Phototherapy Flashcards
(45 cards)
1
Q
Broadband
A
290-320 nm
2
Q
NBUVB range
A
311-313 nm
3
Q
Excimer laser range
A
308 nm
4
Q
UVA1 range
A
340-400 nm
5
Q
UVA2 range
A
320-400 nm
6
Q
St Johns Insitute recommendation for NBUVB starting dose for psoriasis
A
In mJ/cm^2
1: 100, first 3 increments 40, then 20%
2. 120, first 3 increments 50, then 20%
3. 150, first 3 increments 60, then 20%
4. 200, first 3 increments 80, then 20%
5. 300, first 3 increments 120, then 20%
6. 500, first 3 increments 200, then 20%
7
Q
Which wavelengths increase risk of cataracts
A
295-320, with 300 nm representing the most potent wavelength
8
Q
NBUVB twice a week instead of thrice a week means what
A
It takes 1.5 times longer to achieve clearance than thrice weekly - 88 days versus 58
9
Q
According to JAAD guidelines, what dose should skin types 5 and 6 be started on for psoriasis
A
800 mJ/cm^2
10
Q
According to JAAD guidelines, with NBUVB what should you do for each week a patient misses a dosage
A
1 week - hold dose
1-2 weeks - drop by 25%
2-4 weeks - drop by 50%
>4 weeks: return to starting dose
11
Q
What would maintenance therapy be with the JAAD guidelines for psoriasis
A
twice a week for 4 weeks, then once a week for 4 weeks
12
Q
Maximum doses for NBUVB
A
1 & 2: 2000
3 and 4: 3000
5 and 6: 5000
13
Q
JAAD guideline recommendations for vitiligo
A
3.X a week
Starting dose 200 mJ/cm^2 regardless of skin type, increase by 10-20% per treatment
Maximum facial dose 1500, body 3000
Need at least 48 before start to see improvement
No erythema - can increase by 10-20%, but if erythema then hold
Missing guidelines same as psoriasis, except if >3 weeks go back to start
If device calibration occurs: decrease by 10-20%
14
Q
JAAD guideines vitiligo maintenance
A
Twice a week for a month, then once a week for a month, then once a fortnight for 2 wmonths
15
Q
Excimer laser indications
A
Targeted areas: psoriasis, GA, LP, lichen sclerosis, alopecia areata, palmoplantar psoriasis and pustulosis
16
Q
What is turbo uvb
A
Administration of high dose excimer laser - 6-10 X a patient’s MED –> effective in preliminary study of plaque psoriasis
17
Q
Starting dose for targeted therapy for psoriasis
A
Mildly thick: 300 in FP1-3, 400 in 4-6
Moderate: 500 in FP1-3, 600 in 406
Severe: 700 FP1-3, 900 in 4-6
No erythema incr by 25%, slight erythema 15%, mild-mod maintain dose
Severe: reduce dose by 25%
18
Q
UVA1 indications
A
- Eczema
- Localized scleroderma
- Systemic sclerosis
- Urticaria pigmentosa
- CTCL
- Dyshidrotic eczema
- Other: PRP, HES, pit rosea, PLEVA, scleredema
19
Q
UVA1 MOA
A
- ability to penetrate the dermis deeper than UVB: working on dendritic cells, fibroblasts, mast cells, T and B lymphocytes
- Thought to induce T cell apoptosis, suppress proinflammatory cytokines, and upregulate MMPs such as collagenase produced by dermal fibroblasts –> increased collagen breakdown for sclerotic skin
20
Q
UVA1 dosing regimens
A
- Low dose UVA1 refers to 10-20 J/cm2 per single dose.
- Medium dose UVA1 refers to 50-60 J/cm2 per single dose.
- High dose UVA1 refers to 130 J/cm2 per single dose.
