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1.
Am J Dermatopathol ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39288748

RESUMEN

ABSTRACT: Chronic graft-versus-host disease (cGVHD) is the leading cause of morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation. Skin biopsy of cGVHD is recommended when clinical features are not diagnostic, yet the histopathologic features of skin cGVHD are not well described. The objective of this study is to describe the histopathologic features of skin cGVHD in epidermal, sclerotic, and combination cGVHD. Of 49 patients with skin cGVHD, 30 of 49 (61.2%) were male, and mean age was 55 years (SD 11.1). Clinically, 33 of 49 (67.3%) had epidermal cGVHD (E-cGVHD), 1 of 49 (2.1%) had sclerotic cGVHD (S-cGVHD), and 15 of 49 (30.6%) had combination disease. The 49 patients corresponded to 83 unique pathologic specimens with 67 of 83 (80.7%) taken from E-cGVHD, and 16 of 83 (19.3%) from S-cGVHD lesions. Nearly all biopsy specimens from E-cGVHD showed minimal features of active GVHD, including apoptosis in the epidermal basal layer (n = 63, 94.0%), vacuolar change (n = 62, 92.5%), and lymphocyte satellitosis (n = 57, 85.1%). The predominant histologic pattern of E-cGVHD was lichen planus/interface dermatitis (n = 31, 47.0%). S-cGVHD specimens also showed minimal features of active GVHD with apoptosis of the epidermal basal layer (n = 11, 68.8%) and vacuolar change (n = 8, 50.0%). In addition, S-cGVHD showed sclerosis of the papillary and reticular dermis and subcutaneous septae (n = 8, 50.0%; n = 11, 68.8%; n = 5, 31.2%, respectively). The predominant histologic pattern of S-cGVHD was lichen sclerosus/morphea-like pattern (n = 10, 62.5%). Although minimal pathologic features of active GVHD are common, the majority of cGVHD biopsies share features with the inflammatory skin diseases that they clinically resemble. Complete histologic reporting is recommended with implications for disease endotyping and personalized therapy.

2.
Blood Adv ; 8(17): 4651-4657, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-38885484

RESUMEN

ABSTRACT: Cutaneous sclerosis, a highly morbid subtype of chronic graft-versus-host disease (GVHD), demonstrates limited treatment response under current National Institutes of Health (NIH) response measures. We explored novel sclerosis-specific response measures using Chronic GVHD Consortium data. A training cohort included patients with cutaneous sclerosis from a randomized trial of imatinib vs rituximab and a consortium observational study. The validation cohort was a different consortium observational study. Clinician-reported measures (baseline and baseline to 6-month change) were examined for association with 6-month clinician-reported response. Patient-reported measures (baseline and baseline to 6-month change) were studied for association with 6-month patient-reported response. A total of 347 patients were included (training 183 and validation 164). Although multiple skin and joint measures were associated with clinician-reported response on univariate analysis, patient range of motion (PROM) total score, PROM total score change, and NIH 0 to 3 skin change were retained in the final multivariate model (area under the receiver operating characteristic curve [AUC], 0.83 training and 0.75 validation). Similarly, many patient-reported measures were associated, but final multivariate analysis retained the human activity profile adjusted activity score (AAS), 36 item short form health survey (SF36) vitality change, Lee symptom scale (LSS) skin, and LSS skin change in the model (AUC, 0.86 training and 0.75 validation). We identified which sclerosis measures have the greatest association with 6-month clinician- and patient-reported treatment responses, a previously unstudied area. However, given the observed performance in the validation cohorts, we conclude that further work is needed. Novel response measures may be needed to optimally assess treatment response in cutaneous sclerosis.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Adulto , Trasplante Homólogo , Resultado del Tratamiento , Esclerosis
3.
JAMA Dermatol ; 160(7): 741-745, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38809569

