bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic-driven 3D-printed biodegradable swimming microrobots
Authors: Chen Jingfan , Hu Hanwen , Wang Ya
Published: June 2023

A magnetic object subject to an external rotating magnetic field would be rotated due to the alignment tendency between its internal magnetization and the field. Based on this principle, 12 shapes of swimming microrobots around 1 mm long were designed and 3D-printed using biodegradable materials Poly (ethylene glycol) diacrylate (PEDGA). Their surface was decorated with superparamagnetic iron oxide nanoparticles to provide magnetic responsivity. An array of 12 permanent magnets generated a rotating uniform magnetic field (∼100 mT) to impose magnetic torque, which induces a tumbling motion in the microrobot. We developed a dynamic model that captured the behavior of swimming microrobots of different shapes and showed good agreement with experimental results. Among these 12 shapes, we found that microrobots with equal length, width, and depth performed better. The observed translational speed of the hollow cube microrobot can exceed 17.84 mm s−1 (17.84 body lengths/s) under a rotating magnetic field of 5.26 Hz. These microrobots could swim to the targeted sites in a simplified vessel branch. And a finite element model was created to simulate the motion of the swimming microrobot under a flow rate of 0.062 m s−1.
Fractional order interdependent nonlinear chaotic spatiotemporal calcium and Aβ dynamics in a neuron cell
Authors: Pawar Anand , Pardasani Kamal Raj
Published: June 2023

The formation of β-amyloid (Aβ) and its accumulation depend on the calcium ([Ca2+]) signaling in neurons. The individual and independent dynamics of calcium and β-amyloid give very limited information about different cellular mechanisms. Some researchers have explored the interdependent system dynamics of integer-order calcium and β-amyloid, which provides some more crucial information on different regulatory and dysregulatory processes in neurons. However, these integer-order systems are not capable of generating the information on the superdiffusion, cell memory and Brownian motion effects in neuron cells. A nonlinear mathematical model has been framed to explore the fractional-order interdependent chaotic spatiotemporal [Ca2+] and Aβ dynamics in neurons. The proposed model integrates the two-way feedback mechanism between [Ca2+] and Aβ dynamics in neurons. The Crank-Nicolson scheme with the Grunwald approximation is employed for space fractional derivatives and the L1 formula is employed for time fractional derivatives. The Gauss-Seidel iterations are utilized to solve the resultant system of nonlinear algebraic equations. The effects of cell memory, Brownian motion and superdiffusion phenomena with different crucial mechanisms like buffer, source influx, ryanodine receptor, etc on the spatiotemporal interdependent [Ca2+] and Aβ dynamics have been explored in neurons. The numerical findings give novel insights on the regulatory and dysregulatory effects of cell memory, Brownian motion and superdiffusion on the system dynamics of [Ca2+] and Aβ in neuron cells and the conditions that may cause the different neurodegenerative illnesses like Alzheimer’s disease.
001 Does atopic dermatitis in childhood impact later educational attainment? A UK birth cohort study
Authors: Iskandar Rita , Schmidt Sigrún , Mulick Amy , Abuabara Katrina , Langan Sinéad
Published: June 2023

Atopic dermatitis (AD) may impair educational attainment in numerous ways, including poor attention due to itching and disrupted sleep quality. Educational attainment is a social determinant of health; thus, any association with AD, a prevalent chronic disease, is important to understand. We aimed to determine whether AD is associated with lower educational attainment using data collected between 1990 and 2009 on children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) and linked to the National Pupil Database. Participants were 13,956 children alive at 1 year of age and followed up with repeated measures of AD until 11.5 years of age. The outcome was educational attainment, defined as achieving at least five General Certificates of Secondary Education (GCSEs) at grades A*–C by 16 years of age. Using multivariable logistic regression, we assessed the effect of AD on educational attainment, adjusting for potential confounders. We included 7577 children in a complete record analysis: 3258 (43.0%) with evidence of AD (two positive AD reports) and 4319 (57.0%) without AD reports (comparator group). Compared with children without AD, children with AD had 30% increased odds of attaining ≥ 5 A*–C GCSEs [adjusted odds ratio (aOR) 1.30, 95% confidence interval (CI) 1.17–1.45]. Children with AD had a 9.9% absolute excess probability of achieving ≥ 5 A*–C GCSEs vs. children without AD. In a stratified analysis, asthma was shown to enhance the strength of the association of AD with educational attainment [probability in AD vs. no AD groups: 62.7% vs. 47.3%; aOR 1.58, 95% CI 1.19–2.10 (P = 0.04 for interaction)]. AD appeared to be associated with higher educational attainment in English children. Despite the magnitude and strength of the findings, cautious interpretation is required due to the dichotomous outcome measure, poor generalizability and potential unmeasured confounding. Further investigations should evaluate reproducibility in other populations, stratify by AD trajectory–severity phenotypes and use quantitative test scores.
004 Does methotrexate affect treatment persistence or effectiveness of adalimumab for psoriasis? A trial emulation cohort study
Authors: Yiu Zenas , Smith Catherine , Laws Philip , Hampton Philip , Griffiths Christopher , Warren Richard
Published: June 2023

