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

UVB ProtocolUVB Protocol

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

Example of MED determination NB UVB

UVB Treatment Protocol Using MED

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

Fitzpatrick Skin Type?Fitzpatrick Skin Type?

Fitzpatrick Skin Type IFitzpatrick Skin Type I

Fitzpatrick Skin Type?Fitzpatrick Skin Type?

Fitzpatrick Skin Type IIFitzpatrick Skin Type II

Fitzpatrick Skin Type?Fitzpatrick Skin Type?

Fitzpatrick Skin Type IIIFitzpatrick Skin Type III

Fitzpatrick Skin Type?Fitzpatrick Skin Type?

Fitzpatrick Skin Type IVFitzpatrick Skin Type IV

Fitzpatrick Skin Type?

Fitzpatrick Skin Type V & Type III

Fitzpatrick Skin Type?Fitzpatrick Skin Type?

Fitzpatrick Skin Type VIFitzpatrick Skin Type VI

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!!!

Two different boxes with two different input metrics

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!

Thank You!Thank You!

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))