RESUMO
BACKGROUND: Rituximab and mycophenolate mofetil are used to treat pemphigus vulgaris, but they have not been adequately compared in clinical trials. METHODS: In a randomized, controlled trial, we assigned patients with moderate-to-severe pemphigus vulgaris in a 1:1 ratio to receive intravenous rituximab (1000 mg on days 1, 15, 168, and 182) or oral mycophenolate mofetil (2 g per day), in addition to an oral glucocorticoid administered on the same tapering schedule in the two groups. The primary end point was sustained complete remission at week 52, defined as the healing of lesions with no new active lesions, as reflected by a Pemphigus Disease Area Index (PDAI) activity score of 0 (on a scale of 0 to 250, with higher scores indicating greater disease severity), for at least 16 weeks without the use of glucocorticoids. Secondary end points were the cumulative dose of glucocorticoids, the number of disease flares, and the change from baseline in the score on the Dermatology Life Quality Index (DLQI; scores range from 0 to 30, with higher scores indicating greater impairment). RESULTS: Of the 135 patients who underwent randomization, 67 were assigned to receive rituximab and 68 to receive mycophenolate mofetil. The primary outcome was assessed in the modified intention-to-treat population: 62 patients in the rituximab group and 63 in the mycophenolate mofetil group. The median PDAI activity scores at baseline were 22.7 in the rituximab group and 18.3 in the mycophenolate mofetil group. At week 52, sustained complete remission was observed in 25 patients (40%) in the rituximab group and in 6 (10%) in the mycophenolate mofetil group (difference, 31 percentage points; 95% confidence interval [CI], 15 to 45; P<0.001). The mean cumulative glucocorticoid dose during the 52-week treatment period was 3545 mg in the rituximab group and 5140 mg in the mycophenolate mofetil group (difference, -1595 mg; 95% CI, -2838 to -353; P<0.001). There were 6 disease flares in the rituximab group and 44 in the mycophenolate mofetil group (adjusted rate ratio, 0.12; 95% CI, 0.05 to 0.29; P<0.001). The mean change in DLQI score was -8.87 points and -6.00 points, respectively (difference, -2.87 points; 95% CI, -4.58 to -1.17; P = 0.001). Serious adverse events occurred in 15 of 67 patients (22%) in the rituximab group and in 10 of 68 (15%) in the mycophenolate mofetil group. CONCLUSIONS: Rituximab was superior to mycophenolate mofetil in producing sustained complete remission at 52 weeks in patients with pemphigus vulgaris. Rituximab resulted in a greater reduction in glucocorticoid use than mycophenolate mofetil, but more patients in the rituximab group had serious adverse events. Further trials are needed to determine the comparative efficacy and safety of rituximab and mycophenolate mofetil beyond 52 weeks of treatment. (Funded by F. Hoffmann-La Roche; PEMPHIX ClinicalTrials.gov number, NCT02383589.).
Assuntos
Ácido Micofenólico/uso terapêutico , Pênfigo/tratamento farmacológico , Rituximab/uso terapêutico , Administração Oral , Adulto , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Indução de Remissão , Rituximab/efeitos adversosRESUMO
BACKGROUND: Pemphigus vulgaris (PV) is characterized by autoantibodies targeting keratinocytes adhesion proteins desmoglein (Dsg) 1 and 3, and by the HLA-DRB1-0402 predisposition allele. Treatment using rituximab (RTX) combined with short-term corticosteroids (CS) allows disease control and long-lasting remission. OBJECTIVE: The principal aim of this study is to evaluate the impact of RTX on the circulating subpopulations of Dsg-3-specific T lymphocytes that specifically regulate B cell responses: follicular helper (Tfh) and follicular regulatory T (Tfr) lymphocytes. METHODS: Using the HLA-DRB1-0402 tetramer loaded with the Dsg-3 immunodominant peptide, we analysed by flow cytometry the frequency, the polarisation and the activation status of blood Dsg-3-specific follicular T cell populations at baseline, Month 6 and long-term follow-up (Month 60-90) from PV patients. RESULTS: At baseline, we observed a predominance of Tfh1* and Tfh17 subsets and an underrepresentation of the Tfh2 subset among autoreactive Dsg-3-specific Tfh cells as compared with non-autoreactive Tfh cells. RTX treatment induced a decrease of autoreactive Tfh cells with no effect on their polarisation during patients' follow-up. In parallel, we observed the emergence of a Dsg-3-specific Tfr subpopulation with a significant overexpression of the surface activation markers PD1, ICOS, and CD25 that was not observed at the surface of autoreactive Tfh and non-autoreactive Tfr cells of the same PV patients. In contrast, a very few Dsg-3 specific Tfr cells were observed in PV patients treated with CS alone. CONCLUSION: Here we show that the emergence of circulating autoreactive Dsg-3-specific Tfr cells is associated with the long-term efficacy of RTX in PV patients.
