In BP skin lesions, it is detectable, and its level correlates positively with disease activity [104]. Mepolizumab is a humanized IgG1 kappa monoclonal antibody that binds to IL-5 and prevents its interaction with the eosinophil surface receptor. pathogenesis of bullous pemphigoid have allowed investigation of new target therapies against selective pro-inflammatory mediators. These therapies appear to yield satisfactory results with fewer side effects in cases of refractory disease. The review discusses current evidence on these new therapeutic targets and specific drugs under investigation. Keywords: bullous pemphigoid, target therapies, biologics, small molecules, novel treatments 1. Introduction Bullous pemphigoid (BP) is a rare autoimmune skin disease which affects the elderly in the eighth decade of life predominantly [1]. In older populations, multiple coexisting comorbidities and exposure to drugs able to potentially trigger the disease give reasons for the increase of BP incidence in recent years, ranging in Europe from 2.5 to 42.8 cases/million/year [2]. Classic BP is characterized by tense bullous lesions on normal or erythematous/edematous skin and intense itching, mainly located on the groin and axillary folds, the thigh, and the lower abdomen. Furthermore, oral, genital, or esophageal mucosal lesions are involved in 10C20% of cases [3]. The pathogenesis of BP has been identified as the production of autoantibodies against the hemidesmosome antigens BP180 and BP230, leading to a detachment at the dermo-epidermal junction. It is reported in the literature that levels of disease activity correlate with the circulating titers of anti-BP180 Gimeracil IgG and IgE antibodies [4]. IgE promotes the local infiltration of eosinophils, leading to the formation of bullae by two mechanisms. First, anti-BP180 IgE may bind to the FcRI receptors on mast cells, leading to a cross-link Gimeracil with the hemidesmosome, degranulation, and histamine release, amplifying the chemotaxis of eosinophils and neutrophils. Secondly, IgE may directly bind to BP180 on keratinocytes, be internalized, and stimulate the release of interleukin (IL) 6 and IL-8, with a chemotactic effect [5]. BP may be associated with various disorders. A systematic review associates BP with a possible increase in hematological malignancies, although no statistically increased overall risk of developing a malignancy has been identified in BP patients [6]. It has been shown that BP may increase DNM2 thrombotic risk, being a disease mediated by Th1 and Th2 cells, producing inflammatory cytokine cascades and inducing an upregulation of vascular endothelial growth factor and E-selectin, which promotes endothelial cell activation [7]. The prognosis of BP has been evaluated in a meta-analysis showing a 1-year combined mortality rate of 23.5%, and superinfection of skin ulcers is a leading cause of death [8]. Therapy is challenging, as it is based on the use of systemic steroids to induce remission, followed by tapering the dose slowly while trying to prevent new bullae from forming. Because BP is a chronic disease, therapy will have a long duration, and the side effects of chronic steroid intake may occur. Other canonical therapies include drugs defined as steroid-sparing, such as azathioprine, methotrexate, mycophenolate mofetil, dapsone, tetracyclines, and intravenous immunoglobulins [9]. However, the problem of BP being refractory to conventional therapies is the reason that prompted us to carry out a literature review with the purpose of analyzing the different treatment options available and considering some new therapies, in particular biologics. 2. Materials and Methods This scoping review was based on the approach developed by Arksey and OMalley that includes five essential steps: identification of the research question; identification of appropriate studies; selection of studies; tracking of data; and collection, summarization, and reporting of results. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) extension for scoping review criteria was used to guide the conduction and reporting of the review [10]. 2.1. Identification of the Research Question A brainstorming approach involving the entire research team was used to identify the research questions. The research group included six dermatologists with expertise in the research field of bullous diseases and clinical management of patients. At the initial meeting, the group identified the research question and determined the research strategy. The research question was: which novel therapeutic approaches have been/are emerging in the last 10 years for management of patients with bullous pemphigoid? 2.2. Study Selection Process We performed a worldwide systematic review of studies reporting on bullous pemphigoid, using 3 electronic medical databasesCPubMed, EMBASE, and Web of Scienceand considering articles dated 1 January 2012 to 1 1 May 2022. The search terms were selected to identify studies describing novel therapeutic approach to pemphigoids. The keywords used Gimeracil were bullous pemphigoids AND novel treatments, bullous pemphigoids AND biologics, bullous pemphigoids AND small molecules, and bullous pemphigoids AND target therapies. All selected databases were searched from their respective inceptions. In addition, we searched by hand the reference lists of other relevant articles on therapeutic approaches to bullous pemphigoid. In this first phase, 100 records were identified from the selected databases. The.