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1.
Am J Surg Pathol ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34753863

RESUMO

The current classification of Spitz neoplasms in the World Health Organization (WHO), Fourth Edition defines Spitz neoplasms as melanocytic proliferations with characteristic Spitz morphology and a Spitz-associated genomic fusion or HRAS mutation. In contrast, melanocytic neoplasms with BRAF mutations are considered typical of common acquired nevi, dysplastic nevi, and melanomas from intermittent sun-damaged skin. However, increased utilization of ancillary testing methods such as BRAFV600E immunohistochemistry and sequencing studies have made apparent a subgroup of benign-grade and intermediate-grade melanocytic neoplasms with Spitzoid morphology that harbor BRAFV600E mutations. We refer to these cases as BRAF mutated and morphologically Spitzoid (BAMS) nevi and tumors. Two experienced dermatopathologists reviewed a series of 36 BAMS nevi/tumors. Cases in which a diagnosis of melanoma was favored were excluded. The histomorphologic, clinical, and molecular findings were assessed by immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing using validated gene panels. Characteristics of BAMS nevi/tumors were compared with a control set of Spitz tumors with previously reported fusion proteins. BAMS nevi/tumors had a decreased proportion of Kamino bodies (P=0.03) and a higher proportion of cytoplasmic pigmentation (P<0.00001). There were no differences in other morphologic features such as the silhouette, epidermal hyperplasia, pagetosis, and cytologic atypia compared with fusion-induced Spitz tumors. In 6/17 cases where next-generation sequencing studies were available, recurrent mutations in the KMT gene family were seen. This was higher than the proportion of such mutations seen in fusion Spitz tumors and lower than the frequency in cutaneous melanoma.

2.
Am J Surg Pathol ; 45(12): 1597-1605, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34757982

RESUMO

Atypical Spitzoid melanocytic tumors are diagnostically challenging. Many studies have suggested various genomic markers to improve classification and prognostication. We aimed to assess whether next-generation sequencing studies using the Tempus xO assay assessing mutations in 1711 cancer-related genes and performing whole transcriptome mRNA sequencing for structural alterations could improve diagnostic agreement and accuracy in assessing neoplasms with Spitzoid histologic features. Twenty expert pathologists were asked to review 70 consultation level cases with Spitzoid features, once with limited clinical information and again with additional genomic information. There was an improvement in overall agreement with additional genomic information. Most significantly, there was increase in agreement of the diagnosis of conventional melanoma from moderate (κ=0.470, SE=0.0105) to substantial (κ=0.645, SE=0.0143) as measured by an average Cohen κ. Clinical follow-up was available in all 70 cases which substantiated that the improved agreement was clinically significant. Among 3 patients with distant metastatic disease, there was a highly significant increase in diagnostic recognition of the cases as conventional melanoma with genomics (P<0.005). In one case, none of 20 pathologists recognized a tumor with BRAF and TERT promoter mutations associated with fatal outcome as a conventional melanoma when only limited clinical information was provided, whereas 60% of pathologists correctly diagnosed this case when genomic information was also available. There was also a significant improvement in agreement of which lesions should be classified in the Spitz category/WHO Pathway from an average Cohen κ of 0.360 (SE=0.00921) to 0.607 (SE=0.0232) with genomics.


Assuntos
Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Nevo de Células Epitelioides e Fusiformes/genética , Neoplasias Cutâneas/genética , Adulto , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nevo de Células Epitelioides e Fusiformes/mortalidade , Nevo de Células Epitelioides e Fusiformes/patologia , Nevo de Células Epitelioides e Fusiformes/terapia , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia
3.
Expert Rev Precis Med Drug Dev ; 6(4): 281-294, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485698

