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INTRODUCTION: Cutaneous adverse reactions to epidermal growth factor receptor inhibitors (EGFRi) are some of the most common side effects that patients experience. However, cutaneous adverse reactions that cause dyspigmentation in patients have been rarely reported. Erythema dyschromicum perstans (EDP) is a rare pigmentary condition that causes ashy-grey hyperpigmented macules and patches, with a few cases reported from EGFRi in the literature. The disfiguration caused by this condition may negatively impact patients' quality of life. Our study aimed to describe the clinical characteristics of EDP induced by EGFRi to better recognize and manage the condition. METHODS: We conducted a multicenter retrospective review at three academic institutions to identify patients with EDP induced by EGFRi from 2017 to 2023 and included sixteen patients in our study. RESULTS: The median age of patients was 66 years old, with 63% female and 37% male (Table 1). The majority of our patients were Asian (88%). All patients had non-small cell lung cancer and most patients received osimertinib. Median time to EDP was 6 months. The most common areas of distribution were the head/neck region, lower extremities, and upper extremities. Various topical ointments were trialed; however, approximately less than half had improvement in their disease and most patients had persistent EDP with no resolution. All patients desired treatment except one with EDP on the tongue, and there was no cancer treatment discontinuation or interruption due to EDP. Table 1 Patient demographics and clinical characteristics of 16 patients with EDP induced by EGFRi Case no Demographics: age, race, and sex Fitzpatrick skin type Cancer type EGFR therapy Concomitant photosensitive drug(s) Time to EDP (months) Clinical features Distribution Symptoms Treatments and clinical course EDP status from most recent follow up 1 47 y/o Asian male III Stage IV NSCLC Erlotinib None Unknown Brown-blue-gray hyperpigmented patches Bilateral shins Left thigh Xerosis Pruritus Triamcinolone 0.1% ointment for 4 months, improvement of blue discoloration Tacrolimus 0.1% BID for 9 months, improvement but no resolution Ongoing 2 62 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown hyperpigmented patches Bilateral arms Back Forehead Neck Right shin None Tacrolimus 0.1% ointment for 1 year with minor improvement Ongoing 3 69 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown macules and patches Chest Face Forehead Bilateral legs None Tacrolimus 0.1% ointment for 10 months, no improvement Ongoing 4 79 y/o White male II Stage IV NSCLC Osimertinib None 15 Mottled grey-blue hyperpigmented patches and plaques with mild scaling Bilateral arms Back Forehead Neck None Photoprotection, no improvement Ongoing 5 69 y/o Asian female III Stage IV NSCLC Osimertinib Ibuprofen 4 Blue-grey hyperpigmented macules and patches Abdomen Bilateral arms None Tacrolimus 0.1% ointment for 7 months, no improvement Ongoing 6 65 y/o Asian male III Stage IV NSCLC Osimertinib None 20 Hyperpigmented blue gray macules and patches Helix Bilateral shins None Photoprotection, no improvement Ongoing 7 66 y/o Asian female IV Stage IV NSCLC Erlotinib TMP-SMX 6 Ashy grey-brown thin plaques Back Forehead None 2.5% hydrocortisone ointment for 8 months, resolved Resolved 8 82 y/o Asian male III Stage III NSCLC Erlotinib Simvastatin 20 Ash-grey hyperpigmented patches Dorsal feet Forehead Scalp None Photoprotection Ongoing 9 57 y/o Asian female III Stage II NSCLC Erlotinib None 1 Bue-grey discoloration Tongue None No intervention Ongoing 10 51 y/o Asian female III Stage IV NSCLC Osimertinib None 9 Blue-grey hyperpigmented macules and patches Bilateral arms Axillae Groin Neck Trunk None 2.5% hydrocortisone ointment, triamcinolone 0.1% ointment, photoprotection with mild improvement Ongoing 11 67 y/o Asian male III Stage IV NSCLC Osimertinib None 7 Gray-blue macules and patches with mild background erythema and scaling Bilateral arms Ears Face Bilateral shins None Triamcinolone 0.1% ointment, protection for 6 months with mild improvement Ongoing 12 75 y/o Asian female IV Stage III NSCLC Osimertinib TMP-SMX 3 Gray-blue hyperpigmented patches Bilateral arms Abdomen Back Face Bilateral shins Pruritus Triamcinolone 0.1% and betamethasone 0.01% with relief of pruritus, lesions unchanged Triluma cream 6 months, mild improvement Ongoing 13 42 y/o Asian male IV Stage IV NSCLC Afatinib TMP-SMX 24 Grey-brown hyperpigmented patches Back Face None Hydroquinone 4% cream for 2 years with mild improvement Ongoing 14 74 y/o White female III Stage II NSCLC Osimertinib Atorvastatin 4 Grey-brown hyperpigmented patches Bilateral legs Trunk None Photoprotection Ongoing 15 64 y/o Asian female IV Stage IV NSCLC Osimertinib None 3 Gray-brown hyperpigmentation Abdomen Bilateral arms Back Bilateral legs Pruritus Triamcinolone 0.1% cream; No change, minimal concern to patient Ongoing 16 52 y/o Asian female IV Stage IV NSCLC Osimertinib None 42 Gray hyperpigmented patches with digitate shape Abdomen Bilateral flanks None Triamcinolone 0.1% cream Ongoing NSCLC, non-small cell lung cancer, TMP-SMX, Trimethoprim/Sulfamethoxazole CONCLUSIONS: We highlight the largest case series describing EDP from EGFR inhibitors, which mostly affected Asian patients with lung malignancy and on EGFR tyrosine kinase inhibitors. Clinicians should be able to recognize this condition in their patients and assess how it is affecting their quality of life, and refer to dermatology to help with management.
