Photodiagnostic services in the UK and Republic of Ireland: a British Photodermatology Group Workshop Report.

BACKGROUND: Photodiagnostic investigations are essential for the accurate diagnosis of abnormal cutaneous photosensitivity and provide important information for the management of patients with photodermatoses (cutaneous photosensitivity disorders). Although photodiagnosis has been undertaken since the early 1970s, specialist services in the United Kingdom (UK) and Republic of Ireland are limited and there is no formal guidance on diagnostic approach. Indeed, there is a limited literature in this area of methodology and diagnostic practice. OBJECTIVES: The primary objective was to undertake a British Photodermatology Group Workshop to review the role and activities of specialist centres in the UK and Republic of Ireland in order to ascertain whether there were consensus practices. Secondary objectives were to identify key priorities for service, training and research. METHODS: An initial detailed survey review of current activities was undertaken prior to the Workshop and data from this survey were used to inform discussion at the Workshop, which was attended by key photodermatology experts from the UK and Republic of Ireland. RESULTS/CONCLUSIONS: We have undertaken a detailed review of current Photodiagnostic Services in the UK and Republic of Ireland and report on our findings from the 12 centres and we have identified key areas of consensus practice. This is an important step in the process of standardising and optimising procedures and protocols and defining minimum clinical standards for photodiagnostic investigations, which are of such diagnostic importance in Dermatology.

The widespread use of topical antimicrobials enriches for resistance in Staphylococcus aureus isolated from patients with atopic dermatitis.

BACKGROUND: Carriage rates of Staphylococcus aureus on affected skin in atopic dermatitis (AD) are approximately 70%. Increasing disease severity during flares and overall disease severity correlate with increased burden of S. aureus. Treatment in AD therefore often targets S. aureus with topical and systemic antimicrobials. OBJECTIVES: To determine whether antimicrobial sensitivities and genetic determinants of resistance differed in S. aureus isolates from the skin of children with AD and healthy child nasal carriers. METHODS: In this case-control study, we compared S. aureus isolates from children with AD (n = 50) attending a hospital dermatology department against nasal carriage isolates from children without skin disease (n = 49) attending a hospital emergency department for noninfective conditions. Using whole genome sequencing we generated a phylogenetic framework for the isolates based on variation in the core genome, then compared antimicrobial resistance phenotypes and genotypes between disease groups. RESULTS: Staphylococcus aureus from cases and controls had on average similar numbers of phenotypic resistances per isolate. Case isolates differed in their resistance patterns, with fusidic acid resistance (FusR ) being significantly more frequent in AD (P = 0·009). The genetic basis of FusR also differentiated the populations, with chromosomal mutations in fusA predominating in AD (P = 0·049). Analysis revealed that FusR evolved multiple times and via multiple mechanism in the population. Carriage of plasmid-derived qac genes, which have been associated with reduced susceptibility to antiseptics, was eight times more frequent in AD (P = 0·016). CONCLUSIONS: The results suggest that strong selective pressure drives the emergence and maintenance of specific resistances in AD.

Lack of phototoxicity potential with delafloxacin in healthy male and female subjects: comparison to lomefloxacin.

AIMS: Delafloxacin is a fluoroquinolone antibiotic recently approved by the FDA for treatment of acute bacterial skin and skin structure infections (ABSSSI). Delafloxacin was assessed for phototoxicity potential compared with a known phototoxic fluoroquinolone. METHODS: A Phase 1, investigator-blind, placebo/active-controlled, randomized, parallel-group study was conducted in 52 healthy male and female volunteers who received 200 or 400 mg of oral delafloxacin, 400 mg oral lomefloxacin or placebo once daily for 6 days. This study evaluated the photosensitizing potential and possible wavelength dependency of delafloxacin by comparing the response of the skin to ultraviolet A (UVA), ultraviolet B (UVB) and visible radiation prior to and during administration of delafloxacin, lomefloxacin as a positive control, or placebo. Adverse events were monitored throughout the study. RESULTS: Forty-seven subjects completed six days of dosing, and no evidence of phototoxicity was seen with delafloxacin. Delafloxacin at 200 and 400 mg day-1 and placebo did not demonstrate differences in percent change from baseline in minimal erythema dose at all tested wavelengths (295-430 nm) by monochromator and solar simulator. Lomefloxacin, the positive control, had statistically significant differences (p < 0.05) at UVA wavelengths of 335 and 365 ± 30 nm 24 hours after radiation exposure (maximum response). The phototoxic index results were significantly higher for lomefloxacin at 335 nm and 365 nm compared to placebo and delafloxacin. CONCLUSIONS: 200 and 400 mg of delafloxacin administered for 6 days were well tolerated in healthy adult volunteers. Delafloxacin and placebo failed to demonstrate a phototoxic effect but lomefloxacin, the positive control, demonstrated moderate phototoxicity.

