bluuebunny/crossref_metadata_2025 huggingface dataset:
RiboDiffusion: tertiary structure-based RNA inverse folding with generative diffusion models
Authors: Huang Han , Lin Ziqian , He Dongchen , Hong Liang , Li Yu
Published: June 2024

Motivation

RNA design shows growing applications in synthetic biology and therapeutics, driven by the crucial role of RNA in various biological processes. A fundamental challenge is to find functional RNA sequences that satisfy given structural constraints, known as the inverse folding problem. Computational approaches have emerged to address this problem based on secondary structures. However, designing RNA sequences directly from 3D structures is still challenging, due to the scarcity of data, the nonunique structure-sequence mapping, and the flexibility of RNA conformation.

Results

In this study, we propose RiboDiffusion, a generative diffusion model for RNA inverse folding that can learn the conditional distribution of RNA sequences given 3D backbone structures. Our model consists of a graph neural network-based structure module and a Transformer-based sequence module, which iteratively transforms random sequences into desired sequences. By tuning the sampling weight, our model allows for a trade-off between sequence recovery and diversity to explore more candidates. We split test sets based on RNA clustering with different cut-offs for sequence or structure similarity. Our model outperforms baselines in sequence recovery, with an average relative improvement of 11% for sequence similarity splits and 16% for structure similarity splits. Moreover, RiboDiffusion performs consistently well across various RNA length categories and RNA types. We also apply in silico folding to validate whether the generated sequences can fold into the given 3D RNA backbones. Our method could be a powerful tool for RNA design that explores the vast sequence space and finds novel solutions to 3D structural constraints.

Availability and implementation

The source code is available at https://github.com/ml4bio/RiboDiffusion.
Unveil cis-acting combinatorial mRNA motifs by interpreting deep neural network
Authors: Zeng Xiaocheng , Wei Zheng , Du Qixiu , Li Jiaqi , Xie Zhen , Wang Xiaowo
Published: June 2024

Cis-acting mRNA elements play a key role in the regulation of mRNA stability and translation efficiency. Revealing the interactions of these elements and their impact plays a crucial role in understanding the regulation of the mRNA translation process, which supports the development of mRNA-based medicine or vaccines. Deep neural networks (DNN) can learn complex cis-regulatory codes from RNA sequences. However, extracting these cis-regulatory codes efficiently from DNN remains a significant challenge. Here, we propose a method based on our toolkit NeuronMotif and motif mutagenesis, which not only enables the discovery of diverse and high-quality motifs but also efficiently reveals motif interactions. By interpreting deep-learning models, we have discovered several crucial motifs that impact mRNA translation efficiency and stability, as well as some unknown motifs or motif syntax, offering novel insights for biologists. Furthermore, we note that it is challenging to enrich motif syntax in datasets composed of randomly generated sequences, and they may not contain sufficient biological signals.

Availability and implementation

The source code and data used to produce the results and analyses presented in this manuscript are available from GitHub (https://github.com/WangLabTHU/combmotif)
O01 Survey of Scottish Dermatology Society members on the new Medicines and Healthcare products Regulatory Agency isotretinoin recommendations
Authors: Dubash Faisal , Dawe Robert , Affleck Andrew
Published: June 2024

Recent Medicines and Healthcare products Regulatory Agency (MHRA) isotretinoin legislation includes significant changes that will affect clinical practice (Medicines and Healthcare products Regulatory Agency. Drug Safety Update volume 16, issue 9: April 2023: 4). We obtained opinions from members of the Scottish Dermatological Society (SDS) on these recommendations. Five questions were circulated to members using a Microsoft Forms e-survey, and responders were anonymous. In total, 77 of 180 members responded in a 1-week period, with a 43% response rate. Open comments were also captured in a free-text box. The results included the following. Question 1: 95% (73 of 77) of responders stated that the new MHRA legislation is more likely to harm people with severe acne, while 3% (2 of 77) believed the recommendations would help patients with acne. Another 3% (2 of 77) answered ‘other’, with one stating ‘there are some improvements and some issues with this guidance’ and ‘people with severe acne will have to wait longer to start isotretinoin and suffer harm’. Question 2: 92% (71 of 77) felt that the views of people with severe acne were not considered. Question 3: 99% (76 of 77) of SDS members agreed that the new recommendations were not based on good evidence. Question 4: 90% (69 of 77) were against the requirement for two separate healthcare practitioners to approve isotretinoin prescribing in patients aged < 18 years. Question 5: 87% (67 of 77) agreed that clinicians should not need to ask about sexual dysfunction at every consultation, while 13% (10 of 77) believe we should. Open comments highlighted common themes such as ‘significant delays in patient access to isotretinoin, additional staff required for decisions, legislation being a barrier to prescribing effective treatment, additional patient harm such as scarring, effect on quality of life and concerns of worsening mental health due to the guidance’. ‘Further damage to the doctor–patient relationship’ was raised as ‘patients would be victim to a nocebo effect’. There was frustration expressed about the creation of more meaningless tick-box exercises and it was widely perceived that the legislation was authoritarian and disproportionately represented a minority opinion over an ‘unheard’ patient majority. There was also a feeling that there had been a ‘lack of expert dermatological opinion involved in the process of developing the guidance’. Overall, an overwhelming response from SDS members highlighted many concerns with the MHRA guidance and its impact on patient care. Isotretinoin appears to have been demonized without any scientific basis. The results of this survey question the credibility of the MHRA and their recommendations. We propose the creation of an objective working group, with no conflicts of interest, to re-evaluate the MHRA recommend­ations and accurately reflect the current evidence base.
P008 In over our heads?
Authors: Long Amy , Murphy Lisa , Quigley Claire , Leonard Niamh , Wynne Bairbre
Published: June 2024

