruritus of renal failure Pruritus of renal failure Pruritus of liver Disease (e.g., PBC)Pruritus of liver Disease (e.g., PBC)SclerodermaSclerodermaIdiopathic Pruritus of unknown etiologyIdiopathic Pruritus of unknown etiologyCTCLCTCLVitiligoVitiligoEosinophilic folliculitis of HIVEosinophilic folliculitis of HIVWinter Mood Affective DisorderWinter Mood Affective Disorder
Pre-treatment Check List: UV TherapyPre-treatment Check List: UV TherapyReview the patient’s history (Snapshot)?Review the patient’s history (Snapshot)?– What disease is the MD treating?What disease is the MD treating?– Does the patient have co-morbidities that may Does the patient have co-morbidities that may
make UV contraindicated?make UV contraindicated?
UV AGRAVATED DISEASESUV AGRAVATED DISEASES
PMLEPMLESLESLEDLEDLESCLESCLESolar UrticariaSolar UrticariaXeroderma PigmentosaXeroderma PigmentosaChronic Actinic DermatitisChronic Actinic DermatitisCockayne’s Syndrome, BloomsCockayne’s Syndrome, BloomsPCTPCTDermatomyositisDermatomyositisPemphigusPemphigusActinic ReticuloidActinic ReticuloidActinic LPActinic LP
Pre-treatment Check List: UV TherapyPre-treatment Check List: UV TherapyReview the Medications List:Review the Medications List:– Are there any medications listed that are Are there any medications listed that are
photosensitizing?photosensitizing?– Will they be using any topical medications in Will they be using any topical medications in
conjunction with their UV therapy?conjunction with their UV therapy?DovonexDovonex
VecticalVectical
TazoracTazorac
– Are they taking any oral agents to facilitate their Are they taking any oral agents to facilitate their Rx?Rx?
Acitretin, IsotretinoinAcitretin, Isotretinoin
Medications known to Medications known to cause photosensitivitycause photosensitivityEvery light box facility should Every light box facility should have a list such as this one to have a list such as this one to cross check medications prior cross check medications prior to starting UVBto starting UVB
Examples include:Examples include:
Zanolli et al textbook: Zanolli et al textbook: Phototherapy Treatment Phototherapy Treatment Protocols (listed in KP Protocols (listed in KP protocol)protocol)
Litt’s Drug Eruption Reference Litt’s Drug Eruption Reference Manual will also listManual will also list
Pre-treatment Check List: UV TherapyPre-treatment Check List: UV Therapy
Labs:Labs:– Did the MD order any pre-treatment labs?Did the MD order any pre-treatment labs?
Physical Exam:Physical Exam:– Do you agree with the MD’s Fitzpatrick skin type Do you agree with the MD’s Fitzpatrick skin type
assessment?assessment?
Orders:Orders:– Do the orders make sense!Do the orders make sense!
Right protocol for the diseaseRight protocol for the disease
c/w published protocolsc/w published protocols
Broadband UVB vs. Narrow Band UVBBroadband UVB vs. Narrow Band UVB
How do you do it?How do you do it?
What mj do you start at?What mj do you start at?
How much do you increase at each visit?How much do you increase at each visit?
What happens if you miss a day, a week What happens if you miss a day, a week or a month?or a month?
What happens if the patient sunburns?What happens if the patient sunburns?
Do you ask if the patient started any new Do you ask if the patient started any new meds?meds?
Dosing determination for UVBDosing determination for UVB
Optimal done uses minimal erythema dose Optimal done uses minimal erythema dose determination (MED) for individual patients determination (MED) for individual patients by intricate phototestingby intricate phototesting
Not typical used by most Dermatologists Not typical used by most Dermatologists since it is time consuming and nurse since it is time consuming and nurse intensiveintensive
Most Dermatologists use schedules based Most Dermatologists use schedules based on the patients skin typeon the patients skin type
Fitzpatrick Skin TypeFitzpatrick Skin TypeFitzpatrick 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
Initial NB UVB Dosing Initial NB UVB Dosing based on Fitzpatrick Skin Typebased 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 PsoriasisUVB Phototherapy for Psoriasis
Ideally 3X a week (Dr. Koo recommends up Ideally 3X a week (Dr. Koo recommends up to 5X a week)to 5X a week)
Combination therapy is ideal!Combination therapy is ideal!
Calicipotriene + UVB 2X/week = UVB Calicipotriene + UVB 2X/week = UVB 3X/week3X/week
Tazarotene 3X/week added to UVB requires Tazarotene 3X/week added to UVB requires less than ¼ of UVB to achieve 50% PASIless than ¼ of UVB to achieve 50% PASI
Goeckerman, Anthralin, KeratolyticsGoeckerman, Anthralin, Keratolytics
Current Current KaiserKaiser Recommendations regarding Recommendations regarding Dose Escalation based on Skin Type for NB Dose Escalation based on Skin Type for NB
UVBUVB
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 Key Safety Points
Type of box:Type of box:– NB vs. BBNB vs. BB– For clinics with multiple boxes For clinics with multiple boxes
even if same light systemeven if same light system
we assign a pt to a particular box we assign a pt to a particular box
they always use that box even if they have to wait!they always use that box even if they have to wait!
