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BACKGROUND: The nature of the COVID-19 pandemic led to concerns among patients and physicians about the potential impact of immunosuppressive treatments for chronic diseases such as psoriasis on the risk of severe COVID-19. OBJECTIVES: To describe treatment modifications and determine the incidence of COVID-19 infection among psoriasis patients during the first wave of the pandemic, and identify the factors associated with these events. METHODS: Data from PSOBIOTEQ cohort relating to the first COVID-19 wave in France (March to June, 2020), as well as a patient-centred COVID-19 questionnaire, were used to evaluate the impact of lockdown on changes (discontinuations, delays or reductions) in systemic therapies, and to determine the incidence of COVID-19 cases among these patients. Logistic regression models were used to assess associated factors. RESULTS: Among the 1751 respondents (89.3%), 282 patients (16.9%) changed their systemic treatment for psoriasis, with 46.0% of these changes being initiated by the patients themselves. Patients were more likely to experience psoriasis flare-ups during the first wave if they changed their treatment during this period (58.7% vs 14.4%; Pâ¯<â¯0.0001). Changes to systemic therapies were less frequent among patients with cardiovascular diseases (Pâ¯<â¯0.001), and those agedâ¯≥â¯65â¯years (Pâ¯=â¯0.02). Overall, 45 patients (2.9%) reported having COVID-19, and eight (17.8%) required hospitalization. Risk factors for COVID-19 infection were close contact with a positive case (Pâ¯<â¯0.001) and living in a region with a high incidence of COVID-19 (Pâ¯<â¯0.001). Factors associated with a lower risk of COVID-19 were avoiding seeing a physician (Pâ¯=â¯0.002), systematically wearing a mask during outings (Pâ¯=â¯0.011) and being a current smoker (Pâ¯=â¯0.046). CONCLUSIONS: Discontinuation of systemic psoriasis treatments during the first COVID-19 wave (16.9%) - mainly decided by patients themselves (46.0%) - was associated with a higher incidence of disease flares (58.7% vs 14.4%). This observation and factors associated with a higher risk of COVID-19 highlight the need to maintain and adapt patient-physician communication during health crises according to patient profiles, with the aim of avoiding unnecessary treatment discontinuations and ensuring that patients are informed about the risk of infection and the importance of complying with hygiene rules.
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COVID-19 , Psoriasis , Humanos , COVID-19/epidemiología , Pandemias , Control de Enfermedades Transmisibles , Psoriasis/tratamiento farmacológico , Psoriasis/epidemiología , Inmunosupresores/uso terapéuticoRESUMEN
INTRODUCTION: Super-potent topical corticosteroids (CS) are the mainstay of treatment for bullous pemphigoid. Since super-potent topical CS have systemic effects due to their transcutaneous absorption, we assessed whether super-potent CS were responsible for hydro-saline retention (HSR) in bullous pemphigoid patients. PATIENTS AND METHODS: From 2015 to 2017, patients with newly-diagnosed bullous pemphigoid treated using clobetasol propionate cream at a starting daily dose of 20 to 40â¯g were subsequently included in a prospective study. HSR was assessed by longitudinally measuring extracellular water (ECW) volume using bioimpedance analysis (BodyStat QuadScan 4000®) from Day 0 to Day 30 after the initiation of topical CS. Other parameters related to HSR such as weight, blood pressure, natriuresis and proteinuria, were also recorded. RESULTS: Twenty-nine patients (14 men and 15 women) of mean age 81.8⯱â¯9.3â¯years were included and analysed. The mean ECW volume decreased from Day 0 to Day 7 (18.1⯱â¯4.2 vs 16.7⯱â¯2.7, pâ¯=â¯0.0094) and was maintained from Day 7 to Day 30 (16.8⯱â¯2.8 vs 17.0⯱â¯3.4 L; pâ¯=â¯0.8040). Patient weight loss at Day 30 (69.9⯱â¯13.6 vs 72.5⯱â¯14.2â¯kg, pâ¯=â¯0.0085) was closely correlated with the decrease in ECW volume (râ¯=â¯0.6740, pâ¯<â¯0.0001). No significant changes in natriuresis, 24-hour proteinuria or blood pressure were observed from Day 0 to Day 30. CONCLUSION: We found no evidence of HSR in bullous pemphigoid patients treated with super-potent topical CS. Conversely, ECW volume decreased from Day 0 to Day 30, which was correlated with patient weight loss.
