bluuebunny/crossref_metadata_2025_split huggingface dataset:
RF02 Using functional genomic techniques to help us understand the TYK2 pathway in psoriasis
Authors: Elyoussfi Sarah , Rane Shraddha , Eyre Stephen , Warren Richard 
Published: June 2023

Abstract
Genetic screens have identified around 126 genetic signals associated with psoriasis through genome-wide association studies (GWAS) and rare variant analyses (Tsoi LC, Stuart PE, Tian C et al. Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants. Nat Commun 2017; 8:15382). The aim of this study was to use genome-editing techniques to investigate and validate the effect of a psoriasis-associated genetic signal on the expression of TYK2. GWAS have linked TYK2 to psoriasis susceptibility through the association of a protein-changing, exonic variant where TYK2 impairment confers protection against the development of psoriasis and other autoimmune diseases. The vast majority of disease risk-associated variants are found outside gene-coding regions. Functional experimental techniques may help characterize the effect of these variants on gene expression. The development of genome editing technology, clustered regularly interspaced short-palindromic repeat-Cas9 (CRISPR-Cas9), has made it possible to edit cell genomes. We used CRISPR-Cas9 to validate functionally the psoriasis-associated single nucleotide polymorphism (SNP) rs892085 on TYK2 expression in immortal T-cell lines. In-house data from our centre revealed the presence of long-range physical interactions between rs892085 and TYK2. We are the first to investigate functionally this signal and characterize this physical connection. We used CRISPR-Cas9 systems to both activate and inhibit the region around rs892085 and then measured the consequence of this through informative functional readouts using quantitative reverse transcription polymerase chain reaction. This revealed consistent alteration of TYK2 expression upon inhibition and activation of rs892085. This supports previous observations, where this regulatory region harbouring GWAS-implicated variation operates through direct long-distance contact. Previously, the closest or most biologically relevant gene was often assigned to a GWAS variant. We have shown that this is unreliable, with DNA regions looping over large distances to control genes. This work provides the first functional validation of the psoriasis-associated SNP rs892085. TYK2 is a recognized drug target with one therapy, deucravacitinib, approved by the US Food and Drug Administration. Drugs entering the clinical development stage that have used human genetic data to select drug targets may be more likely to succeed. This work demonstrates the potential complexity of how risk alleles may work to dysregulate TYK2 signalling in disease, with both gene function and expression increasing the risk of disease. Ultimately, genetic risk scores, incorporating functional evidence from studies like this, may be generated to predict how patients with different genetically perturbed biology pathways may respond to therapy.
CPC03 Triad of generalized rash, peripheral eosinophilia and coexisting obstructive airway disease
Authors: Willsher Alex , Soriano Livia , Selim Salma , Fong Wei Chen , Fityan Adam 
Published: June 2023