RESUMEN

Importance: Masculinizing gender-affirming hormonal therapy is associated with the development of acne. While isotretinoin is a highly effective acne treatment, little is known about its effectiveness and safety among transgender and gender-diverse individuals receiving gender-affirming hormonal therapy. Objective: To evaluate clinical outcomes of isotretinoin among transgender and gender-diverse individuals receiving gender-affirming hormonal therapy. Design, Setting, and Participants: This multicenter retrospective case series study was conducted at 4 medical centers: Mass General Brigham, University of Pennsylvania, Emory University, and Fenway Health. It included patients aged between 12 and 49 years who were receiving masculinizing gender-affirming hormonal therapy and prescribed isotretinoin for the management of acne between August 14, 2015, and September 20, 2023. Exposure: Isotretinoin therapy for the management of acne. Main Outcomes and Measures: The percentage of patients experiencing improvement or clearance of acne, as well as rates of acne recurrence. Adverse effects and reasons for treatment discontinuation were also evaluated. Results: Among 55 included patients, the mean (SD) age was 25.4 years; 4 (7.3%) were Asian, 2 (3.6%) were Black, 4 (7.2%) were Hispanic, 1 was (1.8%) multiracial, and 36 (65.5%) were White. The median isotretinoin course duration was 6 months (IQR, 4.0-8.0), with a median cumulative dose of 132.7 mg/kg (IQR, 66.4-168.5); the cumulative dose was less than 90 mg/kg for 16 patients (29.1%) and less than 120 mg/kg for 22 patients (40.0%). Isotretinoin was associated with improvement in 48 patients (87.3%) and clearance in 26 patients (47.3%). For the 33 patients treated with a cumulative dose of 120 mg/kg or more, these rates increased to 32 patients (97.0%) and 21 patients (63.6%), respectively. Among the 20 patients who achieved acne clearance and had any subsequent health care encounters, the risk of recurrence was 20.0% (n = 4). The most frequently reported adverse effects were dryness (n = 44; 80.0%), joint pain (n = 8; 14.5%), and eczema (n = 5; 9.1%). Laboratory abnormalities were uncommon. Reasons for premature treatment discontinuation included cost, pharmacy issues, adverse effects, logistical reasons (scheduling), and wound healing concerns for gender-affirming surgery. Conclusion and Relevance: In this case series study of individuals with acne who were receiving masculinizing gender-affirming hormonal therapy and underwent isotretinoin treatment, isotretinoin was often effective and well tolerated. However, premature treatment discontinuation was common and associated with poorer outcomes. Further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving masculinizing gender-affirming hormonal therapy.


Asunto(s)
Acné Vulgar , Fármacos Dermatológicos , Isotretinoína , Personas Transgénero , Humanos , Isotretinoína/administración & dosificación , Isotretinoína/efectos adversos , Acné Vulgar/tratamiento farmacológico , Estudios Retrospectivos , Masculino , Femenino , Personas Transgénero/estadística & datos numéricos , Adolescente , Adulto , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/efectos adversos , Adulto Joven , Niño , Resultado del Tratamiento , Persona de Mediana Edad , Recurrencia
4.
JAMA Dermatol ; 160(4): 393-401, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38416506