RESUMO

Introduction: NRAS was the first mutated oncogene identified in melanoma and is currently the second most common driver mutation in this malignancy. For patients with NRASmutant advanced stage melanoma refractory to immunotherapy or with contraindications to immune-based regimens, there are few therapeutic options including low-efficacy chemotherapy regimens and binimetinib monotherapy. Here, we review recent advances in preclinical studies of molecular targets for NRAS mutant melanoma as well as the failures and successes of early-phase clinical trials. While there are no targeted therapies for NRAS-driven melanoma, there is great promise in approaches combining MEK inhibition with inhibitors of the focal adhesion kinase (FAK), inhibitors of autophagy pathways, and pan-RAF inhibitors. Areas Covered: This review surveys new developments in all aspects of disease pathogenesis and potential treatment - including those that have failed, stalled, or progressed through various phases of preclinical and clinical development. Expert Opinion: There are no currently approved targeted therapies for BRAF wild-type melanoma patients harboring NRAS driver mutations though an array of agents are in early phase clinical trials. The diverse strategies taken exploit combined MAP kinase signaling blockade with inhibition of cell cycle mediators, inhibition of the autophagy pathway, and alteration of kinases involved in actin cytoskeleton signaling. Future advances of developmental therapeutics into late stage trials may yield new options beyond immunotherapy for patients with advanced stage disease and NRAS mutation status.

5.
Surg Pathol Clin ; 14(2): 285-292, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34023106

RESUMO

Pigmented epithelioid melanocytoma (PEM) was originally described based on keen morphologic analysis identifying a group of melanocytic tumors sharing heavily pigmented epithelioid melanocytes. It is defined as heavily pigmented epithelioid, spindled, and dendritic melanocytes with characteristic vesicular nuclei, prominent nucleoli, and melanophages. PEM often involves regional lymph nodes. Recent advances in molecular analysis have allowed for subclassification of PEM into more specific subsets of melanocytic tumors. The most common subsets include PRKCA fusions, which result in pure PEMs with sheets of monomorphic epithelioid melanocytes, and PEMs with combined pattern and mutations in both PRKAR1A and BRAF.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Linfonodos , Melanoma/diagnóstico , Melanoma/genética , Mutação , Neoplasias Cutâneas/genética
6.
Arch Dermatol Res ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33733299

RESUMO

BACKGROUND: It is our experience that parakeratosis with pagetosis is common in early melanoma when there is no history of trauma in the anatomical site. In lesions where the differential diagnosis includes dysplastic nevus (DN) and melanoma, we hypothesize that parakeratosis may be a marker for cases in which immunohistochemistry (IHC) may identify occult pagetosis. METHODS: We performed a retrospective case-control study on cases with a histologic differential diagnosis of DN versus melanoma, including 423 cases with parakeratosis and 125 cases without parakeratosis. IHC staining (Mart-1 and/or Sox-10) was performed in all cases. The frequency of pagetosis and diagnostic upgrades in the cases versus the controls was calculated. RESULTS: The presence of parakeratosis was significantly associated with pagetosis (p < 0.0001). Diagnostic upgrades were more frequent in the cases with parakeratosis versus controls without parakeratosis (p = 0.0029). In the favored moderate DN group, 56% of cases were upgraded compared to 30% of the controls (p = 0.0017). In the favored mild DN and severe DN groups, there were more case upgrades compared to the controls (p = 0.1386, p = 0.2738). CONCLUSIONS: Parakeratosis may be a useful marker to identify lesions with occult pagetosis for which IHC would be appropriate and may result in a diagnostic upgrade.

7.
Pediatr Dermatol ; 38(2): 544-546, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33452694

RESUMO

In this study, we sought to analyze the readability of online patient education materials (PEMs) related to juvenile dermatomyositis (JDM). We analyzed the top 100 Google results and using six different readability scores, found 53 PEMs which had an average grade reading level of 17.4 (graduate level). PEMs by health care providers were written at higher grade levels than those by non-health care providers. Our findings demonstrate a clear need for online JDM PEMs that are written at an appropriate reading level and can be comprehended by patients and families of all levels of health literacy.


