RESUMO
Many treatments are currently proposed for treating patients with bullous pemphigoid (BP). We assessed treatment modalities of BP depending on the different countries, BP extent, and patients' comorbidities. We surveyed worldwide experts about how they treat patients with BP. A total of 61 experts from 27 countries completed the survey. Severe and moderate BP were treated with oral prednisone (61.4 and 53.7%, respectively) or superpotent topical corticosteroids (CSs) (38.6 and 46.3%, respectively). Conventional immunosuppressants were more frequently combined with oral prednisone (74.5%) than with superpotent topical CS (37.5%) in severe BP. Topical CSs were mainly used in Europe in mild (81.1%), moderate (55.3%), and severe (54.3%) BP. In the United States of America and Asia, systemic CSs were mainly proposed for treating severe (77.8 and 100%, respectively), moderate (70 and 77.8%, respectively), and also mild (47.1 and 33.3%, respectively) BP. Most experts reduced the initial dose of oral CS in patients with diabetes mellitus (48.1%) or cardiac insufficiency (40.2%) but rarely changed BP treatment in patients with neurological disorders or neoplasia. This survey showed major differences in the way patients with BP are treated between AmeriPac countries (United State of America, Latin America, and Australia) and Asia on the one hand and Europe and the Middle East on the other hand.
RESUMO
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 terapêuticoRESUMO
Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index.
Assuntos
Penfigoide Mucomembranoso Benigno/diagnóstico , Penfigoide Mucomembranoso Benigno/terapia , Humanos , Guias de Prática Clínica como Assunto , Registros , Resultado do TratamentoAssuntos
Paralisia Facial/complicações , Fasciculação/complicações , Lateralidade Funcional , Polirradiculoneuropatia/complicações , Idoso , Paralisia Facial/diagnóstico , Paralisia Facial/terapia , Fasciculação/diagnóstico , Fasciculação/terapia , Feminino , Humanos , Hanseníase Multibacilar/complicações , Polirradiculoneuropatia/diagnóstico , Polirradiculoneuropatia/terapiaAssuntos
Esclerose Múltipla/imunologia , Penfigoide Bolhoso/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Autoantígenos/sangue , Membrana Basal/imunologia , Proteínas de Transporte , Proteínas do Citoesqueleto , Distonina , Feminino , Humanos , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Proteínas do Tecido Nervoso , Colágenos não Fibrilares/sangue , Penfigoide Bolhoso/complicações , Colágeno Tipo XVIIRESUMO
Linear IgA disease is one of the rarer subepidermal blistering diseases. Linear IgA disease is a chronic, acquired, autoimmune blistering disease that is characterized by subepidermal blistering and linear deposition of IgA basement membrane antibodies. The disease affects both children and adults and, although there are some differences in their clinical presentations, there is considerable overlap with shared immunopathology and immunogenetics.
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Autoantígenos/imunologia , Doenças Autoimunes/diagnóstico , Imunoglobulina A/imunologia , Colágenos não Fibrilares/imunologia , Dermatopatias Vesiculobolhosas/diagnóstico , Pele/imunologia , Adulto , Animais , Autoanticorpos/imunologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/fisiopatologia , Criança , Diagnóstico Diferencial , Gastroenteropatias/complicações , Humanos , Neoplasias/complicações , Pele/patologia , Dermatopatias Vesiculobolhosas/etiologia , Dermatopatias Vesiculobolhosas/imunologia , Dermatopatias Vesiculobolhosas/fisiopatologia , Ferimentos e Lesões/complicações , Colágeno Tipo XVIIRESUMO
Autoimmune blistering disease (AIBD) in pregnancy raises several complex management issues associated with underlying pathogenesis and treatment options. This article considers the effects of the disease as well as its treatment for both mother and fetus. All AIBDs can occur in pregnancy but are relatively rare. Pemphigoid gestationis is a rare AIBD that is specific to pregnancy. The article considers each AIBD in turn and then looks at treatment options for the group as a whole, as there are many issues common to all.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Vesícula/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Troca Materno-Fetal , Penfigoide Bolhoso/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Antibacterianos/uso terapêutico , Vesícula/imunologia , Feminino , Humanos , Imunossupressores/uso terapêutico , Penfigoide Bolhoso/imunologia , Gravidez , Complicações na Gravidez/imunologia , Resultado do TratamentoRESUMO
Linear immunoglobulin A (IgA) disease is an acquired autoimmune blistering disease of the skin and mucous membranes that runs a chronic course over 3 to 6 years before remitting. It typically presents with papulovesicles and blisters configured in an arcuate pattern on an urticated base, with 2 peaks of onset. The first peak is in young prepubescent children, called chronic bullous disease of childhood, and the second peak affects patients older than 60 years of age. In this article, the management of linear IgA in adults is considered.