RESUMEN

Importance: Chronic graft-vs-host disease (GVHD) is associated with impaired quality of life and symptom burden. The independent association of skin involvement with patient-reported outcomes (PROs) and their utility as a clinical prognostic marker remain unknown. Identification of patients with cutaneous chronic GVHD and impaired PROs could assist in initial risk stratification and treatment selection. Objective: To compare the association of sclerotic and epidermal-type chronic GVHD with longitudinal PROs and to evaluate whether PROs can identify patients with cutaneous chronic GVHD at high risk for death. Design, Setting, and Participants: This multicenter prospective cohort study involved patients from the Chronic GVHD Consortium of 9 US medical centers, enrolled between August 2007 and April 2012, and followed up until December 2020. Participants included adults 18 years and older with a diagnosis of chronic GVHD requiring systemic immunosuppression and with skin involvement during the study period. Main Outcomes and Measures: Patient-reported symptom burden was assessed using the Lee Symptom Scale (LSS) skin subscale with higher scores indicating worse outcomes. Quality of life was measured using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) instrument with lower scores indicating worse outcomes. Nonrelapse mortality, overall survival, and their association with PROs at diagnosis were also assessed. Results: Among 436 patients with cutaneous chronic GVHD (median [IQR] age at transplant, 51 [41.5-56.6] years; 261 [59.9%] male), 229 patients had epidermal-type chronic GVHD (52.5%), followed by 131 with sclerotic chronic GVHD (30.0%), and 76 with combination disease (17.4%). After adjusting for confounders, patients with sclerotic chronic GVHD had mean FACT-BMT scores 6.1 points worse than those with epidermal disease (95% CI, 11.7-0.4; P = .04). Patients with combination disease had mean LSS skin subscale scores 9.0 points worse than those with epidermal disease (95% CI, 4.2-13.8; P < .001). Clinically meaningful differences were defined as at least 7 points lower for FACT-BMT and 11 points higher for LSS skin subscale. At diagnosis, clinically meaningful worsening in FACT-BMT score was associated with an adjusted odds of nonrelapse mortality increased by 9.1% (95% CI, 2.0%-16.7%; P = .01). Similarly, for clinically meaningful worsening in LSS skin subscale score, adjusted odds of nonrelapse mortality increased by 16.4% (95% CI, 5.4%-28.5%; P = .003). These associations held true after adjusting for clinical severity by the National Institutes of Health Skin Score. Conclusions and Relevance: The results of this cohort study demonstrated that skin chronic GVHD was independently associated with long-term PRO impairment, with sclerotic and combination disease carrying the highest morbidity. The degree of impairment at skin chronic GVHD diagnosis was a prognostic marker for mortality. Therefore, PROs could be useful for risk stratification and treatment selection in clinical practice and clinical trials.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedades de la Piel , Adulto , Humanos , Masculino , Persona de Mediana Edad , Femenino , Calidad de Vida , Estudios de Cohortes , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Estudios Prospectivos , Enfermedades de la Piel/etiología , Medición de Resultados Informados por el Paciente , Biomarcadores , Enfermedad Crónica
5.
Transplant Cell Ther ; 30(3): 338.e1-338.e6, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38182005

RESUMEN

Muscle cramps in patients with chronic graft-versus-host disease (cGVHD) are common and associated with impaired quality of life and symptom burden. Muscle cramps are not currently captured in the 2014 National Institutes of Health (NIH) response criteria, and thus characterization and response to immunomodulatory therapies are lacking. The objective of this study was to characterize muscle cramp frequency, duration, and pain level in patients with steroid-refractory cGVHD undergoing extracorporeal photopheresis (ECP). A single-center cohort of patients who underwent ECP for the indication of steroid-refractory cGVHD with muscle cramps at treatment initiation were followed from April 2021 to April 2023. Of 22 patients receiving ECP for cGVHD during the study period, 9 (41%) had muscle cramps at ECP initiation (6 males [66%]; median age, 59 years; range, 25 to 66 years). Seven of these 9 patients (78%) had multiple organs involved, and 7 (78%) had severe disease by the NIH Global Severity scale. Over a median treatment duration of 28 weeks (range, 10 to 48 weeks), 8 patients (89%) had decreased frequency of muscle cramps from a median of 5 episodes per week (range, 3 per day to 2 per week) to a median of <1 episode per week (range, 1 per month to 3 per week). The pain and duration of muscle cramps were not changed meaningfully. The NIH Global Severity score remained unchanged in 6 patients (67%) and was improved in 3 patients (33%). Muscle cramping is a morbid feature of cGVHD that may be sensitive to change with standard immunomodulatory therapies. Muscle cramp frequency should be further validated as a response measure in cGVHD.


