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Penfigoide Ampolloso , Neoplasias Cutáneas , Humanos , Penfigoide Ampolloso/complicaciones , Penfigoide Ampolloso/patología , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/patología , Femenino , Carcinoma de Apéndice Cutáneo/patología , Carcinoma de Apéndice Cutáneo/complicaciones , Anciano , Masculino , Anciano de 80 o más AñosAsunto(s)
Anticuerpos Monoclonales Humanizados , Penfigoide Ampolloso , Humanos , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/complicaciones , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Femenino , Resultado del Tratamiento , Tuberculosis/tratamiento farmacológico , Tuberculosis/complicaciones , AncianoRESUMEN
BACKGROUND: Autoimmune blistering disorders (ABDs) might elevate cardiovascular risk, but studies are lacking. OBJECTIVE: The objective of this study was to examine if ABDs elevate the risk of atherosclerotic cardiovascular disease, heart failure, arrhythmia, venous thromboembolism, and cardiovascular death. METHODS: A population-based cohort of Danish patients with ABD (≥18 years of age) diagnosed during 1996-2021 (n = 3322) was compared with an age- and sex-matched comparison cohort from the general population (n = 33,195). RESULTS: Compared with the general population, patients with ABDs had higher 1-year risks of atherosclerotic cardiovascular disease (3.4% vs 1.6%), heart failure (1.9% vs 0.7%), arrhythmia (3.8% vs 1.3%), venous thromboembolism (1.9% vs 0.3%), and cardiovascular death (3.3% vs 0.9%). The elevated risk persisted after 10 years for all outcomes but arrhythmia. The hazard ratios associating ABDs with the outcomes during the entire follow-up were 1.24 (1.09-1.40) for atherosclerotic cardiovascular disease, 1.48 (1.24-1.77) for heart failure, 1.16 (1.02-1.32) for arrhythmia, 1.87 (1.50-2.34) for venous thromboembolism, and 2.01 (1.76-2.29) for cardiovascular death. The elevated cardiovascular risk was observed for both pemphigus and pemphigoid. LIMITATIONS: Our findings might only generalize to patients with ABDs without prevalent cardiovascular diseases. CONCLUSION: Patients with ABDs had an elevated cardiovascular risk compared with age- and sex-matched controls.
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Enfermedades Autoinmunes , Enfermedades Cardiovasculares , Humanos , Masculino , Femenino , Persona de Mediana Edad , Dinamarca/epidemiología , Anciano , Adulto , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Estudios de Cohortes , Insuficiencia Cardíaca/epidemiología , Pénfigo/epidemiología , Pénfigo/complicaciones , Medición de Riesgo/estadística & datos numéricos , Estudios de Casos y Controles , Enfermedades Cutáneas Vesiculoampollosas/epidemiología , Aterosclerosis/epidemiología , Arritmias Cardíacas/epidemiología , Anciano de 80 o más Años , Penfigoide Ampolloso/epidemiología , Penfigoide Ampolloso/complicaciones , Factores de Riesgo de Enfermedad Cardiaca , Adulto JovenRESUMEN
We aimed to systematically review and meta-analyze the association between diabetes mellitus (DM) and bullous pemphigoid (BP). Bullous pemphigoid (BP) is a prevalent autoimmune subepidermal blistering disease. Comorbid health conditions like neurological diseases and malignancies have been associated with BP. Growing evidence suggests that type 2 diabetes mellitus (T2DM) may increase the risk of developing BP. This review aims to synthesize this evidence. A systematic literature review was performed using Medline, PubMed, and Scopus in March 2022. Studies exploring the association between BP and DM were included. Data were extracted, and quality was assessed using the Newcastle-Ottawa scale. Meta-analysis was conducted to identify the odds ratio (OR) and 95% confidence intervals (CI) of the association. Seventeen studies were included, most being case-control studies from Europe and Asia. The pooled OR was 2.06 (95% CI: 1.61-2.62), suggesting a significant association between DM and BP. However, strong heterogeneity (I2 = 88%) was observed. Evidence consolidates a significant relationship between DM and BP, potentially due to alterations in the immune system and skin properties caused by diabetes. Strengths of this review include a comprehensive search, rigorous methodology, large sample size, and heterogeneity evaluation. However, varying study quality, potential publication bias, and unaccounted confounding factors present limitations. There is a potential link between T2DM and an increased risk of BP. Further studies are required to understand this association and the underlying mechanisms.
