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The endothelial glycocalyx, a gel-like layer that lines the luminal surface of blood vessels, is composed of proteoglycans, glycoproteins, and glycosaminoglycans. The endothelial glycocalyx plays an essential role in vascular homeostasis, and its degradation in trauma and sepsis can lead to microvascular dysfunction and organ injury. While there are no proven therapies for preventing or treating endothelial glycocalyx degradation, some initial literature suggests that plasma may have a therapeutic role in trauma and sepsis patients. Overall, the literature suggesting the use of plasma as a therapy for endothelial glycocalyx degradation is non-clinical basic science or exploratory. Plasma is an established therapy in the resuscitation of patients with hemorrhage for restoration of coagulation factors. However, plasma also contains other bioactive components, including sphingosine-1 phosphate, antithrombin, and adiponectin, which may protect and restore the endothelial glycocalyx, thereby helping to maintain or restore vascular homeostasis. This narrative review begins by describing the endothelial glycocalyx in health and disease: we discuss the overlapping disease mechanisms in trauma and sepsis that lead to its damage and introduce plasma transfusion as a potential therapy for prevention and treatment of endothelial glycocalyx degradation. Second, we review the literature on plasma as an exploratory therapy for endothelial glycocalyx degradation in trauma and sepsis. Third, we discuss the safety of plasma transfusion by reviewing the adverse events associated with plasma and other blood product transfusions, and we examine modern transfusion precautions that have enhanced the safety of plasma transfusion. We conclude that the literature proposes that plasma may have the potential to prevent and treat endothelial glycocalyx degradation in trauma and sepsis, indicating the need for further research.
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Glicocálix , Plasma , Sepse , Ferimentos e Lesões , Glicocálix/metabolismo , Glicocálix/fisiologia , Humanos , Sepse/terapia , Sepse/fisiopatologia , Ferimentos e Lesões/terapia , Ferimentos e Lesões/complicações , Plasma/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologiaRESUMO
OBJECTIVE: To investigate and compare trends in incidence rates (IRs) of seropositive and seronegative rheumatoid arthritis (RA) in Denmark using various data sources for serostatus definition. METHOD: This nationwide population-based cohort study was based on data from Danish healthcare and clinical quality registries between 2000 and 2018. Information on anti-cyclic citrullinated peptide and immunoglobulin M rheumatoid factor was obtained, and definitions of seropositivity according to the number of applied data sources were prespecified. Annual age- and sex-standardized IRs were calculated as the number of incident seropositive and seronegative cases, divided by the number of person-years (PY) in the general population in that given year. RESULTS: An increasing temporal trend in IR of seropositive RA and a decreasing trend in seronegative RA were observed. The IRs were higher for seropositive RA than for seronegative RA from 2009 onwards, with a widening of the IR gap between 2009 and 2016 regardless of the definition of seropositivity. When combining laboratory- and physician-reported autoantibody information and ICD-10 codes, the IR of seropositive RA in 2018 was approximately twice that of seronegative RA, at 19.0 and 9.0 per 100 000 PY, respectively. The level of antibody testing increased significantly during the study period. CONCLUSIONS: The IR of seropositive RA increased over time, whereas the IR of seronegative RA decreased. Temporal IR changes may be caused by a real change in the RA serology subtypes, an increase in autoantibody testing and availability, changes in registration practice over time, or a combination of these factors.
