Venous Thromboembolism in Chronic Inflammatory Skin Diseases-The Need to Consider Bullous Pemphigoid-Reply.
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ABSTRACT:
SUBMITTER: Schneeweiss MC
PROVIDER: S-EPMC9552827 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
Publications
Venous Thromboembolism in Chronic Inflammatory Skin Diseases-The Need to Consider Bullous Pemphigoid-Reply.
Schneeweiss Maria C MC Silverberg Jonathan I JI Mostaghimi Arash A
JAMA dermatology 20220301 3
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Project description:ImportanceSeveral studies have linked chronic inflammatory skin diseases (CISDs) with venous thromboembolism (VTE) in a range of data sources with mixed conclusions.ObjectiveTo examine the incidence of VTE in patients with vs without CISD.Design, setting, and participantsA cohort study using commercial insurance claims data from a nationwide US health care database from January 1, 2004, through 2019 was conducted. A total of 158 123 patients with dermatologist-recorded psoriasis, atopic dermatitis, alopecia areata, vitiligo, or hidradenitis suppurativa were included. Risk-set sampling identified patients without a CISD. Patient follow-up lasted until the first of the following occurred: VTE, death, disenrollment, or end of data stream.ExposuresPatients with vs without CISD.Main outcomes and measuresVenous thromboembolism events were identified with validated algorithms. Incidence rates were computed before and after 1:1 propensity-score matching to account for VTE risk factors. Hazard ratios were estimated to compare the incidence of VTE in the CISD vs non-CISD cohorts.ResultsA total of 158 123 patients were identified with CISD: with psoriasis (n = 96 138), atopic dermatitis (n = 30 418), alopecia areata (n = 17 889), vitiligo (n = 7735), or HS (n = 5934); 9 patients had 2 of these conditions. A total of 1 570 387 patients were without a CISD. The median follow-up time was 1.9 years (interquartile range, 0.8-4.0 years) in patients with CISD. The incidence rate (per 1000 person-years) of outpatient or inpatient VTE was 1.57 in psoriasis, 1.83 in atopic dermatitis, 0.94 in alopecia areata, 0.93 in vitiligo, 1.65 in HS and 1.53 in CISD overall, compared with 1.76 in patients without a CISD. Incidence rates increased in patients aged 50 years or older (2.3 per 1000 person-years) and decreased in those aged 18 to 49 years (0.8 per 1000 person-years). After propensity-score matching to patients without a CISD, the hazard ratio (HR) of VTE was 0.86 (95% CI, 0.75-0.99) in psoriasis, 1.19 (95% CI, 0.95-1.48) in atopic dermatitis, 0.97 (95% CI, 0.65-1.46) in alopecia areata, 0.90 (95% CI, 0.49-1.65) in vitiligo, 1.64 (95% CI, 0.82-3.27) in hidradenitis suppurativa, and 0.94 (95% CI, 0.84-1.05) in CISD overall.Conclusions and relevanceIn this large-scale cohort study, CISDs were not associated with an increased incidence of VTE after controlling for relevant VTE risk factors in a representative dermatology patient population.
| S-EPMC8156173 | biostudies-literature
Project description:Background Bullous pemphigoid (BP) and pemphigus vulgaris (PV) share similar pathophysiology with venous thromboembolism (VTE) involving platelet activation, immune dysregulation, and systemic inflammation. Nevertheless, their associations have not been well established. Methods and Results To examine the risk of incident VTE among patients with BP or PV, we performed a nationwide cohort study using Taiwan's National Health Insurance Research Database and enrolled 12 162 adults with BP or PV and 12 162 controls. A Cox regression model considering stabilized inverse probability weighting was used to calculate the hazard ratios (HRs) for incident VTE associated with BP or PV. To consolidate the findings, a meta-analysis that incorporated results from the present cohort study with previous literature was also conducted. Compared with controls, patients with BP or PV had an increased risk for incident VTE (HR, 1.87 [95% CI, 1.55-2.26]; P<0.001). The incidence of VTE was 6.47 and 2.20 per 1000 person-years in the BP and PV cohorts, respectively. The risk for incident VTE significantly increased among patients with BP (HR, 1.85 [95% CI, 1.52-2.24]; P<0.001) and PV (HR, 1.99 [95% CI, 1.02-3.91]; P=0.04). In the meta-analysis of 8 studies including ours, BP and PV were associated with an increased risk for incident VTE (pooled relative risk, 2.17 [95% CI, 1.82-2.62]; P<0.001). Conclusions BP and PV are associated with an increased risk for VTE. Preventive approaches and cardiovascular evaluation should be considered particularly for patients with BP or PV with concomitant risk factors such as hospitalization or immobilization.