RESUMO
BACKGROUND: Interest in the use of omalizumab to treat bullous pemphigoid (BP) in the event of resistance or contraindication to conventional therapies is currently based on limited evidence. OBJECTIVES: To assess the effectiveness and safety of omalizumab in BP and to identify predictive factors in response to treatment. METHODS: We conducted a French national multicentre retrospective study including patients with a confirmed diagnosis of BP treated with omalizumab after failure of one or several treatment lines. We excluded patients with clinically atypical BP, as per Vaillant's criteria. The criteria for clinical response to omalizumab were defined according to the 2012 international consensus conference. Anti-BP180-NC16A IgE enzyme-linked immunosorbent assay was performed on sera collected before initiating omalizumab, when available. RESULTS: Between 2014 and 2021, 100 patients treated in 18 expert departments were included. Median age at diagnosis was 77â years (range 20-98). Complete remission (CR) was achieved in 77% of patients, and partial remission in an additional 9%. CR was maintained 'off therapy' in 11.7%, 'on minimal therapy' in 57.1%, and 'on non-minimal therapy' in 31.2%. Median time to CR was 3â months (range 2.2-24.5). Relapse rate was 14%, with a median follow-up time of 12â months (range 6-73). Adverse events occurred in four patients. CR was more frequently observed in patients with an increased serum baseline level of anti-BP180-NC16A IgE (75% vs. 41%; P = 0.011). Conversely, urticarial lesions, blood total IgE concentration or eosinophil count were not predictive of CR. Patients with an omalizumab dosage > 300â mg every 4 weeks showed a similar final outcome to those with a dosage ≤ 300â mg every 4 weeks, but control of disease activity [median 10â days (range 5-30) vs. 15â days (range 10-60); P < 0.001] and CR [median 2.4â months (range 2.2-8.2) vs. 3.9â months (range 2.3-24.5); P < 0.001] were achieved significantly faster. CONCLUSIONS: We report the largest series to date of BP treated by omalizumab and confirm its effectiveness and safety in this indication. Serum baseline level of anti-BP180-NC16A IgE may predict response to treatment.
Assuntos
Penfigoide Bolhoso , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Penfigoide Bolhoso/diagnóstico , Colágeno Tipo XVII , Omalizumab/uso terapêutico , Estudos Retrospectivos , Colágenos não Fibrilares , Autoantígenos , Imunoglobulina E , AutoanticorposRESUMO
INTRODUCTION: Linear IgA dermatosis (LAD) is a rare subepidermal autoimmune bullous disease (AIBD) defined by predominant or exclusive immune deposits of immunoglobulin A at the basement membrane zone of skin or mucous membranes. This disorder is a rare, clinically and immunologically heterogeneous disease occurring both in children and in adults. The aim of this project is to present the main clinical features of LAD, to propose a diagnostic algorithm and provide management guidelines based primarily on experts' opinion because of the lack of large methodologically sound clinical studies. METHODS: These guidelines were initiated by the European Academy of Dermatology and Venereology (EADV) Task Force Autoimmune Bullous Diseases (AIBD). To achieve a broad consensus for these S2k consensus-based guidelines, a total of 29 experts from different countries, both European and non-European, including dermatologists, paediatric dermatologists and paediatricians were invited. All members of the guidelines committee agreed to develop consensus-based (S2k) guidelines. Prior to a first virtual consensus meeting, each of the invited authors elaborated a section of the present guidelines focusing on a selected topic, based on the relevant literature. All drafts were circulated among members of the writing group, and recommendations were discussed and voted during two hybrid consensus meetings. RESULTS: The guidelines summarizes evidence-based and expert opinion-based recommendations (S2 level) on the diagnosis and treatment of LAD. CONCLUSION: These guidelines will support dermatologists to improve their knowledge on the diagnosis and management of LAD.