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Background and aim: Drug-related problems (DRPs), e.g.drug-drug interactions (DDI), can lead to adversedrug reactions (ADRs) and thus complications during hospitalization. For this reason, such DRP, DDI and ADR should be identified and characterized as early as possible during hospital admission. We aimed to perform a clinical-pharmaceutical medication reconciliation in which patient-related information was collected and compared to drug-related information in a medication review. Investigations: During a 24-week-period, we consecutively invited patients electively admitted to Urology, Otolaryngology, Oral and Maxillofacial Surgery, General and Visceral Surgery, and Oncology Departments of a 300-bed hospital. A clinical pharmacist performed a patient interview asking for medication, ADR, and adherence. The medication reconciliation considered packages for a brown-bag analysis, medication lists, and data from the clinical information-system (CIS). In a medication review, we matched patient-related information to drug-related information from the drug label, guidelines, drug-databases and websites to identify DRPs. Results: In the study, 356 patients (median age: 58 years) taking 1,712 drugs participated. Of all patients, 7.3% reported ADR and 10.7% missing adherence. 5.3% brought packages that enabled a brown-bag analysis and 21.1% a medication list. In 76.7% of patients, information from CIS was incomplete or not up-to-date. Among the most frequently identified DRPs were "Medication without diagnosis" (31.2%) and "Inappropriate timing of administration" (11.5%). The proportion of patients affected by severe DDI ranged from 0.8%-16.6%, depending on the drug information source. Conclusions: Incomplete patient data, frequently identified DRPs and inconsistent drug-based information make pharmaceutical involvement in medication reconciliation on admission a necessity.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Serviço de Farmácia Hospitalar , Humanos , Pessoa de Meia-Idade , Reconciliação de Medicamentos , Preparações Farmacêuticas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Revisão de Medicamentos , Hospitalização , Farmacêuticos , HospitaisRESUMO
Guidelines are systematically developed decision-making aids to ensure appropriate clinical care for specific medical conditions. In Germany, dermatological guidelines are developed under the aegis of the German Dermatological Society (DDG) and the Professional Association of German Dermatologists (BVDD), while European and international guidelines are published by organisations such as the European Centre for Guidelines Development (EuroGuiDerm), founded by the European Dermatology Forum (EDF) in cooperation with the Division of Evidence-Based Medicine at Charité-Universitätsmedizin Berlin. In 2021 and 2022, the German guidelines were revised or developed on topics such as the management of anticoagulation during dermatological procedures, chronic pruritus, contact dermatitis, laser therapy of the skin, psoriasis vulgaris, rosacea, extracorporeal photopheresis, onychomycosis, mucous membrane pemphigoid and prevention of skin cancer. A selection of the most important recommendations and innovations in the guidelines is summarized here.
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Dermatologia , Psoríase , Neoplasias Cutâneas , Humanos , Alemanha , Psoríase/tratamento farmacológico , PeleRESUMO
Injuries and plumage damage (PD) are important indicators of welfare. First priority in turkey fattening is to reduce injurious pecking, which includes aggressive pecking (agonistic behavior) and additionally severe feather pecking (SFP) and cannibalism with their multifactorial reasons. Still, there are few studies available evaluating different genotypes for their welfare status under organic conditions. The aim of this study was to investigate the effects of genotype and husbandry with 100% organic feeding (2 variants with different riboflavin content: V1 and V2) on injuries and PD. During rearing nonbeaktrimmed male turkeys of a slow- (Auburn, n = 256) and fast-growing (B.U.T.6, n = 128) genotype were kept in 2 indoor housing systems (without environmental enrichment (EE) = H1-, n = 144 and with EE = H2+, n = 240). During fattening 13 animals per pen of H2+ were relocated to a free-range system (H3 MS, n = 104). EE included pecking stones, elevated seating platforms and silage feeding. The study included five 4-wk feeding phases. At the end of each phase, injuries and PD were scored to assess animal welfare. Injury scores ranged from 0 (=no damage) to 3 (=severe damage) and PD from 0 to 4. Injurious pecking was observed from the 8th week onward (injuries: 16.5% and PD: 31.4%). Binary logistic regression models showed that both indicators were affected by genotype (each P < 0.001), husbandry (each P < 0.001), feeding (injuries P = 0.004; PD P = 0.003), and age (each P < 0.001). Auburn showed less injuries and PD than B.U.T.6. H1- had the fewest injuries and PD for Auburn animals compared to H2+ or H3 MS. In summary, the use of alternative genotypes (Auburn) in organic fattening improved welfare, but keeping them in free-range systems or in husbandry with EE, does not lead to a reduction of injurious pecking. Therefore, further studies are needed with more and changing enrichment materials, further management measures, changes in housing structure, and even more intensive animal care.
