bluuebunny/crossref_metadata_2025_split huggingface dataset:
P37 An island story: a successful new model of specialist dermatology provision to a rural area
Authors: Abraham Kirstin , Thomas Huw , Bryden Alyson 
Published: June 2023

Abstract
The authors’ health board was invited to take over the dermatology provision of an island health board in 2018. At the point of takeover, the waiting list for new appointments was approximately 33 months. There was a significant burden of return patients, which would take approximately 6 years to process in the previous system. We approached this challenge by implementing several novel strategies. Our own department has an established practice of enhanced vetting of referrals. Essential to this are solid relationships with primary care colleagues to encourage the use of high-quality images within referrals. Referrals are viewed by the vetting dermatology consultant within 48 h. Options following vetting include reassurance regarding benign lesions, or direct treatment advice to the referrer without requiring a clinic appointment. Between August 2018 and December 2022, we were able to deal with 40% of referrals in this way. Other vetting outcomes include direct referral to the local island general surgeons for appropriate lesion removal with advice on excision margins/depth. Pathology results are returned to the dermatologist for interpretation and ongoing care. Vetting consultants can directly book a twice-monthly dermatology video clinic (general or specialist, e.g. paediatric dermatology). Remote monitoring of systemic therapies is undertaken. Dermatology advice is provided for inpatients at the island district general hospital. Suitable patients can be directly booked to see our on-island general practitioner (GP) with a specialist interest in dermatology (GPwSI). We provide quarterly physical visits, consisting of 2 days of consultant-led clinics and complex skin surgery. Our GPwSI colleague is supported by the mainland dermatology team, seeing suitable patients between dermatology visits. They have set up a novel phototherapy service on the islands with support and guidance from the dermatology team. Prior to this, patients needing phototherapy were required to travel to the mainland, often needing prolonged inpatient hospital stays with a significant impact on their jobs, home lives and financial consequences/capacity on the National Health Service. This rural dermatology service is highly effective through the use of enhanced vetting, a well-trained and supported local GPwSI, collaboration with local GPs and general surgeons and remote consulting. The model provides a comprehensive rural service, meaning patients no longer have to travel off island to access general and specialist dermatological services. Using this new model and through dedicated teamworking, there is currently no waiting list for island dermatology patients. Feedback from GPs and patients has been extremely positive.
P38 Integrating proteomics and genomics to investigate the mechanisms of paradoxical eczema developing in patients with psoriasis treated with biologics: a UK multicentre, longitudinal, cohort study
Authors: Al-Janabi Ali , Martin Paul , Khan Adnan , Foulkes Amy , Smith Catherine , Griffiths Christopher , Morris Andrew , Eyre Steve , Warren Richard 
Published: June 2023

Abstract
Few studies have explored the immunology and genetic risk of paradoxical eczema occurring in patients with psoriasis treated with biologics. This study aims to describe the systemic inflammatory signature of paradoxical eczema using proteomics and explore whether it is genetically mediated. Participants were adults treated with biologics for plaque psoriasis, who were corecruited to the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) and Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) studies. To identify differentially expressed proteins and enriched gene sets, we used the Olink Target 96 Inflammation panel on 256 serum samples from BSTOP for 71 cases with paradoxical eczema and 75 controls. Paradoxical eczema was defined as eczema, atopic eczema or atopic dermatitis occurring during biologic exposure. Case samples across three time points [T1: prebiologic (n = 42); T2, postbiologic (n = 45); T3, postparadoxical eczema (n = 41)] were matched 1 : 1 with control samples. Case samples at T2 and T3 were taken during exposure to the same biologic that caused paradoxical eczema. Genes contributing to proteomic signatures were selected, and single-nucleotide polymorphisms (SNPs) that were nonsynonymous or associated with significant expression quantitative trait loci were used to create polygenic risk scores (PRS) in a genotyped cohort of 88 paradoxical eczema cases and 3124 psoriasis controls. Signal transducing adapter molecule 1-binding protein expression was lower in cases at T1 than in controls (log-fold change −0.44, adjusted P = 0.022); no other proteins achieved statistical significance at equivalent time points. Eleven gene sets, including cytokine and chemokine pathways, were enriched in cases at T2 and 10 at T3. Of the 39 proteins contributing to enriched gene sets, 21 are elevated in the sera of patients with atopic dermatitis. A PRS including 38 SNPs linked to enriched gene sets was associated with paradoxical eczema (adjusted P = 0.046). We subdivided the SNPs into those linked to specific gene sets, such as chemokine, cytokine and interleukin (IL)-10 signalling, to generate 10 partitioned PRS. Seven were associated with paradoxical eczema (adjusted P &lt; 0.05). These SNPs do not map to known atopic loci. The paradoxical eczema systemic inflammatory proteome trends toward atopic dermatitis at a gene set level and is detectable before the onset of the phenotype. This signature may be mediated genetically by SNPs associated with these gene sets. Further studies are needed to explore the role of specific pathways (such as IL-10 signalling) in paradoxical eczema and define the inflammatory profile in the skin.