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Clobetasol , Penfigoide Ampolloso , Masculino , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Penfigoide Ampolloso/inducido químicamente , Estudios Prospectivos , Glucocorticoides/uso terapéutico , Administración TópicaRESUMEN
BACKGROUND: Biologics are the cornerstone of treatment of patients with moderate-to-severe plaque psoriasis and switches between biologics are frequently needed to maintain clinical improvement over time. OBJECTIVES: The main purpose of this study was to describe precisely switches between biologics and how their pattern changed over time with the recent availability of new biologic agents. METHODS: We included patients receiving a first biologic agent in the Psobioteq multicenter cohort of adults with moderate-to-severe psoriasis receiving systemic treatment. We described switches between biologics with chronograms, Sankey and Sunburst diagrams, assessed cumulative incidence of first switch by competing risks survival analysis and reasons for switching. We assessed the factors associated with the type of switch (intra-class - i.e. within the same therapeutic class - vs. inter-class) in patients switching from a TNF-alpha inhibitor using multivariate logistic regression. RESULTS: A total of 2153 patients was included. The cumulative incidence of switches from first biologic was 34% at 3 years. Adalimumab and ustekinumab were the most prescribed biologic agents as first and second lines of treatment. The main reason for switching was loss of efficacy (72%), followed by adverse events (11%). Patients receiving a TNF-alpha inhibitor before 2016 mostly switched to ustekinumab, whereas those switching in 2016 or after mostly switched to an IL-17 inhibitor. Patients switching from a first-line TNF-alpha inhibitor before 2016 were more likely to switch to another TNF-alpha inhibitor compared with patients switching since 2018. Patients switching from etanercept were more likely to receive another TNF-alpha inhibitor rather than another therapeutic class of bDMARD compared with patients switching from adalimumab. CONCLUSION: This study described the switching patterns of biologic treatments and showed how they changed over time, due to the availability of the new biologic agents primarily IL-17 inhibitors.
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Productos Biológicos , Psoriasis , Adalimumab/uso terapéutico , Adulto , Productos Biológicos/uso terapéutico , Etanercept/uso terapéutico , Humanos , Interleucina-17 , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa , Ustekinumab/uso terapéuticoRESUMEN
BACKGROUND: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. OBJECTIVE: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. METHODS: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. RESULTS: An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine. CONCLUSION: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.
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Antipsicóticos , Inhibidores de la Dipeptidil-Peptidasa IV , Insulinas , Penfigoide Ampolloso , Enfermedad del Suero , Antipsicóticos/efectos adversos , Autoanticuerpos , Autoantígenos , Vesícula , Dipeptidil Peptidasa 4/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Distonina , Humanos , Hipoglucemiantes/uso terapéutico , Inmunoglobulina G , Insulinas/uso terapéutico , Colágenos no Fibrilares , Estudios Prospectivos , Tiroxina/uso terapéuticoAsunto(s)
Carcinoma de Células Escamosas , Neoplasias Cutáneas , Aloinjertos/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/secundario , Humanos , Riñón/patología , Nivolumab/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoimmune disorders triggered by IgG autoantibodies against mucosal and epidermal desmogleins. There is an unmet need for fast-acting drugs that enable patients to achieve early sustained remission with reduced corticosteroid reliance. OBJECTIVES: To investigate efgartigimod, an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor, thereby reducing serum IgG levels, for treating pemphigus. METHODS: Thirty-four patients with mild-to-moderate pemphigus vulgaris or foliaceus were enrolled in an open-label phase II adaptive trial. In sequential cohorts, efgartigimod was dosed at 10 or 25 mg kg-1 intravenously with various dosing frequencies, as monotherapy or as add-on therapy to low-dose oral prednisone. Safety endpoints comprised the primary outcome. The study is registered at ClinicalTrials.gov (identifier NCT03334058). RESULTS: Adverse events were mostly mild and were reported by 16 of 19 (84%) patients receiving efgartigimod 10 mg kg-1 and 13 of 15 (87%) patients receiving 25 mg kg-1 , with similar adverse event profiles between dose groups. A major decrease in serum total IgG and anti-desmoglein autoantibodies was observed and correlated with improved Pemphigus Disease Area Index scores. Efgartigimod, as monotherapy or combined with prednisone, demonstrated early disease control in 28 of 31 (90%) patients after a median of 17 days. Optimized, prolonged treatment with efgartigimod in combination with a median dose of prednisone 0·26 mg kg-1 per day (range 0·06-0·48) led to complete clinical remission in 14 of 22 (64%) patients within 2-41 weeks. CONCLUSIONS: Efgartigimod was well tolerated and exhibited an early effect on disease activity and outcome parameters, providing support for further evaluation as a therapy for pemphigus.