We present the case of severe circumferential folliculitis decalvans in a 42-year-old White man. He presented to dermatology age 38 years with a 5-year history of a nonpainful, occasionally itchy pustulating process from crown to occipital scalp, resulting in hair loss. A progressive process, it began on the nape of the neck as rough, red skin and slowly spread outwards. Past medical history included teenage acne. He did not smoke. He was on lymecycline at the time of presentation, prescribed by his general practitioner, and no other medications. On examination he had an extensive (25 × 18 cm) area with crud, pustulation with yellow discharge and cicatricial alopecia. There was an indurated red rim. Removal of the crust revealed friable granulation-like tissue. There were no other significant findings on full-skin exam. He had punch biopsies for histopathology and bacterial and fungal culture. Histopathology showed hair-bearing skin with extensive inflammation around hair follicles. There was focal acute folliculitis. The inflammatory infiltrate contained lymphocytes and prominent plasma cells. Fungal and bacterial cultures were negative. His condition had a profound impact on his quality of life. He suffered mentally from the stigma associated with folliculitis decalvans, and the severity of his condition compounded this. Over the proceeding 4 years his engagement with the service diminished and compliance wavered. He was treated with rifampicin and clindamycin, in multiple short courses and once consecutively for 6 months, which yielded some improvement. He declined nurse treatment for debridement and dressings, opting to do so himself at home with his wife’s assistance. He was highly qualified in business, yet remained unemployed. In 2023 he contacted dermatology requesting to be seen. He was off treatment for over 2 years. His scalp disease was extensive with circumferential involvement of his head, including matting of his facial hair with pus. Bacterial swabs grew Staphylococcal aureus. He attended twice-weekly nursing appointments for debridement. Clobetasol propionate was used on overgranulated tissue. He was treated with flucloxacillin (500 mg, four times daily for 2 weeks), followed by doxycycline (100 mg daily for 6 weeks), followed by azithromycin (500 mg, three times weekly for 4 weeks). He has achieved considerable improvement and is being considered for oral dapsone. Folliculitis decalvans is a debilitating disease with far-reaching personal consequence. This case depicts the severe end of the disease spectrum, and the issues that can arise in that context. Challenges faced by his team were not only medical, but also psychological by way of gaining the patient’s trust and managing vulnerabilities.
P014 Eosinophilic dermatosis of haematological malignancy: a chronic relapsing pruritic condition
Authors: Diong Sophie , Vandenberghe Elisabeth , Mellerick Lisa , Wynne Bairbre
Published: June 2024

Eosinophilic dermatosis of haematological malignancy (EDHM) is a rare condition first reported in 1965. Although associated with a myriad of haematoproliferative conditions, it is most commonly linked with chronic lymphocytic leukaemia (CLL). With its typical lesions being intensely pruritic erythematous papules, nodules and bullae, it was initially thought to be a hypersensitivity reaction to insect bites. A 70-year-old man was referred for an 11-year history of an overexuberant response to insect bites. He gave a history of an intermittent blistering rash associated with intense generalized pruritus. He noted lesions occurring on both exposed and nonexposed body sites, and throughout the year. His background was significant for CLL, under surveillance, which was diagnosed a decade ago. Physical examination revealed erythematous papules and nodules on the neck, forehead and limbs, with an intact tense bulla at the left ankle. The morphology observed raised suspicion for Sweet syndrome, bullous pemphigoid, cutaneous T-cell lymphoma and EDHM. Laboratory investigations revealed an elevated lymphocyte count in keeping with his known diagnosis of CLL. Other results were within normal limits. Culture biopsy, and direct and indirect immunofluorescence studies were negative. Biopsies illustrated a dense pandermal perivascular lymphocytic inflammation, with an associated lymphocytic vasculitis. Numerous eosinophils were seen. Immunohistochemistry highlighted no convincing involvement by CLL. No clonal T-cell receptor gene rearrangements were identified. Given both the clinical and pathological features, a diagnosis of EDHM was made. Our patient responded to a course of weaning oral steroids commenced synchronously for a respiratory tract infection, alongside moderate-potency topical steroids. In the event of a future flare, steroid-sparing agents to be considered include dapsone and doxycycline, which have shown efficacy in the literature. EDHM can precede, antedate or occur concurrently with a CLL diagnosis. Although exaggerated arthropod responses are associated with CLL, EDHM is believed to be a separate process. Its pathogenesis remains unknown, but hypotheses include underlying malignancy-­related immune dysregulation, with a shift towards a T helper type 2 response and excess interleukin-4 and interleukin-5 production, which drive eosinophil recruitment and stimulation. This chronic relapsing dermatosis is characterized by clinical polymorphism and suggestive, but nonspecific, histopathological traits. Careful clinicopathological correlation is essential for diagnosis. Management options depend on the severity and frequency of flares. Varying responses to treatment are reported, but there is no gold-standard treatment. It is important that dermatologists are aware of EDHM as its diagnosis carries a potential negative prognostic outlook on the underlying haematological malignancy.
P023 Real-world melanoma miss rate in an NHS hospital dermatology service
Authors: Shirwac Hafsa Faarax , Morgan Hannah , Greenish Huw , Carswell Sarah , Heath Harry , Koutsis James , Guitera Pascale , Anderson Alexander D G
Published: June 2024