Assuntos
Dermatose Linear Bolhosa por IgA , Humanos , Dermatose Linear Bolhosa por IgA/diagnóstico , Dermatose Linear Bolhosa por IgA/tratamento farmacológico , Europa (Continente) , Dermatologia/normasRESUMO
Alopecia areata (AA), especially very severe types, causes patients severe psychological and social distress. Although baricitinib alone has been shown to be effective in conferring complete hair regrowth (HR) in severe AA [Severity of Alopecia Tool (SALT) score 50-94], it gave poor therapeutic results in very severe AA (SALT score ≥ 95). Methotrexate alone is similarly ineffective, but in a recent study of patients with areata totalis or universalis, low-dose prednisone with methotrexate gave a 20% rate of HR, and was effective and well tolerated. In our study of baricitinib 4â mg + prednisone 20â mg per day tapered over 3â months to treat eight women with very severe AA, seven of eight achieved complete HR (SALT score 0) and one had partial HR (SALT score 30).
Assuntos
Alopecia em Áreas , Humanos , Feminino , Alopecia em Áreas/tratamento farmacológico , Alopecia em Áreas/induzido quimicamente , Prednisona/uso terapêutico , Metotrexato/uso terapêutico , Corticosteroides/uso terapêuticoRESUMO
BACKGROUND: Little is known about phototype and the response to systemic treatment in psoriasis. OBJECTIVES: To assess the characteristics of psoriasis, the therapeutic choice and its efficacy according to phototype. METHODS: We included patients from the PsoBioTeq cohort initiating a first biologic. Patients were classified according to their phototype. The evaluation included disease characteristics, choice of the initial biologic and therapeutic response at 12â months based on 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) and Dermatology Life Quality Index (DLQI) 0/1. RESULTS: Of the 1400 patients included, 423 (30.2%), 904 (64.6%) and 73 (5.2%) were in the phototype I-II, III-IV and V-VI groups, respectively. The V-VI group had a higher initial DLQI, and more frequently initiated ustekinumab. Patients in the V-VI group maintained the initial biologic prescribed as did the other phototype groups, even though the proportion of patients reaching PASI 90 and DLQI 0/1 at 12â months was lower in this group than the other groups. CONCLUSIONS: Patient phototype seems associated with quality of life and choice of the initial biologic in psoriasis. The phototype V-VI group less frequently switched treatments than did the other groups when the response was not efficient.
Assuntos
Produtos Biológicos , Psoríase , Humanos , Qualidade de Vida , Ustekinumab/uso terapêutico , Psoríase/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Adverse pregnancy outcomes (APO) occur in 35% of patients with pemphigoid gestationis (PG). No biological predictor of APO has been established yet. OBJECTIVES: To assess a potential relationship between the occurrence of APO and the serum value of anti-BP180 antibodies at the time of PG diagnosis. METHODS: Multicentre retrospective study conducted from January 2009 to December 2019 in 35 secondary and tertiary care centres. INCLUSION CRITERIA: (i) diagnosis of PG according to clinical, histological and immunological criteria, (ii) ELISA measurement of anti-BP180 IgG antibodies determined at the time of PG diagnosis with the same commercial kit and (iii) obstetrical data available. RESULTS: Of the 95 patients with PG included, 42 had one or more APO, which mainly corresponded to preterm birth (n = 26), intrauterine growth restriction (IUGR) (n = 18) and small weight for gestational age at birth (n = 16). From a ROC curve, we identified a threshold of 150 IU ELISA value as the most discriminating to differentiate between patients with or without IUGR, with 78% sensitivity, 55% specificity, 30% positive and 91% negative predictive value. The threshold >150 IU was confirmed using a cross-validation based on bootstrap resampling, which showed that the median threshold was 159 IU. Upon adjusting for oral corticosteroid intake and main clinical predictors of APO, an ELISA value of >150 IU was associated with the occurrence of IUGR (OR = 5.11; 95% CI: 1.48-22.30; p = 0.016) but not with any other APO. The combination of blisters and ELISA values higher than 150 IU led to a 2.4-fold higher risk of all-cause APO (OR: 10.90; 95% CI: 2.33-82.3) relative to patients with blisters but lower values of anti-BP180 antibodies (OR of 4.54; 95% CI 0.92-34.2). CONCLUSION: These findings suggest that anti-BP180 antibody ELISA value in combination with clinical markers is helpful in managing the risk of APO, in particular IUGR, in patients with PG.