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Diabetes Mellitus Tipo 2 , Penfigoide Ampolloso , Humanos , Comorbilidad , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Penfigoide Ampolloso/epidemiología , Penfigoide Ampolloso/complicaciones , Penfigoide Ampolloso/inmunología , Factores de RiesgoRESUMEN
Bullous pemphigoid (BP) is the most common autoimmune blistering disease, which primarily affects the elderly. However, the relationship between BP and malignancy remains controversial in traditional observational studies. The aim of this study, which included only European populations, was to assess the potential causative link between BP and 13 types of malignant tumors in a two-sample Mendelian randomization (MR) study. BP was not associated with an increased risk of developing 13 types of malignant tumors. This study did not find a causal relationship between BP and malignant tumors. However, further research is warranted to examine the generalizability of this conclusion in non-European populations.
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Enfermedades Autoinmunes , Neoplasias , Penfigoide Ampolloso , Humanos , Anciano , Penfigoide Ampolloso/epidemiología , Penfigoide Ampolloso/genética , Penfigoide Ampolloso/complicaciones , Análisis de la Aleatorización Mendeliana , Neoplasias/epidemiología , Neoplasias/genética , Neoplasias/complicaciones , Vesícula , Enfermedades Autoinmunes/complicacionesRESUMEN
PURPOSE: To evaluate ocular surface involvement, tear cytokine levels, and histopathological changes in pemphigus and pemphigoid patients. METHODS: A total of 22 patients (15 pemphigus and 7 pemphigoids) and 21 non-diseased controls were enrolled in our study. All participants underwent ocular surface evaluation, which included ocular surface disease index test, slit lamp observation, dry eye-related examination, tear multicytokine analysis, and conjunctival impression cytology. RESULTS: Pemphigus and pemphigoid patients presented much more severe conjunctivochalasis, corneal epithelial defects, corneal opacity, symblepharon and dry eye. Severe ocular surface squamous metaplasia and a significant increase of tear macrophage inflammatory protein-1beta, tumor necrosis factor-alpha, interleukin (IL)-1ß, IL -6, and IL-8 occurred in pemphigus and pemphigoid patients. CONCLUSIONS: Our results revealed that ocular surface inflammation and dry eye persist in most pemphigus and pemphigoid patients, and do not occur in parallel with the systemic course. Regular ophthalmological examinations and local anti-inflammatory should be provided for pemphigus and pemphigoid patients.