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Anticuerpos Monoclonales Humanizados , Pénfigo , Anticuerpos Monoclonales Humanizados/efectos adversos , Autoanticuerpos , Desmogleína 1 , Estudios de Factibilidad , Antígenos de Histocompatibilidad Clase I , Humanos , Inmunoglobulina G , Recién Nacido , Pénfigo/tratamiento farmacológico , Prednisona/administración & dosificación , Receptores FcAsunto(s)
Dermatología , Preparaciones Farmacéuticas , Anciano , Interacciones Farmacológicas , Humanos , PolifarmaciaRESUMEN
This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue-bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10-25% of patients laminin 332 is recognized. In 25-30% of MMP patients with anti-laminin 332 reactivity, malignancies have been associated. As first-line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first-line regimens. Additional recommendations are given, tailored to treatment of single-site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high-quality randomized controlled trials.
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Dermatología , Penfigoide Benigno de la Membrana Mucosa , Penfigoide Ampolloso , Venereología , Autoanticuerpos , Autoantígenos , Humanos , Membrana Mucosa , Penfigoide Benigno de la Membrana Mucosa/diagnóstico , Penfigoide Benigno de la Membrana Mucosa/tratamiento farmacológicoRESUMEN
This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients' autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the 'Cicatrising Conjunctivitis Assessment Tool' and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course.
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Dermatología , Penfigoide Benigno de la Membrana Mucosa , Penfigoide Ampolloso , Venereología , Autoanticuerpos , Autoantígenos , Humanos , Membrana Mucosa , Penfigoide Benigno de la Membrana Mucosa/diagnóstico , Penfigoide Benigno de la Membrana Mucosa/terapia , Calidad de Vida , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: European guidelines propose a 0·5 mg kg-1 per day dose of oral prednisone as initial treatment for bullous pemphigoid (BP). We assessed the safety and efficacy of this regimen depending on BP extent and general condition of the patients. METHODS: In a prospective international study, we consecutively included all patients diagnosed with BP. Patients received a 0·5 mg kg-1 per day dose of prednisone, which was then gradually tapered 15 days after disease control, with the aim of stopping prednisone or maintaining minimal treatment (0·1 mg kg-1 per day) within 6 months after the start of treatment. The two coprimary endpoints were control of disease activity at day 21 and 1-year overall survival. Disease severity was assessed according to the Bullous Pemphigoid Disease Area Index (BPDAI) score. RESULTS: In total, 198 patients were included between 2015 and 2017. The final analysis comprised 190 patients with a mean age of 80·9 (SD 9·1) years. Control of disease activity was achieved at day 21 in 119 patients [62·6%, 95% confidence interval (CI) 55·3-69.5]; 18 of 24 patients (75%, 95% CI 53·3-90·2), 75 of 110 patients (68·8%, 95% CI 59·2-77·3) and 26 of 56 patients (46.4%, 95% CI 33·0-60·3) had mild, moderate and severe BP, respectively (P = 0·0218). A total of 30 patients died during the study. The overall Kaplan-Meier 1-year survival was 82·6% (95% CI 76·3-87·4) corresponding to 90·9%, 83·0% and 80·0% rates in patients with mild, moderate and severe BP, respectively (P = 0·5). Thresholds of 49 points for BPDAI score and 70 points for Karnofsky score yielded maximal Youden index values with respect to disease control at day 21 and 1-year survival, respectively. CONCLUSIONS: A 0·5 mg kg-1 per day dose of prednisone is a valuable therapeutic option in patients with mild or moderate BP whose general condition allows them to be autonomous.