British Association of Dermatologists and British Photodermatology Group Guidelines for the Safe and Effective Use of Psoralen–Ultraviolet A Therapy 2015

T.C. Ling; T.H. Clayton; J. Crawley; L.S. Exton; V. Goulden; S. Ibbotson; K. McKenna; M.F. Mohd Mustapa; L.E. Rhodes; R. Sarkany; R.S. Dawe

Disclosures

The British Journal of Dermatology. 2016;174(1):24-55.

Purpose and Scope

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the use of psoralen–ultraviolet A (PUVA) photochemotherapy. The document aims to update and expand on the previous guidelines by (i) offering an appraisal of all relevant literature since 1990, focusing on any key developments; (ii) addressing important, practical clinical questions relating to the primary guideline objective; (iii) providing guideline recommendations and, where appropriate, with some health economic implications; and (iv) discussing potential developments and future directions.

The guideline is presented as a detailed review with highlighted recommendations for practical use in the clinic (see section 15.0), in addition to the production of a patient information leaflet [available on the British Association of Dermatologists' (BAD) website, http://www.bad.org.uk].

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Cite this: British Association of Dermatologists and British Photodermatology Group Guidelines for the Safe and Effective Use of Psoralen–Ultraviolet A Therapy 2015 - Medscape - Jan 01, 2016.

Table 1. Advantages of oral vs. topical psoralen–ultraviolet A therapy (PUVA)
Advantages of oral PUVA	Advantages of topical PUVA
Shorter overall outpatient attendance times	No risk of gastrointestinal adverse effects
Less staff involvement	Drug interactions unlikely
Less risk of phototoxic reactions from natural UV exposure (lower concentration of psoralen in the skin after treatment)	Eye protection not always required
Only practical option for whole-body treatment for units with inadequate bath facilities	Shorter periods in treatment cubicle due to smaller dose of UVA

UV, ultraviolet; UVA, ultraviolet A.

Table 2. Controlled studies comparing whole-body topical psoralen–ultraviolet A ('bath PUVA') with oral PUVA
First author (year of publication)	Bath psoralen	Oral psoralen	UVA regimen	Randomized?	Blinded?	Proportion (%) cleared with oral PUVA	Proportion (%) cleared with bath PUVA	Difference (% more clearing with oral PUVA); 95% CI for difference
Turjanmaa (1985)¹²	TMP 3 mg L⁻¹	8-MOP 0·6 mg kg⁻¹	Arbitrary starting doses; three times weekly; incremental regimen not reported	No	No	37/43 (86)	42/50 (84)	2; −12 to 17
Lowe (1986)¹³	3·75 mg L⁻¹	8-MOP 0·6 mg kg⁻¹	Skin phototype-based starting dose and incremental regimen	No	No	8/20 (40)	8/20 (40)	0; −30 to 30
Collins (1992)¹⁰	8-MOP 3·78 mg L⁻¹	8-MOP 0·6 mg kg⁻¹	Skin phototype-based starting doses; three times weekly; no more than 20 treatments	Yes (but allocation not concealed)	No	14/22 (64)	14/22 (64)	0; −28 to 28
Cooper (2000)¹¹	8-MOP 2·6 mg L⁻¹	8-MOP 0·6 mg kg⁻¹	70% MPD starting dose; twice weekly; percentage-based incremental regimen	Yes (but allocation not concealed)	No	14/17 (82)	17/17 (100)	−18; −36 to 0·5

UVA, ultraviolet A; CI, confidence interval; TMP, trimethylpsoralen; 8-MOP, 8 methoxypsoralen; MPD, minimal phototoxic dose.

Table 3. Incidence of side-effects with different phototherapy
Phototherapy type	Rash provocation (%)	Erythema (%)	Pruritus (%)	Herpes simplex (%)
PUVA	12–50	8–67	18–33	–
NB-UVB	62	54	15	–
BB-UVB	53	27	40	20

PUVA, psoralen–ultraviolet A; NB-UVB, narrowband ultraviolet B; BB-UVB, broadband ultraviolet B.

