Sally H. Ibbotson

Guidelines for topical photodynamic therapy: report of a workshop of the British Photodermatology Group

Summary Topical photodynamic therapy (PDT) is effective in the treatment of certain non‐melanoma skin cancers and is under evaluation in other dermatoses. Its development has been enhanced by a low rate of adverse events and good cosmesis. 5‐Aminolaevulinic acid (ALA) is the main agent used, converted within cells into the photosensitizer protoporphyrin IX, with surface illumination then triggering the photodynamic reaction. Despite the relative simplicity of the technique, accurate dosimetry in PDT is complicated by multiple variables in drug formulation, delivery and duration of application, in addition to light‐specific parameters. Several non‐coherent and coherent light sources are effective in PDT. Optimal disease‐specific irradiance, wavelength and total dose characteristics have yet to be established, and are compounded by difficulties comparing light sources. The carcinogenic risk of ALA‐PDT appears to be low. Current evidence indicates topical PDT to be effective in actinic keratoses on the face and scalp, Bowens disease and superficial basal cell carcinomas (BCCs). PDT may prove advantageous where size, site or number of lesions limits the efficacy and/or acceptability of conventional therapies. Topical ALA‐PDT alone is a relatively poor option for both nodular BCCs and squamous cell carcinomas. Experience of the modality in other skin diseases remains limited; areas where there is potential benefit include viral warts, acne, psoriasis and cutaneous T‐cell lymphoma. A recent British Photodermatology Group workshop considered published evidence on topical PDT in order to establish guidelines to promote the efficacy and safety of this increasingly practised treatment modality.

Topical methyl aminolaevulinate photodynamic therapy versus cryotherapy for superficial basal cell carcinoma: a 5 year randomized trial

This multicentre, randomized study compared photodynamic therapy using topical methyl aminolaevulinate (MAL PDT), a non-invasive modality, with cryotherapy for treatment of superficial basal cell carcinoma. Sixty patients with 114 lesions were treated with MAL cream (160 mg/g) applied for 3 hours before illumination (570-670 nm, light dose 75 J/cm) (1 session), and 58 with 105 lesions received cryotherapy (2 freeze-thaw cycles). Patients with an incomplete response at 3 months received 2 further MAL PDT sessions (n = 20) or repeat cryotherapy (n = 16). 100 lesions treated with MAL PDT and 93 lesions treated with cryotherapy were in complete response at 3 months after the last treatment and evaluable for recurrence over 5 years. There was no difference in 5-year recurrence rates with either treatment (20% with cryotherapy vs. 22% with MAL PDT, p = 0.86). However, more patients had an excellent cosmetic outcome with MAL PDT (60% vs. 16% with cryotherapy, p = 0.00078). These results provide support for the use of MAL PDT as a non-invasive, selective treatment alternative for primary superficial basal cell carcinoma.

Topical 5-aminolaevulinic acid photodynamic therapy for cutaneous lesions: outcome and comparison of light sources

Background: Topical 5‐aminolaevulinic acid (ALA) photodynamic therapy (PDT) is increasingly used for superficial non‐melanoma skin cancers and their precursors.

Cutaneous expression of cytochrome P450 CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases

BACKGROUND Treatment of common skin diseases such as psoriasis is complicated by differences between individuals in response to topical drug treatment and photochemotherapy. Individuality in hepatic expression of drug-metabolising enzymes is an important determinant of systemic drug handling; we investigated whether similar variation in cutaneous gene expression contributes to individuality in response to topical therapies. METHODS We used quantitative real-time RT-PCR to demonstrate the expression in skin of a recently identified cytochrome P450, CYP2S1, in healthy volunteers (n=27) and patients with psoriasis (n=29). We also investigated regulation of CYP2S1 by ultraviolet radiation, psoralen-ultraviolet A (PUVA), and topical drugs used to treat psoriasis. FINDINGS We found that CYP2S1 is expressed in skin and showed pronounced individuality in constitutive expression of the enzyme and its induction after ultraviolet irradiation or topical drug treatment. Cutaneous expression of CYP2S1 was induced by ultraviolet radiation, PUVA, coal tar, and all-trans retinoic acid; expression was significantly higher in lesional psoriatic skin than in adjacent non-lesional skin (geometric mean 3.38 [95% CI 2.64-4.34] times higher; p<0.0001), which implies that topical drugs are differentially metabolised in psoriatic plaque and non-lesional skin. We showed that all-trans retinoic acid is metabolised by CYP2S1, which has higher cutaneous expression than CYP26, previously described as the specific cutaneous P450 retinoic-acid-metabolising enzyme. INTERPRETATION These findings increase our understanding of the interaction between therapeutic agents and the skin and suggest a functional role for CYP2S1 in the metabolism of topical drugs and in mediating the response to photochemotherapy in psoriasis.

A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8-20 mm), with a 12-month follow-up.

Objective  To compare the efficacy and cosmetic outcome (CO) of photodynamic therapy with topical methyl aminolevulinate (MAL‐PDT) with simple excision surgery for superficial basal cell carcinoma (sBCC) over a 1‐year period.

The photocarcinogenic risk of narrowband UVB (TL-01) phototherapy: early follow-up data.

Background  Limited information is available on the carcinogenic risk associated with narrowband TL‐01 UVB phototherapy in humans.

Topical 5-aminolaevulinic acid photodynamic therapy for the treatment of skin conditions other than non-melanoma skin cancer.

Summary  Topical 5‐aminolaevulinic acid (ALA) photodynamic therapy (PDT) is used increasingly for superficial non‐melanoma skin cancer (NMSC) and dysplasia. However, the relative accumulation of the photosensitizer protoporphyrin IX (PpIX) in diseased tissue is not specific for neoplastic disease, and has been shown after the application of ALA to benign proliferative skin conditions such as viral warts and psoriasis. This review appraises the quality of evidence available for the use of topical ALA–PDT in the treatment of skin conditions other than NMSC. The diseases that have been studied in most detail are recalcitrant viral warts, acne, psoriasis and cutaneous T‐cell lymphoma. Publications relating to the treatment of other diseases by topical PDT are restricted to small case series or case reports. The relevant literature will be discussed and the potential for topical PDT in the treatment of several skin diseases is highlighted, although more detailed studies are required to clarify the role of PDT beyond the treatment of NMSC.

A randomized, double‐blind, placebo‐controlled study of the efficacy of tetracaine gel (Ametop®) for pain relief during topical photodynamic therapy

Background  Many patients find topical 5‐aminolaevulinic acid (ALA) photodynamic therapy (PDT) painful. Local anaesthetics are not routinely used and their effect on PDT pain has not been examined.

A pilot study of treatment of lentigo maligna with 5% imiquimod cream.

Background  Lentigo maligna (LM) is an in situ form of malignant melanoma, and surgical excision is often unsatisfactory. Imiquimod cream is an immune response modifier and induces a predominantly T‐helper 1 type response.

Photopatch testing: a consensus methodology for Europe

A group of interested European Contact Dermatologists/Photobiologists met to produce a consensus statement on methodology, test materials and interpretation of photopatch testing. While it is recognized that a range of local variables operate throughout Europe, the underlying purpose of the work is to act as an essential preamble to a Pan European Photopatch Test Study focusing particularly on sunscreen chemicals.