tbuckley/cabot-search huggingface dataset:
GATA-3–dependent Gene Transcription is Impaired upon HDAC Inhibition
Authors: Xiangrong Geng, Chenguang Wang, Suhaib Abdelrahman, Thilini Perera, Badeia Saed, Ying S. Hu, Ashley Wolfe, John Reneau, Carlos Murga-Zamalloa, Ryan A. Wilcox
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Many peripheral and cutaneous T-cell lymphoma (CTCL) subtypes are poorly responsive to conventional chemotherapeutic agents and associated with dismal outcomes. The zinc finger transcription factor GATA-3 and the transcriptional program it instigates are oncogenic and highly expressed in various T-cell neoplasms. Posttranslational acetylation regulates GATA-3 DNA binding and target gene expression. Given the widespread use of histone deacetylase inhibitors (HDACi) in relapsed/refractory CTCL, we sought to examine the extent to which these agents attenuate the transcriptional landscape in these lymphomas. Experimental Design: Integrated GATA-3 chromatin immunoprecipitation sequencing and RNA sequencing analyses were performed in complementary cell line models and primary CTCL specimens treated with clinically available HDACi. Results: We observed that exposure to clinically available HDACi led to significant transcriptional reprogramming and increased GATA-3 acetylation. HDACi-dependent GATA-3 acetylation significantly impaired both its ability to bind DNA and transcriptionally regulate its target genes, thus leading to significant transcriptional reprogramming in HDACi-treated CTCL. Conclusions: Beyond shedding new light on the mechanism of action associated with HDACi in CTCL, these findings have significant implications for their use, both as single agents and in combination with other novel agents, in GATA-3–driven lymphoproliferative neoplasms.
Bioactive mesoporous silica nanoparticle-functionalized titanium implants with controllable antimicrobial peptide release potentiate the regulation of inflammation and osseointegration
Authors: Jiyu Dong, Fangman Chen, Yuying Yao, Congcong Wu, Silin Ye, Zunwei Ma, Haipeng Yuan, Dan Shao, Lin Wang, Yingjun Wang
Journal: Biomaterials (2024)
Cardiac resident macrophages: Spatiotemporal distribution, development, physiological functions, and their translational potential on cardiac diseases
Authors: Jing Jin, Yurou Wang, Yueqin Liu, Subrata Chakrabarti, Zhaoliang Su
Journal: Acta Pharmaceutica Sinica B (2024)

Cardiac resident macrophages (CRMs) are the main population of cardiac immune cells. The role of these cells in regeneration, functional remodeling, and repair after cardiac injury is always the focus of research. However, in recent years, their dynamic changes and contributions in physiological states have a significant attention. CRMs have specific phenotypes and functions in different cardiac chambers or locations of the heart and at different stages. They further show specific differentiation and development processes. The present review will summarize the new progress about the spatiotemporal distribution, potential developmental regulation, and their roles in cardiac development and aging as well as the translational potential of CRMs on cardiac diseases. Of course, the research tools for CRMs, their respective advantages and disadvantages, and key issues on CRMs will further be discussed.
The pathophysiology of sepsis and precision-medicine-based immunotherapy
Authors: Evangelos J. Giamarellos-Bourboulis, Anna C. Aschenbrenner, Michael Bauer, Christoph Bock, Thierry Calandra, Irit Gat-Viks, Evdoxia Kyriazopoulou, Mihaela Lupse, Guillaume Monneret, Peter Pickkers, Joachim L. Schultze, Tom van der Poll, Frank L. van de Veerdonk, Alexander P. J. Vlaar, Sebastian Weis, W. Joost Wiersinga, Mihai G. Netea
Journal: Nature Immunology (2024)
P23 Successful Control of Systemic Mastocytosis Symptoms in a Two-Year-Old with Omalizumab
Authors: Miteshkumar Ramwani, Constantinos Kotsapas, Sheila Clark, Jack Bartram, Lea Solman
Journal: British Journal of Dermatology (2024)