Six years' experience of grenz ray therapy for the treatment of inflammatory skin conditions.

BACKGROUND: In 2008, Ninewells Hospital became the first centre in the UK to offer grenz rays as a treatment for inflammatory dermatoses. Since then, 122 courses have been administered for the following conditions; scalp psoriasis (n = 36), nail dystrophies (n = 27), hyperkeratotic eczema/psoriasis (n = 22), palmoplantar pustulosis (n = 9), perianal pruritus (n = 9), warts (n = 4) and other conditions (n = 15). AIM: To review all patients who received grenz rays in order to determine which conditions have been treated successfully and to estimate remission times. METHOD: Patient notes were reviewed, and follow-up was supplemented by subsequent dermatology clinic letters and telephone consultation. RESULTS: For scalp psoriasis, clearance was achieved with 13 courses, marked improvement with 19, minimal improvement in 3 and no change with 1. Treatment of palmoplantar psoriasis/hyperkeratotic eczema showed clearance with 7 courses, marked improvement with 9, minimal change with 2 and no change with 4. Of the courses for nail dystrophies (mainly psoriasis), clearance occurred with 1, marked improvement with 7, minimal change with 8 and no change with 11. In addition to immediate outcomes, the remission times were also evaluated. For scalp psoriasis, only 8 of the initial 32 patients still had clearance or marked improvement at the most recent follow-up. For nail dystrophy, 3 of 8 patients remained in remission, while for hyperkeratotic eczema/psoriasis, 7 of the initial 16 patients who had clearance or marked improvement had sustained this improvement, and only 1 patient with palmoplantar pustulosis still had clearance at the most recent follow-up. CONCLUSIONS: Grenz ray therapy is an effective treatment for some chronic inflammatory skin conditions that are resistant to routine therapies. The period of remission for scalp psoriasis was good for some patients but disappointingly short for others. Future studies involving different cumulative doses with subsets of different dose fractionations may help optimize treatment regimens.

Review of an established UK home phototherapy service 1998-2011: improving access to a cost-effective treatment for chronic skin disease.

OBJECTIVES: To review the Tayside home phototherapy service, including numbers of patients treated, diagnoses and outcomes, side-effects and safety, cost-effectiveness and absolute costs. To consider why home or outpatient phototherapy is not available to all patients who might benefit and how this could be addressed. STUDY DESIGN: Observational and cost analysis. METHODS: Analysis of the Tayside home phototherapy database 1998 and 2011, home phototherapy patient questionnaires, outcome data, costs and a comparison with outpatient phototherapy. Review of literature and current national guidelines for phototherapy, traditional systemic and biologic therapies for psoriasis. RESULTS: 298 courses of home narrowband UVB (NB-UVB) phototherapy were undertaken by 212 patients between 1998 and 2011, five courses in 1998 increasing to 36 in 2011. The main diagnoses treated were psoriasis (72%), atopic dermatitis (8%), and desensitization of photodermatosis (7%). For psoriasis, 74.5% achieved clearance or minimal residual activity in a median of 30 exposures (range 10-60). The estimated costs to the hospital ranged from £229 to £314 per course (£307 to £422 per effective course for psoriasis), compared with £114 for out-patient therapy (£149 per effective course for psoriasis). The total cost to society (hospital and patient costs) is around £410 per course, compared to an estimated £550 for outpatient therapy for this group of patients. Treatment was well tolerated, erythema rates were similar to outpatient therapy, there were no complaints and the vast majority would choose home over outpatient phototherapy if required in the future. CONCLUSIONS: Hospital supervised home phototherapy appears as safe and effective as outpatient therapy and provides equality of access for patients who cannot attend for outpatient therapy. These patients may otherwise be inadequately treated or given more costly and higher risk systemic therapies, particularly for psoriasis. Commissioners and clinicians involved in dermatology services should provide accessible phototherapy for all patients who might benefit, utilizing home phototherapy where outpatient access is not possible.