Abstract
An 87-year-old woman was referred to the acute dermatology service with a 1-week history of a generalized painful rash. She was under the care of the medical team for treatment of pneumonia with symptoms of a cough, fevers and shortness of breath. Her past medical history included adult-onset asthma, hyponatraemia and hypertension. She had never smoked. On examination, she had erythematous smooth papules and plaques on her limbs and torso with palmoplantar involvement, alongside purple macules and patches where older lesions were present. There was no lymphadenopathy and no mucosal involvement. She had an oxygen requirement of 2 L per minute via nasal cannula. Initial blood tests showed eosinophils of 2.8 × 109 cells L−1 and a C-reactive protein (CRP) of 77 mg L−1. A chest radiograph showed bilateral ill-defined shadowing. Two skin punch biopsies were performed for histology and immunofluorescence. Vasculitis screen identified positive antinuclear antibodies (anti-Ro) and reduced complement C4 with negative antineutrophil cytoplasmic antibody (ANCA). The patient remained unwell with increasing CRP and peripheral eosinophilia (up to 9.2 × 109 cells L−1) with rash progressing to exhibit a reticular pattern. Alongside bilateral patchy ground glass opacification on chest computed tomography, a clinical diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) was made. Differential diagnoses included viral exanthem, erythema multiforme and urticarial vasculitis. Screening for cardiac, renal and sinus involvement was undertaken. The patient improved clinically following the initiation of systemic steroids and the peripheral eosinophilia returned to baseline. Skin histology reinforced the clinical diagnosis of EGPA, demonstrating a dermal and perivascular eosinophilic infiltrate with focal extension into vessel walls. EGPA is a rare small- to medium-sized vessel vasculitis with an annual incidence of 0.9–2.4 per million and a median age at diagnosis of 49–59 years. The clinicopathological hallmarks, as in this case, are asthma with peripheral eosinophilia and pulmonary eosinophilic infiltrates. Median time from onset of asthma to presentation with EGPA is 5–9 years. EGPA remains a clinical diagnosis, reinforced by serological and histological findings, although ANCA is reported to be negative in 60–70% of cases. Systemic steroids are the first-line therapy, with a role for second-line immunosuppressants such as methotrexate and rituximab. The key learning points from this case are to keep an open mind in considering a systemic cause for cutaneous manifestations, especially when the patient does not fulfil the usual demographic picture.
CPC05 A case of extensive hypertrophic lupus erythematosus responsive to topical steroids
Authors: Diong Sophie , Woods Graham , Wynne Bairbre 
Published: June 2023

Abstract
Hypertrophic lupus erythematosus (HLE) is a rare variant of lupus erythematosus, occurring in 2% of cases of chronic cutaneous lupus erythematosus (CCLE). It is an exaggerated proliferative epithelial response manifesting as verrucous-appearing hypertrophic indurated lesions occurring on sun-exposed sites. We present a case of the development of extensive HLE in a patient with subacute cutaneous lupus erythematosus (SCLE) with underlying pulmonary malignancy. A 74-year-old woman with Sjögren syndrome presented to dermatology with a 2-month history of a rash affecting her face and décolletage. Laboratory studies illustrated elevated antinuclear and anti-Ro antibodies. Biopsy from her chest confirmed SCLE. Malignancy screening revealed T1aN0 pulmonary lepidic adenocarcinoma, which was successfully managed with a lower lobectomy. Hydroxychloroquine was initially trialled but required discontinuation following intolerable side-effects. Mepacrine was then initiated, which allowed clearance of the rash, alongside yellow discoloration of the skin. Six months later, she developed a raised pruritic rash on her arms, legs and buttocks, resistant to current management alongside a trial of mycophenolate mofetil. Examination revealed violaceous hypertrophic plaques affecting 40% of her body-­surface area. The differential included hypertrophic lichen planus, nodular prurigo and HLE. Repeat lesional biopsies highlighted a lichenoid inflammatory infiltrate with overlying scale, favouring HLE. Owing to patient choice, topical mometasone furoate 0.1% was used to manage cutaneous disease, with a reduction in lesion size. HLE is a distinct subset of CCLE, regarded as a separate entity to SCLE. Twenty per cent of patients with SCLE also exhibit other types of cutaneous lupus erythematosus (CLE) lesions. No cases in the literature describe progression from SCLE to CCLE, or HLE, in particular. Hallmarks of HLE include verrucous lesions, chronicity and treatment resistance. Early recognition and follow-up are essential as malignancy may arise in long-standing lesions. Lung adenocarcinomas and hypertrophic lupus are both associated with p53 mutations and decreased granzyme B expression. Mutated p53 results in constitutive cell proliferation and DNA damage can accumulate in cells. Granzyme B is a protease in cytotoxic T cells involved in immune-mediated cell lysis. Both processes result in the potential to produce exaggerated hyperproliferative lesions, such as those observed in HLE and the lepidic adenocarcinomas. HLE is a rare clinical entity that can be easily misdiagnosed clinically and histopathologically. Increased awareness of this condition is essential to highlight the variety of clinical presentations of uncommon variants of CLE, to ensure they are considered while approaching clinical diagnosis.
CPC09 New-onset agminated Spitz naevi following hypopigmented pityriasis lichenoides chronica
Authors: Adams Laura , Chohan Brinder , Bleiker Tanya 
Published: June 2023