The aim of this retrospective study was to assess the ‘miss rate’ of dermatology clinicians for detecting malignant melanoma among patients referred on the 2-week-wait skin cancer pathway over a 2-year period. We reviewed patient records from the previous 5 years to identify instances where malignant melanoma might have been misdiagnosed. Malignant melanoma can be missed at various stages of the patient’s journey, leading to delayed diagnosis and potentially serious consequences. Our geographically isolated rural county relies exclusively on a single NHS dermatology department for 2-week-wait skin cancer services, providing a unique opportunity to assess the incidence of missed melanoma. We used a regional cancer registry to identify all primary invasive malignant melanomas (ICD-10 C43) diagnosed between August 2020 and July 2022. Records of any patient who had attended the dermatology department within the 5 years preceding diagnosis were reviewed to identify patients where melanoma might have been previously misdiagnosed. In total, 432 primary melanomas were identified. The male-to-female ratio was 202 : 230 and the median age was 71 years (interquartile range 57–79). Stage at presentation was IA (176, 40.7%), IB (98, 22.7%), II (134, 31.0%), III (19, 4.4%) and IV (5, 1.2%). Nine patients (2.1%) had been given an erroneous benign diagnosis for the same lesion and discharged within 13 months of diagnosis (missed melanoma). The stages of the missed melanomas were IA (two patients), IB (four patients) and II (three patients). In a further four cases (0.9%) the melanoma had prompted action, but the diagnosis was delayed; one had an erroneous negative biopsy, one missed an urgent review, one lesion was monitored, leading to a 6-month delay in diagnosis, and one was incorrectly diagnosed as a basal cell carcinoma, leading to a delay in surgery. A final four (0.9%) cases were diagnosed as benign more than 2 years prior to melanoma diagnosis. These were classified as ‘possible’ misses, as they could have evolved into malignant melanomas in the interim period. Our study reveals a low yet quantifiable melanoma miss rate in a high-volume NHS dermatology service. Future multicentre studies with large datasets are required, to identify risk factors for misdiagnosis. Clinicians managing skin lesion clinics may consider melanoma miss rate as a key performance metric. Strategies to improve the accuracy of this important metric might include the use of prospective databases incorporating digital images of lesions suspected to be benign. The utility of this approach should be investigated further.
P024 Skin cancer referrals by nonmedical practitioners: a prospective observational study
Authors: Anderson Alexander D G , Carswell Sarah , Heath Harry , Koutsis James , Guitera Pascale
Published: June 2024

A shortage of general practitioners (GPs) and increasing healthcare burden have led to nonmedical practitioners (NMPs) assuming new roles in many countries. It is now commonplace in the UK for nurses, paramedics and other NMPs to refer patients to secondary care. Despite this, there is little real-world information regarding clinical performance. The aim of this study was to investigate the appropriateness of skin cancer referrals made by NMPs and to compare this with referrals made by local GPs. Data were collected prospectively from patients referred to an NHS hospital dermatology department with a skin lesion of concern on the ‘2-week-wait’ pathway during a 2-month period in 2022. The profession of the referrer was ascertained from review of referral letters, from direct questioning of each patient and by contacting the GP surgery if required. Patient records and subsequent histology reports were reviewed to determine ultimate diagnosis. The proportion of patients diagnosed with skin malignancy (malignant melanoma, malignant melanoma in situ, squamous cell carcinoma, basal cell carcinoma, rare skin cancer) and in whom the dermatology clinician arranged an intervention (biopsy, excision, referral to another specialty for treatment) were recorded. In total, 753 patients were included. The overall malignancy rate was 29.3%. Overall, 668 of 753 patients (88.7%) were referred by a GP vs. 85 of 753 (11.3%) by an NMP. Seventy-two of the NMP referrals were made by 47 named individuals. The remaining 13 were made by unnamed practice nurses. Patients recalled an NMP asking for a second opinion in only 15 of 85 cases (18%) cases. Overall, 73% of NMP referrals were made by nurses, 24% by paramedics and 4% by physicians associates. Following clinic visit, 340 of 668 patients (50.9%) in the GP group and 47 of 85 (55%) in the NMP group were discharged without intervention (P = 0.45). An ultimate diagnosis of skin malignancy was made in 196 of 668 patients (29.3%) in the GP group and 25 of 85 (29%) in the NMP group (P = 0.99). Over 10% of referrals on the suspected skin cancer pathway were made by NMPs. There were no significant differences in diagnostic accuracy (number of malignancies) or referral appropriateness (referrals resulting in intervention) between NMPs and GPs. These early data suggest significant potential for NMPs to become more involved in skin lesion assessment. Further work should focus on understanding successful NMP education and supervision strategies and result in standardization and accreditation of training pathways for this increasingly important cohort of referrers.
P045 An international Delphi consensus to define a clinically appropriate definition of disease modification for plaque psoriasis
Authors: Eyerich Killian , Krueger James , Stahle Mona , Schakel Knut , Conrad Curdin , Gniadecki Robert , Puig Luis , Scoble Thomas , Williams Nick
Published: June 2024