Assuntos
Dermatomiosite , Educação à Distância , Letramento em Saúde , Compreensão , Humanos , Educação de Pacientes como Assunto
9.
Dermatitis ; 32(3): 164-172, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33443378

RESUMO

PURPOSE: Ruxolitinib (Jakafi) is a Janus kinase 1 and 2 small molecule inhibitor that the Food and Drug Administration approved for myelofibrosis and polycythemia vera. It has been expanded to off-label treatment for a variety of dermatologic conditions, with several clinical trials ongoing. A review of available studies and cases of off-label uses was performed to guide clinicians seeking evidence on the efficacy of this Janus kinase inhibitor for dermatologic disorders. MATERIALS AND METHODS: PubMed/MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov databases were searched with the term "ruxolitinib," and results were manually reviewed to identify published data on off-label uses of ruxolitinib. Studies included are structured by quality of evidence available. RESULTS: Ruxolitinib may have utility in the treatment of atopic dermatitis, psoriasis, and vitiligo, with data from open-label and randomized trials supporting efficacy of topical formulations. Evidence of utility for alopecia areata is mixed and differs depending on topical versus oral form. Evidence for numerous other conditions is available through case reports and case series. CONCLUSIONS: There is growing evidence supporting potential off-label use of oral and topical ruxolitinib for a wide range of skin conditions. There are several ongoing investigations of ruxolitinib use in dermatology that will undoubtedly better define its efficacy and appropriate use in dermatology.


Assuntos
Dermatite Atópica/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Nitrilas/uso terapêutico , Uso Off-Label , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Alopecia em Áreas/tratamento farmacológico , Humanos , Nitrilas/efeitos adversos , Psoríase/tratamento farmacológico , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos
10.
J Dermatolog Treat ; 32(4): 399-409, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31581859

RESUMO

PURPOSE: Tofacitinib citrate is an oral Janus kinase 1/3 inhibitor approved for rheumatoid arthritis, ulcerative colitis, and active psoriatic arthritis. Tofacitinib is being increasingly used off-label for dermatological conditions, with varying efficacy across recent studies. A review of these studies will be a helpful resource for dermatologists considering the use of tofacitinib for conditions refractory to first-line therapies. MATERIALS AND METHODS: MEDLINE, Embase, CINAHL Plus, Cochrane Library, Scopus, Web of Science, Clinicaltrials.gov, and the WHO International Clinical Trials Registry Platform were all searched for articles and trials mentioning the term 'tofacitinib', then manually reviewed to identify published data on off-label uses of tofacitinib. The article was structured according to the quality of the evidence available. RESULTS: Tofacitinib appears to show strong efficacy for numerous dermatologic conditions. Randomized controlled trial data is available for atopic dermatitis, alopecia areata, and plaque psoriasis. Case report and case series data is available for numerous other dermatologic conditions. CONCLUSION: While tofacitinib has a wide array of immunoregulatory properties, making it a possible candidate for treating many dermatologic conditions refractory to other treatments, further testing is needed to better characterize its efficacy and utility moving forward, as well as its safety and adverse effect profile.


Assuntos
Piperidinas/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/administração & dosagem , Alopecia em Áreas/tratamento farmacológico , Artrite Psoriásica/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Dermatite Atópica/tratamento farmacológico , Dermatologia , Humanos , Uso Off-Label , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Pediatr Dermatol ; 38(1): 324-326, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33247474

RESUMO

Antihistamine use for primary treatment of atopic dermatitis (AD) is not recommended, but current guidelines state that sedating antihistamines are favored over non-sedating antihistamines for relief of burdensome pruritus. We analyzed the National Ambulatory Medical Care Survey data to compare use of antihistamines between dermatologists and non-dermatologists. Overall, dermatologists are more likely to prescribe sedating than non-sedating antihistamines when compared to non-dermatologists (P < .001, δabs  = 0.45). Patients under 21 years old (P = .03, δabs  = 0.10) and Black patients (P < .001, δabs  = 0.19) were also more likely to receive sedating antihistamines than non-sedating antihistamines. These findings highlight the differential prescribing practices for atopic dermatitis among physicians.


Assuntos
Dermatite Atópica , Eczema , Adulto , Dermatite Atópica/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Prescrições , Prurido , Adulto Jovem
12.
Sci Adv ; 6(49)2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33277263

RESUMO

Therapeutic compression garments (TCGs) are key tools for the management of a wide range of vascular lower extremity conditions. Proper use of TCGs involves application of a minimum and consistent pressure across the lower extremities for extended periods of time. Slight changes in the characteristics of the fabric and the mechanical properties of the tissues lead to requirements for frequent measurements and corresponding adjustments of the applied pressure. Existing sensors are not sufficiently small, thin, or flexible for practical use in this context, and they also demand cumbersome, hard-wired interfaces for data acquisition. Here, we introduce a flexible, wireless monitoring system for tracking both temperature and pressure at the interface between the skin and the TCGs. Detailed studies of the materials and engineering aspects of these devices, together with clinical pilot trials on a range of patients with different pathologies, establish the technical foundations and measurement capabilities.