P39 Methotrexate induces epidermal DNA damage response and filaggrin in atopic eczema
Authors: Hussain Amaani B , Elias Martina , Cockell Simon , Casement John , Smith Graham , Ding Yuchun , Nichols Esme , Reynolds Nick J 
Published: June 2023

Abstract
Methotrexate (MTX) is an effective treatment for atopic eczema (AE), but its mechanism of action remains undefined. Our previous work identified keratinocytes as a direct target of MTX by increasing epidermal differentiation. Evidence supports the concept of DNA damage-induced keratinocyte differentiation; however, this has not been characterized in the context of MTX. We tested the hypothesis that MTX may act therapeutically in AE by inducing DNA damage and activating downstream DNA damage response signalling pathways. Patients with AE starting MTX (initial dose 10 mg weekly) were recruited (n = 12). The FLG status was determined by DNA genotyping. Clinical data and skin biopsies from lesional and nonlesional skin were collected at week 0 (baseline), week 2 [visit 1 (V1)] and week 12 [visit 2 (V2)] following MTX initiation. γH2A.X, a marker of DNA damage, was quantified to explore the relationship between DNA damage secondary to MTX treatment and FLG status. γH2A.X and filaggrin protein epidermal immunostaining were quantified. The male-to-female ratio was 8 : 4 and median participant age was 45 years. Median Eczema Area and Severity Index (EASI) score improved from 23.5 (baseline, n = 12) to 14.6 at V1 (n = 12) and 9.0 at V2 (n = 8). Median Dermatology Life Quality Index reduced from 15 (baseline, n = 12) to 10.5 (V2, n = 8). Four patients were FLG heterozygotes and eight were FLG wild type. In combined analysis of all patients, epidermal γH2A.X increased in lesional skin at both time points [n = 6 (V1: P = 0.022; V2: P = 0.009)] and in nonlesional skin by V2 (n = 6; P = 0.021). γH2A.X increased in lesional skin at V2 in both FLG heterozygotes (P = 0.044) and wild types (P = 0.038). Epidermal filaggrin in lesional and nonlesional skin increased at V1 and V2 in all patients combined (n = 5; P = 0.029). Filaggrin increased in the nonlesional skin of FLG heterozygotes (P = 0.044) and in the lesional skin of FLG wild-type patients (P = 0.009) by V2. Transcriptomic (RNAseq) analysis was performed on skin biopsies (n = 11 patients; n = 42 samples). We explored the relationship of gene expression with severity (EASI) and FLG status. AKR1B10, IL22 and LGALS7 expression increased with disease severity. The AKR1B10 (regulates keratinocyte differentiation) and LGALS7 expression (expressed during barrier dysfunction) response with EASI was enhanced in FLG heterozygotes vs. wild-type patients. Canonical pathways were upregulated in lesional skin at V2 vs. baseline. Through epidermal immunostaining and transcriptomic gene analysis, we demonstrated evidence of DNA damage and filaggrin induction in patients with AE following MTX therapy, with associated improved disease outcomes.