Asunto(s)
Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Estados Unidos , Masculino , Humanos , Persona de Mediana Edad , Calambre Muscular/etiología , Calambre Muscular/terapia , Calidad de Vida , Enfermedad Injerto contra Huésped/terapia , Inmunomodulación , Dolor , Esteroides
6.
J Am Acad Dermatol ; 90(1): 1-16, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-36572065

RESUMEN

Chronic graft-versus-host disease is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 U.S. Food and Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of chronic graft-versus-host disease. Part II discusses disease grading and therapeutic management.


Asunto(s)
Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Calidad de Vida , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Piel/patología , Enfermedad Crónica
7.
J Am Acad Dermatol ; 90(1): 19-36, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-36572064

RESUMEN

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 Federal Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of cGVHD. Part II discusses disease grading and therapeutic management.


Asunto(s)
Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Calidad de Vida , Enfermedad Crónica , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos
9.
Int J Dermatol ; 62(8): 1020-1025, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37203799

RESUMEN

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.


Asunto(s)
Exantema , Psoriasis , Humanos , Rituximab , Piel , Tacrolimus
11.
JAMA Dermatol ; 159(4): 393-402, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36884224

RESUMEN

Importance: Prior studies have demonstrated an association between cutaneous chronic graft-vs-host disease (cGVHD) and mortality. Assessment of the prognostic value of different measures of disease severity would assist in risk stratification. Objective: To compare the prognostic value of body surface area (BSA) and National Institutes of Health (NIH) Skin Score on survival outcomes stratified by erythema and sclerosis subtypes of cGVHD. Design, Setting, and Participants: Multicenter prospective cohort study from the Chronic Graft-vs-Host Disease Consortium including 9 medical centers in the US, enrolled from 2007 through 2012 and followed until 2018. Participants were adults and children with a diagnosis of cGVHD requiring systemic immunosuppression and with skin involvement during the study period, who had longitudinal follow-up. Data analysis was performed from April 2019 to April 2022. Exposures: Patients underwent continuous BSA estimation and categorical NIH Skin Score grading of cutaneous cGVHD at enrollment and every 3 to 6 months thereafter. Main Outcomes and Measures: Nonrelapse mortality (NRM) and overall survival (OS), compared between BSA and NIH Skin Score longitudinal prognostic models, adjusted for age, race, conditioning intensity, patient sex, and donor sex. Results: Of 469 patients with cGVHD, 267 (57%) (105 female [39%]; mean [SD] age, 51 [12] years) had cutaneous cGVHD at enrollment, and 89 (19%) developed skin involvement subsequently. Erythema-type disease had earlier onset and was more responsive to treatment compared with sclerosis-type disease. Most cases (77 of 112 [69%]) of sclerotic disease occurred without prior erythema. Erythema-type cGVHD at first follow-up visit was associated with NRM (hazard ratio, 1.33 per 10% BSA increase; 95% CI, 1.19-1.48; P < .001) and OS (hazard ratio, 1.28 per 10% BSA increase; 95% CI, 1.14-1.44; P < .001), while sclerosis-type cGVHD had no significant association with mortality. The model with erythema BSA collected at baseline and first follow-up visits retained 75% of the total prognostic information (from all covariates including BSA and NIH Skin Score) for NRM and 73% for OS, with no statistical difference between prognostic models (likelihood ratio test χ2, 5.9; P = .05). Conversely, NIH Skin Score collected at the same intervals lost significant prognostic information (likelihood ratio test χ2, 14.7; P < .001). The model incorporating NIH Skin Score instead of erythema BSA accounted for only 38% of the total information for NRM and 58% for OS. Conclusions and Relevance: In this prospective cohort study, erythema-type cutaneous cGVHD was associated with increased risk of mortality. Erythema BSA collected at baseline and follow-up predicted survival more accurately than the NIH Skin Score in patients requiring immunosuppression. Accurate assessment of erythema BSA may assist in identifying patients with cutaneous cGVHD at high risk for mortality.


