tbuckley/cabot-search huggingface dataset:
P21 Bi-allelic TUFT1 variants in two siblings with woolly hair and skin fragility
Authors: Pablo Lopez Balboa, Maria L Bageta, John A McGrath, Gabriela Petrof, Anna E Martinez
Journal: British Journal of Dermatology (2024)

Abstract TUFT1 encodes tuftelin-1, a glycoprotein thought to play a major role in mineralization and structural organization of enamel, but it has not been implicated in any monogenic enamel disorders. Recently, Jackson et al. (2023) identified that tuftelin-1 has a role in desmosomal function. Pathology in desmosomal components causes disorders affecting the skin, hair, and heart. Newly described bi-allelic loss-of-function TUFT1 variants (OMIM600087) cause a novel skin fragility-woolly hair phenotype. We present two siblings from non-consanguineous parents of Irish and British ancestry. Both had normal skin at birth and developed widespread blisters on day two of life, on the limbs, buttocks area and inside the mouth. Although their skin fragility had improved with age, they still developed flare-ups with multiple small blisters, mainly on their limbs when viral illness. They had mild palmoplantar keratoderma and skin peeling. Their most characteristic phenotype was slow-­growing woolly hair that did not need cutting until the age of 5 years old in the older sibling. The eyebrows and eyelashes were unaffected. Recently, the older sibling has developed keratosis pilaris on her arms. The heart was unaffected with normal electrocardiogram and echocardiogram. Whole exome sequencing identified homozygous NM_020127:c.60+1G&amp;gt;A TUFT1 variants in both affected individuals. These two cases reflect a novel condition. The predominant clinical phenotype is woolly hair and early signs of skin fragility. Despite having a role in desmosomal integrity bi-­allelic loss-of-function TUFT1 variants do not appear to cause cardiac pathology.
P14 Midface Toddler Excoriation Syndrome (MiTES): a new mimic of non-accidental injury
Authors: Janine Dewar, Alia Ahmed, Celia Moss, Lea Solman
Journal: British Journal of Dermatology (2024)

Abstract Background Midface Toddler Excoriation Syndrome (MiTES) is a rare genetic condition first described in 2017. Commencing in the first year of life, it is characterised by intense mid-­facial itch with persistent scratching and skin breakdown. Symptoms improve later in childhood, leaving atrophic scarring. Disbelief that infants can damage themselves in this way can lead to an erroneous and damaging misdiagnosis of non-accidental injury (NAI). Cases A boy now aged 11 years presented at 6 months with recurrent scratching of the face, leading to ulceration of the nasal bridge, sides of the nose, infraorbital areas and central forehead. Extensive investigations were unhelpful and NAI was suspected with significant psychosocial sequelae for the family. When his sister, now aged 4 years, presented with strikingly similar lesions MiTES was suspected and confirmed by genetic testing which showed homozygosity for 18 alanine repeats in the PRDM12 gene. Testing of sibling and parents is planned. Both children are now asymptomatic but have significant facial scarring. Discussion Biallelic variants in PRDM12 usually cause hereditary sensory and motor neuropathy type 8 with widespread damage to distal appendages due to pain insensitivity. The specific variant found here and in all reported MiTES cases causes highly localised lesions with rarely any extra-facial ­involvement. Due to its novelty and rarity, MiTES may be misdiagnosed and safeguarding concerns raised, leading to distress for affected families and breakdown of parent-­provider relationships. This case, which for the first time provides longitudinal data on affected siblings, highlights the need for early recognition and diagnosis.
P29 Erosive and vesicular dermatitis
Authors: Christiana Stavrou, Suzy Leech
Journal: British Journal of Dermatology (2024)

Abstract We present a case of a 3 year old girl, born at term via normal vaginal delivery, with significant erosive lesions present from birth. Finger and toenails were small and she was systemically well. At day three, there was already evidence of healing and by week two, the erosions had almost fully healed with residual scaling. Once fully resolved, areas of hypopigmented, reticulate scarring remained. Investigations included swabs for bacterial, fungal and viral infections were negative. There was no concern regarding perinatal infection and apart from oligohydramnios, there were no other issues in pregnancy. She was managed on the burns unit with nutritional support, antibiotics, emollients and dressings. She subsequently developed a left micro-ophthalmia and cataract, right severe myopia and a mild developmental delay with microcephaly. Older siblings aged 7 and 5 had a history of mild developmental delay and microcephaly. Parents had no relevant medical issues and were both of Jewish background. Genetic testing was carried out which did not identify a genetic cause with normal microarrays of her siblings. A diagnosis of vesicular and pustular dermatosis was made, a rare condition, first described in 1985 by Cohen et al. Lesions typically consist of erythema, erosions, crusting, vesicles and fissures which start to heal within 10 days with residual reticulate scarring. Most cases occur in premature infants, making our case less typical. Nail, ophthalmological abnormalities and developmental delay are other associations, seen in our case.
O01 Inborn errors of metabolism - Solving the puzzle of prolidase deficiency
Authors: Lachlan Byth, Tess McPherson
Journal: British Journal of Dermatology (2024)