In moderate-to-severe psoriasis, biologic therapies have achieved high levels of complete skin clearance and maintenance of this response over several years for many patients. However, questions remain as to how the disease can be controlled, brought into remission, or modified. Current definitions and measurement of disease modification are of limited utility in a clinical setting. This work acknowledges that the rapidly developing therapeutic landscape for plaque psoriasis brings into focus the question of potential for disease modification. Our objective was to achieve consensus on a definition of disease modification that can be applied within a clinical setting. In May 2021, a literature review on the topic of disease modification in psoriasis was conducted using the PubMed database. Search terms included but were not limited to ‘disease modification’, ‘disease progression, ‘disease interception’, ‘treatment target’, ‘drug therapy’, ‘biomarker’ and ‘drug-free remission’. Following the review, a panel of experts in psoriasis care from across Europe and North America convened in October 2021. Employing Delphi methodology guided by an independent facilitator, the panellists identified six main topics of focus. These topics were discussed, and 35 statements were developed and used to inform an online Delphi survey. This was distributed through a convenience sampling method to 97 healthcare professionals specializing in psoriasis care across Europe and North America. Respondents were offered a four-point Likert scale to indicate their responses. Completed surveys were anonymously collated and analysed by the independent facilitator. The results were then shared with the expert panel to determine conclusions. Stopping criteria for consensus rounds were defined as a 3-month period to collect responses, a minimum of 50 responses within this timeframe, and 90% of statements passing the threshold for consensus. The a priori threshold for consensus agreement was set at 75% and was further defined to be ‘very high’ at ≥ 90%. In total 63 responses (65% response rate) were received. Consensus was achieved for 32 statements and was not achieved for three statements. Given the high level of agreement with the statements, and that the stopping criteria were met, a second round of testing was not performed. The authors offer a definition of disease modification for plaque psoriasis that could be utilized in a clinical setting: ‘A sustained improvement in the disease course of plaque psoriasis resulting from a change in pathophysiology that minimizes the need for treatment.’ To determine the strength of this definition, the next step will be to test it within a real-world clinical setting.
P048 Immunosuppression and vaccination: a cross-specialty survey on current practices
Authors: Lim Chris Puo Nen , Maliampurakal Akash , Saunders Jayne , Paton Elaine , Drummond Angela
Published: June 2024

According to the 2018 General Medical Services contract in Scotland, the responsibility for vaccination delivery has shifted from general practitioners to secondary care. Dermatologists working in NHS Scotland now have an active role in recommending vaccinations for their patients who are on immunosuppressants. This recommendation is outlined in the Green Book published by the UK Health Security Agency. Currently, dermatology patients on immunosuppressants are required to receive the pneumococcal vaccine before starting treatment and every 5 years thereafter. However, this requirement is not included in the patient group direction produced by Public Health Scotland. As a result, individual prescriptions for the vaccination are needed, which adds to the workload on the services. Our objective was to assess current vaccination practices for patients on systemic medications across multiple specialties (dermatology, rheumatology, gastroenterology) in our local health board. We developed an online questionnaire, which was iteratively refined and distributed between June and August 2023 to clinicians working in dermatology, rheumatology, and gastroenterology locally, as well as other dermatology units in Scotland through the Scottish Dermatological Society. The questionnaire aimed to gather information on clinicians’ recommendations regarding influenza, pneumococcal and COVID-19 vaccines for patients taking various immunosuppressants, including methotrexate, ciclosporin, azathioprine, mycophenolate mofetil, fumaric acid esters, apremilast, biologics, and Janus kinase inhibitors. In total 64 responses were obtained: from dermatology (44 of 64, 69%), rheumatology (8 of 64, 13%) and gastroenterology (12 of 64, 19%). Most respondents in dermatology (68%) and rheumatology (88%) were consultants or associate specialists, while 50% of the respondents in gastroenterology were specialist trainees. Almost all respondents across the three specialties recommended vaccinations routinely in their clinical practice. The majority of respondents recommended yearly vaccinations against influenza. There were mixed responses on recommendations regarding pneumococcal vaccinations, with varying frequencies between yearly and 5-year intervals. A significant proportion of respondents were unsure of the latest COVID-19 vaccine recommendations. Free-text comments revealed an interest in the project and the need for standardization of vaccination recommendations. A review of the Green Book highlighted the following recommendations for patients on immunosuppressants: annual influenza vaccine, one-off pneumococcal vaccine unless in high-risk groups (asplenia, splenic dysfunction, and chronic kidney disease) and booster COVID-19 vaccines during seasonal campaigns. In conclusion, we highlight the variations in vaccination practices among these three specialties, and the importance of standardization in vaccination recommendations.
P058 Healthcare disparity affecting delayed diagnosis in acral lentiginous melanoma
Authors: Wu Xinxin , Lesch Samantha , Griffin Julia , Silberstein Peter
Published: June 2024