Assuntos
Penfigoide Gestacional , Penfigoide Bolhoso , Nascimento Prematuro , Gravidez , Feminino , Humanos , Recém-Nascido , Penfigoide Gestacional/diagnóstico , Estudos Retrospectivos , Penfigoide Bolhoso/diagnóstico , Vesícula , Resultado da Gravidez , Colágenos não Fibrilares , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Autoantígenos , AutoanticorposRESUMO
BACKGROUND: Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans. OBJECTIVES: These guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included. RESULTS: Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients. CONCLUSIONS: These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.
Assuntos
Síndromes Paraneoplásicas do Sistema Nervoso , Síndromes Paraneoplásicas , Animais , Ratos , Doenças Autoimunes , Neoplasias/complicações , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/terapia , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Sociedades MédicasRESUMO
BACKGROUND: A high level of anti-BP180 antibodies on enzyme-linked immunosorbent assay and a persistent positive direct immunofluorescence at the end of treatment (immunologic tests, [ITs]) are predictors of relapse after treatment cessation (TC) in patients with bullous pemphigoid. OBJECTIVE: To evaluate the real-life impact of the immunologic-based decision of TC on the 3- and 6-month relapse rates after TC in bullous pemphigoid. METHODS: Retrospective multicentric study included patients followed almost 6 months after TC. Patients were classified according to whether the TC decision was in accordance with the results of ITs performed during the 3 months before TC, despite the results of ITs or without ITs performed. RESULTS: We included 238 patients. Three months after TC, 36 patients showed relapse: 14 of 95 patients with TC in accordance with IT results (14.7%); 5 of 21 with TC despite ITs (23.8%); and 17 of 122 with TC without ITs (13.9%; P = .5). Six months after TC, the relapse rate was 18.9%, 28.6%, and 18.9% (P = .56), respectively, in the 3 groups. LIMITATIONS: The retrospective design and the limited follow up. CONCLUSION: In real-life practice, in bullous pemphigoid, the 3- and 6-month relapse rates were not significantly reduced with TC decision based on results of ITs as compared with a classic clinical-based decision.
Assuntos
Penfigoide Bolhoso , Autoanticorpos , Autoantígenos , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Testes Imunológicos , Colágenos não Fibrilares , Penfigoide Bolhoso/tratamento farmacológico , Recidiva , Estudos Retrospectivos , Suspensão de TratamentoRESUMO
An improved understanding of the impact of skin cancer on patients' daily life may optimize disease management. This questionnaire survey of adult patients in real-world settings aimed to assess patient perception of the diagnosis announcement, and the impact of the diagnosis on the patients' professional and personal life. Data from 355 patients with melanoma and 320 patients with basal cell carcinoma (BCC) were analysed. Melanoma significantly impacted the couple, and sexual relationships, as well as family and social life, and reduced the patient's libido more significantly than did BCC (all p < 0.05). Melanoma and BCC significantly impacted the patients' professional and personal lives. The word "cancer" used for a BCC announcement has a high anxiety-producing meaning for the patient. The announcement of each skin cancer should be made during a dedicated consultation, with more time devoted to the patient and with specific empathy, in order to improve reassurance of the patient.
Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Melanoma , Neoplasias Cutâneas , Adulto , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Humanos , Melanoma/diagnóstico , Melanoma/patologia , Percepção , Qualidade de Vida , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologiaRESUMO
Drug survival reflects treatment effectiveness and safety in real life. There is limited data on the variation of drug survival with the availability of systemic treatments with additional biological disease-modifying antirheumatic drugs (bDMARDs) or synthetic disease-modifying antirheumatic drugs (sDMARDs). The aim of this study was to determine whether the increasing number of available systemic treatments for psoriasis affects drug survival over time. Patients were selected from the PsoBioTeq cohort, a French prospective observational cohort enrolling patients with moderate to severe psoriasis. All patients initiating a first bDMARD or sDMARD were included. The primary outcome was comparison of drug survival over time. A multivariate Cox proportional hazard ratio model was computed. A total of 1,866 patients were included; 739 females (39%), median age 47 years. In the multivariate Cox model, no association was found between the calendar year of initiation and drug survival (hazard ratio) overlapping from 0.80 (0.42-1.52) to 1.17 (0.64-2.17), p = 0.633). In conclusion, drug survival in psoriasis is not affected by the year of initiation.
Assuntos
Antirreumáticos , Produtos Biológicos , Psoríase , Antirreumáticos/uso terapêutico , Fatores Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Talidomida/efeitos adversos , Talidomida/análogos & derivadosRESUMO
Paediatric psoriasis has been associated with school absenteeism, limitation of physical activities, psychiatric disorders and, in the longer term, with sexual dysfunction and addictions. This raises the hypothesis that childhood onset psoriasis may affect patients' educational development, and further social and professional outcomes. This study evaluated the relationship between childhood onset psoriasis and patients' educational and socioeconomic characteristics, and the development of addictions in adulthood. This cross-sectional ancillary study captured patients' characteristics at baseline in the French PSOBIOTEQ registry. Data in adulthood included: educational (baccalaureate) and socioeconomic (working activity) groups, smoking status (self-reporting of being a current smoker vs past smoker or non-smoker), alcohol consumption (defined as at least 1 glass of alcoholic beverage per day), and living conditions (alone/family/social institutions; child at home). A total of 1,960 patients were included, of whom 26.2% had childhood onset psoriasis. In multivariate analyses, childhood onset psoriasis was associated with smoker status (p = 0.02). No association was observed with educational level, working activity, living conditions, or alcohol consumption. This study provides reassuring data overall with regard to the impact of childhood onset psoriasis on major social outcomes. Evidence for some association with addictive behaviours paves the way for larger prospective studies assessing in depth the social and educational impact of this disease.
Assuntos
Comportamento Aditivo , Psoríase , Adulto , Comportamento Aditivo/epidemiologia , Criança , Estudos Transversais , Escolaridade , Humanos , Estudos Prospectivos , Psoríase/diagnóstico , Psoríase/epidemiologia , Fatores SocioeconômicosRESUMO
OBJECTIVE: To deep sequence the TRIM33 gene in tumours from patients with cancer-associated anti-TIF1γ autoantibody-positive dermatomyositis (DM) as TRIM33 somatic mutations in tumours may trigger this auto-immune disease. METHODS: Next generation sequencing of tumour DNA samples from patients with cancer-associated anti-TIF1γ autoantibody-positive DM. Fourteen tumours from 13 anti-TIF1γ autoantibody-positive DM individuals were sequenced along with two control tumours from non-DM individuals. RESULTS: Fourteen probable somatic variants from four tumours were identified in the TRIM33 gene. CONCLUSION: These results are in accordance with the previous report of Pinal-Fernandez et al. and support the hypothesis of a role of TRIM33 gene mutations in the pathophysiology of anti-TIF1γ autoantibody-positive DM.