Abstract A 6-month-old boy presented to us with diffuse cutaneous mastocytosis, experiencing constant severe pruritus, blistering, urticaria, flushing, diarrhoea, and frequent anaphylaxis episodes. He was found to have hepatosplenomegaly and mast cells in the bone marrow aspirate, confirming systemic mastocytosis. His tryptase was significantly elevated (87 ug/ml). A c-KIT D816V mutation was identified in exon 17 through a skin biopsy and peripheral blood testing. The patient received concomitant treatment with cetirizine (eightfold dosage), hydroxyzine, chlorphenamine, cimetidine, ketotifen, sodium cromoglicate, and montelukast in addition to topical treatment. Despite the treatment, he continued to have frequent episodes of flushing, anaphylaxis, blisters, and severe pruritus. He required oral prednisolone on several occasions, which provided little relief. Treatment with Imatinib was not an option, as patients with mastocytosis who have the c-KIT D816V mutation do not respond to it. Due to his poor quality of life, we initiated monthly injections of omalizumab (150 mg sc). After three doses, his DLQI score decreased from 29/30 to 10/30. He had no further anaphylactic episodes, and he had significant reduction in the episodes of flushing, urticaria and blistering. Unfortunately, there was little improvement in his pruritus, which remains troublesome for him, particularly at night. He had no significant side effects of omalizumab. Conclusion Omalizumab may provide safe and effective management of symptoms in paediatric patients with systemic mastocytosis, refractory to high-dose conventional therapy, particularly in patients who cannot receive imatinib.
P11 A Rare and Serious Cause of “Blueberry Muffin Syndrome”
Authors: Jaimie Oldham, Anna Dunnigan, Elsa Barbosa, Sylvia Huang, Sasha Dhoat, Bryan McDonald, Edel O’Toole, Ravinder Atkar
Journal: British Journal of Dermatology (2024)

Abstract Urgent dermatology review was sought for a neonate born at term via emergency caesarean section for reduced movements. The pregnancy was complicated by gestational diabetes and infection with suspected coxsackie virus in the second trimester. There were 15 purple/blue nodules consistent with “blueberry muffin syndrome” and associated anaemia (118 g/L). Due to hypoxia, she was given antibiotics for suspected sepsis. TORCH screen was negative and USS abdomen and cranium were normal. A blood film showed B cell aplasia and LDH was raised (710 unit/L). CXR showed a mediastinal mass, left pleural effusion and left lung opacity. A skin biopsy was taken, chest drain placed and the baby transferred to Great Ormond Street. She was subsequently diagnosed with acute myeloid leukaemia following bone marrow and lumbar puncture. All three skin biopsies showed a malignant infiltrate with one displaying positivity for CD12 and CD33. CT and MRI scans have shown widespread nodules in the lungs, liver, kidneys, bones and intra-cranially. She is being treated with chemotherapy which has been complicated by a cardiac arrest and severe mucositis leading to colostomy. She is also NG fed and has sensorineural hearing loss. The nodules seen in “blueberry muffin syndrome” are most commonly extramedullary erythropoiesis but can also represent purpura or metastases. The causes are congenital infections, blood disorders or tumours. There is frequently associated anaemia (as in our case) and hepatosplenomegaly. This case demonstrates a rare and concerning cause of the syndrome and highlights the role dermatologists can play in diagnosis.
P24 Improving the patient pathway for timely referral and management of infantile haemangioma
Authors: Jacqueline Scott-Bazaldua, Anna Dubois
Journal: British Journal of Dermatology (2024)

Abstract Infantile haemangiomas (IH) are vascular tumours which typically present soon after birth and grow rapidly at a young age. Complications can arise depending on location and rapidity of growth of the lesion1. Timely treatment with an oral beta-blocker can limit growth and speed up resolution of IH. Not infrequently, we noted babies were being referred at a stage when most of the growth of the IH had already taken place. These patients often had skin breakdown, or a large haemangioma, making successful treatment harder to achieve. We aimed to educate GPs and health-visitors regarding the need for timely referral and to speed up the triage process for these patients. Information was sent to regional GP practices, with instructions on referral criteria according to the BSPAD guidelines for treatment of IH. A photograph of the IH was requested at the time of referral. Submitted referrals were triaged promptly and where appropriate, booked directly into a telephone clinic. After telephone consult, IH meeting the criteria for propranolol were booked directly for commencement of the beta-blocker with a paediatric review. If there was diagnostic doubt or other complications, a timely face to face review was arranged. Patients not requiring oral treatment were discharged back to GP. A patient satisfaction questionnaire revealed that parents appreciated the speed of assessment and reduced hospital visits. We describe an educational intervention and triage strategy resulting in improvement in the timing of referral and management of infantile haemangioma.
P06 Outcomes from a New Combined Allergy and Dermatology Clinic- A Retrospective Review
Authors: Su Yi Liew, Samid Ahmed, Alya Abdul-Wahab, Rosy Wells, Leila Ferguson
Journal: British Journal of Dermatology (2024)