P40 Dupilumab treatment restores skin barrier function in lesional and nonlesional skin of patients with atopic dermatitis and improves patient-reported outcomes
Authors: Cork Michael , Bissonnette Robert , Ramirez-Gama Marco , Taylor Patricia , Praestgaard Amy , Levit Noah , Rossi Ana , Zhang Annie 
Published: June 2023

Abstract
The objective of this analysis is to report the effect of dupilumab treatment on skin barrier function and patient-reported outcomes (PROs) in adults and adolescents with moderate-to-severe atopic dermatitis (AD). BALISTAD (NCT04447417) was an open-label trial in which transepidermal water loss (TEWL) was assessed repeatedly before and after skin tape stripping (STS) samples were taken from lesional and nonlesional skin of 26 patients with AD treated with dupilumab, and from normal skin of 26 matched healthy volunteers aged 12–65 years over a period of 16 weeks. PROs assessed included Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS) and Dermatological Life Quality Index [DLQI; for patients &gt; 17 years old; Children’s DLQI (CDLQI) for patients aged &gt; 12 to &lt; 17 years]. At baseline, the median TEWL after five STS was statistically significantly higher in the lesional and nonlesional skin of patients with AD compared with healthy skin (P &lt; 0.001 and P &lt; 0.01, respectively) and statistically significantly decreased following dupilumab initiation as early as week 2 (P &lt; 0.001 and P &lt; 0.05, respectively). After 16 weeks of dupilumab treatment, there was no statistically significant difference in adjusted mean TEWL in AD lesional and nonlesional skin compared with matched healthy skin (P = 0.225 and P = 0.163, respectively). Significant improvement from baseline [mean (SD) change from baseline] was seen as early as week 2 in mean POEM [−8.4 (5.1)], DLQI [−5.3 (4.7)], CDLQI [−6.2 (4.7)] and PP-NRS [−2.2 (1.8); P &lt; 0.001 and P &lt; 0.05)] for CDLQI. Improvement was sustained through to week 16 [mean (SD) change from baseline; P &lt; 0.001] for POEM [−13.6 (8.5)], DLQI [−8.6 (7.4)] and PP-NRS [−4.2 (2.6)] and with a P-value of &lt; 0.01 for CDLQI [−9.2 (5.0)]. Dupilumab treatment normalizes epidermal barrier function in lesional and nonlesional skin in patients with moderate-to-severe AD, as measured with TEWL, and improves PROs.
Funding sources: research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.
P44 Can dermatologists help save the planet?
Authors: Taheem Anjeli , Gafoor Shafiah Muna Abdul , Woodcock Emma , Nelson Toby 
Published: June 2023

Abstract
The National Health Service (NHS) is England’s largest contributor to public greenhouse gas emissions, accounting for 6.3% of the country’s carbon footprint (Tennison I, Roschnik S, Ashby B et al. Health care’s response to climate change: a carbon footprint assessment of the NHS in England. Lancet Planet Health 2021; 5:e84–92). Promoting sustainable practices within dermatology is often overlooked and remains an understudied area of research. Dermatologists should consider environmental sustainability when choosing their day-to-day personal protective equipment (PPE). An over-reliance on sterile PPE for minor surgical practices costs millions of pounds annually, ultimately occupying landfills and causing detrimental effects to our ecosystem. Are these sterile practices really improving clinical outcomes and reducing the prevalence of surgical site infections (SSIs)? Over the last decade, there has been an emphasis on comparing the use of sterile vs. nonsterile gloves and associated SSI rates in dermatology and Mohs micrographic surgery (MMS). MMS is often conducted with two sterile gloves and two surgical gowns. According to the sustainability guidance published by the British Society for Dermatological Surgery, surgical aprons and nonsterile gloves are preferred to surgical gowns and sterile gloves in procedures such as diagnostic biopsies, simple excision, tumour extirpation stages in MMS and outpatient reconstructive surgeries (https://bsds.org.uk/wp-content/uploads/2022/09/2022-BSDS_Sustainability_Guidance.pdf). Based on this guidance and to reduce our carbon footprint, we decided to use two plastic aprons, one pair of nonsterile and one pair of sterile gloves from August 2020 to September 2022. Of 410 MMS procedures conducted, only 1.7% resulted in a minor postoperative complication related to infection. Our data suggest no significant difference in postoperative wound infections with the use of nonsterile PPE vs. sterile PPE. Moreover, the use of nonsterile PPE has saved our department £1471.90, allowing funding to be distributed to other areas. In line with the NHS multiyear plan to become the world’s first carbon net zero national health system by 2040, we should invest in processes that facilitate sustainable alternatives to construct a fully operational eco-friendly healthcare system. By using less PPE in reconstructive surgeries, we reduce plastic waste. Despite not being able to remove PPE completely, we can make dermatology more sustainable, to help save the planet we live on.
