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BACKGROUND: MEK inhibitors cause a wide spectrum of mucocutaneous toxicities which can delay or interrupt life-saving therapy. PURPOSE: To summarize the morphology, incidence, and clinical presentation of mucocutaneous toxicities from MEK inhibitors via a scoping review of the literature. METHODS: We conducted a scoping review of the published literature, including clinical trials, retrospective and prospective studies, reviews, and case reports and series. All included literature was analyzed by a panel of pediatric and adult oncodermatologists. RESULTS: Of 1626 initial citations, 227 articles met final inclusion criteria. Our review identified follicular reactions, ocular toxicities, xerosis, eczematous dermatitis, edema, and paronychia as the most common mucocutaneous side effects from MEK inhibitor therapy. Grade 1 and 2 reactions were the most prevalent and were typically managed while continuing treatment; however, grade 3 toxicities requiring dose reductions or treatment interruptions were also reported. CONCLUSION: Mucocutaneous toxicities to MEK inhibitor therapy are common and most often mild in severity. Early recognition and treatment can mitigate disruptions in oncologic therapy.
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Inhibidores de Proteínas Quinasas , Humanos , Inhibidores de Proteínas Quinasas/efectos adversos , Antineoplásicos/efectos adversos , Neoplasias/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Erupciones por Medicamentos/etiologíaRESUMEN
BACKGROUND: Childhood cancer survivors (CCS) are at increased risk for keratinocyte carcinomas (KC) however, the long-term incidence of single and multiple KC is not well established. OBJECTIVE: Identify risk factors and quantify KC cumulative incidence and multiple-incidence burden in CCS. METHODS: KC were identified among Childhood Cancer Survivor Study participants, a cohort of five-year cancer survivors diagnosed <21 years of age between 1970-1999 in North America. Cumulative incidence was estimated, and multivariable models assessed relative rates of KC associated with survivor and treatment characteristics. RESULTS: Among 25,658 participants, 1,446 developed 5,363 KC (93.5% basal cell carcinoma, 6.7% squamous cell carcinoma; mean age 37.0 years (range 7.3-67.4), mean latency 25.7 years; 95.3% White and 88.4% with radiotherapy [RT]). Mean lesion count was 3.7 with 26.1% experiencing ≥4. RT imparted a 4.5-fold increase in the rate of any KC and 9.4-fold increase in the rate of ≥4 KC. Allogeneic and autologous hematopoietic cell transplant were associated with a 3.4- and 2.3-fold increased rate of KC, respectively. LIMITATIONS: Participant self-reporting of some data including race without skin phototype and past medical history may have impacted analysis. CONCLUSIONS: The burden of KC in CCS remains high, but predictable risk factors should guide screening.
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Philanthropic donations are an increasingly important funding source for academic medical centers. Minimal published data is available about factors that influence alumni donations to residency programs. We performed a cross-sectional analysis of a single-site dermatology and combined internal medicine-dermatology residency programs to assess factors impacting alumni donations. Donors tended to have graduated less recently (only 20% graduating after 2010) and practice in the same region of their alma mater (50%). Respondents preferred funds be allocated to resident needs over needs of medical students. Strategically engaging senior alumni and offering fund allocation opportunities could increase philanthropy, with alumni perceptions of the residency program warranting further investigation for their impact on donation decisions.