Self-administration of hospital-based narrowband ultraviolet B (TL-01) phototherapy: a feasibility study in an outpatient setting.

BACKGROUND: Self-administration of narrowband (TL-01) ultraviolet (UV)B phototherapy by patients at home is a safe and effective mode of treatment. Could selected patients self-administer phototherapy in hospital? OBJECTIVES: To assess the feasibility of outpatient self-administration of UVB phototherapy as a potential service development. METHODS: A total of 20 patients with psoriasis (n = 15) and eczema (n = 5) (13 female, mean age 32 years, range 17-56 years) were included in this pilot project. Patients underwent a training programme over 2 days, which included a minimal erythemal dose test and supervised treatment, prior to commencing self-administration of phototherapy. Questionnaires were used to gather feedback from patients and staff. RESULTS: Treatment data were collected for 18 of the 20 patients. The mean number of exposures was 25 (range 3-45), and the mean cumulative dose was 16 J cm(-2) (range 0·23-41·27 J cm(-2) ). No unexpected adverse effects were noted. These results were similar to those of a sample group of outpatients who had nurse-administered UVB phototherapy, for whom the mean number of exposures was 24 (range 4-49) and the mean cumulative dose was 17 J cm(-2) (range 0·53-71·16 J cm(-2) ). Thirteen patients completed the questionnaires. All concluded that the training programme sufficiently prepared them for self-administering phototherapy, and 12 reported that they would be happy to self-administer treatment in the future. CONCLUSIONS: Self-administration of UVB phototherapy is practicable, safe and effective for most selected patients. This mode of treatment provides training and support for patients to gain more control over management of their skin disease, empowering them to take an active role in their treatment. Self-administration of UVB phototherapy by outpatients provides an intermediate level of care between nurse-administered hospital phototherapy and self-administered home phototherapy.

A survey of photodynamic therapy services in dermatology departments across Scotland.

There is good evidence to support the use of topical PDT for superficial nonmelanoma skin cancer and dysplasia; however, there is little information available on the structure, process and outcomes of PDT in clinical practice. We undertook a national survey to determine how PDT was being undertaken in dermatology centres in Scotland. We highlight important information on the practicalities of PDT service delivery and the types of patients and diagnoses treated, and provide preliminary information on the outcomes achieved. These data will be invaluable as a starting point to agree on minimum standards for PDT and criteria to audit against these standards.

Glutathione S-transferase genotype is associated with sensitivity to psoralen-ultraviolet A photochemotherapy.

BACKGROUND: There is marked interpatient variation in responses to psoralen-ultraviolet A (PUVA) photochemotherapy. Identification of molecular biomarkers of PUVA sensitivity may facilitate treatment predictability.The glutathione S-transferases (GSTs) influence cutaneous defence against UV radiation-induced oxidative stress and are therefore candidate biomarkers of PUVA sensitivity. Several human GSTs, including GSTM1 and GSTT1, are polymorphic, and null polymorphisms have been associated with increased UVB erythemal sensitivity and skin cancer risk. PUVA also increases skin cancer risk. OBJECTIVES: To investigate the effect of GST genotype on PUVA sensitivity. METHODS: We investigated GST genotype in patients starting PUVA (n=111) and the effects of 8-methoxypsoralen (8-MOP) on antioxidant response element (ARE)-regulated gene expression in mammalian cells. RESULTS: Lower minimal phototoxic doses (MPD) (P=0·022) and higher serum 8-MOP concentrations (P=0·052) were seen in GSTM1-null allele homozygotes compared with patients with one or two active alleles. In a subset of patients with psoriasis (n=50), the GSTM1 genotype was not associated with PUVA outcomes, although MPD [hazard ratio (HR) 1·37; 95% confidence interval (CI) for HR 1·15-1·64] and GSTT1-null (HR 2·39; 95% CI for HR 1·31-4·35) and GSTP1b (HR 1·96; 95% CI for HR 1·10-3·51) genotypes were associated with clearance of psoriasis in this patient group. Exposure of mammalian cells to 8-MOP induced gene expression via the ARE, a regulatory sequence in promoters of cytoprotective genes including GSTs, suggesting that these genes may be implicated in 8-MOP metabolism. CONCLUSION: The polymorphic human GSTs are associated with PUVA sensitivity. Further studies are required to examine the clinical relevance of these preliminary findings.