P47 Management of extramammary paget disease: a current unmet need
Authors: Labbouz Sofia , Sitaraaman Hemalatha Bhuvanai , Keeling Laura , Murphy Ruth 
Published: June 2023

Abstract
Extramammary Paget disease (EMPD) is a rare epithelial malignancy predominantly affecting the anogenital skin. Primary EMPD carries a risk of invasion and metastasis, as well as malignancy in contiguous organs. No UK guidelines for the management of EMPD exist, resulting in a lack of consensus for staging and screening for associated cancers. We collected consecutive cases of histologically diagnosed EMPD at a regional centre (2017–2022). The aim was to characterize disease presentation, staging and treatment. We identified 22 patients [12 (55%) women, 10 (45%) men; mean age 72 years]. Affected sites were the vulva (n = 10; 45%), male genitalia (n = 7; 32%), perianal area/buttocks (n = 3; 14%), suprapubic area (n = 2; 9%) and axilla (n = 1; 4%). One patient had vulval and anal EMPD. All patients were referred from primary care to multiple secondary care services, including dermatology (n = 9; 41%), gynaecology (n = 9; 41%), urology (n = 2; 9%) and colorectal surgery (n = 1; 4.5%). Nine patients (41%) were jointly managed with dermatology. Sixteen (73%) patients were discussed at a multidisciplinary team (MDT) meeting; nine (41%) at the specialist skin cancer MDT and seven (32%) at other MDTs (anal cancer, colorectal, urology, oncology, gynae-oncology). Screening for associated malignancy was performed for 14 patients (64%). Eleven patients (50%) had histological evidence of invasion of their primary EMPD, of which nine (82%) underwent advanced imaging with computed tomography, positron emission tomography or magnetic resonance imaging. Treatment was directed by the stage of the disease (Table 1). Three patients (14%) developed metastatic EMPD and died despite radiochemotherapy or chemotherapy and surgery. Our data confirm a low prevalence of EMPD, but mortality for metastatic EMPD appears high. EMPD is a complex disease involving the skin. Patients are best managed by a specialist skin cancer MDT in conjunction with other relevant cancer MDTs. A greater understanding of this disease is needed to standardize care. Table 1Treatment received by our patient cohort with corresponding staging of extramammary Paget disease (EMPD)TreatmentPatients, n (%)Tumour classificationEMPD stagingTopical agents5 (23)TisIntraepithelial (in situ) EMPDSurgery12 (54)T1Tumour thickness ≤ 4 mm and no lymphovascular invasionChemotherapy/radiotherapy ± surgery5 (23)T2Tumour thickness &gt; 4 mm or lymphovascular invasion
P52 Addressing the overtreatment of basal cell carcinoma and other skin cancer in the UK
Authors: Elmansouri Ahmad , Alcena Jessica , Venables Zoë , van Bodegraven Birgitta , Powell James , Gazzani Paul 
Published: June 2023

Abstract
The incidence of keratinocyte cancers continues to increase in the UK, although survival is favourable compared with other cancers. This, coupled with a progressively ageing population, has resulted in an increasing number of clinical situations in which we question the benefit to the patient of treating their skin cancer. Currently, the main barrier to preventing overtreatment is the lack of a nationally accepted method for determining survival in patients with skin cancers. This study aims to identify trends in national datasets that support decision-making in basal cell carcinoma (BCC) intervention for frail patients. Frailty is multifactorial, but age is an independent predictor of physical frailty. National databases (Get Data Out—CancerData; national life tables from the UK Office for National Statistics) were accessed to identify the average life expectancy at a given age based on the mortality rates experienced between 2018 and 2022. Average life expectancy reduced in a linear fashion with increasing age. At 80 years of age, the average number of years a woman survived was 9.66 years vs. 3.6 years at 93 years of age. Crude rates for BCC in the whole population (total BCC) are lower than the crude rates in the older population (80+ years). Kaplan–Meier survival (i.e. how many patients are alive after 5 years) was 80% overall