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Enfermedades de la Conjuntiva , Síndromes de Ojo Seco , Penfigoide Ampolloso , Pénfigo , Humanos , Penfigoide Ampolloso/complicaciones , Penfigoide Ampolloso/diagnóstico , Pénfigo/complicaciones , Pénfigo/diagnóstico , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/etiología , Síndromes de Ojo Seco/patología , Enfermedades de la Conjuntiva/diagnóstico , Enfermedades de la Conjuntiva/etiología , Conjuntiva/patología , Lágrimas , Interleucina-1beta , Inflamación/diagnóstico , Inflamación/patologíaRESUMEN
BACKGROUND: Previous studies have revealed the factors associated with the relapse of bullous pemphigoid (BP). This study aims to assess the characteristics of BP patients at the time of initial diagnosis and a potential association with subsequent relapse occurrences. METHODS: A retrospective cohort study was conducted on 205 BP patients from January 2009 to May 2022 at the Peking Union Medical College Hospital in Beijing, China. The median follow-up duration was 2.7 years. We conducted univariate and multivariate analyses on various clinical indicators (e.g., lesional involvements and medical history) and laboratory test results. RESULTS: Among the 205 patients, 118 (57.6 %) relapsed during the follow-up period. Univariate analysis revealed several factors associated with relapse, which were greater age [Hazard Ratio (HR)1.018, 95 % confidence interval (CI) 1.004-1.032] (p = 0.010), a past medical history of thyroid diseases [HR 3.674, 95 % CI 1.472-9.167] (p = 0.005), hematological disease complications [HR 4.123, 95 % CI 1.301-13.061] (p = 0.016), negative C3 deposition in direct immunofluorescence [HR 0.574, 95 % CI 0.374-0.883] (p = 0.011) and prealbumin level less than 200 mg/L[HR 0.580, 95 % CI 0.351-0.957] (p = 0.033). Multivariate analysis demonstrated that patients with negative C3 deposition in direct immunofluorescence [HR 0.524, 95 % CI 0.296-0.927] (p = 0.026) and prealbumin levels below 200 mg/L [HR 0.541, 95 % CI 0.301-0.974] (p = 0.041) were associated with further relapses of BP. CONCLUSIONS: Negative C3 deposition in direct immunofluorescence and a prealbumin level below 200 mg/L at initial diagnosis served as predictive markers for future relapses of BP. Systemic evaluation of BP patients at initial diagnosis could be essential in helping prevent recurrences and achieve more effective disease management.
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Penfigoide Ampolloso , Humanos , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/complicaciones , Prealbúmina , Estudios Retrospectivos , Factores de Riesgo , Enfermedad Crónica , RecurrenciaRESUMEN
PURPOSE: Ocular Mucous Membrane Pemphigoid (OcMMP) is an orphan disease characterized by chronic autoimmune-driven conjunctival inflammation leading to progressive scarring, debilitating symptoms, and blinding sequelae. This feasibility study aims to demonstrate conjunctival genetic transcriptomic analyses as a putative tool for interrogation of pathogenic signaling pathways in OcMMP. METHODS: Conjunctival RNA profiling using the NanoString nCounter Human Fibrosis panel was undertaken on RNA extracted from conjunctival swabs obtained from 6 MMP patients (8 eyes; 4 M/2F; median age 78 [range 64-84] years); and 8 age-matched control participants (15 eyes; 3 M/5F; median age 69.5 [range 69-88] years). Data from 770 genes were analyzed with ROSALIND HyperScale architecture and stratified according to the level of clinically visible bulbar conjunctival inflammation. Normalization, fold-changes (≥+1.5-fold or ≤ -1.5-fold) and p-values adjustment (<0.05) using the Benjamini-Hochberg method were calculated. RESULTS: 93 differentially expressed genes (DEGs) were observed between OcMMP versus controls of which 48 were upregulated, and 45 downregulated. The top 4 upregulated DEGs represented fibrosis (COL3A1, COL1A1, FN1 and THBS1) while the key under-expressed genes (SCIN, HMGS2, XCL1/2) were indicative of ocular surface failure (goblet cell loss, keratinization, vulnerability to secondary infections). Forty-four pathways had a global significance score ≥2, the most significant being those related to extracellular matrix (ECM) remodeling, synthesis, and degradation. These pathways were accentuated in eyes with visible inflammation. CONCLUSIONS: NanoString methodology acquired via a simple conjunctival swab identifies profibrotic genes in OcMMP group and differentiates inflamed eyes. Longitudinal sampling and following investigative intervention will further mechanistic insight and development of novel biomarkers to monitor disease progression.