It is unclear whether concomitant methotrexate enhances the effectiveness and/or persistence of adalimumab in treating psoriasis. The OPTIMAP study (Optimizing Adalimumab Treatment in Psoriasis with Concomitant Methotrexate), a randomized controlled trial testing adalimumab against adalimumab + methotrexate, could not adequately answer this question due to under-recruitment. The aim of the current study is to replicate key aspects of the OPTIMAP trial design in a cohort study to provide a more precise estimate for the effect of concomitant methotrexate on adalimumab persistence and effectiveness. We conducted a cohort study using the British Association of Dermatologists Biologics and Immunomodulators Register, a national pharmacovigilance registry for people on systemic treatments for psoriasis, between 2007 and 2021. We included participants ≥ 18 years old who had at least one record of a Psoriasis Area and Severity Index (PASI) ≥ 8 and were naïve to adalimumab. We used the same exclusion criteria as in the OPTIMAP study. Participants received either adalimumab (Humira®) in the comparison arm or adalimumab (Humira) in addition to methotrexate and folic acid, with dosage as determined by the clinician in the intervention arm from initiation at cohort entry, and were censored if they deviated from the treatment strategy. The primary outcome is in the difference in the survival function for adalimumab at 1 year. The secondary outcome was the difference in the proportion of patients achieving a 75% reduction in PASI (PASI 75) at 1 year. We used inverse probability treatment weighting to correct for known differences in participant characteristics precomparison. Missing outcomes were accounted for using inverse probability of censoring weighting. We fitted a flexible parametric survival model and a generalized linear model with an identity link for the primary and secondary outcomes, respectively. There were 219 and 1376 participants in the intervention and comparison arms, respectively. Drug survival for the monotherapy arm at 1 year was 77.5% [95% confidence interval (CI) 75.3–79.8], and for the intervention arm, it was 75.3% (95% CI 66.9–84.7), with a difference of −2.3% (95% CI −11.4 to 6.9). The risk difference for PASI 75 at 1 year was −10.7% (95% CI −29.3 to 8.0), with a PASI 75 rate of 43.5% for the intervention arm (95% CI 25.4–61.9) and 54.2% for the comparison arm (95% CI 49.6–58.7). We did not find any significant difference for the persistence and effectiveness of adalimumab in people with psoriasis on methotrexate vs. those who were not on methotrexate in this study. This result is in keeping with the reported first-year outcomes of OPTIMAP. Clinicians and patients should consider alternative strategies to improve treatment outcomes in people with severe psoriasis.
007 Vitiligo is associated with a reduction in incidence of melanoma and nonmelanoma skin cancer: UK population-based cohort study
Authors: Ferguson John , Eleftheriadou Viktoria , Nesnas John
Published: June 2023

Vitiligo is a common, acquired depigmenting skin disease. There have been concerns that vitiligo and its treatment may increase the risks of skin cancer. In a large UK population-based study, we aimed to establish whether vitiligo is associated with an increased risk of skin cancer. We used routinely collected electronic medical records of adults contributing to the Optimum Patient Care Research Database (2010–2020). Cases of vitiligo were identified using specific diagnosis codes. Those with other depigmenting conditions were excluded. Vitiligo cases were age and sex matched with up to four controls registered at the same general practice and with at least one primary care interaction in the preceding year. The primary outcome was risk of skin cancer; comprisied of melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Individual skin cancers and actinic keratoses (AK) were included as secondary outcomes. Associations between vitiligo and skin cancer were estimated using Cox regression, with adjustment for age, sex, socioeconomic deprivation, ethnicity, body mass index, smoking and alcohol status, immunotherapy, phototherapy and 13 common comorbidities. Prespecified subgroup analysis comprised stratification by sex, age group (18–45 years, 45–65 years and > 65 years), ethnicity (White and non-White) and socioeconomic deprivation. In total, 14 976 patients with vitiligo were matched to 54 392 controls. Over the 10-year study period, 133 patients with vitiligo and 783 controls developed new-onset skin cancer. Vitiligo was associated with a 38% reduced risk of any new-onset skin cancer [adjusted hazard ratio (aHR) 0.62, 95% confidence interval (CI) 0.51–0.74; P < 0.001]. This risk reduction was observed for all individual skin cancer types: melanoma (aHR 0.38, 95% CI 0.23–0.64; P < 0.001), SCC (aHR 0.65, 95% CI 0.48–0.87; P = 0.004), BCC (aHR 0.65, 95% CI 0.51–0.83; P < 0.001) and AK (aHR 0.86, 95% CI 0.75–0.98; P = 0.028). In a subgroup analysis, vitiligo was associated with a reduction in skin cancer risk in people identifying as White (aHR 0.68, 95% CI 0.55–0.84; P < 0.001), but there was no association in those identifying as non-White (aHR 0.93, 95% CI 0.44–1.98). Vitiligo-associated reductions in skin cancer risk were consistently observed in the other prespecified subgroups. Vitiligo is associated with a strong protective effect against common types of skin cancer. Vitiligo-associated risk reduction is most marked for melanoma (62% lower risk). Protective effects associated with vitiligo may be restricted to people with light skin, although skin cancers in the those with darker skin were uncommon, which requires further study.