Assuntos
DNA/genética , Dermatomiosite/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Neoplasias/complicações , Fatores de Transcrição/genética , Idoso , Análise Mutacional de DNA , Dermatomiosite/etiologia , Dermatomiosite/metabolismo , Feminino , Humanos , Masculino , Fatores de Transcrição/metabolismo , Dedos de ZincoRESUMO
BACKGROUND: No long-term maintenance therapy has been tested in patients with seborrheic dermatitis (SD). OBJECTIVE: We sought to compare the efficacy and tolerance of tacrolimus 0.1% ointment versus ciclopiroxolamine 1% cream as maintenance therapy for severe SD. METHODS: This double-blind randomized controlled study was conducted from 2014 to 2017 in 5 Dermatology Departments and 15 dermatology practices in France. Consecutive patients with severe and chronic facial SD were included. Patients were initially treated with desonide 0.05% cream twice daily for 7 days. Patients cleared after this open phase were randomized to receive tacrolimus 0.1% or ciclopiroxolamine 1% cream 2 times a week 24 weeks. The primary endpoint was disease-free-duration, defined as the time from randomization to first relapse. RESULTS: One hundred fourteen patients were randomized (tacrolimus, n = 57; ciclopiroxolamine, n = 57). Twelve patients relapsed in the tacrolimus group after a median delay of 91.5 days (range 15-195 days) versus 23 patients in the ciclopiroxolamine group (median delay, 27 days [range 13-201 days]). Comparison of disease-free duration curves showed that patients in the tacrolimus group had a longer duration of complete remission than those in the ciclopiroxolamine group (P = .018), corresponding to a hazard ratio of relapse of 0.44 (95% confidence interval 0.22-0.89; P = .022). LIMITATIONS: The theoretical sample size was not reached. CONCLUSION: Tacrolimus 0.1% is more effective than ciclopiroxolamine 1% as maintenance therapy for patients with facial SD.
Assuntos
Ciclopirox/administração & dosagem , Dermatite Seborreica/tratamento farmacológico , Dermatoses Faciais/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Tacrolimo/administração & dosagem , Adulto , Dermatite Seborreica/diagnóstico , Método Duplo-Cego , Esquema de Medicação , Dermatoses Faciais/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Obesity is associated with an increased risk of psoriasis. OBJECTIVE: In this study, we examined whether body mass index (BMI) is taken into account when choosing first-line biologic therapy for psoriasis. METHODS: In this cohort study, we compared obese (BMI ≥30 kg/m2) and non-obese patients for the first-line biologic therapy prescribed, its survival, reasons for discontinuation, therapy optimization, co-prescription of methotrexate and factors associated with long drug survival. RESULTS: A total of 931 patients were included: 594 (64%) were male, median age was 46 years (interquartile range 36-56). The most-prescribed biologic agents as first-line treatment were adalimumab (ADA; 42.7%), ustekinumab (UST; 29.9%) and etanercept (ETA; 22.9%); only frequency of infliximab (IFX) prescription differed between groups. Drug survival was significantly shorter for obese than non-obese patients (p < 2.10-4) and was worse for obese than non-obese patients for UST (p = 0.009) and ETA (p = 0.02), with no difference for ADA (p = 0.11). The main reason for discontinuation was primary inefficacy (62%), which was more frequent in obese than non-obese patients. The cumulative incidence of optimization did not significantly differ between the groups, except for ADA (SHR 1.91, 95% CI [1.23-2.96], p = 0.005). On multivariate analysis, risk of discontinuation was associated with only ETA as first-line biologic therapy (HR 1.51, 95% CI 1.04-2.19). CONCLUSION: This study highlighted the lack of difference in prescription of first-line biologic treatment, except for IFX, between obese and non-obese patients presenting moderate-to-severe psoriasis. Drug survival in obese patients is shorter, mainly because of inefficacy, than in non-obese patients. This highlights the need for targeted pharmacological studies in obese individuals to find optimal administration schemes.
