Assuntos
United States Food and Drug Administration , Humanos , Estados Unidos/epidemiologia , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon/agonistas , Peptídeo 1 Semelhante ao Glucagon/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Idoso , Liraglutida/efeitos adversos , Liraglutida/uso terapêutico , Exenatida/efeitos adversos , Exenatida/administração & dosagem , Adulto , Toxidermias/etiologia , Toxidermias/epidemiologiaAssuntos
Leiomiossarcoma , Neoplasias Cutâneas , Humanos , Feminino , Leiomiossarcoma/mortalidade , Leiomiossarcoma/patologia , Leiomiossarcoma/diagnóstico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Masculino , Pessoa de Meia-Idade , Idoso , Fatores Sexuais , Adulto , Disparidades nos Níveis de Saúde , Idoso de 80 Anos ou maisAssuntos
Dermatologia , Medicare , População Rural , Humanos , Estados Unidos , Medicare/economia , Medicare/estatística & dados numéricos , Dermatologia/economia , Dermatologia/estatística & dados numéricos , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Disparidades em Assistência à Saúde/economia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Assistência Ambulatorial/economia , Assistência Ambulatorial/estatística & dados numéricos , Idoso , Feminino , Masculino , Pacientes Ambulatoriais/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricos , Dermatopatias/economia , Dermatopatias/terapia , Dermatopatias/epidemiologiaAssuntos
Leiomiossarcoma , Neoplasias Cutâneas , Humanos , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/patologia , Leiomiossarcoma/etnologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/etnologia , Neoplasias Cutâneas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Etnicidade/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Idoso de 80 Anos ou maisAssuntos
Asiático , Melanoma , Havaiano Nativo ou Outro Ilhéu do Pacífico , Neoplasias Cutâneas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Asiático/estatística & dados numéricos , Melanoma/epidemiologia , Melanoma/mortalidade , Melanoma Maligno Cutâneo , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Fatores Sexuais , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/mortalidadeRESUMO
IMPORTANCE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction occurring 2 to 8 weeks after medication initiation. Diagnosis is clinical; RegiSCAR scoring includes biopsy "suggestive of DRESS," undefined in the literature. OBJECTIVE: This study correlates DRESS dermatopathology, culprit drugs, disease course, and outcome severity compared with maculopapular drug reactions (MDR). METHODS: Between 2014 and 2023, a retrospective cohort study at a tertiary care institute reviewed 55 patients with DRESS, assessing demographics, culprit drug, illness course, and histopathology. Biopsies of 15 patients with DRESS and 15 MDR patients were graded by a predefined histopathological scoring system. Statistical analysis (significant P -value<0.05) included the Fisher exact probability, ANOVA, and correlation tests. RESULTS: Among 55 patients with DRESS (mean age 50.13, 28 female/27 male), 15 (mean age 50.4, 7 female/8 male) had diagnostic biopsies. Compared with MDR patients, patients with DRESS exhibited significantly more interface dermatitis ( P = 0.04), lichenoid dermatitis ( P = 0.0007), pigment incontinence ( P = 0.04), and periadnexal interface dermatitis ( P = 0.002). MDR biopsies displayed perivascular inflammation and higher eosinophils than DRESS, trending toward significance. CONCLUSIONS: Key histopathologic features are interface dermatitis, periadnexal interface dermatitis, lichenoid dermatitis, pigment incontinence, and neutrophils dominance over eosinophils indicate DRESS clinically.