FundingThis research was sponsored by Pfizer. Medical writing and statistical support was provided by Momentum Data and was funded by Pfizer.
010 Enhanced outcome prediction in cutaneous squamous cell carcinoma using deep-learning and computational histopathology (cSCCnet)
Authors: Peleva Emilia , Chen Yue , Rizvi Hasan , Harwood Catherine , Wang Jun
Published: June 2023

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer and leads to a significant disease burden. Although metastases occur in < 5% of patients, effective treatments are limited and 5-year survival is poor, with mortality rates equivalent to those of melanoma in some regions of the world. Despite recent advances in understanding the molecular pathogenesis of cSCC, patient risk stratification is limited and based on clinicopathological staging, with few validated prognostic biomarkers available to guide management [de Jong E, Lammerts MUPA, Genders RE, Bowes Bavinck JN. Update of advanced cutaneous squamous cell carcinoma. J Eur Acad Dermatol Venereol 2022; 36(Suppl. 1):6–10]. In this study, we aimed to use artificial intelligence technology to develop a deep learning model using digitized whole-slide images of cSCC to quantify the risk of metastasis. Routine haematoxylin and eosin-stained slides of 256 primary cSCCs from immunocompetent patients at four collaborating centres were scanned. The area of interest encompassing tumour and peritumoral stroma was annotated, and 512 × 512 pixel tiles were generated from each slide. High-quality tiles (containing sufficient tumour content) were pooled together, with patient-level labels inherited by tiles. We trained multiple models using an 80:10:10 split for training, validation and testing, and the model achieving the highest tile- and slide-level validation accuracy was identified (ResNet50). The final model, namely, cSCCnet, achieved 88% sensitivity, 73% specificity, 64% positive predictive value and 92% negative predictive values on the independent test set. Blinded review of the top predictive tiles by three histopathologists suggested that the predictive features identified by cSCCnet were distinct from histopathological features commonly used by clinicians to estimate metastatic risk. We have demonstrated that it is possible to train a deep learning model using digital pathology to predict the risk of metastasis. cSCCnet surpassed the published performance of currently used staging systems, as well as commercially available gene panel testing (de Jong et al.; Wysong A, Newman JG, Covington KR et al. Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma. J Am Acad Dermatol 2021; 84:361–9). The morphological features and patterns identified by cSCCnet are different from established histopathological high-risk criteria, indicating that this technology can enhance current practice. Although further validation in a prospective cohort is pending, this is an important step toward creating a risk stratification tool that can be incorporated into routine pathology workflows, significantly improving patient outcomes for this common cancer.
RF03 Lentigo maligna 2013–2019 in England: incidence and survival of 18,377 cases
Authors: Karponis Dimitrios , Mistry Khaylen , van Bodegraven Birgitta , Levell Nicholas J , Venables Zoe
Published: June 2023

Lentigo maligna (LM) is a common melanoma in situ with limited national epidemiological data. National data on LM incidence, age groups and 5-year survival in England from 2013 to 2019 were explored using report-level data published openly on the ‘Get Data Out’ National Disease Registration Service (NDRS) programme. In total, 18 377 new cases (49% male, 51% female) of LM were registered in England, with a mean of 2625 new diagnoses per year. The crude incidence rate of LM increased from 4.33/100 000 [95% confidence interval (CI) 4.16–4.51] in 2013 to 4.69/100 000 (95% CI 4.52–4.87) in 2019. The average crude incidence rate of LM per year was 23.4/100 000 [95% CI 22.7–24.9; 35.2 male (95% CI 33.2–37.4), 15.4 female (95% CI 15.2–17.5)] in those aged > 80 years vs. 0.59/100 000 [95% CI 0.55–0.62; 0.65 male (95% CI 0.59–0.71), 0.53 female (95% CI 0.47–0.59)] in those aged < 60 years. Overall, 5-year Kaplan–Meier survival was 83.1% (95% CI 81.5–84.6) for LM diagnosed in 2013, while 5-year overall net survival was 103.7% (95% CI 101.2–106.2) in 2014. By comparison, for invasive melanoma, 5-year overall Kaplan–Meier survival was 79.1% (95% CI 78.3–79.8) and 5-year overall net survival was 88.6% (95% CI 87.6–89.6) for 2013 diagnoses. Important limitations are that registered LM is based on histopathological data or multidisciplinary team discussions; hence, LM treated topically without biopsy or untreated LM were not included. Privately treated patients were also under-represented, as there was no requirement for private laboratory data to be submitted to NDRS, unlike data from National Health Service laboratories. The apparent 5-year LM-specific survival advantage is likely due to fewer frail patients seeking medical attention, being referred or undergoing histological confirmation. We report the largest series of data on LM in Europe to date. The observed increase in the incidence of LM and its excellent 5-year net survival supports further discussion on current clinical practice and treatment options.
CPC07 Lupus comedonicus: a not so common entity
Authors: Diong Sophie , Wynne Bairbre , Leonard Niamh
Published: June 2023