Abstract Inborn errors of metabolism (IEM) may present with ­distinctive cutaneous manifestations as part of a multisystem phenotype. Diagnosis is a multidisciplinary affair, made difficult by their rarity and complex genetic architectures. Knowledge of molecular mechanisms provides hope for targeted therapies, but unmet needs remain in the treatment of skin disease. Prolidase deficiency (OMIM #170100) is a rare IEM characterised by impaired collagen recycling, recalcitrant lower limb ulceration and massive imidodipeptiduria. The cases of two siblings born to related parents are reported, presenting initially in childhood with hydroa vacciniforme-like photosensitivity. Following a decade-long journey, the diagnosis of prolidase deficiency was eventually made. Pitfalls including the limitations of conventional diagnostic modalities and whole genome sequencing are examined, as well as the effects of chronic skin changes and associated disability on quality of life in childhood and adolescence. Therapeutic options, possible connections to hydroa vacciniforme, and prospects for translational research are reviewed. A rational approach to the clinical and genetic diagnosis of IEM in the paediatric dermatology clinic is proposed.
P19 Spontaneous regression of aleukaemic cutis leukaemia in a male infant
Authors: Jadesola Oyedepo, Maria Bageta, Maanasa Polubothu, Jonathan Tan, Michael Gattens, Samantha Levine, Liz Hook
Journal: British Journal of Dermatology (2024)

Abstract Introduction Congenital leukaemia is a rare haematologic disease presenting in the first 4-6 weeks of life. Affected children may present with systemic symptoms of fever, hepatosplenomegaly and skin infiltration in the form of leukaemia cutis. Prognosis is generally poor but some cases of spontaneous regression have been described. We report a case of a 5-week-old who had biopsy confirmed cutis leukaemia which went on to resolve spontaneously. Case A male infant developed widespread erythematous/violaceous patches and nodules in the first week of life. He remained systemically well. A skin biopsy at 5 weeks of age showed features of a malignant haematological infiltrate, favouring a myeloid/monocytic leukaemic process. Baseline bloods were normal including a blood film which did not show any evidence of blasts. Interestingly, following his biopsy, skin lesions began to improve with complete resolution of all skin lesions by six weeks of age. RNA fusion panel analysis of affected skin detected a PICALM::MLLT10 t(10;11) (p12;q14) fusion which is a rare but recurrent finding in acute lymphoblastic leukaemia . He continues monthly haematology surveillance and has remained disease free at 8 months. Conclusion Spontaneous regression of aleukaemic leukaemia cutis is a rare phenomenon. Patients require close ongoing surveillance as some may relapse with systemic disease after several years. Key to management of this case was prompt suspicion of leukaemia cutis and biopsy which enabled an accurate diagnosis despite the brief window of skin lesions and has subsequently enabled accurate genotyping and future rigorous surveillance in this child.
O03 Sarcoidosis in a Boy with Severe Eczema on Dupilumab
Authors: Musarat Shahid, Penny Davis, Saleem Taibjee, Ceilia Moss, Malobi Ogboli
Journal: British Journal of Dermatology (2024)