Assuntos
Síndrome de Hipersensibilidade a Medicamentos , Humanos , Feminino , Masculino , Síndrome de Hipersensibilidade a Medicamentos/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Idoso , BiópsiaAssuntos
Dermatologia , Publicações Periódicas como Assunto , Pessoas Transgênero , Humanos , Dermatologia/tendências , Dermatologia/estatística & dados numéricos , Estudos Transversais , Pessoas Transgênero/estatística & dados numéricos , Publicações Periódicas como Assunto/estatística & dados numéricos , Publicações Periódicas como Assunto/tendências , Masculino , FemininoAssuntos
Estado Civil , Estadiamento de Neoplasias , Programa de SEER , Neoplasias das Glândulas Sebáceas , Humanos , Programa de SEER/estatística & dados numéricos , Masculino , Feminino , Neoplasias das Glândulas Sebáceas/mortalidade , Neoplasias das Glândulas Sebáceas/patologia , Neoplasias das Glândulas Sebáceas/epidemiologia , Pessoa de Meia-Idade , Estado Civil/estatística & dados numéricos , Idoso , Estados Unidos/epidemiologia , Adulto , Adenocarcinoma Sebáceo/patologia , Adenocarcinoma Sebáceo/mortalidade , Adenocarcinoma Sebáceo/epidemiologia , Taxa de Sobrevida , Idoso de 80 Anos ou maisAssuntos
Melanoma , Humanos , Estados Unidos , Estudos Retrospectivos , Melanoma/cirurgia , Etnicidade , Grupos RaciaisRESUMO
Importance: De novo bullous pemphigoid (BP) is a rare immune-mediated adverse event from immune checkpoint inhibitors (ICIs) that can necessitate permanent discontinuation of the anticancer therapy, but the risk factors for developing this toxic effect are unknown. Objective: To compare potential risk factors for BP in patients treated with ICIs who did and did not develop BP. Design, Setting, and Participants: This cohort and nested propensity score-matched case-control study was conducted at the Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Massachusetts General Hospital. All patients at these facilities with de novo BP after ICI treatment were compared with all patients on the cancer registry who were treated with ICIs between October 1, 2014, and December 31, 2020. Patients with incomplete or blinded data regarding the ICI agent or total cycles were excluded. Exposures: In the cohort, assessed potential risk factors included age at ICI introduction, sex, ICI molecular target, and cancer type, which were then used as matching variables. In the propensity score-matched case-control analysis, risk factors assessed included sex, race and ethnicity, cancer stage, metastasis sites, idiopathic BP comorbidities, pre-ICI vaccination, radiation history, body mass index, and derived neutrophil-to-lymphocyte ratio. Main Outcomes and Measures: Diagnosis of BP at any point after ICI treatment, confirmed by direct immunofluorescence, indirect immunofluorescence, autoantibody serologies, or diagnostic consensus among study board-certified dermatologists. Odds ratios (ORs) and 95% CIs were calculated for all risk factors. In the secondary analysis, best overall responses to ICIs between cases and controls were compared by Fisher exact test. Results: Among 5636 patients treated with ICIs at Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Massachusetts General Hospital during the study period, 35 (0.6%; median [IQR] age, 72.8 [13.4] years; 71.4% [25] male patients) developed BP. In a multivariate logistic regression model that assessed 2955 patients with complete data in the cancer registry, age 70 years or older (OR, 2.32; 95% CI, 1.19-4.59; P = .01), having melanoma (OR, 3.21; 95% CI, 1.51-6.58; P < .003), and having nonmelanoma skin cancer (OR, 8.32; 95% CI, 2.81-21.13; P < .001) were significantly associated with developing BP. In the nested 1:2 case-control comparison of all 35 cases to 70 propensity score-matched controls, a complete or partial response on initial restaging imaging was a risk factor for BP development (OR, 3.37; 95% CI, 1.35-9.30; P = .01). Bullous pemphigoid cases also more frequently exhibited overall tumor response to ICIs than matched controls (29 of 35 [82.9%] vs 43 of 70 [61.4%]; P = .03). Conclusions and Relevance: In this cohort study, age 70 years or older and skin cancer were associated with increased risk of developing ICI-associated BP. Given the association of BP with improved initial and best overall tumor responses, early identification and toxic effect-directed treatment should be prioritized, especially in individuals at risk for developing de novo BP.
Assuntos
Melanoma , Penfigoide Bolhoso , Neoplasias Cutâneas , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Masculino , Melanoma/tratamento farmacológico , Melanoma/patologia , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/epidemiologiaRESUMO
The neutrophil NADPH oxidase produces both intracellular and extracellular reactive oxygen species (ROS). Although oxidase activity is essential for microbial killing, and ROS can act as signaling molecules in the inflammatory process, excessive extracellular ROS directly contributes to inflammatory tissue damage, as well as to cancer progression and immune dysregulation in the tumor microenvironment. How specific signaling pathways contribute to ROS localization is unclear. Here we used a systems pharmacology approach to identify the specific Class I PI3-K isoform p110ß, and PLD1, but not PLD2, as critical regulators of extracellular, but not intracellular ROS production in primary neutrophils. Combined crystallographic and molecular dynamics analysis of the PX domain of the oxidase component p47phox, which binds the lipid products of PI 3-K and PLD, was used to clarify the membrane-binding mechanism and guide the design of mutant mice whose p47phox is unable to bind 3-phosphorylated inositol phospholipids. Neutrophils from these K43A mutant animals were specifically deficient in extracellular, but not intracellular, ROS production, and showed increased dependency on signaling through the remaining PLD1 arm. These findings identify the PX domain of p47phox as a critical integrator of PLD1 and p110ß signaling for extracellular ROS production, and as a potential therapeutic target for modulating tissue damage and extracellular signaling during inflammation.