Lupus comedonicus (LC) is an exceedingly rare variant of chronic cutaneous lupus erythematosus (CCLE), with only 13 reported cases in the literature to date. While its aetiology remains unknown, hallmarks include the presence of comedones on erythematous plaques, particularly in seborrhoeic areas. We report a case of LC involving the scalp, concha bowl and upper back. A 53-year-old female smoker with a 20-pack-year history and previous unprovoked pulmonary embolism presented to dermatology with a 2-year history of alopecia and rash affecting her face and upper back. She was initially reviewed by oral medicine for ulcers, where erythematous buccal mucosal plaques with white striations were seen. The initial biopsy showed a patchy lichenoid inflammatory infiltrate, raising suspicions for lichen planus; however, repeat biopsy highlighted perivascular inflammation and keratin plugging suggestive of lupus. Full skin examination revealed patchy scarring alopecia with perifollicular scale and erythema. Erythematous infiltrated plaques were seen on the face with similar more indurated lesions on the upper back associated with open comedones. The eponymous Shuster sign was observed in the left conchal bowl, with associated follicular occlusion. Laboratory studies all returned within normal limits, including antinuclear antibody titres and complement levels. Differential diagnosis included lupus erythematosus tumidus, discoid lupus erythematosus and LC. Lesional biopsies taken from her back confirmed LC, highlighting lichenoid inflammation involving follicles and interfollicular skin, with superficial and deep perivascular infiltrate. We commenced oral hydroxychloroquine at 200 mg once daily for management, with topical mometasone furoate 0.1% to be used while awaiting its full effect. Smoking cessation has also been advised given the potentially antagonistic effect of smoking with lupus and hydroxychloroquine. Hypotheses of the pathogenesis of LC include the effect of sun exposure. Ultraviolet radiation is known to not only enhance the activity of CCLE but may also contribute to the formation of comedones. Actinic damage alters collagen of normal skin, promoting sebum retention and follicular plugging. Given its infrequency, LC could be mistaken for benign conditions, including acne vulgaris, naevus comedonicus and Favre–Racouchot disease. It is plausible that the small case numbers are due to current underdiagnoses. It is important for dermatologists to be aware of and accurately diagnose LC. Apart from its potentially destructive, scarring complications, especially in untreated and misdiagnosed cases, it is associated with systemic lupus in 30% of cases. Delay in diagnosis and therapeutic management can be associated with significant potential morbidity and even mortality.
CPC08 Cutaneous squamous cell carcinoma and MYH9-associated elastin aggregation (MALTA) syndrome
Authors: Fostier William , Husain Akhtar , Rajan Neil
Published: June 2023

MYH9-associated elastin aggregation (MALTA) syndrome is a rare, inherited, irregular elastin aggregation and sweat duct proliferation syndrome caused by pathogenic variants in MYH9. MALTA syndrome was proposed in 2019, unifying Nicolau Balus and Rombo syndromes as phenotypes arising from pathogenic variants in the same gene, but it has not been associated with cutaneous squamous cell carcinoma (cSCC) [Fewings E, Ziemer M, Hörtnagel K et al. Malta (MYH9 associated elastin aggregation) syndrome: germline variants in MYH9 cause rare sweat duct proliferations and irregular elastin aggregations. J Invest Dermatol 2019; 139:2238–41]. Here, we report the clinical features of a family with a novel MYH9 c.1952A>C p.(Lys651Thr) pathogenic variant, providing evidence that cSCC may be an associated feature of MALTA syndrome. A 57-year-old woman presented with a longstanding skin lesion overlying her left infraorbital ridge, which had been present for 13 years. Lesion biopsy revealed a highly infiltrative tumour within the dermis that was composed of keratocysts with small islands of basaloid cells; immunostaining was positive for CK5/6, CK7, CK19, p63 and BerEP4. These histological features were consistent with a microcystic adnexal carcinoma (MAC)-like ductal proliferation, recognized in MALTA. In addition, she had previously developed one cSCC on her left shoulder and two basal cell carcinomas and had cutaneous milia. Her sister had a history of MAC-like ductal proliferation and cSCC, and her brother had two keratoacanthoma-like cSCCs. The copresentation of MAC-like ductal proliferations and early-onset cSCC in this family prompted targeted genetic testing of MYH9. This identified a heterozygous pathogenic variant in a highly conserved region of MYH9 [c.1952A>C p.(Lys651Thr)] that segregated with the phenotype in all three affected members. MYH9 has previously been identified as an important gene in the pathogenesis of cSCC in a genetic screen in transgenic mice, and our family adds novel clinical data, underscoring its importance in cSCC development (Schramek D, Sendoel A, Segal JP et al. Direct in vivo RNAi screen unveils myosin IIa as a tumor suppressor of squamous cell carcinomas. Science 2014; 343:309–13). Based on the recurrent presentation of early-onset cSCC in three members of this family, we propose the inclusion of cSCC in MALTA syndrome. This has implications for skin cancer surveillance of MYH9 pathogenic variant carriers, and the need to consider MALTA syndrome in patients presenting with multiple early-onset cSCC.
CPC11 Immune checkpoint inhibitor-associated eosinophilic fasciitis: a case report
Authors: Ashraf Mariha , Elmansouri Ahmad , Fremlin Georgina , Hejmadi Rahul , Derrett-Smith Emma
Published: June 2023