Abstract Sarcoidosis, a systemic granulomatous disease of unknown aetiology, is rare in children. Presentation varies according to the extent and severity of organ involvement and is typically multisystem in older children. Drug induced sarcoidosis-like reaction (DISR) has recently been reported in patients taking Dupilumab. We describe a patient who developed sarcoidosis while on Dupilumab and question whether this was caused by the drug. A 14-year-old boy with severe eczema developed widespread cutaneous nodules and papules after 30 months on Dupilumab. Histology showed non-caseating granulomas. A raised serum angiotensin converting enzyme level, asymptomatic coarse interstitial markings on chest x-ray and small lung nodules on CT scan were also consistent with sarcoidosis. Dupilumab was stopped and hydroxychloroquine and methotrexate commenced. Joint and liver involvement developed 4 months later so systemic glucocorticoids were and the methotrexate was changed to mycophenolate mofetil. To our knowledge there have been 3 previous reports of DISR on Dupilumab. The clinical picture is almost indistinguishable from sarcoidosis. In this case continuing evolution of sarcoidosis 4 months after stopping Dupilumab argues against DISR. However, as Dupilumab becomes more widely used, it is important to be alert to the possibility of new adverse reactions.
P04 A Complex Case of Urticaria
Authors: Vidya Madhwapathi, Vicky Diba, Malobi Ogboli
Journal: British Journal of Dermatology (2024)

Abstract An 11 year old female, with Type 1 diabetes and no previous atopy or allergy , presented with a 6 week history of facial swelling and a generalised urticaria on the trunk and limbs. She had been seen privately by “Allergy” clinic and diagnosed with chronic spontaneous urticaria with angioedema. Blood tests for common allergens were negative, with a total IgE &amp;lt;20 kU/L. Treatment with Loratadine, Cetirizine 10mg, Fexofenadine 120mg QDS, Acrivastine 8mg BD, Montelukast 10mg OD and prednisolone 20mg OD had only a limited effect. Skin biopsy confirmed urticaria with no evidence of vasculitis. Immunology bloods were negative. Despite reporting compliance, she continued to experience debilitating symptoms with raised UAS scores. Desloratadine 2.5mg BD and multiple intermittent short courses of prednisolone were needed. Omalizumab was started at 300mg monthly for 6 months with partial improvement. However symptoms flared on cessation and following tertiary advice, a 2nd course of Omalizumab was commenced at 300 mg s/c monthly for 3 months &amp; 300mg s/c fortnightly for 3 months with the addition of 100mg BD Ciclosporin and Famotidine 10mg BD. Ciclosporin was discontinued after 1 month due to side effects and substituted with Methotrexate 15mg OW. If control is not obtained, management plans include Mycophenolate Mofetil, or trialing omalizumab 450mg S/C monthly. This is a case of extremely difficult to control urticaria in a child highlighting available systemic treatment options1.
P08 Shingles in two children with no history of chicken pox
Authors: Mark Eisner, Sharmela Darné
Journal: British Journal of Dermatology (2024)

Abstract We present two cases of dermatomal, vesicular eruptions in young children. Both were otherwise well with no history of immunocompromise or prior chickenpox (varicella). Child A was 3 years old and presented with painful erythema and pustules to the left side of his nose and cheek with a sharp midline demarcation. He was admitted by the paediatricians, unwell and treated with antibiotics and acyclovir for presumed impetigo or herpes simplex virus infection. However, the swab was positive for varicella zoster virus (VZV), which in this dermatomal distribution is in keeping with shingles. Child B was an 18-month-old girl who was referred with a dermatomal vesico-pustular eruption on the left forehead, scalp and nose unresponsive to antibiotics. Despite the lack of varicella history, shingles was suspected, and the child was started on aciclovir. Swabs were positive for VZV. Shingles is rare in children and usually associated with immunocompromise. It is especially rare in those with no prior history of chicken pox and of the cases in the literature, almost all have had previous vaccination to chicken pox resulting in latent infection and subsequent shingles. We surmise that our otherwise well patients, with no prior vaccination, had previous asymptomatic chicken pox. There was a delay in the diagnosis of patient A who went on to develop trigeminal trophic syndrome with recurrent paranasal ulceration over 18 months. We highlight these cases to make clinicians aware of the possibility of shingles even in very young, immunocompetent children with no prior history of chickenpox.
P13 ‘Microneedle’ A new horizon of intradermal therapeutics
Authors: Waleed Faisal, Ryan Bamsey
Journal: British Journal of Dermatology (2024)

