Exploring the perspectives of dermatology undergraduates with an escape room game.

BACKGROUND: A UK dermatology curricula review has suggested that undergraduate delivery relies on lectures and is subject to clinical and staffing pressures. Many UK undergraduate students feel less than adequately prepared to manage dermatological conditions, and misconceptions about dermatology are common. Educators have called for innovative solutions, including small group teaching. Escape rooms are games requiring teams to solve puzzles to escape from a room. AIM: To assess the impact of an escape room game on perceptions of dermatology among undergraduate medical students. METHODS: Students were invited to an escape room to consolidate lessons taught in a previous lecture. Students were first asked to complete a questionnaire about their preferred learning environments, perceptions of dermatology and confidence in content. Following the escape room event, these questions were revisited. Focus groups were then held to explore themes raised. RESULTS: In total, 16 students took part in the escape room sessions and in 3 focus groups. Feedback was strongly positive, with 100% of students expressing 'strongly agree' on whether they enjoyed the session. Qualitative data were coded for themes of accessibility, variety of taught content and awareness. The majority (94%) of students stated the escape room made them want to experience more dermatology. CONCLUSION: Prejudices about dermatology exist among medical students, and may act as a barrier to perceived accessibility to the specialty. Escape rooms can provide a shift to a more learner-centred approach, which may aid in combating these negative perceptions. They may act as an enjoyable means of consolidating lecture-based and clinical teaching, and require minimal resources.

Steady-state pharmacokinetics of hydroxychloroquine in patients with cutaneous lupus erythematosus.

Background Hydroxychloroquine (HCQ), a 4-aminoquinolone antimalarial, is regarded as the oral therapy of choice for cutaneous and systemic lupus erythematosus (SLE). It is also licensed for rheumatoid arthritis (RA). Studies of HCQ-treated patients with SLE or RA have demonstrated a positive correlation between whole-blood HCQ levels and clinical response. Such studies have involved measuring whole-blood concentrations at any given time point after HCQ ingestion assuming that steady-state concentrations would undergo limited fluctuation over a daily interval because HCQ has a long half-life. This approach might not sufficiently take into account the potential intra-patient variation in HCQ blood levels that can occur over a 24-hour period. Such variation, if significant, could affect the credibility of any concentration-response relationship provided from these previous studies. Objectives The objectives of this report are to: (a) investigate the intra-patient variation in HCQ whole-blood levels and (b) suggest an optimum time for sampling patients for future studies. Methods Six patients were recruited with cutaneous lupus erythematosus who had each been on HCQ 200 mg twice daily for at least six months, so that they were at steady-state. Each patient was fasted overnight and had standardized meals and dosing schedule. Whole blood was sampled at seven time points over 24 hours. Whole-blood HCQ levels were measured with high-performance liquid chromatography using gradient elution, fluorimetric detection and chloroquine as an internal standard. The assay had a mean inter- and intra-day coefficient of variation of 10% and 5% respectively and a limit of detection of 5ng/ml. Results HCQ levels appeared to follow a biphasic pattern over the sampling period. Maximum levels were noted a median of four hours (range 2-6) after ingestion. Median intra-patient variation between trough and peak levels, 'Cmax' ((peak - trough)/trough × 100%), was 27% (range 8-150%). Conclusions This study demonstrated that whole-blood HCQ levels vary 27% (median, range 8-150%) within an individual over a 12-hour period. Drug levels might differ between individuals because of multiple factors, including variable adherence to medication. Measuring HCQ levels for assessment of drug adherence could be valuable in the 'real-world' clinical setting. This could be assessed by taking a blood sample at any time following HCQ ingestion. If patients were found to have very low or undetectable levels of HCQ, non-adherence to HCQ should be suspected.

Translating translation into patient benefit for atopic eczema.

This review considers, in the context of British Skin Foundation (BSF)-funded translational research into atopic eczema conducted in Newcastle, the complex interactions between clinical and non-clinical scientists in both academia and industry and how this may have impacted on clinical care. However, research in individual centres does not occur in isolation and clinically relevant outcomes from collaborative research are increasingly supported through regional and national networks. This is illustrated by our trial of azathioprine in adults with atopic eczema conducted across centres in the North East of England that employed pharmacogenetic dosimetry. Correspondingly the formation of a UK Translational Network for Translational Research in Dermatology (UK TREND) has facilitated the development of a UK-wide network to support atopic eczema projects based on an e-Delphi prioritisation exercise.