A 67-year-old man presented with a 3-month history of skin tightness associated with shooting, burning pains and numbness on both his upper and lower limbs. The patient had a background of metastatic bladder cancer, treated with six cycles of gemcitabine and cisplatin therapy from September 2019 to January 2020. Following this, he also had radical radiotherapy to the bladder, and in August 2020, he started pembrolizumab therapy. Pembrolizumab was paused in February 2022 due to the development of immunotherapy-related myositis. On examination, the patient had visibly shiny and thickened skin bilaterally involving the upper and lower limbs. Symptoms significantly limited the patient’s mobility and daily activities. A skin biopsy showed marked reduction in elastin fibres and mild fibromuscular thickening around the blood vessels, suggestive of scleroderma. Following a joint rheumatology and dermatology multidisciplinary meeting, a diagnosis of eosinophilic fasciitis (EF) secondary to the checkpoint inhibitor pembrolizumab was made. This was further supported by lower limb magnetic resonance imaging, which demonstrated evidence of bilateral oedema of the soleus muscle tendinous junction. Eosinophilic fasciitis is characterized by inflammatory infiltration, thickening and fibrosis involving the fascia. Unlike scleroderma, patients, such as in our case, with EF do not have sclerodactyly, Raynaud phenomenon, telangiectasias or nailfold capillary changes. Clinical manifestations of EF involve sudden onset, and pain and erythema (usually bilaterally) of the affected extremities. Patients have also been known to develop joint contractures, morphoea-like lesions and inflammatory polyarthritis. The reported triggers and causative agents of EF include trauma, autoimmune disorders and drugs. Only 13 cases have been reported secondary to pembrolizumab therapy, and the median time of symptom onset is 12 months following the commencement of checkpoint inhibitor treatment. According to the literature, there may be an underlying diagnosis of a solid tumour, haematological disorder or autoimmune disease. High-dose prednisolone is the primary treatment of choice, followed by methotrexate. However, some patients have shown spontaneous recovery. Our patient has now started a treatment course of high-dose intravenous methylprednisolone and methotrexate. While the therapeutic outcome is too early to report, he has already noticed improvements in skin tightening of the lower limbs.
CPC13 Cutaneous crystal storing histiocytosis
Authors: Brent Geoffrey , Chong Heung , Ffolkes Lorrette , Reddy Hari , Natkunarajah Janakan
Published: June 2023

A 43-year-old woman presented with a 3-year history of a gradually enlarging lesion on the right upper chest. Her comorbidities included ankylosing spondylitis and recurrent anterior uveitis, and she was taking no regular medications. She had no systemic symptoms. She was initially seen by the breast team, who organized an ultrasound that showed chronic inflammation, and a biopsy that showed granulomatous chronic inflammatory tissue. Topical treatment with fucidin was unsuccessful, and she was referred to dermatology. On examination, she had a 3.5 × 4 cm pink subcutaneous nodule on the right upper anterior chest. There was no lymphadenopathy or organomegaly. Investigations revealed low IgA (0.71 g L−1), raised IgM (4.30 g L−1) and mild thrombocytopenia (141 × 109 cells L−1). Full blood count; urea and electrolytes; liver function tests; IgG; lactate dehydrogenase; thyroid stimulating hormone; serum angiotensin-converting enzyme; autoimmune serology, including antinuclear antigen; Borrelia serology; tuberculosis QuantiFERON; ferritin; erythrocyte sedimentation rate; serum protein electrophoresis and urine Bence Jones protein were normal or negative. Chest X-ray and computed tomography of the thorax, abdomen and pelvis did not reveal any evidence of underlying malignancy. Repeat skin biopsy showed a superficial and deep dermal histiocytic infiltrate. At high power, numerous needle-like eosinophilic crystals were seen within the histiocytes. There was a periadnexal and perifollicular infiltrate of lymphocytes and plasma cells. Light chain staining showed that the plasma cells were lambda light chain restricted and were IgM positive and IgG negative. The features were of a crystal-storing histiocytosis. Cutaneous crystal-storing histiocytosis is a rare condition, with only six reported cases. The pathophysiology involves the accumulation of crystalline material within the cytoplasm of histiocytes. It is strongly associated with an underlying haematological malignancy, including multiple myeloma, lymphoplasmacytic lymphoma and monoclonal gammopathy of undetermined significance (Li JJ, Henderson C. Cutaneous crystal storing histiocytosis: a report of two cases. J Cutan Pathol 2015; 42:136–43). In our case, a bone marrow biopsy was not performed given the lack of systemic symptoms, no significant serum paraprotein and normal imaging. The patient is currently being managed with topical clobetasol propionate 0.05% ointment and is under annual haematology surveillance with serum electrophoresis and immunoglobulins.
P02 Galli Galli disease: a rare variant of the genodermatosis Dowling–Degos disease
Authors: Beatty Paula , Menamin Mairin Mc , Wynne Bairbre
Published: June 2023