Abstract Microneedle array patch (MAP) is a patch of sharp but painless microstructure needles ranging from only a few microneedles to several hundred, attached to an adhesive patch. The arrays penetrate the outer layer of the skin on application and then are given time to dissolve to deliver a local dose of medication intradermally (https://www.youtube.com/watch?v=F6jPA9liUMc ). MAP enable alternative and easier delivery scenarios for physicians as they require less training to apply and not as hazardous as traditional needles. MAP also improve adherence to drug regimens as it makes the administration of drugs to patients safer and less painful. Additionally, microneedles offer suitability for self-administration, no biohazardous sharps waste, and no risk of needle-stick injuries. The work that supported the preliminary research/development have been patented/published (Patent WO 2020/250210). The key opinion leaders KOLs and industry stakeholder feedback confirmed an unmet market need for the MN technology, particularly in support of many topical applications. The in-vivo data showed that the MAP delivers a superior localized drug dose compared current standard of care, which should translate to a reduced treatment-time. Also, the comparative plasma bioavailability of the MAP translates to less side effects. It was also observed that after one week, there was no sign of inflammation or irritation at the site of application. We are seeking potential clinical partners for whom collaboration and MAP technology is advantageous. Such collaboration would ensure rapid product development and industrial production to allow clinical assessment.
O09 Targeted genetic therapy for congenital melanocytic naevi
Authors: Dale Bryant, Sara Barberan-Martin, Ruhina Maeshima, Ignacio Del Valle Torres, Mohammad Rabii, Aimie Sauvadet, Charalambos Demetriou, Nicole Knöpfel, Fanis Michailides, Melissa Riachi, Davide Zecchin, Alan Pittman, Satyamaanasa Polubothu, Steve Hart, Veronica Kinsler
Journal: British Journal of Dermatology (2024)

Abstract Severe cases of congenital melanocytic naevi (CMN) are associated with substantial cutaneous and neurological morbidity and an excess childhood mortality from melanoma. Effective treatments are lacking. This mosaic disorder is caused most commonly by a heterozygous oncogenic variant NRAS c.181C&amp;gt;A, p.(Q61K). As NRAS has multiple downstream effectors we have sought to treat this disease by precision genetic therapy rather than downstream pathway inhibition, hypothesising that silencing of the oncogenic allele may remove cellular protection from RAS induced apoptosis. Using a lead siRNA selected for allele specificity and fewest off-target effects on RNAseq (siNRASQ61K) we show here significant selective knockdown of variant mRNA expression and knockdown of NRAS protein levels. A single treatment to primary naevus cell cultures leads to normalisation of MAPK pathway activation, reduction in proliferation rate, and importantly, triggering of apoptosis. We go on to demonstrate that receptor-targeted lipid nanoparticles (RTNPs) successfully protect siRNA from degradation, deliver cargo to naevus cells in patient skin explants and improve naevus cell targeting. A single intradermal injection of siNRASQ61K-RTNPs into transgenic mice harbouring humanised NRASQ61K(Tyr::NRASQ61K) confirms significant selective knockdown of the variant NRAS allele in vivo.Successful targeting of variant NRAS and triggering of naevus cell apoptosis now paves the way for clinical trials of this genetic therapy for CMN.
P15 A Case of Juvenile Dermatomyositis in a 15-year old African-descent Girl
Authors: Evangelia Vetsiou, Kate Armon, Julia Gass
Journal: British Journal of Dermatology (2024)

Abstract A 15-year-old female with skin of colour (SOC), was diagnosed with Juvenile dermatomyositis (JDM) following a presentation with muscle weakness, swallowing difficulties and rash. Investigations showed CK&amp;gt;1300, positive Mi-2 alpha, beta antibodies and bilateral myositis on MRI pelvis. Her skin features commenced 2 months prior to her rheumatological presentation. They included erythematous pruritic patches on the limbs, generalised hyperpigmentation of the face and trunk, hyperpigmentation of palmar creases and nail folds, flagellate hyperpigmentation of the hands &amp; arms, and hypopigmented macules with follicular sparing across the face. She also presented skin thickening over the interphalangeal joints and nail fold capillary dilatation and infarctions. Skin biopsy showed interface dermatitis, in keeping with dermatomyositis. She was managed with weaning prednisolone, methotrexate, topical tacrolimus and sunscreen. JDM is a small-vessel autoimmune vasculopathy leading to muscle inflammation and skin changes. Unlike adult-onset disease, JDM is not associated with malignancy. The typically described violaceous skin features of JDM including photosensitive rash periorbitally, and over the knees and knuckles (Gottron’s sign) may be hyperpigmented rather than erythematous in skin of colour. Additional skin features described in SOC are generalised hyperpigmentation and pigmentation in skin creases. A flagellate dermatitis is uncommon, but recognised in association with Mi-2 antibodies in JDM. TIF1 antibodies have been reported in association with hypopigmented patches which may mimic vitiligo postulated possibly secondary to interface inflammation perhaps leading to dyspigmnentation. Notably our patient was negative for TIF1. This presentation highlights some of the less commonly described skin features of dyspigmentation in JDM in SOC.
O08 Severely pruritic juvenile dermatomyositis
Authors: Katie Best, Suzy Leech
Journal: British Journal of Dermatology (2024)