and dropped to approximately 55% for the population aged 80+ years. These data support the notion that with increasing age and subsequent frailty, life expectancy in the general population independent of comorbidities shortens. Having hard cutoffs for surgical intervention by age is a reductionist approach. Potential decision aids include frailty scores. Some frailty scores are specifically designed to estimate all-cause mortality. The OPERAM (Optimising Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older People) trial compared several of these mortality scores. The Gagné Index performed most highly with a positive predictive value of 31% and a negative predictive value of 85% (Schneider C, Aubert CE, del Giovane C et al. Comparison of 6 mortality risk scores for prediction of 1-year mortality risk in older adults with multimorbidity. JAMA Netw Open 2022; 5:e2223911). The combination of national data and predictive scoring systems may be helpful in supporting decision-making when considering surgical intervention. Modification of this approach to achieve greater predictive value may be possible in order to achieve better outcomes.
P57 Retrospective review of patients with lentigo maligna treated with topical 5% imiquimod (Aldara®) at a single tertiary UK centre: need for more practical standardized treatment guidelines in the UK
Authors: Sambi Pavan , Ghadiri Sina , Afzal Usamah , Muinonen-Martin Andrew , Mitra Angana 
Published: June 2023

Abstract
Lentigo maligna (LM) is an in situ melanoma arising on chronically sun-damaged skin predominantly on the head and neck. While surgery is the gold standard treatment for LM, imiquimod 5%, which is an immune-response modifier, is a well-reported off-licence treatment in both primary and adjuvant settings. Various treatment regimens have been published. We present our retrospective experience of using imiquimod to treat LM over 10 years at a UK tertiary melanoma centre. We report on indications, treatment regimes, side-effects and treatment efficacy. We identified 71 patients with LM treated with imiquimod with a mean age at diagnosis of 73.3 years. Ninety-three per cent were located on the head and neck. Forty-three per cent (n = 29/67) of patients were treated primarily (following punch biopsy diagnosis or incomplete excision with visible pigmentation remaining) and 57% (n = 38/67) with adjuvant treatment (excision with narrow or close margins, &lt; 3 mm with no visible pigmentation). Invasive disease was seen in 17% of those treated primarily and 45% treated with adjuvant therapy. There were various treatment regimens, but the majority (55%) had treatment prescribed five times weekly for 11–12 weeks, with no significant difference in treatment regimens between the two treatment groups. Inflammation was recorded as none (20%), mild (21%), moderate (21%) and severe (20%). Side-effects were redness (40%), pain (17%), ulceration (7%) and systemic symptoms (6%). Fifty-nine per cent of the primary group had visible clearance; a previous study reported a 71% clinical response in this cohort. Three of the responders relapsed, with two progressing to LM melanoma within 8 years. Forty-eight per cent remained disease free, with a mean follow-up of 27 months. Of those treated with adjuvant therapy, 89% remained clinically disease free at mean follow-up of 19 months. Recurrence in the adjuvant group was reported as 5.6% (Lallas A, Moscarella E, Kittler H et al. Real-world experience of off-label use of imiquimod 5% as an adjuvant therapy after surgery or as a monotherapy for lentigo maligna. Br J Dermatol 2021; 185:675–7). Our limitations include a lack of post treatment biopsies. In 2021, an Australian study reported a practical guide on the use of imiquimod for LM (Guitera P, Waddell A, Paton E et al. A practical guide on the use of imiquimod cream to treat lentigo maligna. Australas J Dermatol 2021; 62:478–85). We propose the need for clearer UK guidelines describing the escalation and de-escalation of treatment in the event of no response and toxicity, respectively. We suggest using a patient application diary to ensure compliance and document changes in treatment and inflammation.