bluuebunny/crossref_metadata_2025 huggingface dataset:
P28 Impact of the COVID-19 pandemic on cutaneous squamous cell carcinoma pathology reports in England and its nine regions: 1127 fewer cSCCs reported in 2020 compared with that in 2019
Authors: Wall James , Venables Zoe , Levell Nick
Published: June 2023

During the COVID-19 pandemic, three waves of infection in 2020–2021 in England were associated with reductions in the reported numbers of many cancers. Possible factors included patient anxiety in attending hospitals, shielding, staff redeployment, and staff and patient sickness. This study analysed national pathology record data to identify whether cutaneous squamous cell carcinoma (cSCC) counts decreased during the COVID-19 pandemic. The Cancerstats2 keratinocyte cancer tool data between January 2016 and December 2021 were assessed. Percentage differences were compared between cSCC reports in England and its regions during each of the three COVID-19 waves and similar time periods in 2019. Crude incidence rates per 100 000 person-years (PY) and incidence rate ratios (IRR) with 95% confidence intervals (CIs) were calculated. From 2016 to 2019, annual cSCC reports totalled 42 180, 44 460, 46 439 and 48 701, respectively (+4.9% mean yearly increase). cSCC reports decreased by 1127 to 47 574 in 2020 (–2.3%), an important finding given the previously increasing trend. cSCC reports increased to 48 798 in 2021 (0% change from 2019). The greatest reductions were in North East England (n = 230; −9.1%) and the East Midlands (n = 299; −9.0%). The crude cSCC incidence rate per 100 000 PY reduced from 86.5 (95% CI 85.7–87.3) in 2019 to 84.1 (95% CI 83.4–84.9) in 2020 (IRR 0.98, 95% CI 0.97–0.99; P < 0.05) and 86.3 (95% CI 85.5–87.1) in 2021 (IRR 1.00, 95% CI 0.99–1.01). During the first wave (April 2020), 42.3% fewer cSCCs were reported in England. In the second (December 2020) and third waves (January 2021), cSCC reports increased (3.6% and 2.5%, respectively). The regional variation in cSCC reports compared with 2019 ranged between −51.4% and −35.5% (first wave), between −6.2% and +35.2% (second wave), and between −23.4% and +26.5% (third wave). This is the largest study to assess the COVID-19 pandemic impact on cSCC counts. The decrease in cSCC reports was less than that reported for melanoma. cSCCs often present symptomatically, possibly making patients more likely to seek medical attention than with melanomas. Study limitations include that the cancerstats2 tool was developed for quality analysis purposes and not for epidemiology. It provides more up-to-date pathology counts but does not undergo the same quality control processes as gold standard, formally registered data. These data are used as a proxy, indicative for diagnoses, but should be interpreted with caution. Although mortality rates for cSCC are low, delayed diagnosis may lead to poorer outcomes. The long-term consequences of delayed cSCC diagnosis during the COVID-19 pandemic will become clearer with time.
P29 Selfies: not ideal!
Authors: Tuckwell William , Godwin Alison
Published: June 2023

We sought to determine whether the quality of photographic referrals from primary care had been impacted by the COVID-19 pandemic. A total of 2411 referrals made in 2020, 2021 and 2022 were retrospectively reviewed. From this, data were collected on urgent suspected cancer (USC) referrals (n = 1174) made between 1 January and 31 March. For each referral, the photographs included were reviewed. Eighty-four per cent of the 271 USC referrals made in 2020 included photos, 90.3% of the 413 referrals in 2021 and 91.2% of the 490 referrals in 2022. We devised criteria to determine quantitatively the quality of photographs based on the presence of a locator image, a close-up image, a ruler, a dermatoscopic image and whether the photos were in focus. Each feature scored 1, generating a quality score of 0–5. The mean quality scores in 2020, 2021 and 2022 were 2.16, 2.13 and 2.30, respectively. A Kruskal–Wallis test was performed to determine whether there was statistical significance to the differences seen between the sample groups. The alternative hypothesis was that the distribution of the quality scores across the sample groups was unequal. An overall P-value of 0.075 was generated, which was below the threshold of 0.1; therefore, the alternative hypothesis was accepted. On paired comparison between the sample groups, there was a statistically significant increase from 2021 to 2022, with an adjusted P-value of 0.069. We also subjectively judged whether the photos from each referral had made a positive impact on the final diagnosis. Seventy-five per cent (n = 170) of referrals in 2020, 251 (67.3%) in 2021 and 356 (79.6%) in 2022 included photos that had a positive impact on the final diagnosis. To conclude, our results showed that there was a significant decrease in the quality of photographs included in USC referrals in 2021 when compared with the sample groups of 2020 and 2022, suggesting that the COVID-19 pandemic had a negative impact on the triage of USC referrals from primary care. This could be explained by the reduction in face-to-face consultations and an increase in the number of patient-provided images. The results highlight that a significant proportion of images sent by general practitioners and patients are of insufficient quality for effective review and diagnosis. Possible solutions proposed include further provision of medical photography services and education. This work will be used as a baseline for the introduction of a teledermatology service.
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