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Galinhas , Perus , Masculino , Animais , Abrigo para Animais , Agressão , Canibalismo , Plumas , Bem-Estar do Animal , Criação de Animais Domésticos , Comportamento AnimalRESUMO
The introduction of (fully) automated vehicles has generated a re-interest in motion sickness, given that passengers suffer much more from motion sickness compared to car drivers. A suggested solution is to improve the anticipation of passive self-motion via cues that alert passengers of changes in the upcoming motion trajectory. We already know that auditory or visual cues can mitigate motion sickness. In this study, we used anticipatory vibrotactile cues that do not interfere with the (audio)visual tasks passengers may want to perform. We wanted to investigate (1) whether anticipatory vibrotactile cues mitigate motion sickness, and (2) whether the timing of the cue is of influence. We therefore exposed participants to four sessions on a linear sled with displacements unpredictable in motion onset. In three sessions, an anticipatory cue was presented 0.33, 1, or 3 s prior to the onset of forward motion. Using a new pre-registered measure, we quantified the reduction in motion sickness across multiple sickness scores in these sessions relative to a control session. Under the chosen experimental conditions, our results did not show a significant mitigation of motion sickness by the anticipatory vibrotactile cues, irrespective of their timing. Participants yet indicated that the cues were helpful. Considering that motion sickness is influenced by the unpredictability of displacements, vibrotactile cues may mitigate sickness when motions have more (unpredictable) variability than those studied here.
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Sinais (Psicologia) , Enjoo devido ao Movimento , Humanos , Movimento (Física)Assuntos
Doença de Crohn , Epidermólise Bolhosa Adquirida , Epidermólise Bolhosa , Humanos , UstekinumabRESUMO
Locked dislocations of the glenohumeral joint are rare but often painful and are associated with limited range of motion in the shoulder. In patients of advanced age, arthroplasty is increasingly indicated as a surgical treatment option. Preoperatively, the direction of dislocation, the presence and extent of a glenoid defect, and the soft tissue situation (rotator cuff status, joint capsule) should be analyzed in a differentiated manner. Based on the above factors, we recommend the subclassification of type 2 according to Boileau: posterior locked dislocation (2a), anterior locked dislocation without glenoid defect (2b), and anterior locked dislocation with glenoid defect (2c). In the case of dorsally locked dislocation, a good clinical result can be achieved by using an anatomical endoprosthesis. For ventrally locked dislocations, we recommend using an inverse total endoprosthesis with, if necessary, bony glenoid reconstruction and transfer of the pectoralis major muscle.Level of evidence: IV.
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1. The present study was carried out to determine the effects of feeding ensiled alfalfa leaves (ALS) as an alternative protein source to laying hens under the terms of an organic diet. Due to the occurrence of unexpected negative health effects and undesirable egg yolk pigmentation in the test groups the trial was prematurely stopped and further analysis was conducted to evaluate the responsible substances.2. Body weights of the test groups decreased significantly already in week 2 of the trial. Performance variables dropped. Olive green pigmented egg yolks were found in groups fed diets containing ALS. Severe comb necrosis occurred in the experimental group receiving the highest level of ALS (20%) combined with the option of free-range access and therefore natural light exposure.3. The noxious agent found in ALS, blood serum and egg yolk was the photosensitising chlorophyll derivate pheophorbid a (PPBa), deriving from a strong depletion of chlorophyll contained in the alfalfa leaves. PPBa caused the olive-green pigmentation found in yolks and led to photosensitivity in groups with the highest level of ALS in the diet in combination with light exposure.4. By aiming for high protein and amino acid levels, harvesting and processing have, unintentionally and initially unnoticed, led to a strong accumulation of phototoxic PPBa. From these results it is strongly advised not to include ensiled alfalfa leaves as a protein source in organic laying hen diets.