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Enfermedades de la Conjuntiva , Conjuntivitis , Penfigoide Benigno de la Membrana Mucosa , Penfigoide Ampolloso , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Penfigoide Ampolloso/complicaciones , Penfigoide Ampolloso/metabolismo , Penfigoide Ampolloso/patología , Conjuntiva/patología , Penfigoide Benigno de la Membrana Mucosa/genética , Fibrosis , Inflamación/metabolismo , Membrana Mucosa , Perfilación de la Expresión Génica , ARN/metabolismo , Enfermedades de la Conjuntiva/metabolismoAsunto(s)
Penfigoide Ampolloso , Psoriasis , Enfermedades Cutáneas Vesiculoampollosas , Humanos , Penfigoide Ampolloso/complicaciones , Penfigoide Ampolloso/tratamiento farmacológico , Psoriasis/complicaciones , Psoriasis/tratamiento farmacológico , Enfermedades Cutáneas Vesiculoampollosas/complicaciones , Interleucina-23RESUMEN
OBJECTIVE: To retrospectively analyze the efficacy and safety of dupilumab in the treatment of bullous pemphigoid. METHODS: From October 2020 to October 2022, the medical records of patients with bullous pemphigoid who were treated with dupilumab in our department were collected retrospectively to analyze the therapeutic effect and changes in laboratory indexes. RESULTS: The records of a total of 11 patients with bullous pemphigoid who were treated with dupilumab was reviewed. Within 2 weeks of the treatment, 10 (90.9%) of the 11 patients had complete or substantial control of the disease. The BPDAI scores of the patients decreased from baseline 113 (62, 181) to 37 (6, 130) at 2 weeks (p = .001) and 4 (0, 37) at 12 weeks after treatment (p < .001). In the 11 patients treated with dupilumab, the relief time of pruritus was 0-3 days (0.5, 7) days, and the pruritus was significantly alleviated after 2 weeks (t = 15.925, p < .001). The DLQI score decreased from (25.5 ± 2.5) before treatment, to (11.8 ± 4.4) at 2 weeks (t = 10.764, p < .001) and (2.1 ± 1.9) at 12 weeks (t = 30.038, p < .001). The patients had high eosinophil counts, high serum IgE levels, low serum total protein levels, and abnormal blood coagulation function. The aforementioned indicators gradually returned to normal after treatment. No adverse reactions occurred during the treatment. CONCLUSION: Dupilumab can effectively control the condition of bullous pemphigoid, efficiently relieve pruritus symptoms, and is relatively safe.
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Penfigoide Ampolloso , Humanos , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/complicaciones , Penfigoide Ampolloso/diagnóstico , Glucocorticoides , Estudios Retrospectivos , Prurito/tratamiento farmacológico , Prurito/etiología , Gravedad del PacienteRESUMEN
Importance: Studies have linked bullous pemphigoid (BP) with venous thromboembolism (VTE) across several data sources finding 6-fold to 15-fold increased incidence rates. Objective: To determine the incidence of VTE in patients with BP compared with similar controls. Design, Setting, and Participants: This cohort study used insurance claims data from a nationwide US health care database from January 1, 2004, through January 1, 2020. Patients with dermatologist-recorded BP were identified (≥2 diagnoses of BP [International Classification of Diseases, Ninth Revision (ICD-9) 694.5 and ICD-10 L12.0] recorded by dermatologists within 1 year). Risk-set sampling identified comparator patients without BP and free of other chronic inflammatory skin diseases. Patients were followed-up until the first of the following events occurred: VTE, death, disenrollment, or end of data stream. Exposures: Patients with BP compared with those without BP and free of other chronic inflammatory skin diseases (CISD). Main outcome: Venous thromboembolism events were identified and incidence rates were computed before and after propensity-score (PS) matching to account for VTE risk factors. Hazard ratios (HRs) compared the incidence of VTE in BP vs non-CISD. Results: Overall, 2654 patients with BP and 26â¯814 comparator patients without BP or another CISD were identified. The mean (SD) age in the BP group was 73.0 (12.6) years and 55.0 (18.9) years in the non-CSID group. With a median follow-up time was 2 years, the unadjusted incidence rate (per 1000 person-years) of outpatient or inpatient VTE was 8.5 in the BP group compared with 1.8 in patients without a CISD. Adjusted rates were 6.7 in the BP group compared with 3.0 in the non-CISD group. Age-specific adjusted incidence rates (per 1000 person-years) in patients aged 50 to 74 years was 6.0 (vs 2.9 in the non-CISD group) and in those aged 75 years or older was 7.1 (vs 4.53 in the non-CISD group). After 1:1 propensity-score matching including 60 VTE risk factors and severity markers, BP was associated with a 2-fold increased risk of VTE (2.24 [1.26-3.98]) vs those in the non-CISD group. When restricting to patients aged 50 years or older, the adjusted relative risk of VTE was 1.82 (1.05-3.16) for the BP vs non-CISD groups. Conclusions: In this nationwide US cohort study, BP was associated with a 2-fold increased incidence of VTE after controlling for VTE risk factors in a dermatology patient population.
