tbuckley/cabot-search huggingface dataset:
BI15 (P048) Immunosuppression and vaccination: a cross-specialty survey on current practices
Authors: Chris Puo Nen Lim, Akash Maliampurakal, Jayne Saunders, Elaine Paton, Angela Drummond
Journal: British Journal of Dermatology (2024)

Abstract 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.
PA33 Mosaic <i>KRAS</i> mutation associated with epidermal naevus and somatic limb overgrowth
Authors: Flora Thu-Ta, Dalvir Singh Bajwa, Suzanne Leech, Anna Dubois, Brian Wilson
Journal: British Journal of Dermatology (2024)

Abstract Mosaic KRAS variants are recognized to cause a range of features including somatic overgrowth, lymphatic and vascular malformations and other anomalies. We present a child with a mosaic variant in this gene and discuss the phenotype of this condition. A 2-year-old boy was noted at birth to have an extensive keratinocytic epidermal naevus and swelling of the left lower limb. The child was born after an uncomplicated pregnancy to unrelated parents. No anomalies had been detected prenatally. The naevus was large, affecting the left side of the body with a central demarcation down the midline of his chest to the left groin. The naevus continued down the volar aspect of the left arm onto the palm of the hand. The left lower limb was hypertrophic throughout, with nonpitting oedema. The perfusion and movement of the limb appeared normal. An infantile haemangioma was noted on the lower back, and later a deeper haemangioma of the anterior neck; neither required treatment. The left testis was undescended initially, with subsequent overgrowth of the skin of the penis and scrotum. Investigations soon after birth revealed a cystic dysplastic left kidney. A magnetic resonance imaging scan of the brain was normal. Initial genetic analysis was performed on blood. Diagnostic testing for a panel of genes associated with segmental overgrowth (R110) detected no pathogenic variant. The mosaic skin disorders deep sequencing panel (R327) showed no pathogenic variant using DNA extracted from blood. This panel was subsequently repeated on DNA extracted from skin, and a mosaic pathogenic KRAS variant c.35G&amp;gt;A, p.Gly12Asp was identified in 30% of next-generation sequencing reads. Mosaic RASopathies affect genes involved in the RAS–mitogen-activated protein kinase signalling pathway. Phenotypes of mosaic RASopathies are often distinct from their germline counterparts. The c.35G&amp;gt;A variant seen in our patient is widely reported, and leads to constitutive overactivation and increased signal transduction in downstream pathways. Epidermal naevi, both keratinocytic and sebaceous, are a common finding resulting from mosaic RAS mutations. Good developmental progress was made; milestones were generally met and although the leg remained enlarged due to lymphatic overgrowth, he was able to walk. No neurological symptoms have been noted, and the eyes have been checked with no anomalies found. The kidneys will be kept under review, as renal tumours have been reported in patients with mosaic KRAS variants. Our patient highlights aspects of the phenotype of a mosaic KRAS variant and adds to the growing knowledge of these conditions.
BI05 Successful treatment with upadacitinib for severe atopic dermatitis in a patient with primary immunodeficiency (CARD11)
Authors: Mishal Iqbal, Daniel O’Driscoll, Michael R Ardern-Jones
Journal: British Journal of Dermatology (2024)

Abstract A 42-year-old woman with a history of multiple severe allergies, asthma, urticaria, atopic dermatitis and recurrent bacterial and viral infections was diagnosed with CARD11 deficiency (heterozygous missense mutation dominant-negative) through whole-genome sequencing in 2017. Since adolescence, she had been treated with multiple systemic therapies for atopic dermatitis, including systemic corticosteroids, omalizumab, dupilumab and tralokinumab, which were eventually withdrawn due to treatment failure or intolerable adverse effects. On examination she had widespread severe eczema [Eczema Area and Severity Index (EASI) 24, Patient-Oriented Eczema Measure (POEM) 28, Dermatology Life Quality Index (DLQI) 16]. After discussion with immunology colleagues, the patient was offered treatment with upada­citinib 15 mg once daily. At follow-up 8 weeks later, there was a marked improvement in her eczema with complete resolution of itch (EASI 4, POEM 6, DLQI 2). After 5 months, she developed an episode of shingles, which responded to a 7-day course of high-dose oral aciclovir. She was able to restart treatment on alternate-day dosing of upadacitinib 15 mg. Her eczema remains well controlled. The CARD11 gene encodes a scaffold protein required for nuclear factor-κB activation in response to lymphocyte receptor binding. Homozygous null mutations in CARD11 lead to severe combined immune deficiency, while gain-of-function mutations are associated with lymphoproliferative disease. As in our patient, recently described dominant-negative mutations in CARD11 have been shown to be associated with a severe atopic phenotype, multiple allergies and variable predisposition to infection (Ma C, Stinson J, Zhang Y et al. Germline hypomorphic CARD11 mutations in severe atopic disease. Nat Genet 2017; 49: 1192–201). It is postulated that aberrant CARD11-dependent T-cell receptor signalling results in deficiencies in T-cell proliferation and a T helper (Th)2 bias in immune responses. Upadacitinib is an oral small-molecule Janus kinase (JAK) inhibitor that preferentially binds JAK1, inhibiting multiple cytokines associated with Th2 signalling. Given the reported increase in infectious adverse events compared with placebo in clinical trials, the use of JAK inhibitors in patients with inborn errors of immunity must be approached with great caution. However, in our patient with a severe atopic phenotype, recalcitrant to multiple systemic therapies, targeting the JAK1 pathway has provided a dramatic clinical benefit.
BI23 ‘Not so, my Lord; I am too much i’ the sun.’ Sun protection behaviours and awareness among an immunosuppressed neurology cohort
Authors: Orla McFeely, Orla Tuohy, Laoise Griffin, Ji Fung Yong, Anita Cozman, Alana Durack, Michael O’Connell, Lyndsey Paul
Journal: British Journal of Dermatology (2024)