Abstract
A 9-year-old girl presented to dermatology with erythematous scaly patches affecting her legs and arms, and hypo­pigmented patches affecting the trunk. She was otherwise fit and well, with no preceding illness or new medications. Treatment with mometasone 0.1% and an emollient was unsuccessful. Two years later, she had continued to develop new hypopigmented patches, as well as dark clustered naevi on the trunk. An incisional biopsy was taken from a hypopigmented patch of the right abdomen and one of the new naevi from the right hip. Incisional biopsy of the hypo­pigmented patch showed scattered necrotic keratinocytes in the epidermis with mild hydropic degeneration of basal cells and a mild superficial and perivascular lymphohistiocytic infiltrate in the dermis, consistent with pityriasis lichenoides chronica (PLC). Incisional biopsy of an eruptive naevus showed a junctional proliferation of melanocytes with overlying epidermal hyperplasia and hyperkeratosis and transepidermal elimination of melanin. Nests of epithelioid melanocytes were present at the rete tips, with no pagetoid spread and no atypia, consistent with an eruptive Spitz naevus. PLC is a benign lymphoproliferative disorder, typically presenting with erythematous scaly papules that relapse and remit. However, cases of PLC presenting with hypopigmentation alone have also been reported, as in this case, which can be part of a postinflammatory dyspigmentation or active disease (Elbendary A, Abdel-Halim MR, Youssef R et al. Hypopigmented lesions in pityriasis lichenoides chronica patients: are they only post-inflammatory hypopigmentation? Aust J Dermatol 2021; 63:68–73). The clustered pattern of Spitz naevi in this patient is termed agminated Spitz naevus. Eruptive disseminated and agminated Spitz naevi are much rarer than the solitary presentation. Triggers of eruptive Spitz naevi include pregnancy, blistering disorders and topical tacrolimus, and in one case following pityriasis lichenoides et varioliformis acuta (Mazzurco J, Menssen K, Schapiro B et al. Eruptive disseminated Spitz nevi in a 26-year-old African-American woman. Int J Dermatol 2012; 51:1270–1), while agminated Spitz naevi are reported to occur after radiotherapy and sunburn, and to arise in naevus spilus or congenitally hypo- or hyperpigmented patches. No cases of malignancy in agminated or eruptive disseminated Spitz naevi have been reported. In this case, the new onset of agminated Spitz naevi may have been triggered by the inflammatory process of PLC. As far as we can ascertain, there have not been previous cases of this published in the literature. Our patient’s hypopigmented areas have now started to self-resolve and we have planned for ongoing monitoring of the agminated Spitz naevi.
P08 Successful treatment of paediatric morphoea with tofacitinib
Authors: Tang Junchi , Zheng Wenyue , Yang Bin 
Published: June 2023