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Penfigoide Ampolloso , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/complicaciones , Estudios de Cohortes , Penfigoide Ampolloso/epidemiología , Penfigoide Ampolloso/complicaciones , Factores de Riesgo , IncidenciaRESUMEN
Bullous pemphigoid (BP) is an autoimmune disease characterized by itchy erythema and tense blisters on the whole body. Recent reports have unveiled the pathogenic roles of eosinophils in BP (e.g., dermal-epidermal separation, generation of pruritus). Thus, eosinophils are considered a therapeutic target. Benralizumab is an anti-IL-5 receptor alpha (IL-5Rα) monoclonal antibody (mAb) that is widely used to treat severe eosinophilic asthma. By affecting IL-5Rα, benralizumab depletes eosinophils and basophils due to apoptosis through antibody-dependent cell-mediated cytotoxicity. The efficacies of benralizumab and other biologics, including bertilimumab (anti-eotaxin-1 mAb) and mepolizumab (anti-IL-5 mAb), were evaluated in several clinical trials. Also, reslizumab, an anti-IL-5 mAb, was reported as a successful treatment option in a case of BP. We present a case of severe asthma treated with benralizumab at 8-week intervals for 3 years before BP developed. Histologically, subepidermal blisters without eosinophilic infiltration were observed. Methylprednisolone pulse therapy followed by 40 mg/day (1 mg/kg/day) of oral prednisolone (PSL) was initiated, but the skin lesions worsened. Additional intravenous immunoglobulin and oral azathioprine enabled the oral PSL to be tapered. The benralizumab was discontinued after the onset of BP because the asthma did not worsen. To the best of our knowledge, there have been no reports of BP developing during anti-eosinophil therapy. BP may occur paradoxically via various pathways during treatment with drugs that are typically effective against BP.
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Asma , Penfigoide Ampolloso , Eosinofilia Pulmonar , Humanos , Penfigoide Ampolloso/inducido químicamente , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/complicaciones , Vesícula , Asma/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Eosinofilia Pulmonar/complicaciones , Prednisolona/uso terapéuticoRESUMEN
Ocular mucous membrane pemphigoid is the manifestation of a systemic autoimmune disease. As autoantibodies circulating in the blood cannot be adequately treated by eye drops, systemic immunosuppressive treatment of this autoimmune disease naturally plays the most important role. Ophthalmic topical or even surgical procedures are only used as supportive measures or usually to control ocular complications that have developed. Patients with the typical clinical picture are treated causally with systemic immunosuppression causally, nurturing eye drops, as well as by minimally invasive surgery if complications arise, if possible in an inflammation-free state, in accordance with the guidelines if the diagnosis is positive but also if the biopsy and serology are repeatedly negative after exclusion of all differential diagnoses. Purely topical anti-inflammatory treatment is insufficient to prevent irreversible progression of scarring conjunctivitis. Corresponding treatment recommendations have been formulated in current European as well as German guidelines and are presented here as an overview.