Acta Dermato-Venereologica 99-1CompleteContent | Page 19

72 INVESTIGATIVE REPORT Mortality in Patients with Bullous Pemphigoid: A Retrospective Cohort Study, Systematic Review and Meta-analysis Khalaf KRIDIN 1 Wesal SHIHADE 2 and Reuven BERGMAN 1,3 1 Department of Dermatology, Rambam Health Care Campus, 2 Biobank and Unit of Epidemiology, Rambam Health Care Campus, School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, and 3 Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel There is little consensus regarding mortality data in bullous pemphigoid (BP). The aim of this study was to evaluate mortality among a relatively large cohort of Israeli patients with BP and to perform a meta-ana- lysis synthesizing existing data on 1-year mortality ra- tes of patients with BP. This retrospective cohort study of 287 patients diagnosed with BP between 2000 and 2015 compared the mortality of patients with BP with age- and sex-matched control subjects in the gene- ral population. The results showed 1-, 5- and 10-year mortality rates of 26.9%, 56.9% and 69.5%, respecti- vely, and a 3.4-fold higher risk of death. A systematic review and meta-analysis were then performed using a random effects model. Including the current study, 25 studies comprising 4,594 patients met the eligibi- lity criteria. The pooled estimate of 1-year mortality rate was 23.5% (95% confidence interval 20.2–26.8; I 2 =81%; p  < 0.001). The pooled 1-year mortality rate of European cohorts was prominently higher relative to the pooled rates of cohorts from the USA and Asia. Key words: bullous pemphigoid; mortality; survival; prognosis; meta-analysis; systematic review. Accepted Mar 27, 2018; Epub ahead of print Mar 27, 2018 Acta Derm Venereol 2019; 99: 72–77. Corr: Khalaf Kridin, Department of Dermatology, Rambam Health Care Campus, POB 9602, Haifa 31096, Israel. E-mail: [email protected] B ullous pemphigoid (BP) is the most common type of autoimmune blistering diseases (1). It is cha- racterized by the presence of circulating IgG autoanti- bodies to BP180 and BP230, which are components of junctional adhesion complexes called hemidesmosomes that promote dermoepidermal cohesion (1, 2). BP180 autoantibodies have been demonstrated to be directly pathogenic by triggering an inflammatory cascade that leads to tissue damage and, ultimately, to subepidermal blister formation (3, 4). The disease is characterized by severe pruritus, tense bullae and urticarial plaques, and usually occurs in elderly patients (5). BP has a chronic relapsing evolution, with spontaneous exacerbations and remissions (6). It is associated with a high rate of fatality, with 1-year mortality rates ranging from 6% to 41% (7, 8). The mortality of patients with BP is estimated to be 2–7-fold higher than age- and sex-matched controls. The calculated mortality rates doi: 10.2340/00015555-2930 Acta Derm Venereol 2019; 99: 72–77 SIGNIFICANCE Mortality data in BP are highly inconsistent. By this retro- spective cohort study, a 3.4-fold increased mortality and 27% 1-year mortality rate were recognized among Israeli patients with BP. Performing a systematic review and meta- analysis led to the conclusion that the pooled estimate of 1-year mortality rate in BP patients is 23.5% worldwide. The stratified pooled estimate is higher in European cohorts as compared to American and Asian ones. These data allow patients to be aware of prognosis and to make informed decisions, and provide clinicians with an indicator of the success of treatment. vary significantly from region to region, and particularly between cohorts originating from Europe and the USA. Studies regarding the prognosis of BP in the Middle-East are lacking. The objective of this study was to determine the over- all mortality of patients with BP relative to an age- and sex-matched population in Israel, tracking a relatively large immunopathologically validated cohort. Due to the controversies concerning the mortality rates of BP, a systematic review and meta-analysis of published data were performed with the aim of providing an accurate overview of true mortality in patients with BP. METHODS Retrospective cohort study Study population and inclusion criteria. This population-based retrospective cohort study comprised all consecutive patients who received a new diagnosis of BP between 1 January 2000 and 31 December 2015, in Rambam Health Care Campus, Haifa, Israel. BP was diagnosed as a blistering disease of the skin with sug- gestive clinical features (9), in conjunction with typical histopa­ thology, i.e. a subepidermal blister with an inflammatory infiltrate usually containing eosinophils in the superficial dermis, alongside at least one of the following immunopathological features: (i) linear deposits of IgG and/or C3 along the basement membrane zone by direct immunofluorescence (IF); (ii) circulating IgG autoantibodies binding to the basement membrane, as demonstra- ted by the use of monkey esophagus, and a standard indirect IF technique; (iii) the presence of circulating IgG antibodies against BP180 using enzyme-linked immunosorbent assay (ELISA) (10). Outcomes. Survival status and date of death among patients with BP were ascertained by linking the study cohort with the National Registry of Deaths Database of Haifa district. All patients were This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.