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

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 < 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

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

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 > 17 years old; Children’s DLQI (CDLQI) for patients aged > 12 to < 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 < 0.001 and P < 0.01, respectively) and statistically significantly decreased following dupilumab initiation as early as week 2 (P < 0.001 and P < 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 < 0.001 and P < 0.05)] for CDLQI. Improvement was sustained through to week 16 [mean (SD) change from baseline; P < 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 < 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

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

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 > 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

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

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, < 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.
P64 Efficacy of baricitinib in patients with different degrees of severe alopecia areata: 52-week results from BRAVE-AA1 and BRAVE-AA2
Authors: Farrant Paul , Egeberg Alexander , Ito Taisuke , Gittens Beatrice , Chiasserini Chiara , Yu Guanglei , Durand Frederick , Huang Yu-Huei
Published: June 2023

Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, demonstrated efficacy in adults with severe alopecia areata (AA) over 36 weeks in two phase III, randomized, double-blind, placebo-controlled trials, BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259). Using integrated data from the long-term extension periods of both trials, we report treatment response to baricitinib by the AA severity subgroup based on the Severity of Alopecia Tool (SALT) score over 52 weeks. Patients randomized to baricitinib at baseline (n = 855) retained their treatment allocation (2 mg/4 mg) through to week 52 in both trials and were included in week 52 analyses; placebo nonresponders were rescued at week 36. Severity of AA at baseline was defined as severe (SALT score 50–94) or very severe (SALT score 95–100). Key inclusion criteria were SALT score ≥ 50, current AA episode lasting > 6 months to < 8 years without spontaneous improvement within 6 months prior to screening, and no previous inadequate response to oral JAK inhibitors. Efficacy endpoints included the proportion of patients achieving a SALT score ≤ 20 and the proportion of patients achieving Clinician-Reported Outcome (ClinRO) Measure for Eyebrow/Eyelash Hair Loss™ 0,1 (no, minimal gaps) with ≥ 2-point improvement from baseline among patients with baseline scores 2,3 (significant gaps, no notable eyebrows/eyelashes). Analyses were presented descriptively for each subgroup up to week 52. Nonresponder imputation was used for missing data. Data collected after permanent study drug discontinuation or at remote visits due to the COVID-19 pandemic were excluded. In total, 1200 patients were enrolled (BRAVE-AA1, n = 654; BRAVE-AA2, n = 546). At baseline, the overall mean (SD) age was 37.5 (12.9) years; 60.7% were female and 46.8% and 53.2% of patients had severe and very severe AA, respectively. At week 52, a SALT score ≤ 20 was achieved by 36.1% and 51.2% of patients on baricitinib 2 mg and baricitinib 4 mg, respectively, with severe AA and 12.4% and 27.7% of patients on baricitinib 2 mg and baricitinib 4 mg, respectively, with very severe AA. Eyebrow/Eyelash Hair Loss™ scores 0,1 with ≥ 2-point improvement from baseline at week 52 were achieved by 19.4% and 26.0% (baricitinib 2 mg) and 37.5% and 38.5% (baricitinib 4 mg) of patients with severe AA and 24.3% and 25.3% (baricitinib 2 mg) and 47.6% and 48.1% (baricitinib 4 mg) of patients with very severe AA. Following 52 weeks of treatment with both baricitinib doses, clinical responses of SALT score ≤ 20 were observed both in patients with severe and very severe AA. Proportions of patients achieving full coverage or minimal gaps in eyebrows and eyelashes were similar at week 52, regardless of scalp hair-loss severity.

