J.L.M. Hawk

Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study

Summary Background In patients with xeroderma pigmentosum the frequency of all forms of skin cancer is higher than in the general population, owing to a genetic defect in DNA repair. The bacterial DNA repair enzyme, T4 endonuclease V, delivered intracellularly, increases the rate of repair of sunlight-induced DNA damage in human cells. We tested the ability of this enzyme in a liposomal delivery vehicle applied topically (T4N5 liposome lotion) to lower the rate of new skin cancers in patients with xeroderma pigmentosum. Methods 30 patients were enrolled in this prospective, multicentre, double-blind study. Patients were randomly assigned T4N5 liposome lotion or a placebo liposome lotion, to be applied daily for 1 year. At 3-monthly visits, new actinic keratoses and basal-cell carcinomas were identified and removed. Analyses were by intention to treat. Findings 20 patients were assigned T4N5 liposome lotion and ten placebo lotion; one placebo-group patient withdrew before treatment and one withdrew with progressive disease at 9 months. The annualised rate of new actinic keratoses was 8·2 among the patients assigned T4N5 liposome lotion and 25·9 among those assigned placebo (difference 17·7 [95% CI 11·8–26·5]; p=0·004 by Poisson modelling). For basal-cell carcinoma, the annualised rates of new lesions were 3·8 in the treatment group and 5·4 in the placebo group (difference 1·6 [0·38–2·82]). No significant adverse effects were found among any of the patients. Interpretation DNA damage has an important role in the development of skin cancer and precancerous skin lesions. The topical application of DNA repair enzymes to sun-damaged skin of patients with xeroderma pigmentosum lowered the rate of development of two forms of these lesions during a year of treatment.

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.

Photoallergic contact dermatitis is uncommon

Background Despite the enormous increase in sunscreen use, allergic contact (AC) and photoallergic (PA) reactions to ultraviolet (UV) filters are considered rare.

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.

PUVA treatment of alopecia areata partialis, totalis and universalis: audit of 10 years' experience at St John's Institute of Dermatology.

Our 10‐year experience with PUVA treatment for alopecia areata. partialis, totalis and universalis was retrospectively reviewed using charts and follow‐up questionnaires for 70 patients at St Johns Institute of Dermatology. In all cases, several previous therapies were judged to be unsatisfactory prior to starting PUVA, and many cases were already deemed clinically refractory prior to referral for PUVA. If cases of vellus hair growth are excluded, and those who lost their PUVA‐induced regrowth rapidly on follow‐up, the effective success rate was at best 6·3% for alopecia areata partialis, 12·5% for alopecia areata totalis and 13·3% for alopecia areata universalis. We affirm that PUVA is generally not an effective treatment for alopecia areata.

Review of the potential photo-cocarcinogenicity of topical calcineurin inhibitors: Position statement of the European Dermatology Forum

ABSTRACT  Topical Calcineurin Inhibitors (TCIs) used for the treatment of atopic eczema modify the immune regulatory function of the skin and may have the potential to enhance immunosuppressive ultraviolet (UV) effects. Current recommendations on UV protection in eczema patients treated with PCIs are inconsistent and have given rise to uncertainty and anxiety in patients. Therefore, the European Dermatology Forum (EDF) developed a position statement which reviews critically the available data with regard to the problem, especially analysing and commenting the limitations of rodent models for the human situation. There is no conclusive evidence from rodent trials to indicate that long‐term application of TCIs is photococarcinogenic. There is a need for further studies to investigate the validity of mouse models as well as long‐term cohort studies in patients using TCIs. Available data suggest that long‐term application of TCIs is safe, that there is no evidence of increased skin cancer risk and that it is ethical to treat patients with TCIs when indicated.