13.
JAMA Netw Open ; 3(12): e2029917, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315114

RESUMO

Importance: Patients with autoimmune disease and lung cancer pose a multidisciplinary treatment challenge, particularly with the advent of immunotherapy. However, the association between autoimmune disease and lung cancer survival is largely unknown. Objective: To determine the association between autoimmune disease and lung cancer survival. Design, Setting, and Participants: Retrospective cohort study between 2003 and 2019 at a single academic medical center (Northwestern University). A query of the Northwestern Medicine Enterprise Data Warehouse identified 349 patients with lung cancer and several autoimmune diseases. Types of lung cancers included small cell, adenocarcinoma, squamous cell carcinoma, non-small cell not otherwise specified, and large cell carcinoma. Autoimmune diseases included rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, myositis, and Sjögren syndrome. Inclusion criteria were biopsy-confirmed lung cancer, autoimmune diagnosis confirmed by a rheumatologist, and death or an encounter listed in the electronic medical record within 2 years of study end. A control group of patients with biopsy-proven lung cancer but without autoimmune disease was identified. Data analysis was conducted from March to July 2020. Exposure: Presence of autoimmune disease. Main Outcomes and Measures: Overall survival and progression-free survival in patients with autoimmune disease. The hypothesis was that patients with autoimmune disease would have worse progression-free survival and overall survival compared with patients in the control group. Results: Of the original 349 patients, 177 met inclusion criteria. Mean (SD) age at lung cancer diagnosis was 67.0 (10.0) years and 136 (76.8%) were women. Most common autoimmune diseases were rheumatoid arthritis (97 [54.8%]), systemic sclerosis (43 [24.3%]), and systemic lupus erythematous (15 [8.5%]). Most common lung cancers were adenocarcinoma (99 [55.9%]), squamous cell carcinoma (29 [16.4%]), and small cell lung cancer (17 [9.6%]). A total of 219 patients (mean [SD] age at diagnosis, 65.9 [4.1] years; 173 [79.0%]) were identified as having lung cancer without autoimmune disease and included in the control cohort. Compared with patients in the control group, patients with autoimmune disease experienced no difference in overall survival (log-rank P = .69). A total of 126 patients (69.5%) with autoimmune disease received standard of care vs 213 patients (97.3%) in the control group (P < .001). No individual autoimmune disease was associated with worse prognosis, even among patients with underlying interstitial lung disease. Conclusions and Relevance: Compared with institutional controls, patients with autoimmune disease experienced no difference in survival despite the fact that fewer patients in this group received standard-of-care treatment. No individual autoimmune disease was associated with worse prognosis. Future multicenter prospective trials are needed to further evaluate autoimmune disease and lung cancer survival.


Assuntos
Neoplasias Pulmonares , Pulmão/patologia , Idoso , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/terapia , Autoimunidade , Biópsia/métodos , Biópsia/estatística & dados numéricos , Comorbidade , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Pesquisa Interdisciplinar , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Estadiamento de Neoplasias , Noroeste dos Estados Unidos/epidemiologia , Prognóstico , Estudos Retrospectivos , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia , Padrão de Cuidado/organização & administração , Padrão de Cuidado/estatística & dados numéricos , Análise de Sobrevida
15.
Ann Surg ; 272(3): e246-e248, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32487803