Funding sources: Eli Lilly and Company.
P65 Vitamin D deficiency is associated with atopic dermatitis severity in a Bangladeshi population living in the UK
Authors: McCarthy Rebecca L , Thomas Bjorn R , Tawfik Soha S , Atkar Ravinder , McDonald Bryan , Dhoat Sasha , Hughes Aaron , O’Toole Edel
Published: June 2023

Atopic eczema is a common chronic inflammatory skin condition with considerable heterogeneity. South Asian people living in the UK frequently have low vitamin D levels, and those with atopic disease can present with severe eczema. The association between vitamin D insufficiency and eczema severity and the role of vitamin D supplementation in atopic eczema is inconsistent, and it is under-researched in people with Asian ancestry living in low-ultraviolet (UV) areas. This cross-sectional study investigates the association between serum 25-hydroxy vitamin D3 [25(OH)D3] and eczema severity in a cohort of South Asian children and young adults living in the UK. Eligible participants were Bangladeshi children and young adults aged 0–30 years with eczema, participating in the THEA study. Data for the study were collected via parent/patient self-reporting, clinical history and examination and hospital databases. Levels of 25(OH)D3 were documented retrospectively, if available, from hospital databases. Eczema severity was classified by an Eczema Area and Severity Index (EASI) score less than or greater than 10. Multivariate logistic regression was used to adjust for confounding factors. In total, 682 patients were recruited between May 2018 and December 2021. The EASI score was available for 681 participants [mean (SD) 7.9 (9.1)] and 25(OH)D3 results were available for 49.7% (n = 339). Eighty-four per cent were deficient (< 25 nmol L−1) or insufficient (< 50 nmol L−1) in 25(OH)D3. Vitamin D3 levels were inversely correlated with the EASI score (Spearman’s rank R2 = –0.22; P < 0.001). After adjustment, there was a significant association between eczema severity (EASI > 10) and lowest 25(OH)D3 [odds ratio (OR) 0.973, 95% confidence interval (CI) 0.956–0.988; P < 0.001], working class (OR 0.542, 95% CI 0.295–0.991; P = 0.047), previous immunosuppression/biologic therapy (OR 2.432, 95% CI 1.189–5.077; P = 0.016), mild-to-moderate potency topical steroid use on the face and neck (OR 3.566, 95% CI 1.730–7.696; P < 0.001) and topical calcineurin inhibitor use on the face and neck (OR 3.421, 95% CI 1.140–10.288; P = 0.027). These findings demonstrate an inverse correlation between 25(OH)D3 level and eczema severity in a cohort of exclusively South Asian children and young adults living in a low-UV region. Vitamin D plays a role in the modulation of proteins required for skin barrier function and regulation of the innate immune system, suggesting that vitamin D deficiency in this population may contribute to inflammation in the skin. Further research on the role of vitamin D supplementation in atopic eczema, particularly in people with skin of colour, is required.
P68 Liver fibrosis is independent of methotrexate use in patients with moderate-to-severe psoriasis
Authors: Babakinejad Parastoo , Lapsley Rebecca , Foster Lara , McPherson Stuart , Pearce Mark , Reynolds Nick , Slack Emma , Weatherhead Sophie , Hampton Philip
Published: June 2023