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Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Eritema/induzido quimicamente , Eritema/etiologia , Acrilamidas/efeitos adversos , Acrilamidas/administração & dosagem , Toxidermias/etiologia , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Qualidade de VidaRESUMO
Cutaneous oncology is currently a rapidly evolving field. Dermoscopy, total body photography, biomarkers, and artificial intelligence are affecting the way skin cancers, especially melanoma, are diagnosed and monitored. The medical management of locally advanced and metastatic skin cancer is also changing. In this article, we will discuss recent developments in cutaneous oncology with a particular focus on treatment of advanced cancers.
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Inteligência Artificial , Neoplasias Cutâneas , Humanos , Oncologia , Neoplasias Cutâneas/diagnósticoRESUMO
BACKGROUND: New inpatient virtual care models have proliferated in response to the challenges presented by the coronavirus disease 2019 (COVID-19) pandemic; however, few of these programs have yet been evaluated for acceptability and feasibility. OBJECTIVE: Assess feasibility and provider experience with the Virtual Team Rounding Program (VTRP), a quality improvement project developed and rapidly scaled at Brigham and Women's Hospital in Boston, MA, in response to the surge of COVID-19 patients in the spring of 2020. METHODS: We surveyed 777 inpatient providers and 41 providers who served as 'virtual rounders' regarding their experience with the program. Inpatient providers were asked about their overall satisfaction with the program, whether the program saved them time, and if so, how much and their interest in working with a similar program in the future. Providers who had worked as virtual rounders were asked about their overall satisfaction with the program, the overall difficulty of the work and their interest in participating in a similar program in the future. RESULTS: We find that among both groups the program was well-received, with 72.5% of inpatient providers and 85.7% of virtual rounders reporting that they were 'satisfied' or 'very satisfied' with their experience with the program. Among inpatient providers who worked with the program, two-thirds reported the program saved them time on a daily basis. Inpatient respondents who had worked with virtual rounders were more likely to say that they would be interested in working with the VTRP in the future compared with respondents who never worked with a virtual rounder (75.3 vs 52.5%, P < 0.001). CONCLUSION: As the pandemic continues, rapidly implementing and studying virtual care delivery programs is crucial for hospitals and health systems. We demonstrate the feasibility and acceptability of a 'virtual rounding' program assisting inpatient providers. Future work should examine the impact of these programs on patient outcomes.
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COVID-19 , Telemedicina , Feminino , Humanos , Pandemias , Satisfação Pessoal , SARS-CoV-2Assuntos
Dermatomiosite/epidemiologia , Eosinofilia/epidemiologia , Fasciite/epidemiologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Lúpus Eritematoso Cutâneo/epidemiologia , Esclerodermia Localizada/epidemiologia , Idoso , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Dermatomiosite/sangue , Dermatomiosite/induzido quimicamente , Dermatomiosite/imunologia , Eosinofilia/sangue , Eosinofilia/induzido quimicamente , Eosinofilia/imunologia , Fasciite/sangue , Fasciite/induzido quimicamente , Fasciite/imunologia , Feminino , Humanos , Lúpus Eritematoso Cutâneo/sangue , Lúpus Eritematoso Cutâneo/induzido quimicamente , Lúpus Eritematoso Cutâneo/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Estudos Retrospectivos , Esclerodermia Localizada/sangue , Esclerodermia Localizada/induzido quimicamente , Esclerodermia Localizada/imunologiaRESUMO
Accurately determining and classifying different types of skin cancers is critical for early diagnosis. In this work, we propose a novel use of deep learning for classification of benign and malignant skin lesions using dermoscopy images. We obtained 770 de-identified dermoscopy images from the University of Missouri (MU) Healthcare. We created three unique image datasets that contained the original images and images obtained after applying a hair removal algorithm. We trained three popular deep learning models, namely, ResNet50, DenseNet121, and Inception-V3. We evaluated the accuracy and the area under the curve (AUC) receiver operating characteristic (ROC) for each model and dataset. DenseNet121 achieved the best accuracy (80.52%) and AUC ROC score (0.81) on the third dataset. For this dataset, the sensitivity and specificity were 0.80 and 0.81, respectively. We also present the SHAP (SHapley Additive exPlanations) values for the predictions made by different models to understand their interpretability.