A 35-year-old woman presented with a 4-year history of a persistent pruritic rash affecting her upper and lower limbs, concerning to the patient for cosmetic reasons. She denied any precipitating factors and reported no improvement with the use of topical clobetasol propionate. Notably, her mother had a similar rash, which had also developed in her 30s and continued to progress over time. Physical examination revealed a bilateral symmetrical papular eruption with superficial scale affecting extensor surfaces of her upper and lower limbs. The patient’s mother was also reviewed and had similar clinical findings, although a more generalized distribution was noted. Skin biopsy from the right thigh of the daughter showed acantholysis in the stratum spinosum with dyskeratotic cells. Biopsy from the left thigh of the patient’s mother showed elongation of rete ridges with foci of increased basal pigmentation and intraepidermal acantholysis. The presence of acantholysis and elongation of rete ridges with basal pigmentation histologically confirmed the diagnosis of the Galli–Galli variant of Dowling–Degos disease (DDD). The genetic basis for DDD involves a heterozygous loss of expression mutation affecting KRT5. Other implicated mutations include POGLUT1, POFUT1 and PSENEN, which are important in melanosome transfer, and the differentiation of melanocytes and keratinocytes. Galli–Galli disease remains a therapeutic challenge. Reported treatments trialled include topical retinoids, oral corticosteroids, and narrowband ultraviolet, although the outcomes have been disappointing. Successful treatment with erbium : yttrium aluminium garnet laser has been reported. Owing to the progressive nature of this condition, patient counselling regarding treatment expectations is important.
P06 Porokeratosis ptychotropica: a rare and recalcitrant genitogluteal eruption
Authors: Dear Kate , Watchorn Richard , Bunker Chris
Published: June 2023

A 45-year-old man with a history of psoriasis presented to our male genital dermatology clinic with a several-year history of pruritic, painful, hyperkeratotic red–brown plaques on both buttocks. He had previously been treated unsuccessfully with cryotherapy and topical imiquimod and podophyllotoxin for suspected condyloma acuminata. A 4-mm punch biopsy from the left buttock showed hyperkeratosis, hypergranulosis, papillomatosis and multiple columns of parakeratin with underlying agranulosis and dyskeratosis, consistent with cornoid lamella formation. A diagnosis of porokeratosis ptychotropica was made. He was treated with Dovobet® ointment and Trimovate® cream, with little improvement. He underwent four cycles of topical photodynamic therapy to his right buttock and two cycles to his left buttock, with minimal improvement. Oral isotretinoin was also trialled, but this led to lipid derangement prior to any observed benefit, so it was stopped. Porokeratosis ptychotropica is a rare and under-recognized variant of porokeratosis, characterized by epidermal keratinization that manifests as keratotic papules in the genitogluteal region. It is often misdiagnosed as psoriasis, tinea cruris or condyloma acuminata, as in our case. Typically, multiple cornoid lamellae are seen on histology (Lucker GP, Happle R, Steijlen PM. An unusual case of porokeratosis involving the natal cleft: porokeratosis ptychotropica? Br J Dermatol 1995; 132:150–1). The aetiology of porokeratosis ptychotropica is unknown, but there is potential for malignant transformation (Mazori DR, Shvartsbeyn M, Meehan SA et al. Transformation of porokeratosis ptychotropica into invasive squamous cell carcinoma. Int J Dermatol 2017; 56:679–80). It is commonly recalcitrant to treatment, with varying reports of success with topical retinoids, keratolytics, tacrolimus, calcipotriol, topical 5-fluorouracil, imiquimod, systemic retinoids, psoralen ultraviolet A, intralesional bleomycin, cryotherapy, photodynamic therapy, excision, dermabrasion and CO2 laser.
P11 Acrodermatitis chronica atrophicans: a sign of late lyme disease
Authors: Morgan Elsa , Wiggins James , Mowbray Megan , Tidman Michael
Published: June 2023

Borrelia infection manifests a variety of signs and symptoms, and its insidiousness and heterogeneity mean that its diagnosis can be delayed. We describe two patients from south-east Scotland who presented with unilateral asymptomatic atrophic areas of skin discoloration. The first was a 71-year-old woman, who presented with a 4-month history of a nonprogressive, mottled, erythematous rash involving her right thigh, buttock and calf. Case 2 was a 56-year-old woman with a 2-year history of an erythematous area of atrophic skin involving the medial aspect of her left thigh and shin. Histology from case 1 showed a normal epidermis with a largely ‘top-heavy’ superficial and deep, predominantly interstitial and focally perivascular, lymphohistiocytic infiltrate, with a predominance of mononuclear histiocytes and with focal extension to deep reticular dermis. Scattered plasma cells were identified, but eosinophils were not a prominent feature. Well-formed granulomas were absent, as were interface dermatitic activity and vasculitic changes. On close questioning, each patient remembered ‘insect’ bites in the vicinity of the cutaneous changes, although neither recalled rashes that could have been consistent with erythema chronicum migrans. In both cases, serology confirmed infection with Borrelia burgdorferi (sensu lato) and diagnoses of acrodermatitis chronica atrophicans (ACA) were made. Both patients responded well to oral treatment with doxycycline. ACA is a cutaneous sign of late-stage Lyme disease and is caused by ongoing active skin infection by tick-borne bacteria of the Lyme disease group of Borrelia species. The tick bite has usually occurred months or years before symptom onset. Typically, there is an early, unilateral inflammatory stage with bluish-red discoloration of the skin and an oedematous appearance. This is followed by an atrophic stage where the skin becomes thin and wrinkled (‘cigarette paper’-like), with the loss of epidermal and dermal structures. Histological features usually include marked atrophy of the epidermis and dermis, loss of adnexal structures and an absence of elastic tissue. A band-like lymphocytic infiltration with plasma cells and mast cells is seen in the dermis, especially in the early stage of disease. Laboratory-confirmed cases of Lyme borreliosis in the UK have risen steadily since reporting began in 1986. ACA is likely to be underdiagnosed and, if there is a clinical suspicion, a detailed history, careful skin examination, Borrelia serology and skin biopsy should be undertaken. Early recognition and treatment reduce the risk of irreversible skin changes and systemic symptoms.
P15 Progressive papulonodular eruption following COVID-19 infection: a rare diagnosis and review of the literature
Authors: Sheppeard Rhian , Austin Stephanie , Morgan Caroline , Ashton-Key Margaret
Published: June 2023