Abstract A 7-year-old female with type IV skin and autism spectrum disorder presented with a 4 month history of progressive proximal myopathy, weight loss and 20 month history of a worsening, intensely pruritic rash. Cutaneous examination showed a widespread eczematous eruption, post-inflammatory hypopigmentation, heliotrope rash and firm subcutaneous changes, in addition to palmar-plantar papules, pustules and burrows. Extra-cutaneous findings included multiple fixed flexion deformities and muscle wasting. Investigations revealed a normocytic anaemia, elevated muscle enzymes, strongly positive anti-nuclear antibodies and negative myositis-specific antibodies. Whole body MRI reported proximal muscle oedema. Skin biopsy demonstrated lichenoid and perifollicular inflammation, dermal mucin and subcutaneous calcification. Clinical findings were consistent with a diagnosis of juvenile dermatomyositis (JDM), complicated by concurrent scabies. Prednisolone in combination with methotrexate was commenced as first-line therapy in line with current consensus JDM treatment plans, in addition to topical steroids and sun protection. Muscle power started to improve after 5 months but ongoing cutaneous inflammation prompted second-line therapy with IV immunoglobulin. Oral ivermectin was required for the management of scabies due to topical permethrin failure. JDM is a rare autoimmune small-vessel vasculopathy with significant morbidity and limited evidence-based guidelines. Unlike adult-onset disease there is no racial predilection or association with malignancy. Calcinosis is more common in children but early treatment reduces disease complications. JDM has a variable disease course with a median time to remission of 4.67 years. Residual skin changes are increasingly recognised to be an early predictor of prolonged recovery time and these patients may benefit from biologic agents.
Increasing radiation therapy and lower survival for human papillomavirus–related oropharynx cancer associated with a shift to community cancer center care
Authors: Danielle R Trakimas, Wojtek Mydlarz, Leila J Mady, Wayne Koch, Harry Quon, Nyall R London, Carole Fakhry
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Studies have shown lower overall survival for patients with head and neck cancer treated at low-volume or community cancer centers. As the incidence of human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma steadily rises in the United States, we hypothesized that a greater proportion of patients with HPV-related oropharyngeal squamous cell carcinoma is being treated at community cancer centers, with a shift toward primary nonsurgical treatment. Methods This cohort study included patients from the US National Cancer Database who received a diagnosis of HPV-related oropharyngeal squamous cell carcinoma from 2010 to 2019 and underwent treatment at a community cancer center or academic cancer center. The proportion of patients with HPV-related oropharyngeal squamous cell carcinoma treated at community cancer centers and receiving primary nonsurgical treatment was analyzed over time. Four-year overall survival was compared between community cancer centers and academic cancer centers. Results The majority (67.4%) of 20 298 patients were treated at an academic cancer center, yet the proportion of patients treated at community cancer centers increased by 10% from 2010 to 2019 (P &amp;lt; .01 for trend). The proportion of patients undergoing primary nonsurgical treatment increased from 62.1% to 73.7% from 2010 to 2019 (P &amp;lt; .01 for trend), and patients were statistically significantly more likely to undergo nonsurgical treatment at community cancer centers than at academic cancer centers (adjusted odds ratio = 1.20, 95% confidence interval = 1.18 to 1.22). Treatment at community cancer centers was associated with worse survival overall (adjusted hazard ratio = 1.19, 95% confidence interval = 1.09 to 1.31), specifically for patients receiving primary nonsurgical treatment (adjusted hazard ratio = 1.22, 95% confidence interval = 1.11 to 1.34). Conclusions Treatment of HPV-related oropharyngeal squamous cell carcinoma has recently shifted to community cancer centers, with an increase in the proportion of nonsurgical treatment and worse overall survival at these centers compared with academic cancer centers. Concentration of care for HPV-related oropharyngeal squamous cell carcinoma at academic cancer centers and dedicated head and neck cancer centers may increase access to all available treatment modalities and improve survival.