21
Q
Light sources for UVA1
A
- Generated by fluorescent tubes or filtered metal halide lamps that filter out UVA2
- Fluorescent lamps can deliver 20 mW/cm^2
- Metal-halide units can do 40-60
- Not efficient due to their broad spectrum of 200-500 nm and need for 3 filters to get rid of the unneccessary wavelengths
- Light emitting diodes are being investigated
22
Q
Dosing for UVA1
A
- Half dose of UVA1 is used as a provocation challeng to assess sensitivity to UVA1 –> if no erythema develops then can proceed with required dose
- Treatment ranges from 10 minutes to 1 hour
- 3-5 times a week
- Dosing is held constant throughout the treatment
23
Q
UVA1 a/e
A
- Mild:
- Hyperpigmentation
- Erythema
- Xerosis and pruritus
- Skin darkening
- Moderate:
- Phototoxicity has been reported, although less erythemoegnic than UVA2
- HSV reactivation
- PMLE
- No severe a/e reported
- Overall less severe than UVB and UVA2
- Long term
- Photoaging and photocarcinogenesis (latter not fully explored with evidence yet, but theoretical)
- Until we know more abuot it, should be limited to treating diseases with periods of severe, acute exacerbations and in general, one treatment cycle should not exceed 15-20 successively administered exposures, and should not be repeated more than once or twice a year (once Bolognia, twice Dermnet)
24
Q
What plant does psoralens come from
A
Apiaceae and Rutaceae families: fig, lime, celery, parsnip
25
Pharmacokinetics of psoralens oral
- Variable absorption:
- dissolved preparations are better absorbed than micronized, crystalline formulations
- Food intake reduces absorption
- Interindividual variability: first-pass effect may vary
- Serum levels correlate with skin reactivity, epidermis is proportional to skin reactivity
- Distribution: 75-80% reversibly bound to serum albumin, rapidly distributed to all organs. Without UBA, the binding is short lived and it is rapidly metabolized
- Metabolized: liver
- Excreted: urine
- Drug interactions: those that induce CYP450 accelerate metabolism
26
Topical psoralens MOA
- Depends on method of aplication
- Methoxsalen 0.15% emulsion or solution applied topically to large body areas leads to plasma levels comparable to oral administration
- Whole body bath PUVA: plasma levels are very low, bathwater delivered psoralens are readily absorbed in the skin but promptly eliminated without cutaneous accumulation. So readily absorbed in skin, but promptly eliminated without cutaneous accumulation
27
Psoralen MOA
- Penetrate into cells and intercalate between DNA base pairs in absence of UV exposure
- Once UVA exposure: psoralen molecules absorb photons: become chemically activated and covalently bond with DNA base pairs producing interstrand crosslinks of the double helix
- The DNA crosslinking suppresses DNA synthesis and mitoses, causing cell apoptosis through p53 pathway activation
- Cells with sublethal damage are able to repair the DNA, resulting in mutagenesis and photocarcinogenesis
- Also interferes with other cells like mitochondria and produces ROS
28
Suggested doses of 8MOP
Soft gelatin capsule: 0.4 mg/kg 1 hour prior
Hard gelatin capsule: 0.6 mg/kg 2 hours prior
Lotion: 10 mg/mL lotion diluted 1:10 with ethanol to deliver 0.1% strength
29
MOA of PUVA
1. Inhibition of cell proliferation: interferes with mTOR signaling
2. Immunosuppression: cytokine interference, lymphocyte apoptosis
3. Melanogenesis: stimulated melanocyte proliferation, melanogenesis and transfer of melanosomes to keratinocytes
30
PUVA photosensitivity
- Delayed photoxic erythem
- Usually appears 36-48 horus after exposure to UVA, peak 48-96 hours later or even up to 120 hours
- Erythema intensity proportional to dose of psoralen and UVA radiation
- Occurs in ~ 10% of patients
- Excessive doses: blistering, intense pruritus, skin pain
- Pigmentation
- Can occur without erythema - less so with 8-MOP
- Peaks ~ 7 days post exposure and can last weeks-months
- Tan is deep
31
Difference between soft gelatin and hard gelatin methoxsalen
Soft absorbed faster, more likely to be nausea
32
Oral PUVA dosage and increments
- MPD: barely perceptible but well defined erythema when template areas of skin are exposed to increasing doses of UVA after psoralen ingestion
- Erythema reading at 48 or 72 hours, although St Johns Guidelines say review at 96 hours for PUVA, test doses usually not required if localized
- Treatment is then started at 50-70% of MPD
If no erythema increase by 0.5-1 J/cm^2
33
Does the whole body respond the same with oral PUVA
No - trunk responds quicker, may need to increase dosage for limbs, or cover trunk when clears
34
Bath PUVA infor
- becoming more popular because it provides uniform drug distribution and bypasses GIT and potential ocular effects
- Whole body immersion or localized skin soaking in 0.5-3 mg/L solution of methoxsalen for 15-30 minutes
- UVA occurs immediately after
- Eye protection still required since its detectable in blood
- Not widely available
- Long term effects not know
- Skin psoralen levels are highly reproducible, and photosensitivy lasts no more than 2 hourrs
- Peak erythema is delayed to 96-120 hours
- Have a lower starting dose
- 15-20 minutes whole body immersion in solution 0.5-5 mg of 8-MOP per litre of bath water