Asunto(s)
Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Niño , Humanos , Femenino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Esclerosis , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Crónica , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Eritema/etiología , Gravedad del Paciente
12.
Cutis ; 111(1): 18-21, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36947773

RESUMEN

Epidermal growth factor receptor (EGFR) inhibitors cause numerous cutaneous adverse events (AEs), including papulopustular eruptions, paronychia, acral fissures, xerosis, alopecia, and trichomegaly. Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous reaction that has been uncommonly reported in association with EGFR inhibitors, though the optimal management strategy for this condition is unknown. We present 2 cases of SDRIFE secondary to EGFR inhibitor therapy in which the EGFR inhibitor was successfully continued while topical therapy was administered for effective control of symptoms. We also review the literature on EGFR inhibitor-related SDRIFE to assess the range of approaches to treating this condition. Our analysis suggests that the dermatologist is critical in diagnosing and treating this cutaneous AE, which may be supported with skin-directed therapy and may not require discontinuation of cancer treatment.


Asunto(s)
Erupciones por Medicamentos , Exantema , Humanos , Exantema/inducido químicamente , Exantema/diagnóstico , Exantema/complicaciones , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/etiología , Piel , Administración Cutánea , Receptores ErbB
14.
AIDS ; 36(11): 1493-1500, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35848549

RESUMEN

OBJECTIVE: Antiretroviral therapy (ART) extends the life of people with HIV (PWH), but these individuals are at increased risk for obesity, dyslipidemia, diabetes, and cardiovascular disease. These comorbidities may be a consequence of HIV-related chronic inflammation and/or adverse effects of ART on tissue regulatory adipose tissue macrophages (ATMs). We sought to determine the effects of HIV/ART on metabolically beneficial ATM populations and functions. DESIGN: We examined subcutaneous ATMs from PWH on integrase inhibitor-containing ART ( n  = 5) and uninfected persons ( n  = 9). We complemented these studies with ex vivo and in vitro analyses of peripheral blood mononuclear cell (PBMC) and murine macrophage lipid metabolism and fatty acid oxidation gene expression. METHODS: ATM populations were examined by flow cytometry. Macrophage lipid metabolism and fatty acid oxidation gene expression were examined by Seahorse assay and quantitative PCR. RESULTS: Adipose tissue from PWH had reduced populations of metabolically activated CD9 + ATMs compared to that of uninfected controls ( P  < 0.001). PBMCs of PWH had lower fatty acid metabolism compared to those of uninfected controls ( P  < 0.01). Analysis of murine macrophages revealed that dolutegravir reduced lipid metabolism ( P  < 0.001) and increased expression of the fatty acid beta-oxidation enzyme enoyl-CoA hydratase, short chain 1 ( P  < 0.05). CONCLUSIONS: We report the loss of metabolically beneficial ATM populations in PWH on ART, altered fatty acid metabolism of blood immune cells, and evidence that dolutegravir alters macrophage fatty acid metabolism. Future studies should examine direct or indirect effects and mechanisms of dolutegravir, and other integrase inhibitors and ART classes, on fatty acid beta-oxidation.


Asunto(s)
Infecciones por VIH , Inhibidores de Integrasa VIH , Tejido Adiposo , Animales , Ácidos Grasos/metabolismo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Inhibidores de Integrasa VIH/uso terapéutico , Humanos , Leucocitos Mononucleares , Macrófagos , Ratones
15.
Am J Clin Dermatol ; 23(4): 449-457, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35486323