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Doenças Autoimunes/tratamento farmacológico , Imunoglobulina A/efeitos dos fármacos , Dermatopatias Vesiculobolhosas/tratamento farmacológico , Sulfonas/uso terapêutico , Doença Crônica , Fármacos Dermatológicos/uso terapêutico , Humanos , Resultado do TratamentoRESUMO
Linear IgA disease is one of the rarer subepidermal blistering diseases. Linear IgA disease is a chronic, acquired, autoimmune blistering disease that is characterized by subepidermal blistering and linear deposition of IgA basement membrane antibodies. The disease affects both children and adults and, although there are some differences in their clinical presentations, there is considerable overlap with shared immunopathology and immunogenetics.
Assuntos
Membrana Basal/imunologia , Imunoglobulina A/imunologia , Dermatopatias Vesiculobolhosas , Pele/imunologia , Idade de Início , Membrana Basal/patologia , Humanos , Pele/patologia , Dermatopatias Vesiculobolhosas/etiologia , Dermatopatias Vesiculobolhosas/imunologia , Dermatopatias Vesiculobolhosas/patologiaRESUMO
OBJECTIVE: To investigate the relationship between bullous pemphigoid (BP) and neurologic disease. DESIGN: Case-control study. SETTING: Tertiary care center for immunobullous diseases and skin tumor clinics at a university hospital in Oxford, England. PARTICIPANTS: Ninety consecutive patients with BP and 141 controls. MAIN OUTCOME MEASURES: Age-adjusted prevalence of neurologic disease in patients and controls. Time interval between the diagnosis of neurologic disease and BP and type of associated neurologic disease. RESULTS: At least 1 neurologic diagnosis was present in 42 patients (46%) compared with 16 controls (11%). Patients had significantly increased odds for neurologic diseases regardless of age and sex (crude odds ratio [OR], 6.8; 95% confidence interval [CI], 3.5-13.3; adjusted OR, 6.2; 95% CI, 3.1-12.4). Four major neurologic diagnoses were observed (cerebrovascular disease, dementia, Parkinson disease, and epilepsy), with statistical significance for cerebrovascular disease and dementia (crude OR for cerebrovascular disease, 6.3; 95% CI, 2.8-14.2; adjusted OR, 6.0; 95% CI, 2.6-13.6; crude OR for dementia, 10.7; 95% CI, 2.3-49.0; adjusted OR, 7.9; 95% CI, 1.7-37.3). When accurate data on time of onset of neurologic disease were present (36 of 42 patients [85%]), BP followed neurologic disease in most patients (26 of 36 patients [72%]), with a median interval of 5.5 years. CONCLUSION: Bullous pemphigoid is significantly associated with cerebrovascular disease and dementia.
Assuntos
Transtornos Cerebrovasculares/complicações , Demência/complicações , Penfigoide Bolhoso/complicações , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Epilepsia/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicaçõesRESUMO
Autoantibodies to basement membrane proteins BP180 and BP230 are characteristic of bullous pemphigoid and other subepidermal immunobullous disorders. These antibodies are, however, reported in other pruritic dermatoses, non-bullous disorders and non-cutaneous disease. Few studies have assessed basement membrane antibodies in normal subjects; antibody prevalence in this population is not clear. This study aims to examine basement membrane zone antibodies in normal middle-aged to elderly subjects. Sera from 61 healthy subjects (majority age 50-70 years) were assessed by immunoblot, indirect immunofluorescence and enzyme-linked immunosorbent assay. Ninety-one bullous pemphigoid patients acted as positive controls. Antigenic target, antibody class and titre were examined; sera binding BP180 were assessed for reactivity to the non-collagenous 16A (NC16A) domain. Thirty-six normal subjects (59%) had antibodies to either BP180 or BP230 on immunoblot analysis. BP180 was the commonest target antigen, detected in 35 subjects; binding to the immunodominant NC16A domain was not detected. Immunofluorescence was positive in three subjects. Of the bullous pemphigoid sera, 88% were positive on immunoblot or immunofluorescence; a higher frequency had antibodies against BP230. In conclusion, significant numbers of normal healthy subjects have circulating autoantibodies to basement membrane proteins, chiefly BP180 detectable by immunoblot, but these do not bind the NC16A domain.
Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Membrana Basal/imunologia , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/imunologia , Idoso , Autoantígenos/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Immunoblotting , Masculino , Pessoa de Meia-Idade , Colágenos não Fibrilares/sangue , Colágeno Tipo XVIIRESUMO
Six out of 10 patients with chronic wounds suffer from persistent wound pain. A multinational and multicenter randomized double-blind clinical investigation of 122 patients compared two moist wound healing dressings: a nonadhesive foam dressing with ibuprofen (62 patients randomized to Biatain Ibu Nonadhesive Coloplast A/S) and a nonadhesive foam without ibuprofen (60 patients to Biatain Non-Adhesive-comparator). Patients were recruited from September 2005 to April 2006. The ibuprofen foam was considered successful if the pain relief on a five-point Verbal Rating Scale was higher than the comparator without compromising safety including appropriate healing rate. Additional endpoints were change in persistent wound pain between dressing changes and pain at dressing change on days 1-5 (double blind) and days 43-47 (single blind). The primary response variable, persistent pain relief, was significantly higher in the ibuprofen-foam group, as compared with the comparator on day 1-5, with a quick onset of action (p<0.05). Wound pain intensity was significantly reduced with the ibuprofen foam during day 1-5 with 40% from baseline, compared with 30% with the comparator (p<0.001). At day 43-47, the patients in the ibuprofen-foam group had a significant (p<0.05) reemergence of persistent pain and pain at dressing change (p<0.05) when the active dressing was changed to the comparator. Wound healing was similar in the ibuprofen foam and comparator group. No difference in adverse events between the comparator and the ibuprofen foam with local sustained release of low-dose ibuprofen was observed in this study. It was generally found that women reported less pain intensity than men, and pain intensity decreased with increasing age. In addition, pain intensity increased with initial pain intensity and increasing wound size. This study has demonstrated that the ibuprofen-foam dressing provided pain relief and reduced pain intensity without compromising healing or other safety parameters.
Assuntos
Analgésicos não Narcóticos/administração & dosagem , Bandagens , Ibuprofeno/administração & dosagem , Dor/etiologia , Dor/prevenção & controle , Úlcera Varicosa/complicações , Idoso , Analgésicos não Narcóticos/efeitos adversos , Bandagens/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Ibuprofeno/efeitos adversos , Masculino , Preparações FarmacêuticasRESUMO
Microsporum canis is the causative organism in less than 10% of all tinea capitis infections in the UK. Transmission is generally via contact with an infected family pet and there are only rare reports of case clustering. This article describes an outbreak of M. canis in a primary school classroom demonstrating human-to-human spread from an index case who was presumed to have acquired the infection prior to arriving in the UK. There was no suggestion of clinical improvement following 4 weeks of oral terbinafine 125 mg daily and treatment was changed to griseofulvin. The Health Protection team screened class members and confirmed cases (either clinically or mycologically) were also treated with griseofulvin 10-20 mg/kg/day for 10 weeks. Classmates and siblings of classmates were recommended to use selenium sulphide or ketoconazole-containing shampoo twice weekly.