| S-EPMC10547313 | biostudies-literature
Project description:IntroductionWe here thought to dissect the inflammatory signature in lesions of three skin disorders, which show a common adaptive immune response against autoantigens of the skin but are characterized by diverging clinical phenotypes. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are type-2-dependent, IgG autoantibody-driven blistering disorders of mucous membranes and skin, which target desmoglein (Dsg)3 and bullous pemphigoid (BP)180, respectively. In contrast, lichen planus (LP) is a common chronic inflammatory disease of the skin and mucous membranes with a pronounced dermal T cell infiltrate. We previously identified peripheral type 1 and 17 T cell responses against Dsg3 and BP180 in a cohort of LP patients strongly suggesting that the underlying inflammatory T cell signature may drive the evolving phenotype.MethodsParaffin-embedded skin biopsies from well-characterized patients with LP (n=31), BP (n=19), PV (n=9), and pemphigus foliaceus (PF) (n=2) were analysed. Areas with the most prominent inflammatory infiltrate were excised with punch biopsies and tissue microarrays (TMA) containing multiple biopsies were created. Using multicolor immunofluorescence, the inflammatory infiltrate was stained with antibodies against multiple cellular markers, i. e. CD3ϵ, CD4, CD15, TCR-δ, the cytokine IL-17A, and the transcription factors, T-bet and GATA-3.ResultsIn LP, there was a higher number of CD4+ T cells expressing T-bet compared to GATA-3. In contrast, CD4+ T cells in PV and BP skin lesions more frequently expressed GATA-3 than T-bet. IL-17A+ cells and IL-17A+ T cells were found to a similar extent in all the three disorders. IL-17A+ granulocytes were more predominant in BP than in LP or PV. Of note, the majority of IL-17A+ cells in LP were neither T cells nor granulocytes.DiscussionOur findings in inflammatory skin infiltrates clearly show a predominant type 1 signature in LP in contrast to a preponderance of type 2 T cells in PV and BP. In contrast to LP, granulocytes and to a much lesser extent CD3+ T cells were a cellular source of IL-17A in BP and PV. These data strongly suggest that different inflammatory cell signatures drive evolving clinically diverse phenotypes of LP, PV and BP despite common target antigens of the skin.
| S-EPMC10321708 | biostudies-literature
Project description:Eosinophils are typically associated with unique inflammatory settings, including allergic inflammation and helminth infections. However, new information suggests that eosinophils contribute more broadly to inflammatory responses and participate in local immune regulation and the tissue remodeling/repair events linked with a variety of diseases. Eosinophilic infiltration has long been a histologic hallmark of bullous pemphigoid (BP), a subepidermal autoimmune blistering disease characterized by autoantibodies directed against basement membrane protein BP180. However, the exact role of eosinophils in disease pathogenesis remains largely unknown. We show here that eosinophils are necessary for IgE autoantibody-mediated BP blister formation in a humanized IgE receptor mouse model of BP. Disease severity is IgE dose dependent and correlates with the degree of eosinophil infiltration in the skin. Furthermore, IgE autoantibodies fail to induce BP in eosinophil-deficient mice, confirming that eosinophils are required for IgE-mediated tissue injury. Thus, eosinophils provide the cellular link between IgE autoantibodies and skin blistering in this murine model of BP. These findings suggest a role for eosinophils in autoimmune disease and have important implications for the treatment of BP and other antibody-mediated inflammatory and autoimmune diseases.
| S-EPMC7531612 | biostudies-literature
Project description:BackgroundBullous pemphigoid (BP) is the most common autoimmune blistering disease in the West. Oral steroids are the standard treatment.This is an update of the review published in 2005.ObjectivesTo assess treatments for bullous pemphigoid.Search strategyIn August 2010 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials), MEDLINE, EMBASE, and the Ongoing Trials registers.Selection criteriaRandomised controlled trials of treatments for participants with immunofluorescence-confirmed bullous pemphigoid.Data collection and analysisAt least two authors evaluated the studies for the inclusion criteria, and extracted data independently.Main resultsWe included 10 randomised controlled trials (with a total of 1049 participants) of moderate to high risk of bias. All studies involved different comparisons, none had a placebo group. In 1 trial plasma exchange plus prednisone gave significantly better disease control at 1 month (0.3 mg/kg: RR 18.78, 95% CI 1.20 to 293.70) than prednisone alone (1.0 mg/kg: RR 1.79, 95% CI 1.11 to 2.90), while another trial showed no difference in disease control at 6 months.No differences in disease control were seen for different doses or formulations of prednisolone (one trial each), for azathioprine plus prednisone compared with prednisone alone (one trial), for prednisolone plus azathioprine compared with prednisolone plus plasma exchange (one trial), for prednisolone plus mycophenolate mofetil or plus azathioprine (one trial), for tetracycline plus nicotinamide compared with prednisolone (one trial). Chinese traditional medicine plus prednisone was not effective in one trial.There were no significant differences in healing in a comparison of a standard regimen of topical steroids (clobetasol) with a milder regimen (RR 1.00, 95% 0.97 to 1.03) in one trial. In another trial, clobetasol showed significantly more disease control than oral prednisolone in people with extensive and moderate disease (RR 1.09, 95% CI 1.02 to 1.17), with significantly reduced mortality and adverse events (RR 1.06, 95% CI 1.00 to 1.12).Authors' conclusionsVery potent topical steroids are effective and safe treatments for BP, but their use in extensive disease may be limited by side-effects and practical factors. Milder regimens (using lower doses of steroids) are safe and effective in moderate BP. Starting doses of prednisolone greater than 0.75 mg/kg/day do not give additional benefit, lower doses may be adequate to control disease and reduce the incidence and severity of adverse reactions. The effectiveness of adding plasma exchange, azathioprine or mycophenolate mofetil to corticosteroids, and combination treatment with tetracycline and nicotinamide needs further investigation.
