RESUMO
BACKGROUND: UK guidelines for managing adults with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), published by the British Association of Dermatologists (BAD) in 2016, outline a set of audit standards. OBJECTIVES: To audit current management of SJS/TEN in adults against standards in the BAD guidelines. METHODS: BAD members were invited to submit data on five consecutive adults with SJS/TEN per department over an 8-week period in 2022. RESULTS: Thirty-nine dermatology centres in the UK (29%) participated, and data for 147 adults with SJS/TEN were collected. Within 24â h of the diagnosis being made or suspected, the following were documented, per 147 submitted cases: Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) for 76 (52%), list of medications for 113 (77%) and timelines for commencement/alterations of medications for 104 (71%). The initial assessment was documented of the eyes by an ophthalmologist in 71 (48%), of the mouth in 130 (88%), of the genital skin in 103 (70%) and of the urinary tract in 93 (63%). During the first 10â days after a suspected or confirmed diagnosis of SJS/TEN, daily assessments of the mouth were documented in 26 of 147 cases (18%), of the eyes in 12 (8%), and of the urinary tract and genital skin in 14 (10%). At discharge, a drug was declared to be the cause of SJS/TEN for 130 of 147 cases (88%), while 9 (6%) were thought to be secondary to infection. Eleven of 147 (8%) had no response to this question. Documentation regarding advice was present on avoidance of the culprit drug in 76 of 130 declared SJS/TEN cases (58%), and on requesting a MedicAlert® bracelet/amulet in 9 of the 147 cases (6%). CONCLUSIONS: This audit suggests that a clinical review checklist might be needed to enable colleagues to maintain standards outlined in the guidelines, including documentation of SCORTEN, daily assessments of mucosal areas, and advice to avoid culprit drug(s) and to request a MedicAlert® bracelet/amulet.
Assuntos
Guias de Prática Clínica como Assunto , Síndrome de Stevens-Johnson , Síndrome de Stevens-Johnson/terapia , Síndrome de Stevens-Johnson/diagnóstico , Humanos , Adulto , Reino Unido , Masculino , Feminino , Pessoa de Meia-Idade , Auditoria Clínica , Idoso , Índice de Gravidade de Doença , Adulto Jovem , Dermatologia/normas , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Erosive pustular dermatosis of the scalp (EPDS) is a chronic condition characterized by erosive plaques and subsequent scarring alopecia as a result of local trauma or inflammation. A number of therapeutic approaches have been described in the literature but there is no consensus of opinion on optimal treatment of the disease. OBJECTIVES: To provide evidence-based recommendations for topical and systemic treatment of adult patients with EPDS by performing a systematic review. METHODS: The MEDLINE, MEDLINE In-Process, Embase and Cochrane databases were searched from inception to 26 June 2019 in accordance with the PRISMA guidelines for studies involving adult patients treated for EPDS with at least one reported response to treatment. The study was registered on PROSPERO. Texts were reviewed independently by two authors. The risk of bias and quality of the studies were assessed using the Quality Appraisal Checklist for Case Series Studies. RESULTS: In total 75 studies were included, involving 168 patients. Many treatments have been reported in the literature, with varying degrees of therapeutic success. The results were highly heterogeneous and methodological quality was very low. We were unable to perform a meta-analysis on the data. CONCLUSIONS: The limited available evidence supports use of topical corticosteroids, with or without oral zinc, followed by maintenance therapy with topical calcineurin inhibitors as being effective in managing this condition. Topical photodynamic therapy is also potentially beneficial in the management of EPDS. Prospective, comparative, randomized controlled trials are required in order to provide further evidence to guide treatment.