RESUMO

OBJECTIVE: To assess public response to cancellations of elective surgeries following the American College of Surgeons' (ACS) recommendation on March 13. METHODS: We queried text comments from Reddit, a social media platform and the fifth most popular website in the United States. Comments were manually reviewed to assess for relevance to elective surgery in the United States during the global coronavirus outbreak, whether the text was written by a healthcare worker (HCW), whether the user was based in the United States, and whether the text documented cancellations of surgery, expected cancellations of surgery, or surgery ongoing after the ACS announcement. Analysis of overall sentiment and negativity in comment text was performed using the Valence Aware Dictionary for sEntiment Reasoning (VADER), a validated natural language processing tool previously used in studies of health behaviors using social media. Non-parametric tests were used for subgroup comparisons based on posting date and characteristics identified during manual review. RESULTS: Following manual review, 1272 comments were included for analysis. Overall sentiment among non-HCWs became significantly more negative following the ACS announcement (P = 0.037). Overall sentiment did not significantly differ between HCWs and non-HCWs prior to the ACS announcement (P = 0.98), but non-HCW sentiment became significantly more negative than HCW sentiment after the announcement (P = 0.027). Negativity scores in posts describing cancellations were significantly higher among posts written by non-HCWs than HCWs (P = 0.028). CONCLUSIONS: Cancellation of elective surgeries had an adverse emotional impact on non-HCWs. This finding highlights the importance of access to elective surgery to patients' emotional well-being.


Assuntos
COVID-19/epidemiologia , Controle de Doenças Transmissíveis/organização & administração , Procedimentos Cirúrgicos Eletivos , Opinião Pública , Mídias Sociais , COVID-19/prevenção & controle , COVID-19/transmissão , Humanos , Estados Unidos
16.
Oncotarget ; 11(21): 1953-1960, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32523650

RESUMO

INTRODUCTION: Roughly one third of new non-small cell lung cancer (NSCLC) is diagnosed at early stages. While lobectomy can improve mortality in this group, about 30-55% of patients will experience disease recurrence. Increased investigation into the factors affecting recurrence, particularly tumor molecular genetics such as EGFR mutations, is needed. MATERIALS AND METHODS: We conducted a single-center retrospective study of 282 patients with early or locally advanced lung adenocarcinoma, with or without EGFR mutations, who underwent definitive therapy. We then assessed recurrence, stage at recurrence, time to recurrence and progression-free survival (PFS). RESULTS: We identified 142 patients with EGFR-mutated and 140 EGFR-wildtype lung adenocarcinoma. Overall progression between groups was equivalent at ~40% at 5 years; no difference in PFS was observed at any time-point. However, among those who recurred, EGFR-mutated lung cancer had increased rates of metastatic recurrence compared to EGFR-wildtype disease (97% vs 68%, p = 0.007). CONCLUSIONS: EGFR-mutated disease may be associated with a higher risk of metastatic recurrence. Molecular testing may be a promising tool for risk stratification and surveillance following definitive management for early stage disease. Future prospective, multi-center cohort studies are needed to confirm these findings and improve our understanding of how EGFR mutation contributes to prognosis and clinical outcomes.

17.
JAMA Dermatol ; 156(5): 521-528, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32236497

RESUMO

Importance: First-line systemic therapy for morphea includes methotrexate with or without systemic corticosteroids. When this regimen is ineffective, not tolerated, or contraindicated, a trial of mycophenolate mofetil (MMF) or mycophenolic acid (MPA)-referred to herein as mycophenolate-is recommended; however, evidence to support this recommendation remains weak. Objective: To evaluate the effectiveness and tolerability of mycophenolate for the treatment of morphea. Design, Setting, and Participants: A retrospective cohort study was conducted from January 1, 1999, to December 31, 2018, among 77 patients with morphea from 8 institutions who were treated with mycophenolate. Main Outcomes and Measures: The primary outcome was morphea disease activity, severity, and response at 0, 3 to 6, and 9 to 12 months of mycophenolate treatment. A secondary outcome was whether mycophenolate was a well-tolerated treatment of morphea. Results: There were 61 female patients (79%) and 16 male patients (21%) in the study, with a median age at disease onset of 36 years (interquartile range, 16-53 years) and median diagnostic delay of 8 months (interquartile range, 4-14 months). Generalized morphea (37 [48%]), pansclerotic morphea (12 [16%]), and linear morphea of the trunk and/or extremities (9 [12%]) were the most common subtypes of morphea identified. Forty-one patients (53%) had an associated functional impairment, and 49 patients (64%) had severe disease. Twelve patients received initial treatment with mycophenolate as monotherapy or combination therapy and 65 patients received mycophenolate after prior treatment was ineffective (50 of 65 [77%]) or poorly tolerated (21 of 65 [32%]). Treatments prior to mycophenolate included methotrexate (48 of 65 [74%]), systemic corticosteroids (42 of 65 [65%]), hydroxychloroquine (20 of 65 [31%]), and/or phototherapy (14 of 65 [22%]). After 3 to 6 months of mycophenolate treatment, 66 of 73 patients had stable (n = 22) or improved (n = 44) disease. After 9 to 12 months of treatment, 47 of 54 patients had stable (n = 14) or improved (n = 33) disease. Twenty-seven patients (35%) achieved disease remission at completion of the study. Treatments received in conjunction with mycophenolate were frequent. Mycophenolate was well tolerated. Gastrointestinal adverse effects were the most common (24 [31%]); cytopenia (3 [4%]) and infection (2 [3%]) occurred less frequently. Conclusions and Relevance: This study suggests that mycophenolate is a well-tolerated and beneficial treatment of recalcitrant, severe morphea.