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Antifúngicos/uso terapêutico , Transmissão de Doença Infecciosa , Microsporum/isolamento & purificação , Instituições Acadêmicas , Tinha do Couro Cabeludo/tratamento farmacológico , Tinha do Couro Cabeludo/transmissão , Criança , Relação Dose-Resposta a Droga , Humanos , Masculino , Tinha do Couro Cabeludo/microbiologia , Resultado do TratamentoRESUMO
Six out of 10 patients with chronic wounds suffer from persistent wound pain. A multinational and multicentre, randomised, double-blind clinical investigation of 122 patients compared two moist wound-healing dressings, a non adhesive foam dressing with ibuprofen (62 patients randomised to Biatain-Ibu non adhesive, Coloplast A/S) with a non adhesive foam without ibuprofen (60 to Biatain non adhesive). The ibuprofen-foam was regarded successful, if the pain relief on a 5-point verbal rating scale was higher than the comparator without compromising safety, including appropriate healing rate. Additional endpoints were change in persistent wound pain between dressing changes and pain at dressing change on days 1-5 and days 43-47. The primary response variable, persistent pain relief, was significantly higher in the ibuprofen-foam group compared with the comparator on days 1-5, with a quick onset of action (P < 0.05). The patients in the ibuprofen-foam group had a significant (P < 0.05) higher reduction in the persistent wound pain from baseline (40%) as the comparator (30%). Women reported less pain intensity than men, and pain intensity decreased with increasing age. In addition, pain intensity increased with increasing initial pain intensity and increasing wound size. Wound healing was similar in the ibuprofen-foam group to that of the comparator group. No difference in adverse events between placebo and local sustained release of low-dose ibuprofen was observed in this study. This study has demonstrated that the ibuprofen-foam dressing provided pain relief and reduced pain intensity without compromising healing or other safety parameters. The full report of this study will be published in Wound Repair and Regeneration.
Assuntos
Analgésicos não Narcóticos/administração & dosagem , Bandagens , Ibuprofeno/administração & dosagem , Manejo da Dor , Dor/etiologia , Úlcera Varicosa/complicações , Administração Tópica , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Resultado do Tratamento , Úlcera Varicosa/terapia , CicatrizaçãoRESUMO
The skin disease erythrokeratoderma variabilis (EKV) has been shown to be associated with mutations in GJB3 and GJB4 encoding connexin (Cx)31 and Cx30.3, respectively. Gap junctions composed of Cx proteins are intracellular channels providing a mechanism of synchronized cellular response facilitating metabolic and electronic functions of the cell. In the skin, Cx31 and Cx30.3 are expressed in the stratum granulosum of the epidermis with a suggested role in late keratinocyte differentiation. Molecular investigations of GJB3 and GJB4 were performed in five pedigrees and three sporadic cases of EKV. Mutational analyzes revealed disease-associated Cx31 or Cx30.3 mutations in only three probands of which two were novel mutations and one was a recurrent mutation. These genetic studies further demonstrate the heterogeneous nature of the erythrokeratodermas as not all individuals that were clinically diagnosed with EKV harbor Cx31 or Cx30.3 mutations.
Assuntos
Conexinas/genética , Hiperceratose Epidermolítica/diagnóstico , Hiperceratose Epidermolítica/genética , Análise Mutacional de DNA , Feminino , Humanos , Hiperceratose Epidermolítica/tratamento farmacológico , Masculino , Mutação , Linhagem , Polimorfismo Genético , Retinoides/uso terapêuticoRESUMO
The case is presented of a 29-year-old female who, at the age of 13 years, developed bilateral verrucous thickening of her areolae. Despite the condition causing her significant psychosocial morbidity, a specialist referral was initially denied on the grounds that no treatment was apparently available. The condition progressively deteriorated over the subsequent 14 years. She was eventually referred for a dermatology opinion, and the diagnosis of nevoid hyperkeratosis was made. Topical therapy with keratolytics was unsuccessful, and she was referred for a plastic surgery review. Bilateral shave excision of the lesion was performed under general anesthesia, with a satisfactory outcome and no evidence of recurrence at 10 months.
Assuntos
Doenças Mamárias/cirurgia , Ceratose/cirurgia , Mamilos , Adulto , Feminino , HumanosRESUMO
A 16-year-old boy presented with painless swellings localized to the radial and ulnar aspects of his second through to the fifth fingers on the left hand, with more subtle changes affecting two fingers on the opposite hand. This had developed in the absence of mechanical trauma. Investigations for an arthropathy were negative, while a biopsy showed marked epidermal hyperplasia and an expanded dermis. These features are typical of pachydermodactyly, a benign dermatosis of uncertain aetiology. The interesting feature of this case is the presence of knuckle pads in the father of the patient, which raises the possibility that these two similar entities are related.