Long-term response to hydroxychloroquine in patients with discoid lupus erythematosus.

BACKGROUND: The recommended first-line oral therapy for discoid lupus erythematosus (DLE) is the antimalarial hydroxychloroquine. To the best of our knowledge, there is no published information regarding the long-term (i.e. > 6 months) response of DLE to hydroxychloroquine in clinical practice. OBJECTIVES: To describe the long-term clinical response of DLE to hydroxychloroquine after 6 months of use. METHODS: A multicentre retrospective cohort study was conducted in patients with DLE who had received treatment with hydroxychloroquine. All patients were recruited and interviewed by a single investigator and response to hydroxychloroquine assessed by the same individual through a retrospective review of case notes using a specified protocol. RESULTS: A total of 200 patients with DLE were recruited (F:M = 4 : 1) with a median age at diagnosis of 40 years (range 16-81) and median follow-up of 8 years (range 0·5-37). An adequate clinical response to hydroxychloroquine was recorded in 91 patients (45·5%) but nonresponse occurred in 85 patients (42·5%). The remainder of patients either had partial response or withdrew from therapy due to toxicity or were unclassifiable. Importantly, of those individuals that did respond to hydroxychloroquine within the first 6 months of use, almost one in five eventually lost their response, despite continued administration, after a median interval of 2 years. These patients often regained disease control if treated with a combination of hydroxychloroquine and mepacrine. Of those that did not respond to hydroxychloroquine within the first 6 months of use, almost one in 10 became eventual responders either after continued administration for up to 2 years or when rechallenged on hydroxychloroquine. The remaining nonresponders relied frequently on oral corticosteroid. CONCLUSIONS: In this cohort of patients with DLE, long-term clinical response to hydroxychloroquine occurred in less than 50% of patients. Nonresponders to hydroxychloroquine frequently required oral steroid to achieve disease control. These findings merit further investigation through a multicentre prospective study using a validated disease activity measure.

Measuring disease activity and damage in discoid lupus erythematosus.

BACKGROUND: Discoid lupus erythematosus (DLE) is a disfiguring inflammatory skin disease. There is no specific tool for measuring disease severity. OBJECTIVES: To determine the features needed in a score measuring activity and damage in DLE and to investigate the score's reliability and its correlation with the physician's global assessment of disease severity and the patient-reported Dermatology Quality of Life Index (DLQI). METHODS: The content of the score was determined following a peer review, pilot work in patients and a preliminary inter-rater reliability study. The Score of Activity and Damage in DLE (SADDLE) measures severity of activity (erythema, scale, induration) and damage (scarring/atrophy and dyspigmentation) attributable to DLE. Summed scores range between 0 and 195. Inter- and intrarater reliability of the score was tested using six assessors and nine patients with DLE. Intraclass correlation coefficients (ICCs) > 0.7 were considered evidence of good inter- and intrarater agreement. RESULTS: The mean +/- SD SADDLE score of nine patients in the inter-rater reliability study was 47 +/- 22 (range 14-102). There was good inter-rater agreement for the total score [ICC 0.82; 95% confidence interval (CI) 0.61-0.95] and for the activity and damage scales, the individual physical signs and the total scores at individual body sites. The total score demonstrated excellent intrarater reliability (ICC 0.98; 95% CI 0.86-1.00). Although there was poor inter-rater agreement for global assessments (ICC 0.28; 95% CI 0.06-0.66), a good correlation was demonstrated between total scores and global assessments (r = 0.7). A weaker positive correlation was observed between disease activity scores and DLQI (r = 0.4). CONCLUSIONS: The SADDLE measures activity and damage in patients with DLE. It demonstrates good inter- and excellent intrarater agreement, over and above that for global assessment. It correlates well with global assessment scores. Further studies are required to investigate SADDLE's responsiveness to change with therapy.

An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczema.