We report a rare case of primary cutaneous CD8+ aggressive epidermotrophic cytotoxic T-cell lymphoma with striking clinical and histopathological features. A 51-year-old man, originally from Cameroon, presented to the department with a 6-week history of a progressive, itchy papulosquamous eruption that started on the lower abdomen shortly following infection with COVID-19. It became widespread over a short number of weeks, with blistering and ulceration in some areas. The patient reported fatigue with an intermittent low-grade pyrexia, but no systemic symptoms otherwise, and he was previously fit and well. Physical examination revealed an extensive, infiltrated papulonodular eruption with thick scale that was more marked in the skinfolds and involving the acral surfaces. Histology from three morphologically different sites showed marked epidermal hyperplasia and a prominent epidermotrophic infiltrate of medium-sized atypical lymphoid cells. There were frequent mitotic figures and evidence of apoptosis. Immunohistochemistry revealed that the atypical lymphoid cells in the epidermis were T cells expressing CD3, CD7 and CD8, together with cytotoxic markers and a high Ki67 proliferation fraction. These features were consistent with a diagnosis of CD8+ aggressive epidermotrophic cytotoxic T-cell lymphoma. Initial bloods and imaging were fairly unremarkable. Since the diagnosis, the patient has been treated with multiple types and courses of chemotherapy, with relapses in between. Most recently, the patient has been referred for total skin electron beam therapy with investigations for allogenic stem cell transplant ongoing. Owing to its rarity, primary cutaneous CD8+ aggressive epidermotrophic cytotoxic T-cell lymphoma is categorized only as a provisional entity in the most recent World Health Organization classification (Gilson D, Whittaker SJ, Child FJ et al. British Association of Dermatologists and U.K. Cutaneous Lymphoma Group Guidelines for the management of primary cutaneous lymphomas 2018. Br J Dermatol 2018; 180:496–526). Despite a variable and polymorphic presentation, the histology is distinctive in showing monomorphous, medium-sized atypical lymphocytes in the epidermis. We discuss the epidemiology of the disease and the paucity of therapeutic guidelines. In addition, our patient’s disease developed soon after COVID-19 infection; hence, we review the growing literature on the association between COVID-19 infection and vaccination and diagnosis, and relapse and remission of cutaneous T-cell lymphoma.
P16 Cutaneous renal cell carcinoma metastasis with scrofuloderma as the initial presentation of metastatic renal cell carcinoma: a diagnostic challenge
Authors: Kothari Rohit
Published: June 2023

Renal cell carcinoma (RCC) with cutaneous metastasis is uncommon and accounts for approximately 3–5% of metastatic RCC, with an unfavourable prognosis. We present an unusual and difficult case of advanced RCC presenting initially with cutaneous metastasis and scrofuloderma, with identical morphology of the lesions. It also highlights the importance of dermatologists in the early diagnosis and management of such cases. A 50-year-old man presented with gradually progressive, multiple erythematous discharging nodules over the right side of his neck of 3 months’ duration. He described a weight loss of 10 kg, intermittent undocumented fever with headache and two episodes of uninvestigated transient haematuria in the last 6 months. He had received multiple courses of antibiotics without any relief. A skin biopsy and immunohistochemistry confirmed cutaneous RCC metastasis with a primary advanced metastatic left RCC, involving the brain as well. A total left nephrectomy was done and he was started on lenvatinib, everolimus and radiotherapy, following which there was suboptimal response and he started developing similar nodular lesions over the left axilla and chest wall, and a puckered crusted plaque over the left lateral abdomen 1 week post treatment. Follow-up at 8 weeks revealed a significant response in the neck lesions; however, the new lesions on the left side did not respond, following which a dermatology consultation was sought again. A skin biopsy from the new lesions confirmed scrofuloderma. Tissue polymerase chain reaction and culture were positive for mycobacterium tuberculosis. He was diagnosed as having scrofuloderma and started on daily isoniazid, rifampicin, ethambutol and pyrazinamide for 2 months followed by daily isoniazid and rifampicin for 4 months. Follow-up at 6 months revealed well-healed lesions, and the systemic symptoms and discharge had abated. The cutaneous metastatic lesions had also healed completely. Here, we present an interesting case of cutaneous RCC metastasis with coexisting scrofuloderma as the initial manifestation of an advanced RCC, posing a diagnostic challenge due to similar morphology. On this background, a recurrence of cutaneous metastasis was the first possibility considered for the new skin lesions. The delay in diagnosis led to significant morbidity in our patient, emphasizing the role of early dermatology consultation in the management of such cases. A high index of suspicion for conditions masquerading as cutaneous metastasis, as well as a lower threshold for skin biopsy, may improve the prognosis dramatically.
P17 Photosensitive rashes in the context of alcoholism: a diagnosis to remember
Authors: Davies Anna , Stone Natalie , Ponnambath Nabil
Published: June 2023