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Dermatología , Internado y Residencia , Humanos , Dermatología/educación , Dermatología/estadística & datos numéricos , Internado y Residencia/estadística & datos numéricos , Estudios Transversales , Encuestas y Cuestionarios/estadística & datos numéricos , Estudiantes de Medicina/estadística & datos numéricos , Femenino , Masculino , Medicina Interna/educación , Medicina Interna/estadística & datos numéricos , Centros Médicos Académicos/estadística & datos numéricosRESUMEN
Importance: Chronic skin disorders in children frequently are visible and can cause stigmatization. However, the extent of stigmatization from chronic skin disease and association with mental health needs further study. Objective: To examine the extent of stigma, dependence on disease visibility and severity, and association with mental health and quality of life (QOL) in chronic pediatric skin disease. Design, Setting, and Participants: A cross-sectional, single-visit study was conducted at 32 pediatric dermatology centers in the US and Canada from November 14, 2018, to November 17, 2021. Participants included patients aged 8 to 17 years with chronic skin disease and 1 parent. Main Outcomes and Measures: Using the Patient-Reported Outcomes Measurement Instrumentation System (PROMIS) Stigma-Skin, the extent of stigma with child-, caregiver-, and physician-assessed disease visibility (primary outcome) and severity was compared, as well as reduced QOL (assessed by Skindex-Teen), depression, anxiety, and poor peer relationships (PROMIS child and proxy tools) (secondary outcomes). Results: The study included 1671 children (57.9% female; mean [SD] age, 13.7 [2.7] years). A total of 56.4% participants had self-reported high disease visibility and 50.5% had moderate disease severity. Stigma scores significantly differed by level of physician-assessed and child/proxy-assessed disease visibility and severity. Among children with chronic skin disorders, predominantly acne, atopic dermatitis, alopecia areata, and vitiligo, only 27.0% had T scores less than 40 (minimal or no stigma) and 43.8% had at least moderate stigma (T score ≥45) compared with children with a range of chronic diseases. Stigma scores correlated strongly with reduced QOL (Spearman ρ = 0.73), depression (ρ = 0.61), anxiety (ρ = 0.54), and poor peer relationships (ρ = -0.49). Overall, 29.4% of parents were aware of bullying of their child, which was strongly associated with stigma (Cohen d = -0.79, with children who were not bullied experiencing lower levels of stigma). Girls reported more stigma than boys (Cohen d = 0.26). Children with hyperhidrosis and hidradenitis suppurativa were most likely to have increased depression and anxiety. Conclusions and Relevance: The findings of this study suggest that physician assessment of disease severity and visibility is insufficient to evaluate the disease impact in the patient/caregiver. Identifying stigmatization, including bullying, and tracking improvement through medical and psychosocial interventions may be a key role for practitioners.
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Salud Mental , Calidad de Vida , Enfermedades de la Piel , Estigma Social , Humanos , Femenino , Masculino , Niño , Adolescente , Estudios Transversales , Enfermedades de la Piel/psicología , Enfermedad Crónica , Canadá , Estereotipo , Índice de Severidad de la Enfermedad , Depresión/epidemiología , Depresión/psicología , Depresión/etiología , Estados Unidos , Ansiedad/psicología , Ansiedad/epidemiología , Ansiedad/etiología , Medición de Resultados Informados por el PacienteAsunto(s)
Supervivientes de Cáncer , Neoplasias , Humanos , Neoplasias/mortalidad , Neoplasias/terapiaRESUMEN
High-flow vascular malformations have been associated with multiple syndromes including capillary malformation-arteriovenous malformation (CM-AVM) syndrome, hereditary hemorrhagic telangiectasia syndrome, and less commonly, phosphatase and tensin homolog hamartoma tumor syndrome (PHTS). We present a series of three patients with clinically challenging complex AVMs who were found to have underlying PHTS. In all patients, diagnosis was delayed, and the presence of the AVM prompted sampling and genetic testing for PHTS in the absence of other clinical features of the condition. This series highlights the importance of screening for PHTS in the setting of high-flow vascular malformations.
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Malformaciones Arteriovenosas , Capilares/anomalías , Síndrome de Hamartoma Múltiple , Mancha Vino de Oporto , Telangiectasia Hemorrágica Hereditaria , Malformaciones Vasculares , Humanos , Síndrome de Hamartoma Múltiple/complicaciones , Síndrome de Hamartoma Múltiple/diagnóstico , Síndrome de Hamartoma Múltiple/genética , Malformaciones Arteriovenosas/complicaciones , Malformaciones Arteriovenosas/diagnóstico , Malformaciones Arteriovenosas/genética , Doxorrubicina , Fosfohidrolasa PTEN/genéticaAsunto(s)
Tiña del Cuero Cabelludo , Tiña , Niño , Humanos , Estudios Retrospectivos , Antifúngicos/uso terapéutico , Tiña/diagnóstico , Tiña/tratamiento farmacológico , Resultado del Tratamiento , Tiña del Cuero Cabelludo/diagnóstico , Tiña del Cuero Cabelludo/tratamiento farmacológico , TrichophytonRESUMEN
Patients who undergo solid organ transplantation are at an increased risk of developing atopic dermatitis, potentially due to long-term use of calcineurin inhibitors which results in a shift towards the Th2 immune response. The effectiveness and safety of dupilumab for atopic dermatitis in posttransplant patients is not established. Previous reports of dupilumab use in posttransplant patients have been in adult patients. In this series, we report three young posttransplant patients treated successfully with dupilumab.