Acral lentiginous melanoma (ALM) is a rare subtype of cutaneous malignant melanoma that arises in patients with minimal correlation to ultraviolet radiation exposure, unlike many other melanoma subtypes (Arrington JH 3rd, Reed RJ, Ichinose H, Krementz ET. Plantar lentiginous melanoma: a distinctive variant of human cutaneous malignant melanoma. Am J Surg Pathol 1977; 1: 131–43). The 5-year overall survival rate for stage I disease is 98%, which can drop as low as 10% for stage IV. A concerning trend in diagnosis has shown that many patients present with this disease later in the disease process and are thus subject to high morbidity and mortality. Of additional concern is that ALM disproportionately affects non-White populations. A previous Surveillance, Epidemiology and End Results study (n = 1724) reported that Black patients, on average, presented with more advanced disease than their White counterparts (Huang K, Fan J, Misra S. Acral lentiginous melanoma: incidence and survival in the United States, 2006–2015, an ana­lysis of the SEER registry. J Surg Res 2020; 251: 329–39). This calls into question the role of socioeconomic inequities in the stage of disease at which patients are diagnosed. A retrospective cohort study of 3683 patients diagnosed with stage I and stage IV ALM between 2004 and 2020 in the National Cancer Database was compared via binary logistics regression to determine factors associated with later diagnosis. On multivariate analysis, Black race and male sex were associated with later stage at diagnosis (P = 0.001 and P < 0.001, respectively). Population density, insurance status, facility location, education level, income status, age and Hispanic status did not have statistically significant associations with patients diagnosed with stage I vs. stage IV ALM. These results illustrate that Black male patients disproportionately face disparities in the diagnosis of this subtype of melanoma. This study highlights the need for continued research on ALM and the factors that affect its prompt recognition, diagnosis and treatment.
P060 An analysis of eye colour and iris pattern as a risk factor for skin cancer in immunosuppressed renal transplant recipients
Authors: Leahy Marion , Laing Mary
Published: June 2024

Renal transplant recipients (RTRs) are at increased risk of keratinocyte skin cancers, with a tendency to have multiple, aggressive and difficult-to-treat tumours. The eye and the skin share the same embryological ectoderm. Iris pattern has recently been reported as a predictive risk factor for skin cancer in nonimmunosuppressed Southern European and Irish populations. Our aim was to analyse whether an individual’s iris pattern is an independent risk factor for the development of keratinocyte carcinoma in RTRs. Iris patterns of 110 RTRs were evaluated using the Simionescu visual three-step technique (iris periphery, collarette and iris freckling). Established risk factors for skin cancer in patients with transplants were recorded as confounding factors. This was an observational cross-sectional study. Among the 110 RTRs, 31 participants had skin cancer. In the skin cancer group, iris periphery was blue/grey in 74% (P = 0.053, odds ratio 2.5), the collarette was light brown in 57% (P < 0.004) and iris freckles were present in 55% (P = 0.04). Dark brown and blue collarettes were observed in controls. Binary logistic regression analysis showed that light brown collarette is a significant independent risk factor for skin cancer (odds ratio 4.54, confidence interval 1.56–10.6, P = 0.02). Within this RTR population a blue iris periphery, light brown collarette and presence of freckling confer an independent risk for skin cancer. Iris pattern is a useful tool for identification of transplant patients at risk of skin cancer and an easy-to-use technique for risk evaluation in this cohort. This is the first study to investigate iris pattern and skin cancer risk in RTRs.
P064 Prevention is better than cure: acitretin and chemoprevention
Authors: Hussain Fazleenah Ajmul , Yesudian Paul Devakar
Published: June 2024

Solid organ transplant recipients (SOTRs) have an increased incidence of cutaneous malignancy, especially nonmelanoma skin cancers (NMSC), where the risk is estimated to be up to 65 times higher than that of the general population. A 10-fold increase in mortality has been reported for NMSC in SOTRs. There are currently no guidelines on chemoprevention of recurrent keratinocyte tumours (KTs) in patients with or without transplants, leading to variation in clinical practice. We undertook an online survey analysing acitretin use for NMSC chemoprevention among British dermatologists. The questionnaire was distributed through email to dermatologists in the UK. We received 52 responses, of which 37 (71%) were from consultants. Most responses came from dermatologists practising in Scotland (34, 65%). The cohort was highly experienced, with 20 (38%) having > 20 years’ dermatology experience and 13 (25%) responders having 11–20 years’ experience. Overall, 24 (46%) saw fewer than five SOTRs in their clinic in a month and 20 (38%) saw hardly any. In nontransplant patients, 26 (50%) dermatologists prescribed acitretin for recurrent KTs, whereas 13 (25%) did not. The preferred dosing was 10 mg for the majority (29, 60% of those with data). Prescribers (n = 25, 53%) commenced patients on acitretin after they developed at least two to five KTs; one prescriber started acitretin after development of at least one KT. In the SOTR group, acitretin was prescribed after development of recurrent KT and not pre-emptively; 10 mg was the preferred dose for majority (22, 47%). For both SOTRs and nontransplant patients, acitretin was prescribed indefinitely by 31 (63%) responders. Interestingly, 17 (35%) dermatologists did not prescribe acitretin in SOTRs and 10 (20%) did not prescribe acitretin in either SOTRs or nontransplant patients. Thirteen (25%) did not prescribe acitretin in nontransplant patients with recurrent KT. Side-effects of acitretin were not severe enough to lead to discontinuation according to 16 (35%) responders. Some commented that adverse events were patient and dose dependent, and by minimizing the dose of acitretin, they reduced side-effects. In total, 47 (92%) provided regular photoprotective advise to patients with recurrent KTs. Overall, 49 (94%) did not encounter patients with skin of colour with recurrent KTs in their practice. To our knowledge, this is the first survey assessing the practice of acitretin use in chemoprevention in both transplant and nontransplant patients. Our survey suggests discrepancies in practice among dermatologists prescribing acitretin in SOTRs and nontransplant patients. More than one-third did not prescribe acitretin in SOTRs with recurrent KTs. There is good evidence that acitretin reduces the incidence of KT in SOTRs, and hence its use should be encouraged in this cohort.
P065 Attitudes and practices of patients with inflammatory bowel disease towards skin cancer risk and sun protection
Authors: Herlihy Maeve , Blake Eve , Courtney Garry
Published: June 2024