Assuntos
Dermatoses do Couro Cabeludo , Couro Cabeludo , Alopecia , Inibidores de Calcineurina , Humanos , Estudos Prospectivos , Dermatoses do Couro Cabeludo/tratamento farmacológicoAssuntos
Neoplasias do Ânus , Doença de Bowen , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Lesões Intraepiteliais Escamosas , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Doença de Bowen/diagnóstico , Doença de Bowen/terapia , Doença de Bowen/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/patologia , DermatologistasRESUMO
Multiple biologic treatments are licensed for psoriasis. The lack of head-to-head randomized controlled trials makes choosing between them difficult for patients, clinicians, and guideline developers. To establish their relative efficacy and tolerability, we searched MEDLINE, PubMed, Embase, and Cochrane for randomized controlled trials of licensed biologic treatments for skin psoriasis. We performed a network meta-analysis to identify direct and indirect evidence comparing biologics with one another, methotrexate, or placebo. We combined this with hierarchical cluster analysis to consider multiple outcomes related to efficacy and tolerability in combination for each treatment. Study quality, heterogeneity, and inconsistency were evaluated. Direct comparisons from 41 randomized controlled trials (20,561 participants) were included. All included biologics were efficacious compared with placebo or methotrexate at 3-4 months. Overall, cluster analysis showed adalimumab, secukinumab, and ustekinumab were comparable in terms of high efficacy and tolerability. Ixekizumab and infliximab were differentiated by very high efficacy but poorer tolerability. The lack of longer term controlled data limited our analysis to short-term outcomes. Trial performance may not equate to real-world performance, and so results need to be considered alongside real-world, long-term safety and effectiveness data. These data suggest that it is possible to discriminate between biologics to inform clinical practice and decision making (PROSPERO 2015:CRD42015017538).
Assuntos
Fatores Biológicos/uso terapêutico , Terapia Biológica/métodos , Psoríase/tratamento farmacológico , Humanos , Metanálise em RedeRESUMO
A comprehensive evaluation of the risk of serious infections in biologic therapies for psoriasis is lacking. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies reporting serious infections in people taking any licensed biologic therapy for psoriasis compared with those taking placebo, nonbiologic therapy, or other biologic therapies. The quality of the studies was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. No significant heterogeneity was detected in data from 32 RCTs (n = 13,359 participants) and one cohort study (n = 4,993 participants). In adults, low- to very-low-quality RCT data showed no significant difference between any biologic therapy and placebo at weeks 12-16 (overall pooled Peto odds ratio = 0.71, 95% confidence interval = 0.36-1.41) and weeks 20-30 (odds ratio = 2.27, 95% confidence interval = 0.45-11.49). No significant differences were found in any of the other comparisons in underpowered RCT data. Prospective cohort study data of low quality suggests that only adalimumab (adjusted hazard ratio [adjHR] = 2.52, 95% confidence interval = 1.47-4.32) was associated with a significantly higher risk of serious infection compared with retinoid and/or phototherapy in adults. No association between biologic therapies and serious infections in patients with psoriasis who were eligible for RCTs was detected. Further observational studies are needed to inform the uncertainty around this risk in the real world.
Assuntos
Produtos Biológicos/uso terapêutico , Infecções/complicações , Psoríase/complicações , Psoríase/terapia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Terapia Biológica , Humanos , Metotrexato/uso terapêutico , Razão de Chances , Fototerapia/métodos , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Retinoides/uso terapêutico , Fatores de Risco , Fatores de Tempo , Ustekinumab/uso terapêuticoAssuntos
Psoríase , Terapia Biológica , Humanos , Metanálise em Rede , Psoríase/tratamento farmacológicoRESUMO
Two diastereomeric analogues of ring C of nisin incorporating a novel norlanthionine residue have been synthesized via a triply orthogonal protecting group strategy. A full structural study was carried out by NMR, which elucidated the conformational properties of the two peptides and enabled the identity of each diastereoisomer to be proposed.
Assuntos
Alanina/análogos & derivados , Alanina/química , Hidrocarbonetos Aromáticos com Pontes/química , Peptídeos Cíclicos/síntese química , Sulfetos/química , Estrutura Molecular , Nisina/química , Peptídeos Cíclicos/química , Conformação Proteica , EstereoisomerismoRESUMO
Synthetic approaches to the lantibiotics, a family of thioether-bridged antimicrobial peptides, require flexible synthetic routes to a variety of orthogonally protected derivatives of lanthionine 1. The most direct approaches to lanthionine involve the reaction of cysteine with an alanyl beta-cation equivalent. Several possibilities exist for the alanyl beta-cation equivalent, including direct activation of serine under Mitsunobu conditions: however, the low reactivity of sulfur nucleophiles in the Mitsunobu reaction has previously precluded its use in the synthesis of the lantibiotics. We report here a new approach to the synthesis of protected lanthionine, using a novel variant of the Mitsunobu reaction in which catalytic zinc tartrate is used to enhance the nucleophilicity of the thiol. In the course of these studies, we have also demonstrated that the synthesis of lanthionine from trityl-protected beta-iodoalanines is prone to rearrangement, via an aziridine, to give predominantly trityl-protected alpha-iodo-beta-alanines, and hence norlanthionines, as the major products.