Abstract Early introduction to known allergens such as peanuts can reduce subsequent development of allergies [1]. In 2019, an audit in our department of 35 babies under age 1 referred with eczema showed that 4 were concomitantly referred to allergy and 20 were referred to allergy after dermatology consultation. The majority had moderate/severe eczema and 31% had implemented dietary restrictions before the dermatology consultation. In 2021, a combined allergy and dermatology clinic was introduced to provide a holistic approach, particularly for young children. Patients are triaged from GP referrals or as follow-up from either team. We conducted a retrospective notes review to explore the benefits/outcomes. 57 patients were included with an average age of 4.75 years and 58% were below age 2. 58% had their dermatology plans changed. Before the clinic, 81% had dietary exclusions but only 46% had new allergies confirmed. 29% of the patients who underwent testing tested negative to all allergens, which allowed parents to reintroduce foods at an early age. This review shows that the combined clinic allowed young patients early access to allergy testing due to streamlined services, preventing unnecessary dietary exclusions. Additionally, patients with severe eczema without allergies benefit from early dermatology intervention. In fact, 44% of patients were suitable for discharge from dermatology directly from the combined clinic or at first follow-up appointment.
P01 Pigmented and purpuric patches in sun protected areas of a 9 year old child
Authors: Cristina Grechin, Ruth Law, Sinead Collins
Journal: British Journal of Dermatology (2024)

Abstract Pigmented purpuric dermatosis-like mycosis fungoides (PPD-like MF) is a rare variant of paediatric mycosis fungoides (MF). Clinically, it can be challenging to diagnose and differentiate from pigmented purpuric dermatosis (PPD). Usually, has an indolent course if diagnosed in the early stage. The lesions often localize to sun-protected areas with three stages: patch, plaque, and tumour. Clinical features alone are insufficient for diagnosis and a skin biopsy is mandatory.1 We report a nine year old boy who presented with a three year history of a persistent, slowly progressing, mildly pruritic and scaling rash on the right buttock and medial thighs bilaterally. He was otherwise well with no other relevant medical or family history of note. The physical examination revealed erythematous to purpuric, mild scaly patches with confluent involvement on the right buttock extending to less defined involvement of the both inner thighs. The body surface area involved was less than &amp;lt;10%. No other clinical findings on examination. A punch biopsy for haematoxylin and eosin (H&amp;E) staining was consistent with mycosis fungoides. T cell receptor gene rearrangement testing detected a monoclonal T-cell population. A diagnosis of pigmented purpuric dermatosis-like mycosis fungoides was made. The patient responded well to a potent topical steroid (mometasone furoate) daily which was gradually tapered to twice weekly/intermittent usage to maintain response.
O07 CHILD syndrome and ILVEN: disorders on the same spectrum?
Authors: Pratima Paudel, Maryam Salimi, Rebecca Igbokwe, Saleem Taibjee, Malobi Ogboli, Celia Moss, Samantha Ibbs
Journal: British Journal of Dermatology (2024)