RESUMEN

BACKGROUND: Methotrexate cutaneous ulceration is a rare methotrexate complication, and has only been described in case reports and case series. OBJECTIVE: To document patient characteristics, morphologic features, and mortality risk factors for methotrexate cutaneous ulceration. METHODS: A systematic literature review of PubMed and Embase (last date 1 November 2021) was performed with data collected from case reports and case series. This study was limited to cases of cutaneous ulceration; presence of oral ulceration was collected from within these cases. RESULTS: 114 cases (men = 57.9%, mean age = 61 years) of methotrexate cutaneous ulceration met inclusion criteria. Psoriasis (69.3%), rheumatoid arthritis (18.4%), and mycosis fungoides (6.1%) were the most common indications for methotrexate use. Morphologies included erosions localized to psoriatic plaques (33.3%), epidermal necrosis/necrolysis (35.1%), localized ulceration (16.7%), and skin-fold erosions (5.3%). Methotrexate dose preceding toxicity varied greatly; median 20 mg/week, interquartile range 15-40 mg/week, range 5-150 mg/week. Most patients had risk factors for serum toxicity (baseline renal dysfunction = 37.8%, concurrent NSAID use = 28.1%, inadequate folic acid use = 89.1%). Thirty percent of cases involved mistakenly high methotrexate doses. Fourteen patients (12%) died. Absence of folic acid use (69% vs. 100%, p value < 0.001), pancytopenia (33% vs. 86%, p value < 0.001), and renal dysfunction at presentation (47% vs. 92%, p value < 0.001) were associated with increased mortality. LIMITATIONS: Selection bias present due to abstraction from case reports and case series. CONCLUSION: Methotrexate cutaneous ulceration is commonly preceded by dosage mistakes, absence of folic acid supplementation, and concurrent use of nephrotoxic medications. Renal impairment, pancytopenia, and absence of folic acid supplementation are key risk factors for mortality from this adverse medication reaction. Providers should regularly monitor methotrexate dosing adherence, drug-drug interactions, and perform routine laboratory evaluation. Index of suspicion for this toxicity should remain high given the varied clinical presentation and high mortality.


Asunto(s)
Erupciones por Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Enfermedades Renales , Pancitopenia , Neoplasias Cutáneas , Úlcera Cutánea , Erupciones por Medicamentos/etiología , Ácido Fólico , Humanos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/complicaciones , Enfermedades Renales/tratamiento farmacológico , Masculino , Metotrexato/efectos adversos , Persona de Mediana Edad , Pancitopenia/inducido químicamente , Pancitopenia/complicaciones , Pancitopenia/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Úlcera Cutánea/inducido químicamente
18.
Blood Adv ; 5(6): 1585-1593, 2021 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-33710336

RESUMEN

Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. A nonlive adjuvanted recombinant zoster vaccine (RZV) has been developed to prevent herpes zoster (HZ), but there are no recommendations for use in this population. In this single-center prospective observational cohort study, we assessed the safety and reactogenicity of RZV, as well as incidence of graft-versus-host disease (GVHD) and confirmed cases of HZ after vaccination. Between December of 2018 and June of 2020, patients aged ≥18 years received 2 doses of RZV between 9 and 24 months after HCT, with the doses separated by ≥8 weeks. One hundred and fifty-eight patients (mean age, 55 years; 42% women) received ≥1 dose (total vaccinated cohort), and 150 patients (95%) received 2 doses (modified total vaccinated cohort). Solicited reactions occurred in 92.1% of patients (grade 3, 32.5%), owing mostly to injection site pain, which occurred in 86% (grade 3, 16%). The cumulative incidence of GVHD in the peri-vaccination period was no different than in historical controls (adjusted incidence rate ratio, 1.05; 95% confidence interval, 0.8-1.38). There were 4 cases of HZ in the total vaccinated cohort (2.5%) and 3 cases in the modified total vaccinated cohort (28.3/1000 person-years). Among recipients of allogeneic HCT, RZV was safe, tolerable, and did not increase rates of GVHD. Future clinical trials are needed to determine the immunogenicity and efficacy of RZV in this population.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Vacuna contra el Herpes Zóster , Herpes Zóster , Adolescente , Adulto , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpes Zóster/epidemiología , Herpes Zóster/prevención & control , Vacuna contra el Herpes Zóster/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Vacunas Sintéticas
19.
J Am Acad Dermatol ; 82(6): 1393-1399, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31881295