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BACKGROUND: Cutaneous immune-related adverse events (cirAEs) remain a prevalent and common sequelae of immune checkpoint inhibitor (ICI) therapy, often necessitating treatment interruption and prolonged immune suppression. Treatment algorithms are still poorly defined, based on single-institution case reports without adequate safety assessments, and subject to publication bias. METHODS: Data in this registry were collected through a standardized REDCap form distributed to dermatologists via email listserv. RESULTS: Ninety-seven cirAEs were reported from 13 institutions in this registry. Topical and systemic steroids were the most common treatments used; however, targeted treatment matched to disease morphology was identified at numerous sites. Novel cirAE therapy uses that to our knowledge have not been previously described were captured including tacrolimus for the treatment of follicular, bullous, and eczematous eruptions and phototherapy for eczematous eruptions. Moreover, further evidence of cirAE treatment applications sparsely described in literature were also captured in this study including dupilumab and rituximab for bullous eruptions, phototherapy for lichenoid and psoriasiform eruptions, and acitretin for psoriasiform eruptions, among others. No serious adverse events were reported. Numerous targeted therapeutics including dupilumab, rituximab, and psoriasis biologics, among others, were associated with a cirAE grade improvement of ≥2 grades in every patient treated. CONCLUSION: This study suggests that a multi-institutional registry of cirAEs and management is not only feasible but that the information collected can be used to detect, evaluate, and rigorously assess targeted treatments for cirAEs. Further expansion and modification to include treatment progression may allow for sufficient data for specific treatment recommendations to be made.
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Exantema , Psoríase , Humanos , Rituximab , Pele , TacrolimoRESUMO
PROBLEM: The SARS-CoV-2 (COVID-19) pandemic presented numerous challenges to inpatient care, including overtaxed inpatient medicine services, surges in patient censuses, disrupted patient care and educational activities for trainees, underused providers in certain specialties, and personal protective equipment shortages and new requirements for physical distancing. In March 2020, as the COVID-19 surge began, an interdisciplinary group of administrators, providers, and trainees at Brigham and Women's Hospital created an inpatient virtual staffing model called the Virtual Team Rounding Program (VTRP). APPROACH: The conceptual framework guiding VTRP development was rapid-cycle innovation. The VTRP was designed iteratively using feedback from residents, physician assistants, attendings, and administrators from March to June 2020. The VTRP trained and deployed a diverse set of providers across specialties as "virtual rounders" to support inpatient teams by joining and participating in rounds via videoconference and completing documentation tasks during and after rounds. The program was rapidly scaled up from March to June 2020. OUTCOMES: In a survey of inpatient providers at the end of the pilot phase, 10/10 (100%) respondents reported they were getting either "a lot" or "a little" benefit from the VTRP and did not find the addition of the virtual rounder burdensome. During the scaling phase, the program grew to support 24 teams. In a survey at the end of the contraction phase, 117/187 (62.6%) inpatient providers who worked with a virtual rounder felt the rounder saved them time. VTRP leadership collaboratively and iteratively developed best practices for challenges encountered during implementation. NEXT STEPS: Virtual rounding provides a valuable extension of inpatient teams to manage COVID-19 surges. Future work will quantitatively and qualitatively assess the impact of the VTRP on inpatient provider satisfaction and well-being, virtual rounders' experiences, and patient care outcomes.
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COVID-19/terapia , Educação a Distância/métodos , Corpo Clínico Hospitalar/provisão & distribuição , Equipe de Assistência ao Paciente/organização & administração , Visitas de Preceptoria/métodos , Humanos , Pacientes Internados/psicologia , Satisfação do Paciente , Avaliação de Programas e Projetos de Saúde , SARS-CoV-2RESUMO
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive malignancy derived from the plasmacytoid dendritic cell that commonly involves the skin. Cutaneous involvement is often the initial presentation, with deep purple or red-brown macules, plaques, or tumors. As such, dermatologists may be the first to see these patients and, in addition to oncologists, should be familiar with its presentation to facilitate early diagnosis, helping to distinguish it from acute myelogenous leukemia cutis.