Abstract Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects (CHILD syndrome) is a rare X-linked dominant disorder caused by hemizygous variants in the NSDHL gene. Typically, affected girls are born with unilateral skin lesions in a Blaschkoid distribution due to random X-inactivation, and ipsilateral limb reductions. We report a genetically confirmed case without significant limb reductions and consider the relationship of CHILD syndrome to inflammatory linear verrucous epidermal naevus (ILVEN) also sometimes caused by mosaic variants in NSDHL. A 9-month-old girl presented with extensive congenital red, scaly lesions in a Blaschkoid distribution confined to the right side of her body. Examination was otherwise normal apart from sensorineural deafness in the right ear and overlapping right 4th and 5th toes. Histology showed the characteristic foamy histiocytes of CHILD syndrome and genetic testing revealed a heterozygous pathogenic variant of NSDHL, c.262C&amp;gt;T p.(Arg88*) previously reported in CHILD syndrome. Patients clinically diagnosed with ILVEN but with NSDHL mutations have sometimes been reclassified as CHILD syndrome (König A et al. ILVEN encompasses a spectrum of inflammatory mosaic disorders. Am. J.Med.Genet. 2000;90:339-46). The histology of ILVEN is less specific than CHILD syndrome, without the characteristic foamy histiocytes. Nonetheless these conditions could be on a spectrum, with limb defects arising if mutant skin cells overlie the primitive limb bud (Moss C, Burn J. Hypothesis: CHILD+ILVEN=PEN or PENCIL J.Med.Genet. 1990;27:390-391). NSDHL controls cholesterol synthesis and the topical treatment with statins plus cholesterol effective in CHILD syndrome could be considered in some cases of ILVEN.
P18 Giant Periocular Juvenile Xanthogranulomas Treated with Trametinib
Authors: Pratima Poudel, Gerard Millen, Malobi Ogboli
Journal: British Journal of Dermatology (2024)

Abstract Juvenile Xanthogranuloma (JXG), the commonest type of non-Langerhans cell histiocytosis, is regarded as a benign self-limiting condition of infancy, characterised by asymptomatic yellow brown papulonodular lesions, usually confined to the skin but occasionally affecting the eyes or internal organs. Skin lesions characteristically regress spontaneously within 3-6 years. We describe an unusually aggressive cutaneous presentation requiring input from paediatric oncology. A 6 year old boy presented with extensive soft yellowish papules, plaques and nodules particularly around the eyes but also over the chest and leg. Biopsy confirmed the clinical diagnosis of JXG. The lesions enlarged progressively with new lesions appearing, causing significant distortion of the upper and lower eyelids with reduced ability to open the eyes, discomfort and distress. Treatment was started with topical steroids, progressing to intralesional and systemic steroids, but with minimal effect. In view of the severity, vinblastine and subsequently cytarabine were added, again with limited benefit. The periocular lesions were surgically debulked and he was commenced on Trametinib (a MEK inhibitor) with a good response. Now aged 9 years, and the patient displayed a favourable clinical response after 3 months of being on Trametinib. JXG rarely requires treatment, but there is no recognised therapy for the occasional problematic lesions. In this case trametinib was effective and well-tolerated. The efficacy of trametinib in histiocytosis has been attributed to the presence of activating BRAF and MAP2K1 mutations. Genetic analysis of JXG may guide future therapies.
P33 A lichenoid eruption and severe eczema in association with IMAGe syndrome
Authors: Garret O’Connell, Mary Bennett
Journal: British Journal of Dermatology (2024)

Abstract IMAGe syndrome is a rare genetic disorder. IMAGe is an acronym for; (1)Intrauterine restricted growthMetaphyseal dysplasiaCongenital adrenal hypoplasiaGenitourinary abnormalities in males (cryptorchidism, micropenis, and hypospadias) Diagnosis is established by molecular genetic testing with heterozygous CDKN1C pathogenic mutation or a proband with suggestive findings in the PCNA (proliferating cell nuclear antigen)- binding domain of the maternally expressed allele. Additional features include characteristic facies (frontal bossing), developmental delay, immunodeficiency, osteoporosis and scoliosis. Severe, early onset eczema has been described in association with this syndrome. (2) We present the case of a 15-year-old boy with proven IMAGe syndrome, longstanding history of atopic dermatitis, and new onset lichenoid eruption on the forearms.
O04 Vulval Psoriasis in Children: A Clinical Audit and Review of Literature
Authors: Michelle Wu, Gayle Fischer
Journal: British Journal of Dermatology (2024)