RESUMEN

BACKGROUND: Renal involvement in adult Henoch-Schönlein purpura is a major cause of morbidity and can lead to significant long-term renal impairment. The prognostic significance of normal or minimal urinary abnormalities at diagnosis is unknown. OBJECTIVE: To assess the risk of long-term renal impairment in patients with Henoch-Schönlein purpura who present with normal or minimal urinary abnormalities. METHODS: Retrospective cohort study of adult Henoch-Schönlein purpura patients presenting with normal urinalysis results, microscopic hematuria, or low-grade proteinuria. Patients were followed for development of long-term renal impairment, with adjusting for comorbidities. RESULTS: Forty-seven patients were included, with median follow-up 73.9 months (interquartile range 35 to 98 months). Thirty-nine patients (83.0%) had abnormal urinalysis results, of whom 15 (38.5%) progressed to long-term renal impairment. In contrast, 8 patients (17%) had normal urinalysis results, of whom only 1 (12.5%) developed long-term renal impairment (adjusted hazard ratio 10.58; 95% confidence interval 1.18-94.73). Renal events occurred at a median 36.1 months (interquartile range 17.1 to 61 months) from diagnosis, earlier in patients with comorbidities compared with those with none, and in a constant event rate over time. LIMITATIONS: Small sample size. CONCLUSIONS: Microscopic hematuria and low-grade proteinuria at Henoch-Schönlein purpura diagnosis is a poor prognostic sign for the development of long-term renal impairment. This population should be targeted for prolonged surveillance.


Asunto(s)
Vasculitis por IgA/fisiopatología , Vasculitis por IgA/orina , Enfermedades Renales/fisiopatología , Enfermedades Renales/orina , Riñón/fisiopatología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Vasculitis por IgA/complicaciones , Enfermedades Renales/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Urinálisis
20.
Circ Heart Fail ; 12(11): e006214, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31658831

RESUMEN

BACKGROUND: Racial inequities for patients with heart failure (HF) have been widely documented. HF patients who receive cardiology care during a hospital admission have better outcomes. It is unknown whether there are differences in admission to a cardiology or general medicine service by race. This study examined the relationship between race and admission service, and its effect on 30-day readmission and mortality Methods: We performed a retrospective cohort study from September 2008 to November 2017 at a single large urban academic referral center of all patients self-referred to the emergency department and admitted to either the cardiology or general medicine service with a principal diagnosis of HF, who self-identified as white, black, or Latinx. We used multivariable generalized estimating equation models to assess the relationship between race and admission to the cardiology service. We used Cox regression to assess the association between race, admission service, and 30-day readmission and mortality. RESULTS: Among 1967 unique patients (66.7% white, 23.6% black, and 9.7% Latinx), black and Latinx patients had lower rates of admission to the cardiology service than white patients (adjusted rate ratio, 0.91; 95% CI, 0.84-0.98, for black; adjusted rate ratio, 0.83; 95% CI, 0.72-0.97 for Latinx). Female sex and age >75 years were also independently associated with lower rates of admission to the cardiology service. Admission to the cardiology service was independently associated with decreased readmission within 30 days, independent of race. CONCLUSIONS: Black and Latinx patients were less likely to be admitted to cardiology for HF care. This inequity may, in part, drive racial inequities in HF outcomes.


Asunto(s)
Centros Médicos Académicos , Negro o Afroamericano , Servicio de Cardiología en Hospital , Accesibilidad a los Servicios de Salud , Disparidades en Atención de Salud/etnología , Insuficiencia Cardíaca/terapia , Hispánicos o Latinos , Admisión del Paciente , Población Blanca , Anciano , Anciano de 80 o más Años , Boston/epidemiología , Femenino , Disparidades en el Estado de Salud , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etnología , Insuficiencia Cardíaca/mortalidad , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
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