Abstract The effect of immunomodulatory medications in the development of skin cancer was first reported over 50 years ago in the context of transplant recipients. Immunosuppressant medications used to treat autoimmune conditions, such as inflammatory bowel disease and multiple sclerosis, have been implicated in the development of nonmelanoma skin cancer. While there are reports emphasizing the need for skin cancer awareness among immunosuppressed gastroenterology patients, the same cannot be said of a high-risk neurology cohort. We aimed to explore the sun protection behaviours and knowledge of an outpatient immunosuppressed neurology population. We distributed anonymous questionnaires to patients prescribed immunomodulatory treatments in a dedicated multiple sclerosis clinic. Baseline demographics including sex and age were collected, as well as underlying diagnosis, name and duration of immunosuppressant treatment, history of previous skin cancer and sun protection measures undertaken. Of the patients who were included in this study, the median patient age was 32 years and all patients were female. The median time of prescribed immunosuppressive treatment was 4 years. Half of the patients reported performing self-skin examinations and no patient had undergone healthcare professional skin examinations. All patients reported factor 50 sunscreen use and 33% of patients reported sunscreen application year round. Overall, 66% of patients were uncertain of sinister skin changes to look for. No patient had a prior history of skin cancer. In total, 33% of patients were actively seeking a tan, with a further 33% describing sunbed use. This study highlights that sun protection measures and skin cancer awareness are lacking in this immunosuppressed neurology cohort. Consequently, these patients practise suboptimal sun protection measures. To the authors’ knowledge, this is the first study emphasizing the need for further education regarding safe sun habits among this population.
BI10 Nonmelanoma skin cancers and immunosuppression: identifying keratinous red flags
Authors: William Tuckwell, Ruth Omenyo, Nitya Malladi, Girish Patel
Journal: British Journal of Dermatology (2024)

Abstract Immunosuppression increases the risk of keratinocyte carcinomas, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), notably among organ transplant recipients on immunosuppressant therapies (Lanz J, Bouwes Bavinck JN, Westhuis M et al. Aggressive squamous cell carcinoma in organ transplant recipients. JAMA Dermatol 2019; 155: 66–71). Whether actinic keratoses (AKs), as treatable precursors for keratinocyte carcinoma, are more frequently associated with SCC and BCC in patients who are immunosuppressed remains to be determined. Our null hypothesis was that the AK frequency and grading should be similar between immunocompetent and immunosuppressed individuals with SCC and BCC. All keratinocyte carcinoma excisions for 2021 were retrospectively reviewed. Immunosuppressed individuals were identified from electronic records using the terms ‘immunosuppression’, ‘transplant’, ‘lymphoma’ and ‘chemotherapy’ and a review of current medication. Patient photographs were used to identify, enumerate and grade (Olsen grading) AKs in the surrounding anatomical region. A two-tailed χ2-test of independence was used to test the null hypothesis. A total of 827 keratinocyte carcinomas were excised in this centre, for which medical photography before excision was available for 728 keratinocyte carcinomas. Of the 286 patients with SCC and 432 patients with BCC, AKs were present in the anatomical region in 226 patients with SCC (79.0%) and 260 patients with BCC (60.2%). The head and neck was the most common site of keratinocyte carcinoma [202 patients with SCC (70.6%); 240 patients with BCC (55.6%)]. A total of 93 individuals (13%) were defined as immunosuppressed [61 patients with SCC (21%); 32 patients with BCC (7%)]. The frequency of AKs surrounding SCC was 1.11-fold greater in immunosuppressed (44 of 51, 86%) vs. immunocompetent (182 of 235, 77.4%) patients, but did not reach statistical significance. Olsen grade 3 AKs were more prevalent in immunosuppressed individuals with SCC (P &amp;lt; 0.05). Among patients with BCC, 85% (n = 23) of immunosuppressed and 59% (n = 237) of immunocompetent patients had AKs within the anatomical region (P &amp;lt; 0.01). Keratinocyte carcinomas in immunosuppressed individuals often have AKs within the surrounding anatomical region, which are often hyperkeratotic. Therefore, strategies for treating field cancerization in immunosuppressed individuals should also address the presence of hyperkeratotic AKs.
BI07 (P063) Understanding the landscape of Kaposi sarcoma hospitalizations in the USA: demographic associations stratified by AIDS/HIV status
Authors: Roy Mendoza, Norma Espinoza, Jessica Saoub, Leslie Kieron, Shaokui Ge
Journal: British Journal of Dermatology (2024)