BACKGROUND: Treatment options for moderate-to-severe atopic eczema are limited. Although methotrexate (MTX) is a widely used and effective treatment for psoriasis, there have been no previous prospective trials of its use in refractory atopic eczema, despite a few small, retrospective reports suggesting that it is a well-tolerated and effective treatment. OBJECTIVES: We have assessed the safety and efficacy of oral MTX in 12 adults with moderate-to-severe atopic eczema in an open-label, dose-ranging, prospective trial using objective outcome measures. METHODS: All patients had previously received other second-line therapies and had disease only partially responsive to potent topical steroids and emollients. During the 24-week MTX treatment period, unrestricted use of standard topical therapy was permitted. We used an incremental MTX dose regime, starting at 10 mg per week (following a 5-mg test dose) and increasing by 2.5 mg weekly until response was achieved or treatment was limited by toxicity. Disease activity [six area six sign atopic dermatitis (SASSAD) score] was assessed every 4 weeks during treatment and 12 weeks after stopping MTX. The primary endpoint was 24-week change in disease activity. RESULTS: On average, disease activity improved by 52% from baseline (95% confidence interval 45-60%). There were significant improvements in quality of life, body surface area affected and loss of sleep and itch scores. Global response was rated as 'marked improvement' in five of 12 and six of 12 patients, by investigators and patients, respectively. In all patients, the majority of improvement in disease activity was seen by week 12, and, interestingly, patients who had not responded well over this period despite reaching a dose of 15 mg weekly failed to improve with further dose escalation. Only one patient withdrew due to minor adverse effects. MTX was well tolerated by the remaining 11 patients, all of whom completed treatment, achieving a median dose of 15 mg weekly. Importantly, eight of nine patients had a persistent improvement 12 weeks after stopping MTX, with mean disease activity remaining 34% below baseline. CONCLUSIONS: We have shown that MTX is an effective, well-tolerated treatment for moderate-to-severe atopic eczema, and response appears to compare favourably with other second-line therapies. A randomized, controlled trial is now warranted.

Elevated expression and genetic association links the SOCS3 gene to atopic dermatitis.

In a systematic analysis of global gene-expression patterns, we found that SOCS3 messenger RNA was significantly more highly expressed in skin from patients with atopic dermatitis than in skin from healthy controls, and immunohistochemical analysis confirmed a similar elevation of SOCS3 protein. Furthermore, we found a genetic association between atopic dermatitis and a haplotype in the SOCS3 gene in two independent groups of patients (P<.02 and P<.03). These results strongly suggest that SOCS3, located in a chromosomal region previously linked to the disease (17q25), is a susceptibility gene for atopic dermatitis.

Photosensitive pityriasis rubra pilaris.

Exacerbation of pityriasis rubra pilaris (PRP) with ultraviolet exposure is well recognized. However, the initial presentation of PRP in a photoexposed distribution is infrequently reported, and only rarely confirmed with phototesting. We describe such a case of photosensitive PRP. Phototesting revealed exquisite ultraviolet (UV) sensitivity, which was particularly marked to UVB, a feature shared with previously reported cases.

Raised limb bands developing in infancy.

Congenital cutaneous constriction bands are rare and often occur with other abnormalities, including the presence of rudimentary digits. This diverse syndrome lacks a precise definition and a satisfactory explanation. We describe two unusual cases with features previously undescribed, in which predominantly raised, annular limb bands became apparent postnatally. One infant was also born with foreshortened digits and a constricting limb band, suggesting a shared aetiology with other congenital cases. The development of raised bands during infancy would be difficult to reconcile with the widely held 'amniotic band hypothesis', and would be more in keeping with a multifocal developmental abnormality in limb growth.

Azathioprine for atopic dermatitis.

For adults with atopic dermatitis (AD) refractory to topical treatment, the choices of second-line therapy are limited. Furthermore, there are concerns about the long-term safety of treatments such as cyclosporin. Limited open studies suggest that azathioprine may be effective, although controlled trial data is lacking. Nevertheless, many UK dermatologists use azathioprine to treat patients with severe AD, despite the potential risk of serious toxicity. Azathioprine myelotoxicity and drug efficacy are now known to be related to the activity of a key enzyme in azathioprine metabolism, thiopurinemethyltransferase (TPMT). Recently, the facility for TPMT measurement has become more widely available, providing the possibility to optimize the therapeutic effect of azathioprine, yet minimise the risk of toxicity. We review the evidence concerning the use of azathioprine for AD, and have identified 128 cases in eight open studies, including our own prospective trial. Improvement in the majority was noted in seven studies, although objective measures of disease activity were used in only one trial. Measurements of TPMT activity were performed in the two most recent studies only. These data underscore the requirement for a prospective randomised controlled trial, and highlight the need to further investigate the role of TPMT measurement in azathioprine usage.