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Dermatitis Atópica , Adulto , Humanos , Dermatitis Atópica/tratamiento farmacológico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Resultado del Tratamiento , Índice de Severidad de la EnfermedadRESUMEN
There are little published data on the transition of care in EB. We conducted a survey study recruiting EB patients from the Dystrophic EB Research Association (debra) website and centers caring for high numbers of EB patients in the United States and internationally from Sept 17, 2019 to Nov 3, 2021. The majority of participants had not discussed the transition of care with their healthcare providers, nor the healthcare needs to be required as an adult. Ongoing pediatric subspecialty care was reported by 12% of adults, most commonly in pediatric dermatology. Identified barriers to transition included the perceived lack of adult providers' knowledge about EB patient healthcare needs. The results suggest the need for transition guidelines, early discussions with families about transition, and practical information for the adult providers accepting care.
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Epidermólisis Ampollosa Distrófica , Epidermólisis Ampollosa , Niño , Adulto , Humanos , Transferencia de Pacientes , Epidermólisis Ampollosa/terapia , Encuestas y Cuestionarios , Personal de SaludRESUMEN
Pathogenic variants in SOX18 are associated with hypotrichosis-lymphedema-telangiectasia-renal defects syndrome (HLTRS) and hypotrichosis-lymphedema-telangiectasia syndrome (HLTS). Eleven patients with SOX18 related HLTRS/HLTS have been previously described. Cardinal features include varying degrees of hypotrichosis, lymphedema and telangiectasias. We report a 15-year-old female patient with a likely de novo SOX18 pathogenic variant identified on duo exome sequencing. In addition to the classic features, the currently reported patient presented with novel clinical features including musculoskeletal abnormalities and strikingly poor wound healing. Chronic skin ulcers have been a major cause of morbidity for the patient and have led to significant functional limitation. Further, our experience with wound management has been detailed. We hope to improve understanding of the clinical spectrum of this ultra-rare disorder by reviewing the phenotypic features in all reported patients including our patient.
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Hipotricosis , Linfedema , Telangiectasia , Adolescente , Alopecia , Femenino , Glomerulonefritis Membranoproliferativa , Humanos , Hipotricosis/genética , Linfedema/genética , Factores de Transcripción SOXF , Telangiectasia/genéticaRESUMEN
Plantar dermatoses (PD) are common, occurring either spontaneously on healthy skin or developing secondarily from previously established foot disease. PD share similar symptoms and morphology, making them challenging to differentiate. A few of the most frequently encountered PD include tinea pedis, psoriasis, contact dermatitis, dyshidrotic dermatitis (or recurrent vesicular palmoplantar dermatitis), and juvenile plantar dermatosis. This review offers practical advice for diagnosing and treating the most common PD in the primary care office.
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Tiña del Pie , Humanos , Tiña del Pie/diagnóstico , Tiña del Pie/terapiaRESUMEN
Conradi-Hünermann-Happle syndrome is rare X-linked dominant syndrome associated with stippled epiphyseal calcifications, congenital cataracts, Blaschkoid ichthyosiform scaling, and follicular atrophoderma. This case describes a novel finding of hypocalcemia and hypoparathyroidism in an infant with Conradi-Hünermann-Happle syndrome.