Abstract Kaposi sarcoma (KS), a low-grade vascular tumour associated with human herpesvirus 8 (KSHV/HHV-8), has demonstrated a notable increase among Black men despite an overall decreasing trend in the USA. Given the lack of information regarding the national rates of KS in the USA, this study aims to characterize the national inpatient burden of individuals affected by KS, exploring demographic disparities on a broader scale. We queried the National Inpatient Sample (NIS), a subset of the Healthcare Cost and Utilization Project database containing US hospital discharge data, from 2016 to 2019, to identify all patients aged ≥ 18 years with a diagnosis of KS. We used the data to estimate the national representation and KS-relevant hospital admissions compared with the national civilian population. Stratifying by HIV/AIDS status (AIDS-related KS vs. non-AIDS-related KS), we examined the demographic associations of inpatients with KS using a Wald χ2-test. We determined the incidence rate ratios of admission for KS-related concerns using a Poisson regression model. All statistical analyses were performed with SAS 9.4 (SAS Institute Inc., Cary, NC, USA). In total, 12 246 patients with KS were estimated from the NIS. Overall, the inpatients with KS were predominantly male (91.1%), Black (41.4%) and in the 18–44-year age group (47.7%). AIDS-related KS constituted the majority of patients with KS (10 065, 82.2%), predominantly affecting Black individuals (45.7%) compared with patients classified as White, Hispanic and other (30.2%, 17.6% and 6.5%, respectively). Male patients were more often affected, at a 16 : 1 male-to-female ratio, the largest recorded thus far. Black patients with AIDS had a significantly higher risk of hospitalization. Non-AIDS-related KS comprised 17.8% of cases, primarily among White (51.4%) and male (77.5%) patients, and those aged 65–84 years (49.3%). Despite the differences by KS type, Black patients and those aged ≥ 85 years with non-AIDS-related KS still faced a heightened risk of hospitalization. This study underscores the distinct demographic patterns of inpatients with KS by HIV/AIDS status. For AIDS-related KS, focused efforts are required for Black individuals – addressing their elevated risk, initiating early therapeutic intervention, and promoting adherence to antiretroviral therapy. In cases of non-AIDS-related KS, attention must be given to the older age groups, especially those with a history of immunosuppression. These findings advocate for specialized dermatological strategies considering demographic nuances, contributing to more effective and targeted care for patients with KS.
BI44 Latent tuberculosis reactivation in a patient with chronic plaque psoriasis treated with ustekinumab with a review of the literature
Authors: Sylvia Amini, Fatma Hamed, Kate Johnason, Sarah Mahmoud
Journal: British Journal of Dermatology (2024)