Abstract
Morphoea is a chronic autoimmune fibrosing condition causing inflammation, skin sclerosis and underlying soft tissue. The Janus kinase (JAK)-STAT pathway is considered to be the downstream mediator in the process of promoting fibrosis by transforming growth factor-β, interleukin-6 and other factors and plays a signal transduction role in the process of fibrosis. JAK inhibitors have been shown in preclinical studies to inhibit the fibrotic pathway in systemic sclerosis (Celada LJ, Kropski JA, Herazo-Maya JD et al. PD-1 up-regulation on CD4(+) T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-beta1 production. Sci Transl Med 2018; 10). Here, we report the successful use of tofacitinib in two paediatric patients. Case 1 was a 6-year-old girl with a 4-year history of morphoea; case 2 was a 13-year-old boy, also with a 4-year history of morphoea. In case 1, we initiated tofacitinib therapy 2.5 mg twice daily, reduced the dose after 2 months and stopped using it after 8 months. For case 2, the dose was 5 mg twice daily for 5 months, considering the patient’s height and weight. We have seen a significant improvement in the appearance and pathology of the lesions. The Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) was used to assess the disease activity and damage, and the post-treatment scores for both cases were significantly lower than before treatment. Skin biopsy in both cases after tofacitinib therapy revealed that collagen bundles were decreased in size and number, with decreased lymphocytic infiltration in the peripheral tissue. Immunofluorescence staining for case 1 showed that activated α-smooth muscle actin and myofibroblasts were significantly decreased after treatment of tofacitinib, mostly in the dermal papillary layer. The two patients remain under follow-up; neither of them has so far relapsed. To our knowledge, these are the first two paediatric cases of morphoea treated with tofacitinib to be reported in the literature. Disease progression was found to have been inhibited clinically and pathologically. The traditional treatment of morphoea with methotrexate, cyclophosphamide or mycophenolate mofetil is not invariably effective in our experience, especially in antifibrosis (Zhao M, Wu J, Wu H et al. Clinical treatment options in scleroderma: recommendations and comprehensive review. Clin Rev Allergy Immunol 2022; 62:273–91). Our results provide the rationale for large prospective cohort studies of tofacitinib in morphoea and other fibrotic disorders.
P18 A novel presentation of glycogenic acanthosis of the lip
Authors: Cosgrave Niall , Clowry Julianne , Coady Laoise , McMenamin Mairin , Moran Benvon 
Published: June 2023

Abstract
Glycogenic acanthosis (GAc) is a benign epithelial disorder, commonly observed in the oesophagus during endoscopy as multiple raised nodules affecting otherwise normal oesophageal mucosae (Tsai SJ, Lin CC, Chang CW et al. Benign esophageal lesions: endoscopic and pathologic features. World J Gastroenterol 2015; 21:1091). Despite its indolent disease course, oesophageal GAc is a minor diagnostic criterion for Cowden syndrome (CS). Glycogenic acanthosis affecting tissues other than the oesophagus is extremely rare. There have only been six cases of oral GAc reported to date, with no confirmed reports of GAc affecting the lip. We present the case of a 65-year-old White man with a 6-month history of asymptomatic white papules on the left lower lip. He was a lifelong nonsmoker. His past medical history was notable for colorectal cancer, which was in remission posthemicolectomy. He had also undergone ablative treatment for nasal polyps. He had no history of gastro-oesophageal reflux disease, or of thyroid disease, benign or malignant. Prominent facial actinic damage was present, and a biopsy was performed to rule out dysplasia. Histology demonstrated thickened hyperplastic epidermis and cytoplasmic clearing in the superficial epidermis. Keratinocytes with enlarged cytoplasm were positive on periodic acid–Schiff staining, supporting a diagnosis of GAc. On review, 3 months later, a single residual white papule was observed on the left lower lip. There were no other cutaneous features suggestive of CS. CS is caused by mutations in PTEN and is part of a spectrum of disorders known as PTEN hamartoma tumour syndrome (PHTS). It is associated with increased risk of solid-organ malignancies. Of the prior six reported cases of oral GAc, only one (Nishizawa A, Satoh T, Watanabe R et al. Cowden syndrome: a novel mutation and overlooked glycogenic acanthosis in gingiva. Br J Dermatol 2009; 160:1116–18) had a confirmed association with CS. Our patient remains under endoscopic surveillance but does not currently meet the criteria for either diagnosis or further genetic evaluation of CS. Oral glycogenic acanthosis may be an under-recognized entity due to its subtle clinical presentation. Biopsy and full-skin examination are warranted in suspected cases, to identify any association with an underlying genodermatosis.
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

Abstract
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 &lt; 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

Abstract
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.