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Esclerose Lateral Amiotrófica , Gema de Ovo , Feminino , Animais , Gema de Ovo/química , Galinhas , Medicago sativa/química , Esclerose Lateral Amiotrófica/veterinária , Dieta/veterinária , Ração Animal/análise , OvosRESUMO
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 , Inibidores da Dipeptidil Peptidase IV , Insulinas , Penfigoide Bolhoso , Doença do Soro , Antipsicóticos/efeitos adversos , Autoanticorpos , Autoantígenos , Vesícula , Dipeptidil Peptidase 4/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Distonina , Humanos , Hipoglicemiantes/uso terapêutico , Imunoglobulina G , Insulinas/uso terapêutico , Colágenos não Fibrilares , Estudos Prospectivos , Tiroxina/uso terapêuticoRESUMO
Background: Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease of the skin affecting the elderly. BP is immunopathologically characterized by autoantibodies against BP180 and BP230. With the growing evidence of cell-mediated autoimmunity in the pathogenesis of BP, it still remains unclear whether mast cells (MCs) are involved, due to conflicting data obtained from Kit-dependent MC-deficient mouse models. Objectives: To clarify the role of MCs in experimental BP; the dynamics in cutaneous MC numbers, associated immune cells and the development of disease in Kit-independent MC-deficient mouse model. Methods: Employing a recently established murine adult passive transfer model of BP induced by the transfer of pathogenic immunoglobulin G (IgG), lesional skin biopsies were investigated histologically and immunohistochemically for the time-dependent MC accumulation and dermal infiltration. Results: The numbers of cutaneous MCs increased following the induction of BP, in part, maintained by MC proliferation. Numbers of T cells, neutrophils and eosinophils in the skin also increased after BP induction, with eosinophils showing a preferential co-localization with MCs. Furthermore, clinical disease manifestation in MC-deficient Mcpt5Cre/Dicer fl/fl mice remained unchanged compared to MC-sufficient Dicer fl/fl mice. The composition of the immune cell infiltration including as T cells, neutrophils and eosinophils was largely unaffected by the absence of MCs. Conclusion: MCs do not play a pivotal role in the pathogenesis of passive IgG-transfer mediated BP model. Their increase in number may be a bystander effect following tissue injury. We therefore suggest caution regarding the selection of MCs as sole targets for the development of novel drugs for BP.
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BACKGROUND: The association of autoimmune bullous diseases (AIBDs) with thyroid disorders remains to be profoundly investigated. OBJECTIVE: To evaluate the epidemiological association between six AIBDs and thyroid disorders. METHODS: A population-based cross-sectional study enrolled patients with bullous pemphigoid (BP), mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita (EBA), pemphigoid gestationis (PG), pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Patients with these six AIBDs were compared with six age- and sex-matched control groups regarding the prevalence of thyroiditis and hyperthyroidism. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for thyroid disorders. RESULTS: The study population included 1,743, 251, 106, 126, 860 and 103 patients with BP, MMP, EBA, PG, PV and PF respectively. The corresponding control groups consisted of 10,141, 1,386, 606, 933, 5,142 and 588 matched controls respectively. A significant association was found between thyroiditis and BP (OR, 1.98; 95% CI, 1.18-3.35; P = 0.010), MMP (OR, 7.02; 95% CI, 1.87-26.33; P = 0.004) and PV (OR, 2.73; 95% CI, 1.45-5.15; P = 0.002). With regards to hyperthyroidism, PF was the only AIBD to demonstrate significant comorbidity (OR, 2.42; 95% CI, 1.13-5.21; P = 0.024). EBA and PG were not found to cluster with any of the investigated thyroid conditions. CONCLUSION: Patients with BP, MMP, PV and PF experience an elevated burden of thyroid disorders. Patients with these AIBDs presenting with suggestive symptoms may be carefully screened for comorbid thyroid disorders.