Methotrexate has been implicated for liver disease in patients with psoriasis for many years. Liver fibrosis (LF) has various established risk factors, but data on the impact of methotrexate on LF in patients with psoriasis are lacking. This cross-sectional cohort study aimed to determine the prevalence of LF using noninvasive LF markers in patients with psoriasis, and to evaluate the relationship between LF and the cumulative dose of methotrexate and other liver disease risk factors. Adults with moderate-to-severe chronic plaque psoriasis diagnosed by a dermatologist, who were selected for a LF assessment, were recruited from dermatology clinics in a tertiary centre between June 2020 and March 2021. Data were recorded as part of standard clinical care and at the time of recruitment. Patients underwent transient elastography to evaluate LF. Three values for liver stiffness measurement (LSM) were used, indicating ≥ mild LF (≥ 7 kPa), ≥ moderate LF (≥ 7.9 kPa) and ≥ advanced LF (≥ 9.5 kPa). Both continuous and categorical LSM values were used for evaluation. A total of 225 patients were included [median age 48, interquartile range (IQR) 37–57, 51% female]. Fifty-six per cent had a body mass index (BMI) ≥ 30 kg m−2, and the median alcohol use disorders identification test (AUDIT) score was 4 (IQR 1–7, 23% score ≥ 8). Ninety-one per cent had received methotrexate for a median duration of 36 months (IQR 14–78). Prevalence rates of LF were 31%, 21% and 13% using LSM ≥ 7 kPa, ≥ 7.9 kPa and ≥ 9.5 kPa, respectively. There was no association between methotrexate and continuous LSM values [unadjusted coefficient 0.16, 95% confidence interval (CI) 0.49–0.82; P = 0.63] or using the categorical LSM cutoff values: 7 kPa (unadjusted coefficient 1.06, 95% CI 0.98–1.15; P = 0.19), 7.9 kPa (unadjusted coefficient 1.03, 95% CI 0.94–1.12; P = 0.58) and 9.5 kPa (unadjusted coefficient 1.01, 95% CI 0.91–1.12; P = 0.84). Similarly, no significant relationship was found when adjusting for other risk factors for LF. The following risk factors were associated with higher LSM values: BMI (P < 0.001), waist circumference (P < 0.001), metabolic syndrome (P < 0.001), AUDIT score (P = 0.020) and Fib-4 score (P = 0.03). This study confirms a high prevalence of significant LF in patients with moderate-to-severe psoriasis. More importantly, it shows that cumulative methotrexate was not associated with LF, and other risk factors including BMI, waist circumference, metabolic syndrome, alcohol intake and Fib-4 score are important predictors for LF. The findings suggest that these risk factors should be assessed in this group of patients to identify patients requiring regular liver health monitoring. Further research is needed to determine whether methotrexate contributes to the progression of LF in the context of pre-existing LF.
P70 A randomized open-label study to compare two different dosage regimens of oral tranexamic acid in treatment of moderate-to-severe facial melasma
Authors: Keshavamurthy Vinay , Bhattacharjee Rajsmita , Hanumanthu Vinod , Thakur Vishal , Bishnoi Anuradha , Parsad Davinder , Kumaran Muthu Sendhil
Published: June 2023

Oral tranexamic acid (TXA) demonstrates promising results in melasma treatment; however, TXA dosing in melasma management has been a cause for persistent speculation. There is still no consensus to guide dosing, duration of TXA therapy and need for maintenance treatment. Our aim was to evaluate and compare the efficacy of two different TXA dosing regimens, 250 mg twice daily vs. 500 mg twice daily in patients with melasma using the modified Melasma Area and Severity Index (mMASI) score. This was a randomized open-label study involving 50 patients aged > 18 years with moderate-to-severe melasma. Patients were randomized into group A (oral TXA 250 mg twice daily) and group B (oral TXA 500 mg twice daily) for 12 weeks and later followed-up monthly to 24 weeks. The primary outcome measure was the proportion of patients achieving a 75% reduction in mMASI (mMASI-75) at 12 weeks from baseline, and a reduction in mMASI and Melasma Quality of Life (MelasQOL) score at 12 and 24 weeks. The proportion of patients achieving mMASI-75 at 12 weeks was 20% in group A and 25% in B (P = 0.71). Both groups showed a statistically significant reduction in mean (SD) mMASI [4.8 (2.2) in group A and 6.8 (3.4) in group B; P = 0.02] at 12 weeks. mMASI remained stable after 12 weeks and was 4.9 (2.43) and 4.92 (2.85) in groups A and B, respectively, at 24 weeks (P = 0.97). The mean (SD) percentage reduction rates in MelasQOL in groups A and B were 41.8 (15.3) and 29.5 (21.5), respectively (P = 0.03). No adverse effects were observed in either group. Both dosing regimens showed comparative efficacy in terms of mMASI reduction at 12 weeks. The improvements achieved were well maintained even after 12 weeks of discontinuing treatment. Hence, lower doses of TXA (i.e. 250 mg twice daily) are equally as effective and safe as higher doses (i.e. 500 mg twice daily). With regard to maintenance dosing, few patients relapsed; hence, not all patients will require tapering or dosing maintenance.
P73 Laboratory safety from a 16-week phase III study of dupilumab in patients aged 6 months–5 years with moderate-to-severe atopic dermatitis
Authors: Paller Amy S , Cork Michael J , Wollenberg Andreas , Siegfried Elaine C , Gonzalez Mercedes E , Lockshin Benjamin , Khokhar Faisal A , Chen Zhen , Gonzalez Tayler , Simcox Elizabeth , Prescilla Randy
Published: June 2023