Skin cancer is the most common form of cancer in Ireland, with over 13 000 new cases diagnosed annually. People with inflammatory bowel disease (IBD) may be at higher risk of skin cancer. A meta-analysis performed on more than 170 000 patients diagnosed with IBD found that patients with IBD had a 37% higher risk of developing melanoma than expected in the general population (relative risk 1.37, 95% confidence interval 1.10–1.70). This increased risk was independent of IBD treatment. Additionally, many of the treatments used for IBD involve supressing or altering the immune system. Immunosuppression is a risk factor for all types of skin cancer, and cutaneous malignancies in immunocompromised patients tend to behave more aggressively compared with those in the general population. The British Association of Dermatologists has published preventive guidelines for patients on immunosuppression, but specific gastroenterology recommendations are lacking. Prevention and early detection are therefore of paramount importance. Our aim was to assess knowledge of skin cancer risk factors and photoprotective behaviours in an Irish cohort of at-risk patients with IBD. A questionnaire was given to patients attending our IBD clinic. Clinical data were recorded including diagnosis, immunosuppressants, skin cancer risk factors and photoprotective behaviours. In total, 87 patients (52% women) with IBD (63% Crohn disease, 35% ulcerative colitis) were included. All participants were White, with 77% recorded as having fair or very fair skin. Most patients (97%) were on treatment for their IBD (66% on biologics, 25% on immunomodulators). Over one-third of participants (35%) were unaware of an increased skin cancer risk associated with IBD. Four patients had a history of skin cancer, two of which were melanoma. Half of patients (48%) had been sunburnt in the last year, and 36% had more than 10 burns in their lifetime. In total, 57% of patients reported a history of blistering sunburn and 22% of patients had used sunbeds. Knowledge of skin cancer risk factors and worrisome features was generally good, and the majority of our cohort (74%) always wore suncream abroad. However, less than half wore suncream frequently in Ireland (37%) or when it is cloudy (22%), and also did not take other important measures, such as reapplying suncream every 2 h (43%), or wearing a hat (26%) or protective clothing (32%). Our study highlights gaps in the education of our IBD cohort regarding skin cancer risk and prevention, and suggests that primary prevention of skin cancer in this IBD cohort is suboptimal. Ideally, educational interventions to enhance patient awareness and encourage adequate photoprotection and skin self-surveillance should be undertaken and assessed.
P073 Prevalence, mortality and healthcare resource use for generalized pustular psoriasis compared with plaque psoriasis in England: a population-based cohort study
Authors: Frysz Monika , Patel Smit , Li Marie , Griffiths Christopher , Warren Richard B , Ashcroft Darren
Published: June 2024

Generalized pustular psoriasis (GPP) is a rare, chronic inflammatory skin condition that is potentially life-threatening. Accumulating evidence suggests that GPP is distinct from the more common plaque psoriasis in terms of aetiology and clinical and dermatological features. The aim of this study was to describe the epidemiology, comorbidities, mortality and healthcare resource use (HCRU) in patients with GPP compared with those with plaque psoriasis in England. A retrospective cohort study of the Clinical Practice Research Datalink (CPRD) Aurum database linked with hospital and mortality data, between 2008 and 2019, was conducted, and HCRU between 2015 and 2019 was calculated. Prevalence rates, comorbidities and survival rates were estimated for GPP and plaque psoriasis. Diagnoses were based on CPRD medical codes and International Classification of Diseases 10th Revision codes (L40.1 for GPP, and L40.0 for plaque psoriasis). In total, 373 patients with GPP (62.5% female) and 224 223 patients with plaque psoriasis (49.4% female) were identified. The mean age (SD) was 55.9 years (18.6) for GPP, and 48.5 years (19.1) for patients with plaque psoriasis. A higher proportion of patients with GPP had at least one comorbidity, compared with plaque psoriasis (76.4% vs. 55.9%, respectively). From 2008 to 2019, the prevalence rates per 100 000 persons ranged from 1.61 to 3.0 for GPP, and from 1771 to 1904 for plaque psoriasis. In total, 78 of the 373 (20.9%) patients with GPP died during the study period, compared with 20 771 of 224 223 (9.3%) patients with plaque psoriasis. Compared with plaque psoriasis, survival rates were lower for patients with GPP, particularly those who were over 55 years old and those with a history of at least one comorbidity. Overall, 297 patients with GPP and 181 925 with plaque psoriasis were included in HCRU analysis. Hospitalizations, outpatient visits and accident and emergency visits were more frequent in patients with GPP compared with plaque psoriasis (78% vs. 47%, 92% vs. 75% and 71% vs. 52%, respectively). Our results support previous findings that GPP is a distinct disease from plaque psoriasis with a different epidemiology. Compared with plaque psoriasis, patients with GPP had higher mortality and were found to have higher disease burden, demonstrating a high unmet need in this patient group. The study was supported and funded by Boehringer Ingelheim. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy, as well as intellectual property considerations.
P079 The lifetime risk of vitiligo across sociodemographic groups: a UK population-based cohort study
Authors: Eleftheriadou Viktoria , Ahmed Alia , Nesnas John , Nagra Ranjit
Published: June 2024