Abstract Ustekinumab, a monoclonal antibody against interleukin (IL)-12 and IL-23, is used for the treatment of psoriasis and psoriatic arthritis. The IL-12 pathway also plays an important role in regulating immunity to Mycobacterium tuberculosis. A multicentre, double-blind, randomized clinical trial study of 121 Korean patients with moderate-to-severe psoriasis revealed at least 75% improvement in Psoriasis Area and Severity Index (PASI) score after 12 weeks of ustekinumab treatment. Ten cases of latent tuberculosis infection (LTBI) were reported. Lupea-Chilom et al. [Lupea-Chilom DS, Solovan CS, Farcas SS et al. Latent tuberculosis in psoriasis patients on biologic therapies: real-world data from a care center in Romania. Medicina (Kaunas) 2023; 59: 1015] conducted a retrospective observational study on a total of 97 patients with severe psoriasis who were on different biologics. That study showed that two of seven patients on monotherapy ustekinumab developed LTBI. In this abstract, we present the case of a 49-year-old White woman with resistant moderate-to-severe chronic psoriasis without psoriatic arthritis who developed LTBI while on ustekinumab. She was diagnosed with psoriasis in 2012 with involvement of the scalp, flexural, vulval and gluteal regions as well as the nails. She was started on ustekinumab in October 2013 following a satisfactory prebiologics screen (including a negative QuantiFERON test). Her PASI score was zero at week 12. In 2017, she developed a malar rash and positive antinuclear antibody test, which was not tested prior to starting biologics. As lupus is a potential adverse effect of this medication, the ustekinumab was stopped in April 2017. Further rheumatological investigations ruled out lupus and ustekinumab was restarted in November 2017. As part of the screening process prior to restarting treatment, she had a repeat QuantiFERON test, which was positive. The respiratory team reviewed the patient and issued a 3-month course of rifampicin and isoniazid to treat LTBI. Following a few months of monitoring, it was deemed safe to restart ustekinumab in December 2018 and her PASI improved. In February 2020, due to the COVID pandemic, this medication had to be stopped. She was started on acitretin as an alternative in 2021 with a resulting worsening of her condition. In December 2021, the patient was restarted on ustekinumab. In this abstract, we illustrate that ustekinumab has the potential to reactivate latent tuberculosis, a phenomenon that is infrequently reported and attributed to its impact on the IL-12 pathway. To address this concern, we recommend conducting repeated annual screening during treatment in addition to a comprehensive baseline evaluation, including a chest X-ray and QuantiFERON test. Additionally, it is advisable to consider initiating isoniazid chemoprophylaxis concurrently with ustekinumab treatment as a precautionary measure.
Poster presentationsBI18 The management of vulval intraepithelial neoplasia in immunosuppressed women: outcome and recommendations from a multidisciplinary vulval clinic
Authors: Radhika Bali, Jenny Chung, Caroline English, Jacqueline McDermott, Helen Staley, Sapna Harish, Charlotte Cohen, Elaine Palmer, Claire Fuller, John Butler, Randa Akel
Journal: British Journal of Dermatology (2024)

Abstract Vulval intraepithelial neoplasia (VIN) is a premalignant change of the vulval epithelium that can progress to squamous cell carcinoma (SCC). Immunosuppressed patients are a high-risk subset, with a greater risk of recurrence with standard treatment. To date, there is limited research focusing on this vulnerable population. A retrospective study was designed to review the treatment outcomes of immunosuppressed patients with VIN in a tertiary, multidisciplinary vulval service. In total, 104 biopsy-proven adults with VIN were identified from a histological database from 1 April 2013 to 31 March 2023. Patient demographic data, disease type and treatment outcome were collected. Electronic records and medical photography, where available, were used to retrospectively map each vulval lesion in quadrants. Complete response (CR) was defined as being clinically and/or pathologically clear of disease at 3 months’ follow-up. Recurrence was defined as lesions reappearing in the same quadrant after achieving CR. Data analyses were performed using IBM SPSS Statistics for univariate analyses. Overall, 31 of 104 patients (30%) were immunosuppressed, developing 47 lesions in the study period. This was due to HIV (n = 9), diabetes (n = 5), active malignancy (n = 10) and other causes (n = 7). The mean age was 54 years (range 20–94) with a mean follow-up duration of 70 months (range 11–132). The histological subtypes of VIN included low-grade squamous intraepithelial lesion (11%), high-grade squamous intraepithelial lesion (72.3%), differentiated VIN (4.3%) and microinvasive SCC (14.9%). Immunosuppressed patients were more likely to have multifocal disease (57.4% vs. 29.8%, P = 0.003) with previous human papillomavirus (HPV) burden (66.7% vs. 36.6%, P = 0.008). For those screened during the study period, immunosuppressed patients were more likely to have associated anal intraepithelial neoplasia (25.8% vs. 6.9%, P = 0.02) and cervical intraepithelial neoplasia (29.0% vs. 15.2%, P = 0.031). The CR rate from first-line treatment (imiquimod, surgery, laser or PlasmaJet®) was 54.8% in the immunosuppressed cohort compared with 75.6% in the control group (P = 0.073). There was no difference in the rate of recurrence or progression to SCC. There was no death due to disease observed in the immunosuppressed group, compared with three patients in the control group. In summary, our high-risk population with VIN was found to have a higher burden of HPV and was more likely to have multicentric disease. The treatment outcome was noninferior to the control group’s, unlike similar previous case series. This highlights the need for multidisciplinary clinics offering long-term close monitoring, with early treatment and HPV surveillance.