Previous studies of dupilumab treatment in adults, adolescents and children aged 6–11 years with moderate-to-severe atopic dermatitis (AD) showed no clinically meaningful changes in laboratory parameters. Here, we evaluate laboratory safety data for dupilumab-treated children aged 6 months–5 years with moderate-to-severe AD. In LIBERTY AD PRESCHOOL (NCT03346434 part B), a placebo-controlled phase III trial, 162 children aged 6 months–5 years with moderate-to-severe AD were randomized to receive dupilumab 200 mg or 300 mg every 4 weeks (n = 83) based on baseline weight (200 mg: ≥ 5 to < 15 kg; 300 mg: ≥ 15 to < 30 kg), or placebo (n = 79) for 16 weeks. Low-potency topical corticosteroids were initiated from day −14. At baseline, mean (SD) haematology parameters were similar in both treatment groups: eosinophils [dupilumab: 1.1 × 109 cells L−1 (0.7); placebo: 1.1 × 109 cells L−1 (0.7)], platelets [dupilumab: 397.7 × 109 cells L−1 (103.2), placebo: 385.6 × 109 cells L−1 (112.9)] and neutrophils [dupilumab: 3.54 × 109 cells L−1 (1.56); placebo: 3.85 × 109 cells L−1 (1.73)]. Mean (SD) counts of neutrophils [dupilumab: 3.18 × 109 cells L−1 (1.94); placebo: 3.79 × 109 cells L−1 (1.91)] remained within the normal reference interval (RI) at week 16. Mean (SD) change in platelet count at week 16 was −16.3 × 109 cells L−1 (78.5) in the dupilumab group and 17.4 × 109 cells L−1 (106.6) in the placebo group. In the dupilumab group, the mean (SD) change in eosinophil count increased at week 4 [0.48 × 109 cells L−1 (1.8)] and trended downward by week 16 [0.31 × 109 cells L−1 (1.4)], while minimal changes were noted in the placebo group at week 4 [0.1 × 109 cells L−1 (0.7)] and week 16 [−0.2 × 109 cells L−1 (0.7)]. The mean (SD) values for creatine kinase [dupilumab: 144.2 U L−1 (84.8); placebo: 130.7 U L−1 (46.39)], alkaline phosphatase [dupilumab: 273.4 U L−1 (80.01); placebo: 233.2 U L−1 (65.98)] and lactate dehydrogenase [dupilumab: 283.8 U L−1 (44.74); placebo: 317.4 U L−1 (67.58)] at week 16 remained within the normal RI in all treatment groups. Two patients treated with dupilumab reported cases of severe and moderate eosinophilia. Neither event was associated with clinical symptoms nor led to the discontinuation of study treatment. No clinically meaningful changes in haematology or chemistry laboratory safety parameters in children aged 6 months–5 years with moderate-to-severe AD were seen with 16 weeks of dupilumab treatment. These data demonstrate that, as with adults, adolescents and older children, routine laboratory monitoring is unnecessary in this population.

Funding sources: research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.
P78 Amyopathic dermatomyositis: a retrospective review of 21 cases
Authors: Sambi Pavan , Khan Wajeeha , Laws Phil
Published: June 2023

