Lesley E. Rhodes

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.

Guidelines for topical photodynamic therapy: update.

Multicentre randomized controlled studies now demonstrate high efficacy of topical photodynamic therapy (PDT) for actinic keratoses, Bowen’s disease (BD) and superficial basal cell carcinoma (BCC), and efficacy in thin nodular BCC, while confirming the superiority of cosmetic outcome over standard therapies. Long‐term follow‐up studies are also now available, indicating that PDT has recurrence rates equivalent to other standard therapies in BD and superficial BCC, but with lower sustained efficacy than surgery in nodular BCC. In contrast, current evidence does not support the use of topical PDT for squamous cell carcinoma. PDT can reduce the number of new lesions developing in patients at high risk of skin cancer and may have a role as a preventive therapy. Case reports and small series attest to the potential of PDT in a wide range of inflammatory/infective dermatoses, although recent studies indicate insufficient evidence to support its use in psoriasis. There is an accumulating evidence base for the use of PDT in acne, while detailed study of an optimized protocol is still required. In addition to high‐quality treatment site cosmesis, several studies observe improvements in aspects of photoageing. Management of treatment‐related pain/discomfort is a challenge in a minority of patients, and the modality is otherwise well tolerated. Long‐term studies provide reassurance over the safety of repeated use of PDT.

An update and guidance on narrowband ultraviolet B phototherapy: a British Photodermatology Group Workshop Report.

Summary These guidelines for use of narrowband (TL‐01) ultraviolet B have been prepared for dermatologists by the British Photodermatology Group on behalf of the British Association of Dermatologists. They present evidence‐based guidance for treatment of patients with a variety of dermatoses and photodermatoses, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of background photobiology.

Topical methyl aminolaevulinate photodynamic therapy in patients with basal cell carcinoma prone to complications and poor cosmetic outcome with conventional treatment

Background  Conventional treatment of basal cell carcinoma (BCC) causes morbidity and/or disfigurement in some patients because of the location (e.g. mid‐face) and size of the lesion.

Multicentre intraindividual randomized trial of topical methyl aminolaevulinate–photodynamic therapy vs. cryotherapy for multiple actinic keratoses on the extremities

Background Methyl aminolaevulinate–photodynamic therapy (MAL‐PDT) is an effective treatment in facial/scalp actinic keratosis (AK).

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

Psoralen photochemotherapy [psoralen ultraviolet A (PUVA)] plays an important part in dermatological therapeutics, being an effective and generally safe treatment for psoriasis and other dermatoses. In order to maintain optimal efficacy and safety, guidelines concerning best practice should be available to operators and supervisors. The British Photodermatology Group (BPG) have previously published recommendations on PUVA, including UVA dosimetry and calibration, patient pretreatment assessment, indications and contraindications, and the management of adverse reactions .1 While most current knowledge relates to oral PUVA, the use of topical PUVA regimens is also popular and presents a number of questions peculiar to this modality, including the choice of psoralen, formulation, method of application, optimal timing of treatment, UVA regimens and relative benefits or risks as compared with oral PUVA. Bath PUVA, i.e. generalized immersion, is the most frequently used modality of topical treatment, practised by about 100 centres in the U.K., while other topical preparations tend to be used for localized diseases such as those affecting the hands and feet. This paper is the product of a recent workshop of the BPG and includes guidelines for bath, local immersion and other topical PUVA. These recommendations are based, where possible, on the results of controlled studies, or otherwise on the consensus view on current practice.

The role of sunlight exposure in determining the vitamin D status of the U.K. white adult population.

Background  Vitamin D is necessary for bone health and is potentially protective against a range of malignancies. Opinions are divided on whether the proposed optimal circulating 25‐hydroxyvitamin D [25(OH)D] level (≥ 32 ng mL−1) is an appropriate and feasible target at population level.

Recommended summer sunlight exposure levels can produce sufficient (?20 ng ml-1) but not the proposed optimal (?32 ng ml-1) 25(OH)D levels at UK latitudes

Recommendations on limitation of summer sunlight exposure to prevent skin cancer may conflict with requirements to protect bone health through adequate vitamin D levels, the principal source being UVB in summer sunlight. We determined whether sufficient (> or =20 ng ml(-1)) and proposed optimal (> or =32 ng ml(-1)) 25(OH)D levels are attained by following UK guidance advising casual short exposures to UVB in summer sunlight, and performed the study under known conditions to enhance the specificity of future recommendations. During wintertime, when ambient UVB is negligible, 120 white Caucasians, aged 20-60 years, from Greater Manchester, UK (53.5 degrees N) received a simulated summers sunlight exposures, specifically 1.3 standard erythemal dose, three times weekly for 6 weeks, while wearing T-shirt and shorts. The baseline winter data predict that 5% (confidence interval (CI): 2.7-8.6) of Greater Manchester white Caucasians have deficient (<5 ng ml(-1)) 25(OH)D, 62.5% (CI: 55.2-69.4) have insufficient, and only 2.9% (CI: 1.4-5.6) have proposed optimal levels. After the simulated summer exposures, 90 (CI: 84.9-93.7) and 26.2% (CI: 20.1-33.2) reached 20 and 32 ng ml(-1) 25(OH)D, respectively. Assuming midday UVB levels, sufficient but suboptimal vitamin D status is attained after a summers short (13 minutes) sunlight exposures to 35% skin surface area; these findings will assist future public health guidance on vitamin D acquisition.

Evidence-based practice of photopheresis 1987-2001: a report of a workshop of the British Photodermatology Group and the U.K. Skin Lymphoma Group.

Photopheresis or extracorporeal photochemotherapy (ECP) is a novel immunomodulatory therapy which involves separation of the patients leucocyte‐rich plasma, followed by ex vivo administration of a photosensitizer and ultraviolet A radiation, before reinfusion. ECP has been used successfully for the treatment of cutaneous T‐cell lymphoma (CTCL: Sézary syndrome), graft‐versus‐host disease (GVHD) and cardiac transplant rejection. ECP has a dose‐sparing effect on concurrent immunosuppressive therapy. The procedure induces apoptosis of the irradiated lymphocytes, but the exact mechanism by which ECP exerts its therapeutic effect in these different conditions is uncertain. The treatment has very few adverse effects and in particular is not associated with an increased incidence of opportunistic infections. The evidence for the efficacy of ECP has been appraised by a combined British Photodermatology Group and U.K. Skin Lymphoma Group workshop on the basis of evidence published up to the end of 2001 and on the consensus of best practice. There is fair evidence for the use of ECP in erythrodermic CTCL and steroid‐refractory GVHD, but randomized controlled studies are needed. There is good evidence supporting the use of ECP in preventing cardiac rejection following transplantation. Randomized controlled trials have also shown a therapeutic benefit in type 1 diabetes mellitus, but the inconvenience associated with the procedure outweighed the clinical benefit. There is fair evidence not to use ECP for the treatment of systemic sclerosis and multiple sclerosis, and good evidence not to use ECP for other forms of CTCL.

The role of sunlight exposure in determining the vitamin D status of the UK white Caucasian adult population.

Background  Vitamin D is necessary for bone health and is potentially protective against a range of malignancies. Opinions are divided on whether the proposed optimal circulating 25‐hydroxyvitamin D [25(OH)D] level (≥ 32 ng mL−1) is an appropriate and feasible target at population level.