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Células Dendríticas/patologia , Transtornos Mieloproliferativos/diagnóstico , Pele/patologia , Biópsia , Diagnóstico Diferencial , Gerenciamento Clínico , Humanos , Transtornos Mieloproliferativos/etiologia , Transtornos Mieloproliferativos/metabolismo , Transtornos Mieloproliferativos/terapia , Prognóstico , Neoplasias Cutâneas/diagnóstico , Avaliação de SintomasRESUMO
A 52-year-old man was referred to our dermatology clinic for a diagnosis of melanoma. At the time, his melanoma was excised he developed an annular, polycyclic, scaling eruption consistent with subacute cutaneous lupus erythematosus (SCLE). Skin biopsy and laboratory evaluation confirmed this diagnosis. The patient had been using pantoprazole for gastro-oesophageal reflux disease for the last 3 years. The patient's melanoma was treated surgically, and his SCLE was treated with topical steroids and hydroxychloroquine. His SCLE cleared rapidly, his steroids and hydroxychloroquine were stopped and he remains free of SCLE off of treatment. The parallel course of the patient's SCLE and melanoma prompted consideration of SCLE as paraneoplastic to melanoma in this case. The clinical picture was complicated by the patient's use of a proton pump inhibitor, which are common causes of drug-induced SCLE. To our knowledge, this is the first reported case of possible paraneoplastic SCLE associated with melanoma.
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Lúpus Eritematoso Cutâneo/diagnóstico , Melanoma/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Neoplasias Cutâneas/diagnóstico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
This case series describes 3 patients who developed cutaneous aphthosis while taking an epidermal growth factor receptor inhibitor in combination with an MEK inhibitor.
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Síndrome de Behçet , Neoplasias , Pentoxifilina , Estomatite Aftosa , Humanos , Pentoxifilina/uso terapêutico , PeleAssuntos
Calciofilaxia/induzido quimicamente , Pirazóis/efeitos adversos , Quinoxalinas/efeitos adversos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Idoso , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Biópsia , Calciofilaxia/sangue , Calciofilaxia/diagnóstico , Calciofilaxia/patologia , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Feminino , Humanos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Pele/patologia , Coxa da PernaRESUMO
STUDY DESIGN: Experimental, human cadaveric study. OBJECTIVE: To assess the fixation effects of injecting cement augmentation before screw insertion or after insertion of fenestrated screws; the effect of modulating cement viscosity; and the effects of these techniques on screw removal. SUMMARY OF BACKGROUND DATA: It seems clear that cement augmentation can enhance pedicle screw fixation in osteoporotic bone. What remains to be demonstrated is the aspects of optimal technique such that fixation is enhanced with the greatest safety profile. METHODS: Part I: Human osteoporotic vertebrae were instrumented with solid (nonaugmented) screws, solid screws with polymethylmethacrylate (PMMA), partially cannulated fenestrated (Pfen) screws, or fully cannulated fenestrated (Ffen) screws through which PMMA was injected. Screw fixation was tested in pullout. Part II: Ffen screws were augmented with standard low-viscosity PMMA versus high-viscosity PMMA. Part III: Sample cohorts were extracted from vertebrae to assess required torque and characterize difficulty of extraction. RESULTS: Part I: Pfen screws demonstrated the greatest fixation with mean failure force of 690 ± 182 N. All methods of cement augmentation demonstrated significant increases in screw fixation. Part II: Ffen screws did not demonstrate a significant difference in pullout strength when high-viscosity PMMA was used as compared with low-viscosity PMMA. Part III: Mean extraction torque values for solid augmented screws, Ffen screws, and Pfen screws were 1.167, 1.764, and 1.794 Nm, respectively, but these differences did not reach significance. None of the osteoporotic vertebrae sustained catastrophic failure during augmented screw extraction. CONCLUSION: Polymethylmethacrylate cement augmentation clearly enhances pedicle screw fixation in osteoporotic vertebrae when tested in pure pullout. The technique used for cement injection and choice of specialty screws can have a significant impact on the magnitude of this effect. Fenestrated screws have the capacity to confine cement placement in the vertebral body and may provide enhanced safety from cement extrusion into the spinal canal. It is feasible to inject high-viscosity PMMA through this fenestration geometry, and higher-viscosity cement may enhance the fixation effect.