Table 4. Recommendations in particular clinical situations
Psoriasis	All dermatology phototherapy units should offer bath PUVA, as well as oral PUVA to treat psoriasis (strength of recommendation B)
	PUVA should usually be offered before oral systemic therapy for patients with chronic plaque psoriasis that has not responded adequately to other therapies, including narrowband UVB (strength of recommendation B)
	PUVA should be considered before biological therapy to treat chronic plaque psoriasis (strength of recommendation C)
	Although PUVA may occasionally be appropriate as a first-line phototherapy treatment for especially thick and/or extensive plaque psoriasis it should usually only be considered in patients with chronic plaque psoriasis, if NB-UVB has not been adequately effective (strength of recommendation B)
Atopic eczema	PUVA should be considered in patients with atopic eczema only if NB-UVB has not been adequately effective (strength of recommendation D)
CTCL of the MF type	PUVA is the first-line treatment for plaque-stage CTCL (strength of recommendation B)
	Maintenance therapy may be considered to prevent relapse in quickly recurrent plaque-stage CTCL (strength of recommendation D)
	NB-UVB is as effective as PUVA and is the treatment of choice for patch-stage CTCL (strength of recommendation D)
	Combination therapy with PUVA and IFN or retinoids/rexinoids should be considered in the treatment of early stage MF, if the response to monotherapy is slow (strength of recommendation B)
Vitiligo	PUVA should only be considered for widespread vitiligo if NB-UVB has been not shown to be adequately effective (strength of recommendation A)
PLE	PUVA should be considered if UVB has failed, or has previously triggered the eruption sufficiently to compromise a course of therapy, or if there are other practical issues. PUVA should be considered before other systemic treatments (strength of recommendation D)
CAD	In the treatment of CAD, PUVA should be considered in a specialist unit experienced in managing this disease, with full knowledge of the individual patient's action spectrum. Special precautions, including inpatient supervision and topical/oral corticosteroid cover, may be required (strength of recommendation D)
Idiopathic SU	In the management of SU (after full assessment, including definition of the action spectrum), PUVA can be considered. The treatment should be carried out with full knowledge of the patient's action spectrum, in a specialist unit experienced in managing this disease (strength of recommendation D)
EPP	PUVA is rarely appropriate in EPP; NB-UVB is the phototherapy of first choice (strength of recommendation D)
AP	NB-UVB may be a safer therapeutic option in terms of phototherapy-associated carcinogenic risk in patients with AP, particularly in children, and should be considered before PUVA (strength of recommendation D)
Hyperkeratotic palmoplantar eczema	Oral PUVA should usually be considered as the first-line PUVA treatment for patients with palmoplantar dermatoses [strength of recommendation D (GPP)]
Palmoplantar psoriasis	PUVA using topical or oral psoralen should be considered as a treatment for palmoplantar psoriasis (strength of recommendation C)
Palmoplantar pustulosis	PUVA using oral psoralen should be considered as a treatment for palmoplantar pustulosis (strength of recommendation C)
Palmoplantar pustulosis	Unless there are contraindications, the combination of oral PUVA with oral retinoids should be considered as a treatment for palmoplantar pustulosis (strength of recommendation A)
Pregnancy	It is recommended that female patients should avoid conception during PUVA therapy and that if despite this advice pregnancy does occur, PUVA should be discontinued (strength of recommendation D)

PUVA, psoralen–ultraviolet A; UVB, ultraviolet B; NB-UVB, narrowband UVB; CTCL, cutaneous T-cell lymphoma; MF, mycosis fungoides; IFN, interferon; PLE, polymorphic light eruption; CAD, chronic actinic dermatitis; SU, solar urticaria; EPP, erythropoietic protoporphyria; AP, actinic prurigo; GPP, good practice point.

Appendix

Levels of evidence

Level of evidence	Type of evidence
1++	High-quality meta-analyses, systematic reviews of RCTs or RCTs with a very low risk of bias
1+	Well-conducted meta-analyses, systematic reviews of RCTs or RCTs with a low risk of bias
1–	Meta-analyses, systematic reviews of RCTs or RCTs with a high risk of bias^a
2++	High-quality systematic reviews of case–control or cohort studies
2++	High-quality case–control or cohort studies with a very low risk of confounding, bias or chance, and a high probability that the relationship is causal
2+	Well-conducted case–control or cohort studies with a low risk of confounding, bias or chance, and a moderate probability that the relationship is causal
2−	Case–control or cohort studies with a high risk of confounding, bias or chance, and a significant risk that the relationship is not causal^a
3	Nonanalytical studies (e.g. case reports, case series)
4	Expert opinion, formal consensus
RCT, randomized controlled study. ^aStudies with a level of evidence '−' should not be used as a basis for making a recommendation.

Strength of recommendation

Class	Evidence
A	At least one meta-analysis, systematic review or RCT rated as 1++, and directly applicable to the target population
	A systematic review of RCTs or a body of evidence consisting principally of studies rated as 1+, directly applicable to the target population and demonstrating overall consistency of results
	Evidence drawn from a NICE technology appraisal
B	A body of evidence including studies rated as 2++, directly applicable to the target population and demonstrating overall consistency of results
B	Extrapolated evidence from studies rated as 1++ or 1+
C	A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results
C	Extrapolated evidence from studies rated as 2++
D	Evidence level 3 or 4
	Extrapolated evidence from studies rated as 2+
	Formal consensus
D(GPP)	A good practice point (GPP) is a recommendation for best practice based on the experience of the guideline development group
RCT, randomized controlled trial; NICE, National Institute for Health and Care Excellence.

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British Association of Dermatologists and British Photodermatology Group Guidelines for the Safe and Effective Use of Psoralen–Ultraviolet A Therapy 2015

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