UVA sunbeds: tanning, photoprotection, acute adverse effects and immunological changes

The effects on 31 normal subjects following exposure to sunbeds containing UVA lamps with minimal UVB emission have been compared in a double‐blind study with the effects on nine control subjects of a similar exposure course three times weekly for 4 weeks to sunbeds emitting visible light. On previously untanned areas, all those subjects on active treatment developed a mild tan; in tanned areas they all developed a moderate tan, while all control subjects developed a minimal to mild tan. The mean protection factor against later UVB‐induced erythema was 3.2±0.3 after the active course and 1.6±0.2 among the controls. Significantlsy more frequent adverse cutaneous effects for active subjects were pruritus, erythema, freckling, burning sensation, dryness and polymorphic light eruption. Cutaneous Langerhans cell numbers, and blood CD3+ (pan T‐cell) and CD4+ (helper T‐cell) lymphocyte subsets were reduced in both active and control groups. CD8+ (cytotoxic/suppressor T‐cell) counts were significantly reduced in both groups. The changes found in both groups seem attributable to small amounts of UVB emission from both active and control lamps.

Photosensitivity disorders: cause, effect and management

Abnormal photosensitivity syndromes form a significant and common group of skin diseases. They include primary (idiopathic) photodermatoses such as polymorphic light eruption (PLE), chronic actinic dermatitis (CAD), actinic prurigo, hydroa vacciniforme and solar urticaria, in addition to drug- and chemical-induced photosensitivity and photo-exacerbated dermatoses. They can be extremely disabling and difficult to diagnose.PLE, characterized by a recurrent pruritic papulo-vesicular eruption of affected skin within hours of sun exposure, is best managed by restriction of ultraviolet radiation (UVR) exposure and the use of high sun protection factor (SPF) sunscreens. If these measures are insufficient, prophylactic phototherapy with PUVA, broadband UVB or narrowband UVB (TL-01) for several weeks during spring may be necessary. CAD manifests as a dermatitis of chronically sun-exposed skin. Again, UVR exposure needs to be restricted; cyclosporine, azathioprine or PUVA may also be necessary. Actinic prurigo is characterized by the presence of excoriated papules and nodules on the face and limbs, most prominent and numerous distally. Actinic prurigo is managed again by restriction of UVR and the use of high SPF sunscreens; PUVA or broadband UVB therapy, or low doses of thalidomide may be necessary. Hydroa vacciniforme causes crops of discrete erythematous macules, 2 to 3mm in size, that evolve into blisters within a couple of days of sun exposure. Treatment for this rare disease is difficult; absorbent sunscreens and restricted UVR exposure may help. Solar urticaria is characterized by acute erythema and urticarial wealing after exposure to UVR. Treatment options for solar urticaria include non-sedating antihistamines such as fexofenadine and cetirizine; other options include absorbent sunscreens, restriction of UVR at the relevant wavelength, maintenance of a non-responsive state with natural or artificial light exposure and plasmapheresis.Industrial, cosmetic and therapeutic agents can induce exogenous drug- or chemical-induced photosensitivity. The clinical pattern is highly varied, depending on the agent; treatment is based on removal of the photosensitizer along with restriction of UVR exposure.Predominantly non-photosensitive dermatoses may also be exacerbated or precipitated by UVR; exposure to UVR should be reduced and sunscreens should be advocated, along with appropriate treatment of the underlying disease.

A candidate gene analysis of three related photosensitivity disorders: cutaneous lupus erythematosus, polymorphic light eruption and actinic prurigo

Background Polymorphic light eruption (PLE) is a common inherited photosensitivity disorder, which may predispose to several related but distinct conditions, including subacute cutaneous lupus erythematosus (SCLE), discoid lupus erythematosus (DLE) and actinic prurigo (AP).

Enzyme therapy of xeroderma pigmentosum: safety and efficacy testing of T4N5 liposome lotion containing a prokaryotic DNA repair enzyme

Xeroderma pigmentosum (XP) is a rare genetic disease in which patients are defective in DNA repair and are extremely sensitive to solar UV radiation exposure. A new treatment approach was tested in these patients, in which a prokaryotic DNA repair enzyme specific for UV‐induced DNA damage was delivered into the skin by means of topically applied liposomes to supplement the deficient activity. Acute and chronic safety testing in both mice and humans showed neither adverse reactions nor significant changes in serum chemistry or in skin histology. The skin of XP patients treated with the DNA repair liposomes had fewer cyclobutylpyrimidine dimers in DNA and showed less erythema than did control sites. The results encourage further clinical testing of this new enzyme therapy approach.