Amyopathic dermatomyositis (ADM) is a clinical subtype of dermatomyositis, which can be associated with malignancy and lung disease. We report a retrospective review of 21 cases of ADM presenting to a tertiary clinic. We discuss the clinical presentations, investigation, and cancer and lung associations. Patients were included if they met the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria for ADM. We identified 21 patients with ADM (16 women and five men). Mean age at diagnosis was 61 years (range 35–81). Clinical features were as follows: Gottron papules (n = 15; 71%), nailfold involvement (n = 16; 76%), heliotrope rash (n = 12; 57%), shawl sign (n = 11; 52%), Raynaud phenomenon (n = 9; 43%), scalp disease (n = 6; 29%) and calcinosis (n = 3; 14%). Antinuclear antibody (ANA) was positive in 76% of patients (n = 16) and 41% (n = 9) had myositis-specific antibodies. Four patients had a prediagnosed malignancy. One patient had prostate cancer detected on malignancy screen. One nerve sheath tumour was diagnosed within 1 year of ADM diagnosis and one cholangiocarcinoma within 3 years. Three patients were found to have mild lung fibrosis, but none was found to have severe interstitial lung disease. Patients were treated with corticosteroids (n = 16), hydroxychloroquine (n = 11), metho­trexate (n = 10), mycophenolate (n = 6), cyclophosphamide (n = 3), rituximab (n = 3), intravenous immunoglobulin (n = 3), mepacrine (n = 2), azathioprine (n = 1), ciclosporin (n = 1) and thalidomide (n = 1). In conclusion, in our study, a female preponderance and cutaneous findings involving extremities were seen in the majority of patients (95%), in keeping with other published data (el-Azhary RA, Pakzad SY. Amyopathic dermatomyositis: retrospective review of 37 cases. J Am Acad Dermatol 2002; 46:560–5). Our study further highlights the heterogeneity of cutaneous clinical presentation of ADM, which is broadly consistent with other reported cohorts [el-Azhary and Pakzad; Tang K, Zhang H, Jin H. Clinical characteristics and management of patients with clinical amyopathic dermatomyositis: a retrospective study of 64 patients at a tertiary dermatology department. Front Med (Lausanne) 2021; 8:783416]. We report high levels of hand and nail involvement, emphasizing the need for formal assessment of hands, including dermoscopy of nails. ANA was positive in 76% of patients; other reported data suggest that it is positive in 31.6–71% (el-Azhary and Pakzad; Tang et al.). Although previous studies have found myositis-specific antibodies in 87.5% (Tang et al.), only 42% in our cohort had positive antibodies; therefore, a high index of suspicion is required to detect cases and appropriately screen for associated morbidity (lung disease and malignancy). In addition, a third of patients had associated malignancy prediagnosed or within 3 years of diagnosis, highlighting the importance of baseline screening and ongoing follow-up.
P84 Efficacy and safety of lebrikizumab at 16 weeks: pooled analyses from ADvocate1 and ADvocate2 phase III trials in patients with moderate-to-severe atopic dermatitis
Authors: Warren Richard B , Silverberg Jonathan I , Guttman-Yassky Emma , Thaçi Diamant , Irvine Alan , Gold Linda Stein , Blauvelt Andrew , Simpson Eric L , Chu Chia-Yu , Liu Zhuqing T , Lima Renata Gontijo , Pillai Sreekumar , Gil Esther Garcia , Seneschal Julien
Published: June 2023

Lebrikizumab (LEB) is a high-affinity monoclonal antibody targeting interleukin (IL)-13, preventing IL-13 signalling via the IL-4Rα/IL-13Rα1 receptor complex. Here, we report 16-week efficacy and safety outcomes of LEB monotherapy in patients with moderate-to-severe atopic dermatitis from two 52-week, randomized, double-blinded, placebo-controlled phase III trials, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Eligible adults and adolescents (aged 12–17 years, weighing ≥ 40 kg) from ADvocate1 and ADvocate2 were randomized (2 : 1) to subcutaneous LEB 250 mg (500 mg loading dose at baseline and week 2) or placebo every 2 weeks (Q2W). Efficacy analyses included proportions of patients achieving Investigator’s Global Assessment (IGA) 0/1 and Eczema Area and Severity Index (EASI)-75 (coprimary endpoints), EASI-90, and pruritus numeric rating scale (NRS) ≥ 4-point improvement from baseline to week 16. This was a pooled analysis of ADvocate1 and ADvocate2, where IGA 0/1 and EASI-75 and EASI-90 were analysed in 564 and 287 patients (LEB 250 mg and placebo), respectively, and pruritus NRS in 516 and 264 patients, respectively. Cochran–Mantel–Haenszel with Markov chain Monte Carlo multiple imputation was performed. Patients treated with LEB 250 mg and placebo for 16 weeks achieved, respectively, IGA 0/1 response rates of 38.1% (n = 215) and 11.7% (n = 34; P < 0.001); EASI-75 responses of 55.4% (n = 313) and 17.2% (n = 49; P < 0.001); EASI-90 responses of 34.5% (n = 195) and 9.2% (n = 26) (P < 0.001); and pruritus NRS ≥ 4-point improvement responses of 42.9% (n = 221) and 12.2% (n = 32; P < 0.001). The percentage of patients reporting one or more treatment emergent adverse event(s) was lower in the LEB group (49.6%) than in the placebo group (59.0%; P = 0.009). These data suggest that LEB 250 mg Q2W for 16 weeks is an efficacious and safe treatment option for adult and adolescent patients with moderate-to-severe atopic dermatitis.

Funding sourcesThis study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Almirall has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including atopic dermatitis, in Europe. Lilly has exclusive rights for development and commercialization of lebrikizumab in the United States and the rest of world outside Europe.