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Condrodisplasia Punctata , Hipocalcemia , Condrodisplasia Punctata/complicaciones , Condrodisplasia Punctata/diagnóstico , Condrodisplasia Punctata/genética , Humanos , Hipocalcemia/complicaciones , Hipocalcemia/diagnóstico , Hipocalcemia/tratamiento farmacológico , Lactante , Recién NacidoRESUMEN
Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating genodermatosis characterized by dysfunctional collagen VII protein resulting in epithelial blistering of the skin, mucosa, and gastrointestinal tract. There is no cure for RDEB, but improvement of clinical phenotype has been achieved with bone marrow transplantation and subsequent epidermal allografting from the bone marrow transplant donor. Epidermal allografting of these patients has decreased wound surface area for up to 3 years after treatment. This study aimed to determine the phenotype of the epidermal allograft cells responsible for durable persistence of wound healing and skin integrity. We found that epidermal allografts provide basal keratinocytes coexpressing collagen VII and basal stem cell marker keratin 15. Characterization of RDEB full-thickness skin biopsies with single-cell RNA sequencing uncovered proinflammatory immune and fibroblast phenotypes potentially driven by the local environment of RDEB skin. This is further highlighted by the presence of a myofibroblast population, which has not been described in healthy control human skin. Finally, we found inflammatory fibroblasts expressing profibrotic gene POSTN, which may have implications in the development of squamous cell carcinoma, a common, lethal complication of RDEB that lacks curative treatment. In conclusion, this study provides insights into and targets for future RDEB studies and treatments.
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Epidermólisis Ampollosa Distrófica , Aloinjertos/metabolismo , Aloinjertos/patología , Trasplante de Médula Ósea , Colágeno Tipo VII/genética , Colágeno Tipo VII/metabolismo , Epidermólisis Ampollosa Distrófica/genética , Epidermólisis Ampollosa Distrófica/patología , Epidermólisis Ampollosa Distrófica/terapia , Fibroblastos/metabolismo , Humanos , Queratina-15 , Queratinocitos/metabolismo , Piel/patología , Trasplante HomólogoRESUMEN
For infantile hemangiomas (IH) requiring treatment, including those in high-risk locations or in the setting of ulceration, oral propranolol is first-line therapy. Here, we present three cases of infantile hemangioma with worsening ulceration following initiation or escalation of oral propranolol at standard doses.
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Hemangioma Capilar , Hemangioma , Neoplasias Cutáneas , Administración Oral , Antagonistas Adrenérgicos beta/efectos adversos , Hemangioma/tratamiento farmacológico , Hemangioma Capilar/tratamiento farmacológico , Humanos , Lactante , Propranolol/efectos adversos , Neoplasias Cutáneas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Epidermolysis bullosa (EB) is a group of genetic blistering diseases characterized by mechanically fragile skin and mucocutaneous involvement. Historically, disease management has focused on supportive care. The development of new genetic, cellular, and recombinant protein therapies has shown promise, and this review summarizes a unique gene and cell therapy phenomenon termed revertant mosaicism (RM). RM is the spontaneous correction of a disease-causing mutation. It has been reported in most EB subtypes, some with relatively high frequency, and has been observed in both keratinocytes and fibroblasts. RM manifests as identifiable patches of unaffected, blister-resistant skin and can occur through a variety of molecular mechanisms, including true back mutation, intragenic crossover, mitotic gene conversion, and second-site mutation. RM cells represent a powerful autologous platform for therapy, and leveraging RM cells as a therapeutic substrate may avoid the inherent mutational risks of gene therapy/editing. However, further examination of the genomic integrity and long-term functionality of RM-derived cells, as well in vivo testing of systemic therapies with RM cells, is required to realize the full therapeutic promise of naturally occurring RM in EB.
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Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is an autosomal dominant condition characterized by multifocal, noncontiguous pink patches on the skin that often have a surrounding pale halo. In some cases, an association with a fast flow, arteriovenous malformation (AVM) can be identified. Here, we describe a case report of a 16-year-old woman with CM-AVM syndrome and significant cardiac compromise successfully treated with trametinib, a mitogen-activated protein kinase (MEK) inhibitor.