Remember units matter:Remember units matter:– 800 milljoules vs. 800 Joules800 milljoules vs. 800 Joules
………….Burn Unit!!!.Burn Unit!!!
Not all UV light is EqualNot all UV light is Equal
Minim al Erythem a Dose MED for Skin Type III
3J/ cm UV A 30 m J/cm UV BBroad band
200-300 m J UV BNarrow band
20-30 m ins sunl ightNYC in S um m er
Noontim e
M E D
Key Safety PointsKey Safety Points
Physicians should order the UVB in Physicians should order the UVB in Health Connect using the units that you Health Connect using the units that you will enter into the box (i.e., avoid unit will enter into the box (i.e., avoid unit conversion issues: how many conversion issues: how many millijoules = a joule?)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 ProtocolsNB UVB ProtocolsRemember different diseases use different Remember different diseases use different protocolsprotocols– Vitiligo protocol Vitiligo protocol quitequite different then psoriasis different then psoriasis– Atopic dermatitis protocol different then Atopic dermatitis protocol different then
psoriasis (e.g., much lower max dose)psoriasis (e.g., much lower max dose)
Remember the Kaiser Permanente protocol Remember the Kaiser Permanente protocol is a quite conservative NB UVB protocol for is a quite conservative NB UVB protocol for the treatment of psoriasis imho the treatment of psoriasis imho When in doubt whether the protocol is When in doubt whether the protocol is appropriate for the disease being treated appropriate for the disease being treated ask the ordering MD to verify!ask the ordering MD to verify!
Vitiligo NB UVB ProtocolVitiligo NB UVB ProtocolTreatment frequency is typically twice weeklyTreatment frequency is typically twice weekly
Start at all patients at 200 mJ/ cmStart at all patients at 200 mJ/ cm22
Incremental DosingIncremental Dosing– If skin was pink the previous night If skin was pink the previous night andand::
Pink now: Skip treatment & notify the MDPink now: Skip treatment & notify the MD
Not Pink now: Treat at same doseNot Pink now: Treat at same dose– If skin was not pink the previous night:If skin was not pink the previous night:
Increase by 50 mJ/cmIncrease by 50 mJ/cm22
Maximum dose is 500-800 mJ /cmMaximum dose is 500-800 mJ /cm22
Missed Treatments of NBUVB for Vitiligo:Missed Treatments of NBUVB for Vitiligo:4-7 days4-7 days 100% (same as last dose)100% (same as last dose)
8-14 days8-14 days decrease dose by 50%decrease dose by 50%
15-21 days15-21 days start overstart over
© 2003 Elsevier - Bolognia, Jorizzo and Rapini: Dermatology - www.dermtext.com
Fig. 134.5 Narrowband phototherapy for vitiligo.
Before treatment after 10 mos of NB UVB twice weekly
What’s New in PhototherapyWhat’s New in Phototherapy
Narrow Band UVB 311Narrow Band UVB 311
UVA – 1UVA – 1
Photodynamic TherapyPhotodynamic Therapy– Blue LightBlue Light– Red LightRed Light
Excimer LaserExcimer Laser
New LasersNew Lasers
UV FACTSUV FACTS
UV is a discrete, oscillating UV is a discrete, oscillating electromagnetic pulse of energy, E (joules, electromagnetic pulse of energy, E (joules, J) and a wavelength, lambda (nanometres, J) and a wavelength, lambda (nanometres, nm, 10 -9nm, 10 -9thth m), travelling through space at m), travelling through space at velocity, c (3x10 8velocity, c (3x10 8thth m/s), such that m/s), such that E=hc/lambda, where h= 6.63 X 10 -34E=hc/lambda, where h= 6.63 X 10 -34thth J/s (Planck’s Constanat).J/s (Planck’s Constanat).
Common TermsCommon Terms
Watt (W) = Unit of powerWatt (W) = Unit of power
Energy (Joules) = Power (W) x time (sec)Energy (Joules) = Power (W) x time (sec)– Joule (J) = Unit of energyJoule (J) = Unit of energy– 1000 Millijoules (mJ) = 1 Joule1000 Millijoules (mJ) = 1 Joule
Fluence (Dose) = Energy delivered to a Fluence (Dose) = Energy delivered to a unit area (J/cmunit area (J/cm22 ) )
Irradiance = Power delivered to a unit area Irradiance = Power delivered to a unit area (W/m(W/m22))