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Doenças Autoimunes , Epidermólise Bolhosa Adquirida , Hipertireoidismo , Penfigoide Mucomembranoso Benigno , Penfigoide Bolhoso , Pênfigo , Dermatopatias Vesiculobolhosas , Doenças da Glândula Tireoide , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/epidemiologia , Estudos Transversais , Humanos , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/epidemiologiaRESUMO
The numerical understanding of cichlids and stingrays was examined regarding addition and subtraction abilities within the number space of one to five. Experiments were conducted as two-alternative forced-choice experiments, using a delayed matching to sample technique. On each trial, fish had to perform either an addition or subtraction, based on the presentation of two-dimensional objects in two distinct colors, with the color signaling a particular arithmetic process. Six cichlids and four stingrays successfully completed training and recognized specific colors as symbols for addition and subtraction. Cichlids needed more sessions than stingrays to reach the learning criterion. Transfer tests showed that learning was independent of straightforward symbol memorization. Individuals did not just learn to pick the highest or lowest number presented based on the respective color; instead, learning was specific to adding or subtracting 'one'. Although group results were significant for both species in all tests, individual results varied. Addition was learned more easily than subtraction by both species. While cichlids learned faster than stingrays, and more cichlids than stingrays learned the task, individual performance of stingrays exceeded that of cichlids. Previous studies have provided ample evidence that fish have numerical abilities on par with those of other vertebrate and invertebrate species tested, a result that is further supported by the findings of the current study.
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Ciclídeos , Rajidae , Animais , Aprendizagem , MatemáticaRESUMO
OBJECTIVE: To investigate the incidence and prevalence of rheumatoid arthritis (RA) in the adult Danish population. METHOD: In this nationwide register-based cohort study, patients with incident RA between 1998 and the end of 2018 were identified using Danish administrative registries. The age- and sex-standardized incidence rate (IR), incidence proportion (IP), lifetime risk (LR), and point prevalence (PP) of RA were calculated. RA was defined as a first-time RA diagnosis registered in the Danish National Patient Registry combined with a redeemed prescription of a conventional synthetic disease-modifying anti-rheumatic drug in the following year. In addition, three different case definitions of RA were explored. RESULTS: The overall age- and sex-standardized IR of RA from 1998 to 2018 was 35.5 [95% confidence interval (CI) 35.1-35.9] per 100 000 person-years while the IP was 35.2 (95% CI 34.8-35.5) per 100 000 individuals. The IR was two-fold higher for women than for men. The LR of RA ranged from 2.3% to 3.4% for women and from 1.1% to 1.5% for men, depending on the RA case definition used. The overall PP of RA was 0.6% (95% CI 0.5-0.6%) in 2018: 0.8% (95% CI 0.7-0.8%) for women and 0.3% (95% CI 0.3-0.4%) for men. The prevalence increased about 1.5-fold from 2000 to 2018. CONCLUSION: The IR and PP were approximately two-fold higher for women than for men. The prevalence of RA in Denmark increased significantly from 2000 to 2018. The RA case definition had more impact on the results than the choice of denominator.
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Artrite Reumatoide , Adulto , Masculino , Humanos , Feminino , Incidência , Prevalência , Estudos de Coortes , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/diagnóstico , Sistema de Registros , Dinamarca/epidemiologiaRESUMO
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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Anticorpos Monoclonais Humanizados , Pênfigo , Anticorpos Monoclonais Humanizados/efeitos adversos , Autoanticorpos , Desmogleína 1 , Estudos de Viabilidade , Antígenos de Histocompatibilidade Classe I , Humanos , Imunoglobulina G , Recém-Nascido , Pênfigo/tratamento farmacológico , Prednisona/administração & dosagem , Receptores FcRESUMO
BACKGROUND: The incidence of hospital-treated concussion is 100-300/100,000 person years. Reporting of long-lasting post-concussion symptoms (PCS) is estimated at 5-15%. Attachment insecurity is a potential vulnerability factor for physical illness and poorer disease outcomes in general. This study aimed to explore associations between attachment insecurity and PCS in young people sustaining a concussion. METHODS: This cross-sectional study was embedded in a cohort of 15-30-year-old patients (n = 3080) 3 months after sustaining a concussion. Data were obtained from a database and questionnaires. PCS were measured by the Rivermead Post-Concussion Symptoms Questionnaire and attachment dimensions (anxiety and avoidance) by the Experiences in Close Relationships-Relationship Structures Questionnaire. Multiple linear regression models were performed to investigate the association between the attachment dimensions and PCS with adjustment for demographic, injury-related and psychological factors and with additional testing for interaction between the attachment dimensions. RESULTS: In the final study sample, comprising 973 patients (31.6%), we found an interaction between the attachment dimensions. Hence, the effect of attachment anxiety on PCS was statistically insignificant at low avoidance (25th percentile) but significant at high avoidance (75th percentile, ß = 0.64 (95%CI: 0.02; 1.26)), whereas the effect of attachment avoidance was significant regardless of level of attachment anxiety (25th percentile, ß = 1.09 (95%CI: 0.18; 2.01); 75th percentile, ß = 2.71 (95%CI: 1.80; 3.61)). CONCLUSION: Attachment insecurity, especially characterised by high avoidance in combination with high anxiety, also called fearful attachment, is associated with PCS. Considering the attachment perspective can potentially improve health care for this patient group.