Abstract Objective Vulval psoriasis is frequently under-recognised, under-­diagnosed and under-treated in children due to its nonspecific presentation. This retrospective chart review is aimed to describe the symptoms, signs, and management of vulval psoriasis in children in a private vulval disease referral practice. Materials and methods A retrospective, single-centre cohort study of children was undertaken at a large, combined dermatology and gynaecology practice from January 2016 to January 2023. Clinical photographs and treatment data were systematically collected and recorded in an online patient database. Treatment regimens were individualised and titrated to clinical response. Results This seven-year retrospective cohort study included a total of 100 children with vulval psoriasis. The most common presentation was nonspecific erythema (85%) that is well-demarcated in one-third of children and appears as a raised plaque in one-fifth of children. In 78% of the patients, evidence of psoriasis was found on other parts of the skin. Initial induction treatment with potent topical corticosteroid followed by maintenance treatment with less potent topical steroids and topical tar creams. 5% of children required systemic treatment. Conclusions and Relevance Vulval psoriasis often presents as a nonspecific chronic erythematous vulvitis without vaginitis. It is a chronic relapsing skin condition that requires long-term management. Systematic treatment is required in a small proportion of children.
P27 Successful treatment of severe eczema and plane warts with Dupilumab in a child with Dedicator of Cytokinesis 8 (DOCK8) deficiency (Autosomal recessive form of hyper-IgE syndrome)
Authors: Jadesola Oyedepo, Austen Worth, Lea Solman
Journal: British Journal of Dermatology (2024)

Abstract A six-year-old girl first presented with severe eczema at the age of 6 months, which was difficult to control with topical treatments. She was found to have severely elevated total IgE and multiple food allergies. Due to recurrent ear and chest infections, and persistent varicella zoster, she was screened for a primary immunodeficiency and found to have a homozygous exon 29-46 deletion in the DOCK8 gene. Her eczema remained challenging, with coalescing warts on her limbs. She started Methotrexate with an initial good response; however, the frequency of infections and hospitalizations increased. After the diagnosis of DOCK8 deficiency was confirmed, she started Dupilumab, resulting in the complete resolution of her eczema and warts. She is awaiting haematopoietic stem cell transplant (HSCT) . DOCK8 deficiency is an autosomal recessive hyper-IgE syndrome that presents early in life with severe eczema, skin abscesses, multiple food allergies, recurrent respiratory tract infections, and severe viral (including skin) infections. Older patients invariably develop bronchiectasis and are at high risk of malignancy. Patients have a combined immunodeficiency, with T-cell lymphopenia, reduced thymic output and T-cell skewing to a Th2 response. Children with this condition often present to dermatologists because of severe eczema, which is usually difficult to treat with standard topical treatments. The decision to treat with systemic immunosuppression is often challenging due to recurrent infections. Although HSCT is the curative treatment for DOCK8 deficiency, Dupilumab can be used to reduce inflammation and infections, and improve quality of life in patients awaiting HSCT.
P03 EB or not EB? A report of two neonates with congenital blisters
Authors: Maria Bageta, Catherine Miller, Branavan Sivakumar, Pablo Lopez Balboa, Razan Dodein, Gabriela Petrof, Anna E Martinez
Journal: British Journal of Dermatology (2024)

Abstract Neonatal compartment syndrome (NCS) is extremely rare, with less than 100 cases reported. The affected limb usually presents with significant swelling and sentinel skin changes such as desquamation, blisters and skin necrosis. Risk factors that predispose infants to a hypercoagulable state or trauma have been implicated, but the exact cause remains elusive. We report two neonates with no family history of note, except for oligohydramnios in patient 1, who presented with congenital bullae over the upper extremity which led to an open wound. They were both referred to our service with a provisional diagnosis of epidermolysis bullosa (EB). Patient 1 also presented with a reduction in spontaneous movements of the hand shortly after birth. The wound took weeks to heal with scaring and subcutaneous tissue and muscle loss resulting in significant ulnar deviation by age 9 weeks. This was managed with stretching exercises, splints and surgical intervention. Despite this there remained noticeable limb length discrepancy and functional limitations to date. Patient 2 had a lack range of motion and restricted passive motion on the affected limb by the age of 4 weeks. Subsequent neurophysiological studies showed evidence of a severe chronic median and ulnar neuropathy with distal axonal loss and a right radial neuropathy at the site of the scar. Clinically, both cases were in keeping with NCS. A skin biopsy and molecular analysis ruled out EB. NCS requires early recognition and intervention as it can lead to long-term sequelae including Volkmann contracture, limb length discrepancies and permanent nerve damage.