Assuntos
Terapia Biológica , Fármacos Dermatológicos/uso terapêutico , Obesidade/complicações , Psoríase/complicações , Psoríase/tratamento farmacológico , Adalimumab/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Índice de Massa Corporal , Estudos de Coortes , Etanercepte/uso terapêutico , Feminino , França , Humanos , Infliximab/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Seleção de Pacientes , Ustekinumab/uso terapêuticoRESUMO
During a meeting in Munich, Germany, a presymptomatic attendee with severe acute respiratory syndrome coronavirus 2 infected at least 11 of 13 other participants. Although 5 participants had no or mild symptoms, 6 had typical coronavirus disease, without dyspnea. Our findings suggest hand shaking and face-to-face contact as possible modes of transmission.
Assuntos
Betacoronavirus/patogenicidade , Busca de Comunicante/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Surtos de Doenças , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Adulto , Doenças Assintomáticas , Betacoronavirus/fisiologia , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Congressos como Assunto , Infecções por Coronavirus/diagnóstico , Alemanha/epidemiologia , Humanos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , SARS-CoV-2 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios XRESUMO
Pemphigus consists of a group of rare and severe autoimmune blistering diseases mediated by pathogenic autoantibodies mainly directed against two desmosomal adhesion proteins, desmoglein (Dsg)1 and Dsg3 (also known as DG1 and DG3), which are present in the skin and surface-close mucosae. The binding of autoantibodies to Dsg proteins induces a separation of neighbouring keratinocytes, in a process known as acantholysis. The two main pemphigus variants are pemphigus vulgaris, which often originates with painful oral erosions, and pemphigus foliaceus, which is characterised by exclusive skin lesions. Pemphigus is diagnosed on the basis of either IgG or complement component 3 deposits (or both) at the keratinocyte cell membrane, detected by direct immunofluorescence microscopy of a perilesional biopsy, with serum anti-Dsg1 or anti-Dsg3 antibodies (or both) detected by ELISA. Corticosteroids are the therapeutic mainstay, which have recently been complemented by the anti-CD20 antibody rituximab in moderate and severe disease. Rituximab induces complete remission off therapy in 90% of patients, despite rapid tapering of corticosteroids, thus allowing for a major corticosteroid-sparing effect and a halved number of adverse events related to corticosteroids.
Assuntos
Azatioprina , Imunossupressores , Pênfigo , Rituximab , Corticosteroides/efeitos adversos , Azatioprina/uso terapêutico , Desmogleína 1 , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/imunologia , Imunossupressores/uso terapêutico , Pênfigo/classificação , Pênfigo/diagnóstico , Pênfigo/tratamento farmacológico , Pênfigo/patologia , Rituximab/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management. OBJECTIVE: We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations. METHODS: A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus. RESULTS: The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion. LIMITATIONS: Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. CONCLUSIONS: We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.
Assuntos
Fatores Imunológicos/administração & dosagem , Pênfigo/diagnóstico , Pênfigo/terapia , Plasmaferese , Guias de Prática Clínica como Assunto , Academias e Institutos/normas , Administração Intravenosa , Antígenos CD20/imunologia , Terapia Combinada/métodos , Terapia Combinada/normas , Consenso , Técnica Delphi , Dermatologia/métodos , Dermatologia/normas , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Europa (Continente) , Glucocorticoides/administração & dosagem , Humanos , Pênfigo/imunologia , Rituximab/administração & dosagem , Índice de Gravidade de DoençaRESUMO
The prevalence of psychological disorders in patients with common skin diseases was assessed in a large representative sample of the French adult population. General health, as measured by the EQ5D score, was significantly lower if patients reported having rosacea, atopic dermatitis, urticaria, fungal infections, psoriasis or acne. The proportions of participants reporting being extremely anxious or depressed were higher in those who reported having rosacea, atopic dermatitis or contact dermatitis. Difficulties in sexual and conjugal life were frequently reported by people with psoriasis, atopic dermatitis, contact dermatitis, urticaria and, in particular, acne. Sleep disorders were present in 30-50% of those who reported having acne, rosacea, eczema, psoriasis or urticaria. Sleep disorders may be related not only to pruritus, but also to disfiguring skin diseases. Anxiety and depression complications were mainly reported by those with disfiguring diseases. Sexual and conjugal dysfunctions were associated with all dermatoses (with the exception of warts).