The lifetime risk for vitiligo has not previously been estimated using large-scale population data. It is also not clear how the lifetime risk for vitiligo differs by sex, ethnicity and levels of socioeconomic deprivation. We aimed to estimate the lifetime incidence of vitiligo in the UK, overall and across sociodemographic subgroups. Incident cases of vitiligo were identified using a large database (Optimum Patient Care Database) of routinely collected primary care records in the UK between 1 January 2004 and 31 December 2020. Lifetime incidence of vitiligo was estimated at age 80 years using modified time-to-event models, adjusted for competing risk of death, with age as the timescale. Lifetime incidence was estimated for the study population overall and stratified by ethnicity, sex and deprivation. We identified 9460 adults and children newly diagnosed with vitiligo during the study period. The overall cumulative lifetime incidence in the population was 0.92% at age 80 years [95% confidence interval (CI) 0.90–0.94]. Lifetime incidence was similar in female (0.94%, 95% CI 0.92–0.97) and male patients (0.89%, 95% CI 0.86–0.92). There were substantial differences in lifetime incidence across ethnic groups: Asian (3.58%, 95% CI 3.38–3.78), Black (2.18%, 95% CI 1.85–2.50), mixed (2.03%, 95% CI 1.58–2.47), other (1.05%, 95% CI 0.94–1.17) and White ethnicity (0.73%, 95% CI 0.71–0.76). There were also substantial differences in the lifetime incidence across sociodemographic subgroup, with higher lifetime risk in the most deprived quintile (1.25%, 95% CI 1.20–1.31) compared with the least deprived quintile (0.81%, 95% CI 0.77–0.86). However, these differences appear to result from a higher proportion of people from non-White ethnicities in the lower socioeconomic subgroups. In post hoc analysis when restricting the sociodemographic analysis to those of White ethnicity only, the socioeconomic differences were negligible. Our estimates of lifetime incidence suggest that 1 in 109 people will develop vitiligo over their lifetime. Clinicians should be aware of the markedly increased incidence of vitiligo in people of non-White ethnicity, in particular for those of Asian ethnicity (1 in 28 people). The negative impact of vitiligo on mental health, work and healthcare utilization highlights the importance of monitoring people with vitiligo to identify those who need additional support. The study protocol for this retrospective observational study was registered a priori with ClinicalTrials.gov (identifier: NCT06097494). This research was sponsored by Pfizer. Project management, medical writing and statistical support were provided by Momentum Data, UK, and funded by Pfizer.
P081 A highly selective Janus kinase 1 inhibitor, ivarmacitinib ointment, for the treatment of atopic dermatitis: results from a phase II study
Authors: Li Baoping , Goh Joshua S H , Wang Duoqin , Xu Jinhua , Goh Aik Han
Published: June 2024

Atopic dermatitis (AD) is a pruritic chronic inflammatory skin disorder. Ivarmacitinib, a highly selective inhibitor of Janus kinase 1, potently suppresses cytokine signalling involved in AD pathogenesis. A randomized, double-blind, vehicle-controlled, seamless and adaptive-designed phase II/III study was conducted to evaluate the efficacy and safety of ivarmacitinib ointment in patients with AD. The results of phase II are reported here. The study was registered with ClinicalTrials.gov (NCT04717310). In total, 128 patients aged 18–65 years with mild-to-moderate AD were randomly assigned (1 : 1 : 1 : 1) to receive twice-daily topical ivarmacitinib ointment 2%, 1% or 0.5%, or vehicle for 8 weeks. Efficacy evaluation included Eczema Area and Severity Index (EASI), Investigator’s Global Assessment (IGA), Scoring of Atopic Dermatitis (SCORAD), Pruritus numerical rating scale (NRS) and Dermatology Life Quality Index (DLQI). At week 8, all three doses met the primary endpoint, mean percentage change of EASI from baseline. The results in the arms with ivarmacitinib 2%, 1% and 0.5% were −56.1%, −54.6% and −66.9% (P = 0.06, 0.08, 0.002, respectively), compared with vehicle (−40.2%). The ivarmacitinib 0.5% ointment group also achieved IGA response (IGA score of 0/1 with ≥ 2 points improvement from baseline) compared with vehicle. Other endpoints including SCORAD, NRS and DLQI all showed therapeutic benefit at week 8 in the ivarmacitinib ointment regimens. The ivarmacitinib ointment demonstrated good safety results and was well tolerated. In conclusion, ivarmacitinib ointment at 2%, 1% or 0.5% strength significantly improved signs and symptoms compared with vehicle and was well tolerated in adult patients with mild-to-moderate AD. This study was funded by Reistone Biopharma Co., Ltd.
P088 Physician-assessed effectiveness, patient-reported outcomes, and safety in adult and adolescent patients with atopic dermatitis treated with dupilumab: real-world insights 1 year into the GLOBOSTAD multinational prospective observational study
Authors: Ferrucci Silvia M , Calzavara-Pinton Piergiacomo , Murrell Dédée F , Fougerousse Anne-Claire , Karlová Iva , Lapeere Hilde , Holzer Gregor , Al-Ahmad Mona , Chu Chia-Yu , Foti Caterina , Pérez-García Bibiana , Petrova Anastasia , Wu Jiangming , Ardeleanu Marius , Bosman Kwinten
Published: June 2024