- Irradiation imediately after
- TMP more phototoxic after topical, so used in lower concentration, and phototoxic threshold declines during early treatment
35
Topical PUVA info
- Alternative, for limited plaque or palmoplantar psoriasis, hand eczema or localized vitiligo
- 8-MOP 0.1-0.01% creams/ointments/lotions
- For example: methoxsalen 1% lotion can be diluted 1:10 with ethanol to yield a 0.1% solution that is applied to affected skin 15 minutes before exposure to UVA radiation
- Vitiligo: initial exposure 0.5 J, and increase by 0.25 until light pink erythema is achieved, then can hold at this level, or just adjust with goal of maintaining a faint erythema
- Disadvantages:
- Non-uniform distribution on skin surface
- Unpredictable phototoxic erythema reactions
- Inadvertant application to uninvolved skin
- Hyperpigmentation
- Laborious and time consuming
- Can cause increase in plasma levels
- Mainly just do for psoriasis
36
Safety measures for PUVA
- Eye goggles, then wraparound UV blocking glasses should be worn when the patient is exposed to sunlight until sunset that same day
- Photoprotection of face: SPF50 or cloth barrier, sun avoidance. Fluorescent lights at home don't have any effects
- Male genitalia: underwear
37
PUVA drug interactions
- Phototoxic drugs: thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides and topicals - anthralin or coal
- Warfarin and phenytoin --> do not give
- Retinoids ok, start PUVA 14 days after patient starts taking, if added during course then keep dosage same for 14 days
38
PUVA contraindications
Absolute
Xeroderma pigmentosum
Lupus erythematosus with photosensitivity or positive Ro antibody
Pregnancy (category C)
Lactation
Relative
Photosensitivity and/photosensitizing medications
History or family history of melanoma
History of nonmelanoma skin cancer and/or extensive solar damage
Previous treatment with ionizing radiation or arsenic
Severe liver, renal, or cardiac disease
Young age
Not contraindicated in cataracts or aphakia because the cataracts are protection of the retina
39
PUVA a/e
- 8-MOP causes nausea 30% and vomiting 10%, more common with liquid than crystalline preparations
- Take with small amount of food with high fat content or milk
- If nausea persists, can drop methoxsalen to 10 mg
- Ginger and anti-emetics
- No evidence causes liver problems
- ?ANA positivity
Short term:
- Redness, swelling
- Pruritus: PUVA itch - often with erythema, and deep burning itch --> thought to be phototoxic damage of dermal nerve endings. Treat symptomatically. Generally begins outer aspect of arms, thighs, buttocks and breasts. Discontinue PUVA and then resume after 1-3 weeks with 10-20% reduced dose
- Pain: thought to be dermal nerve damage too
- Blistering
- Subacute phototoxicity: widespread scaly erythema accompanied by intense pruritus, may occur at any point during treatment, spares areas not exposed to UVA
- Cease PUVA
- Emollients, cool baths, antiprurituc
- Resume at 30-40% lower than last dose
- Excessive pigmentation
- Systemic: fever, malaise
- can treat with NSAIDs, topical steroids and prednisone
- Ocular
- Require ocular lens
- Could induce cataracts by forming psoralen protein photoproducts
- Other: HSV, bronchoconstriction, drug fever, tachcyardia, photo-onycholysis, melanonychia, friction blisters, ankle oedema. CNS: headache, dizziness, depression, insomnia, hyperactivity
Long-term
- Actinic damage
- Photoaging: hypertrichosis as well
- Pigmentary changes, xerosis, loss of elasticity, wrinkle formation
- Dark, stellate lentigines - PUVA lentiginosis, no risk of melanoma identified
- Risk of SCC - high levels of UVB exposure appear to increase the risk in PUVA-treated patients
- <150 treatments had a modest effect on SCC risk
- Men at increased risk of genital skin cancer
- Jury is out on melanoma risk
40
St Johns Guidelines for bath PUVA dosage
Bath PUVA: 30 mL of 8-MOP 1.2% added to 100 L of water at 37 degrees, patient is immersed for 15 minutes, then immediate PUVA, no need to shower but sunscreen to areas
FP1: 0.1 J, 2 is 0.2 J, and so forth
If used MPD, increment 20%, max dose 8
41
St Johns Guidelines for Gel PUVA
Gel PUVA: 0.005% gel applied to disease area using a gloved hand, UV exposure 30 mins later
42
St Johns Guidelines for oral PUVA
8-MOP taken 2 hours before, at a dose of 25 mg/m^2 --> calculate BSA with a nomogram
43
St Johns Guidelines for missed treatment with PUVA
- <7 days no change
- 8-10 repeat last dose
- 11-15 - reduce dose by 20%, or if this is below the starting dose, give the starting ose
- 16-20 - reduce by 35%, or starting dose if higher
- 21+ - give a dose wbetween the starting dose and 50% of previous dose, depending on skin type etc
44
St Johns Guidelines recommended oral PUVA dosage commencement with 8-MOP without MPD
1: 0.5 J, incr by 0.5
2: 1 J, incr by 1 J
3. 1.5 J, incr by 1.5
4. 2 J, incr by 2 J
5: 2.5 J, incr by 2 J
6: 3 J, incr by 2.5 J
Or if use MPD, 70% of that, increment by 20%, max 15 J/cm^2
45
St Johns - maximum dosage for PUVA
```
Oral: 15 J
Bath: 8 J
Oral for vitiligo: 5
Bath for vitiligo: 1
Gel for vitiligo: 1
Han foot immersion: 8
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