| S-EPMC7138251 | biostudies-literature
Project description:Bullous skin diseases are a group of dermatoses characterized by blisters and bullae in the skin and mucous membranes. The etiology and pathogenesis of bullous skin diseases are not completely clear. The most common are pemphigus and bullous pemphigoid (BP). Autoantibodies play critical roles in their pathogenesis. Abnormalities in the adhesion between keratinocytes in patients with pemphigus leads to acantholysis and formation of intra-epidermal blisters. Anti-desmoglein autoantibodies are present both in the circulation and skin lesions of patients with pemphigus. The deficient adhesion of keratinocytes to the basement membrane in BP patients gives rise to subepidermal blisters. Autoantibodies against the components of hemidesmosome can be detected in BP patients. Many novel therapeutics based on knowledge of the pathogenesis have emerged in recent years.
| S-EPMC7388362 | biostudies-literature
Project description:Bullous pemphigoid (BP) is a subepidermal skin blistering disease characterized immunohistologically by dermal-epidermal junction (DEJ) separation, an inflammatory cell infiltrate in the upper dermis, and autoantibodies targeted toward the hemidesmosomal proteins BP230 and BP180. Development of an IgG passive transfer mouse model of BP that reproduces these key features of human BP has demonstrated that subepidermal blistering is initiated by anti-BP180 antibodies and mediated by complement activation, mast cell degranulation, neutrophil infiltration, and proteinase secretion. This model is not compatible with study of human pathogenic antibodies, as the human and murine antigenic epitopes are not cross-reactive. The development of two novel humanized mouse models for the first time has enabled study of disease mechanisms caused by BP autoantibodies, and presents an ideal in vivo system to test novel therapeutic strategies for disease management.
| S-EPMC2064945 | biostudies-other
Project description:The gold standard for diagnosing bullous pemphigoid (BP) is the detection of linear deposition of IgG and/or C3 at the dermoepidermal junction using direct immunofluorescence (DIF). Because DIF has several disadvantages, primarily the requirement for frozen specimens, we assessed the diagnostic value of immunohistochemical (IHC) staining for BP detection. Eighty-eight patients with bullous lesions were included in this study. IHC staining for C3d, C4d, and IgG was performed on 88 samples, which included specimens from patients with DIF-confirmed BP (n = 43), clinicopathologically suspected BP with negative DIF results (n = 9), and other bullous diseases (n = 36). Diagnosis based on positive results for C3d, C4d, or IgG in IHC staining detected 86% of DIF-confirmed BP cases. The sensitivity of IHC staining for the detection of DIF-confirmed BP cases and clinicopathologically suspected BP cases was similar to that of DIF (80.8% vs. 84.3%), but the specificity was higher (83.3% vs. 75.0%). Five of the nine clinicopathologically suspected BP cases were diagnosed using IHC staining. Thus, IHC staining of routine biopsy material could be an alternative method for diagnosing BP. IHC staining has considerable diagnostic potential, especially in cases with a high suspicion of BP, but negative or suboptimal DIF results.Please check and confirm the author names and initials are correct. Author 2: Given name: [Chul Hwan] Family name: [Kim], Author 3: Given name: [Yoo Jin] Family name: [Lee].Checked it.
| S-EPMC9217790 | biostudies-literature
Project description:Bullous pemphigoid antigen 2 (BPAG2) is targeted by autoantibodies in patients with bullous pemphigoid (BP), and absent in patients with one type of epidermolysis bullosa (OMIM #226650). A keratin 14 promoter construct was used to produce transgenic (Tg) mice appropriately expressing human BPAG2 (hBPAG2) in murine epidermal basement membrane (BM). Grafts of Tg skin placed on gender-matched, syngeneic wild type (Wt) or major histocompatibility complex I (MHC I)-/- mice elicited IgG that bound human epidermal BM and BPAG2. Production of such IgG in grafted mice was prompt (detectable within 16+/-2 days), robust (titer > or = 1,280), durable (present > or = 380 days), and correlated with the involution and loss of Tg skin grafts. MHC II-/- mice grafted with Tg skin did not develop anti-hBPAG2 IgG or graft loss indicating that MHC II:CD4+ T cell interactions were crucial for these responses. Tg skin grafts on Wt mice developed neutrophil-rich infiltrates, dermal edema, subepidermal blisters, and deposits of immunoreactants in epidermal BM. This model shows fidelity to alterations seen in patients with BP, has relevance to immune responses that may arise in patients with epidermolysis bullosa following BPAG2 gene replacement, and can be used to identify interventions that may block production of IgG against proteins in epidermal BM.
| S-EPMC2546607 | biostudies-literature
Project description: Not available
| S-EPMC7256243 | biostudies-literature