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Concussão Encefálica , Síndrome Pós-Concussão , Adolescente , Adulto , Ansiedade/epidemiologia , Concussão Encefálica/epidemiologia , Estudos Transversais , Humanos , Síndrome Pós-Concussão/epidemiologia , Inquéritos e Questionários , Adulto JovemRESUMO
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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Dermatologia , Penfigoide Mucomembranoso Benigno , Penfigoide Bolhoso , Venereologia , Autoanticorpos , Autoantígenos , Humanos , Mucosa , Penfigoide Mucomembranoso Benigno/diagnóstico , Penfigoide Mucomembranoso Benigno/tratamento farmacológicoRESUMO
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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Dermatologia , Penfigoide Mucomembranoso Benigno , Penfigoide Bolhoso , Venereologia , Autoanticorpos , Autoantígenos , Humanos , Mucosa , Penfigoide Mucomembranoso Benigno/diagnóstico , Penfigoide Mucomembranoso Benigno/terapia , Qualidade de Vida , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Apart from bullous pemphigoid (BP), the association of other autoimmune bullous diseases (AIBDs) with neurological conditions is poorly understood. OBJECTIVE: To estimate the association between a wide array of AIBDs and neurological conditions. METHODS: A retrospective cross-sectional study recruited patients with BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita (EBA), pemphigoid gestationis (PG), pemphigus vulgaris (PV) and pemphigus foliaceus (PF). These patients were compared with their age- and sex-matched control subjects with regard to the lifetime prevalence of Parkinson's disease (PD), Alzheimer's disease (AD), stroke, epilepsy and multiple sclerosis (MS). Logistic regression was used to calculate OR for specified neurological disorders. RESULTS: The current study included 1743, 251, 106, 126, 860 and 103 patients diagnosed with BP, MMP, EBA, PG, PV and PF, respectively. These patients were compared with 10 141, 1386, 606, 933, 5142 and 588 matched controls, respectively. Out of the investigated neurological conditions, PD associated with BP (OR, 2.71; 95% CI, 2.19-3.35); AD with BP (OR, 2.11; 95% CI, 1.73-2.57), MMP (OR, 2.37; 95% CI, 1.03-5.47), EBA (OR, 6.00; 95% CI, 1.90-18.97) and PV (OR, 2.24; 95% CI, 1.40-3.60); stroke with BP (OR, 1.84; 95% CI, 1.55-2.19) and EBA (OR, 2.79; 95% CI, 1.11-7.01); and epilepsy with BP (OR, 2.18; 95% CI, 1.72-2.77) and PV (OR, 1.80; 95% CI, 1.19-2.73). MS did not significantly cluster with any of the six AIBDs. CONCLUSION: In addition to BP, EBA and PV were found to cluster with neurological comorbidities. Patients with these AIBDs with compatible symptoms may be carefully assessed for comorbid neurological disorders.