Pellagra is a disease defined by a deficiency in niacin and its precursor tryptophan. It is a clinical diagnosis characterized by the ‘four Ds’: dermatitis, dementia, diarrhoea and death (Badawy AA. Pellagra and alcoholism: a biochemical perspective. Alcohol 2014; 49:238–50; Pipili C. The diagnostic importance of photosensitivity dermatoses in chronic alcoholism. Dermatol Online J 2008; 14:15). It is predominantly a disease of non-Western countries with low niacin-containing diets, based on maize, with little meat or vegetables. In Western populations, the commonest causes of pellagra include alcoholism, gut malabsorption, some drugs and, rarely, carcinoid, which causes increased conversion of tryptophan to serotonin, depleting niacin precursor stores. The histopathological features of pellagra are nonspecific; however, pallor and keratinocyte ballooning in the upper third of the epidermis can be suggestive. We present two cases of pellagra in the context of alcoholism. Patient 1 was a 58-year-old woman who presented with a 6-week history of a rash on the dorsal hands which spread to the forearms and dorsum of both feet. Examination revealed a photodistributed erythematous rash with a prominent leading edge, wrinkling and hyperkeratosis. She described loss of appetite, diarrhoea and increasing confusion. A punch biopsy from the right forearm showed focal parakeratosis, perivascular inflammation and mild spongiosis with increased mucin in the superficial dermis. A clinical diagnosis of pellagra was suspected, and empirical niacin was prescribed. Patient 2 was a 60-year-old woman who presented with a 1-month history of a progressive itchy rash affecting her arms and legs. Examination revealed a striking photosensitive erythematous rash of her arms and legs, with complete sparing of the inner aspect of the arms. Skin biopsy showed mild keratosis, with subtle thickening of capillary walls. A diagnosis of pellagra was suspected and treatment with oral niacin commenced. Both patients drank alcohol to excess. Both had negative plasma porphyrins and had not started any new drugs and autoimmune screens were normal. The clinical appearance was identical in both cases. Patient 1 continued to drink excess alcohol, but the rash resolved with niacin supplementation. Patient 2 only took a short course of niacin due to significant flushing, but she managed to reduce her alcohol intake significantly and her rash fully resolved. Pellagra is a rare diagnosis in a Western population, but it is an important diagnosis to remember in patients presenting with a photosensitive rash, particularly in the context of alcohol abuse.
P19 Diagnostic conundrums in paraneoplastic pemphigus
Authors: Fleming Sarah , Setterfield Jane , Mee John , Barrett Helen , Eustace Karen
Published: June 2023

Paraneoplastic pemphigus (PNP) is a subset of pemphigus, a group of autoimmune blistering skin disorders. A 51-year-old man presented with paraneoplastic pemphigus associated with a hepatic neoplasm. He described an epigastric mass and associated mucositis affecting the orogenital mucosae, as well as the sclerae. Both computed tomography and magnetic resonance imaging demonstrated a 14-cm mass arising from the left lobe of the liver. A liver biopsy showed features of an atypical spindle-cell neoplasm, but a definite diagnosis was not possible. A diagnostic skin biopsy was taken from his outer lip mucosae. Histology showed surface ulceration with an acute inflammatory infiltrate, lichenoid lymphoplasmacytic infiltrate with focal basal vacuolar change, degenerate keratinocytes and adjacent suprabasal acantholysis and spongiosis. Perilesional direct immunofluorescence (DIF) was negative; however, indirect immunofluorescence (IIF) showed intercellular IgG antibodies on transitional epithelium with a high titre of 1 : 800 to rat bladder. These finding were consistent with the suspected clinical diagnosis of paraneoplastic pemphigus. The patient was commenced on oral prednisolone 1 mg kg−1 daily. Topical therapy included budesonide mixed with sweetener applied to the oral mucosae. Following this, a trial of 3 days of intravenous methylprednisolone along with 2% cocaine mouthwash, triple mouthwash (betamethasone, doxycycline and nystatin) and Dermovate® ointment was commenced, with improvement noted in pain, haemorrhage and ulceration. Intravenous immunoglobulin was administered preoperatively. The patient was subsequently transferred to a specialist centre for hepatobiliary surgery and listed for debulking of the liver mass. Postoperatively, he had plasmapheresis, with a noted reduction in mucosal ulceration and significant improvement in pain. Chemotherapy with doxorubicin and ifosfamide was initiated thereafter. PNP is a severe autoimmune blistering disorder characterized clinically by flaccid blisters and erosions. Although much is yet to be understood regarding the pathophysiology of PNP, studies show that the development of autoantibodies to the plakin family and desmogleins 1 and 3 play a particular role in its pathogenesis. In addition to autoantibodies, CD8+ T cells have also been shown to contribute to the development of PNP. In adults, the majority of cases are associated with an underlying haematological malignancy and, rarely, a solid-organ tumour. DIF findings include IgG and C3 deposition along the intercellular and basement membrane zones, while IIF detects autoantibodies to proteins found in transitional or stratified squamous epithelium. As in our case, reports have shown that the DIF can be negative, with one study showing a positive DIF in only 41% of cases. This case highlights the complex diagnostic and treatment challenges practitioners face when dealing with PNP and the patients it affects.