Assuntos
Imunossupressores/administração & dosagem , Ácido Micofenólico/administração & dosagem , Esclerodermia Localizada/tratamento farmacológico , Adolescente , Corticosteroides/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Hidroxicloroquina , Imunossupressores/efeitos adversos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
18.
J Dermatolog Treat ; : 1-14, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32279586

RESUMO

Purpose: Anakinra (Kineret®) is an interleukin-1 receptor antagonist (IL-1Ra) FDA approved for use in rheumatoid arthritis and in neonatal-onset multisystem inflammatory disease (NOMID). It has been used off-label for a variety of dermatologic conditions. A review of the available studies and cases of these off-label uses would be valuable to the dermatologist considering alternative treatments for these oftentimes poorly studied conditions.Materials and methods: The PubMed/MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov databases were searched with the term 'anakinra.' Results were manually screened to identify published data on off-label uses of anakinra in dermatologic conditions and systemic conditions with prominent dermatologic manifestations.Results: Anakinra appears to show efficacy for numerous dermatologic conditions, with the strongest evidence for hidradenitis suppurativa, Bechet's disease, Muckle-Wells syndrome, and SAPHO syndrome. Case reports and case series data are available for numerous other dermatologic conditions.Conclusion: Anakinra is a potential option for patients with certain difficult-to-treat dermatologic diseases, given its relatively benign adverse effect profile and its effectiveness in a wide array of conditions. Overall, anakinra appears to be a promising option in the treatment of numerous dermatologic inflammatory conditions refractory to first line therapies, but further and higher-quality data is needed to clarify its therapeutic role.

19.
J Dermatolog Treat ; 31(2): 131-140, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30935262

RESUMO

Purpose: Apremilast is a phosphodiesterase-4 inhibitor FDA approved for psoriatic arthritis and moderate to severe plaque psoriasis. In recent years, multiple studies have suggested other potential uses for apremilast in dermatology. A summary of these various studies will be a valuable aid to dermatologists considering apremilast for an alternative indication.Materials and methods: The PubMed/MEDLINE and ClinicalTrials.gov databases were queried with the term 'apremilast,' with results manually screened to identify published data on off-label uses of apremilast. The article was structured by the quality of evidence available.Results: Apremilast use in dermatology beyond plaque psoriasis and psoriatic arthritis is frequently described in the literature, with a mixture of positive and negative results. Randomized controlled data is available for Behçet's disease, hidradenitis suppurativa, nail/scalp/palmoplantar psoriasis, alopecia areata, and atopic dermatitis.Conclusion: The relatively safe adverse effect profile of apremilast and its broad immunomodulatory characteristics may make it a promising option in the future for patients with difficult to treat diseases in dermatology, refractory to first line therapies, but further studies will be necessary to clarify its role.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Talidomida/análogos & derivados , Alopecia em Áreas/tratamento farmacológico , Anti-Inflamatórios não Esteroides/efeitos adversos , Síndrome de Behçet/tratamento farmacológico , Hidradenite Supurativa/tratamento farmacológico , Humanos , Náusea/etiologia , Uso Off-Label , Ensaios Clínicos Controlados Aleatórios como Assunto , Talidomida/efeitos adversos , Talidomida/uso terapêutico
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