Real-world studies complement randomized controlled trials (RCTs) by providing data from a more heterogeneous population treated in a normal practice environment. In several RCTs, dupilumab has demonstrated robust efficacy with acceptable safety in patients with moderate-to-severe atopic dermatitis (AD). The main objectives of the ongoing GLOBOSTAD study (NCT03992417) are characterizing the patient population treated with dupilumab, their AD treatment patterns, long-term effectiveness, and safety of dupilumab in the real world. The GLOBOSTAD 5-year, multinational, prospective, observational study enrolled patients aged ≥ 12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information, and assessments were performed at baseline, 3 months (± 1 month), 6 months (± 2 months) and 12 months (± 2 months). The data are reported as observed for the enrolment/safety (n = 955; data cutoff March 2023) and follow-up (n = 903) populations. In total, 758, 863 and 705 patients completed at least one follow-up assessment at 3, 6 and 12 months, respectively, with a mean (SD) treatment period of 11.7 (1.2) months. The mean (SD) Eczema Area and Severity Index (EASI; > 21 = severe; ≤ 7 = mild/no disease) at baseline was 25.1 (12.8). During the study, ≥ 75% (EASI 75) and ≥ 90% (EASI 90) reductions in mean EASI scores from baseline were observed in 66.2% and 35.6% of patients at 3 months, 74.6% and 42.4% at 6 months, and 81.0% and 55.8% at the end of the observation period (12 months), respectively. The patient-reported mean (SD) weekly average pruritus numerical rating scale (NRS, range 0–10) at baseline was 6.3 (2.2). A three-point and four-point improvement from baseline or a score of 0 in pruritus NRS was observed in 66.9% and 57.1% of patients at 3 months, 73.6% and 64.1% at 6 months, and 79.0% and 70.3% at 12 months, respectively. Of the follow-up population, 67.4% achieved an absolute pruritus NRS score of ≤ 3 at 3 months, 76.4% at 6 months, and 80.3% at 12 months. Adverse events considered related to dupilumab that led to permanent discontinuation occurred in 2.4% of patients. Patients enrolled in the GLOBOSTAD study achieved rapid improvements in AD signs and symptoms on initiating dupilumab treatment, which were sustained until the end of the 1-year observation period. Safety was consistent with the known dupilumab safety profile. This research was sponsored by Sanofi and Regeneron Pharmaceuticals Inc.
P094 Oral tofacitinib monotherapy for the management of moderate-to-severe alopecia areata in children and adolescents: a retrospective analysis of 36 cases
Authors: Mehta Hitaishi , Mahajan Rahul , De Dipankar , Handa Sanjeev
Published: June 2024

Alopecia areata (AA) poses a significant challenge in the paediatric population, with limited treatment options. Oral tofacitinib has emerged as a promising modality, with case reports and small series suggesting safe and effective use in children with AA. This retrospective analysis sought to expand the knowledge base around tofacitinib’s role in managing AA in the younger population and to provide valuable insights into challenges encountered when faced with no responsive to treatment. This retrospective chart review spanned from January 2021 to December 2023 and included 36 patients aged ≤ 16 years with moderate-to-severe AA [Severity of Alopecia Tool (SALT) score > 25], who received ≥ 6 months of oral tofacitinib therapy. The treatment response was defined as ≥ 75% reduction in SALT score (SALT 75) at 6 months. Other outcome measures of interest included times to attain SALT 50, SALT 75, SALT 90 and SALT 100, and incidence of adverse events. In total 36 patients were included, with a mean age of 10.1 years (SD 3.8, range 3–16), with 17 male and 19 female patients. AA subtypes included patchy (19%), ophiasis (17%), subtotalis (28%), totalis (8%) and universalis (28%). The mean SALT score at baseline was 73.1 (SD 26.7). The mean duration of oral tofacitinib treatment was 8.69 months (SD 3.17, range 6–16). SALT 50 was achieved by 26 patients, with an equivalent number attaining SALT 75. Additionally, 24 patients reached SALT 90, while 19 patients reached SALT 100. The mean (SD, range) durations in months to achieve SALT 50, SALT 75, SALT 90 and SALT 100 were 2.81 (1.16, 1–6), 4.08 (1.69, 1–8), 5.71 (2.14, 3–10) and 6.74 (2.35, 3–12), respectively. Ten of the 36 patients (28%) were classified as nonresponders. Nonresponders exhibited a higher median total duration of illness, higher baseline SALT score, and higher incidence of atopy and nail involvement compared with responders. Adverse events were noted in nine patients, with two cases necessitating treatment discontinuation due to adverse events. Among those not showing a response, three patients each underwent a transition to combination therapy of oral steroids with methotrexate and topical immunotherapy with diphenylcyclopropenone. Notably, regrowth was observed in two patients from the former group, while none from the latter group experienced similar positive outcomes after the therapeutic strategy shift. Limitations of the study include the retrospective nature and small sample size. This comprehensive analysis enriches the existing literature on the role of tofacitinib in paediatric AA, addressing gaps in approved treatments and providing valuable guidance for clinicians navigating the challenges of nonresponsiveness in this vulnerable population.