Search Results (39)

Background/Objectives: Anti-p200 pemphigoid is a rare and likely underdiagnosed autoimmune blistering disorder. Laminin γ1 and laminin β4 have been implicated as potential target antigens in its pathogenesis. Recently, a novel indirect immunofluorescence assay targeting anti-laminin β4 antibodies has been developed, demonstrating high sensitivity and specificity, and offering a valuable tool for improved diagnosis. Methods: Of the 451 patients, 21 were selected for further laboratory analysis based on medical records. Sera from 10 patients, which showed a positive direct immunofluorescence (DIF) result and negative results in multiplex enzyme-linked immunosorbent assays (ELISAs) and/or mosaic six-parameter indirect immunofluorescence (IIF) for various autoimmune bullous diseases, were tested for the presence of anti-laminin β4 antibodies. Additionally, sera from 11 patients with positive DIF and positive ELISA for antibodies against BP180 and/or BP230 were analyzed. Results: Among the 10 patients with positive DIF and negative ELISA and/or mosaic six-parameter IIF, 6 sera were positive for anti-laminin β4 antibodies. These patients presented with atypical clinical features. In contrast, all 11 sera from patients with both positive DIF and positive ELISA for BP180 and/or BP230 were negative for anti-laminin β4 antibodies. Conclusions: In patients with a positive DIF result but negative ELISA and/or mosaic six-parameter IIF findings, testing for anti-laminin β4 antibodies should be considered. Furthermore, in cases presenting with atypical clinical features—such as acral distribution of lesions, intense pruritus, or erythematous–edematous plaques—the possibility of anti-p200 pemphigoid should be included in the differential diagnosis. Full article

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) represent the most prevalent conditions among autoimmune bullous skin diseases, considered a major cause of severe morbidity and, in certain cases, mortality. The hallmark of the two diseases is the presence of autoantibodies directed against proteins located in the basement membrane of the skin, which determines the formation of blisters. In recent years, interest in the role of microbiota in relation to health-disease status has progressively increased. In particular, based on the gut–skin axis, accumulating evidence has emerged on the potential association between the composition and diversity of microbial communities in the gut, skin, and even in the oral cavity and the risk of developing BP and PV. Dysbiosis, characterized by a generally higher relative abundance of Firmicutes and a depletion of probiotics/beneficial species, might contribute to the pathogenesis of both diseases. Despite the still limited number of studies and the need for further large-scale multicenter studies, the knowledge gathered so far is suggestive of a novel modifiable risk factor representing a potential target for adjuvant treatments of these disabling and life-threatening conditions. Full article

Background/Objective: Bullous Pemphigoid (BP) is a well-recognized autoimmune subepidermal blistering disease. However, its occurrence following allogeneic hematopoietic stem cell transplantation (HSCT) is extremely rare. The objective of this study is to systematically review the available data on BP following an allogeneic HSCT with focus on treatment options. Methods: A systematic review of studies evaluating BP following allogeneic HSCT, incorporating a highly treatment-resistant case from our graft-versus-host disease (GvHD) dermatology clinic, of a 47-year-old patient, notable as the only reported instance of BP following HSCT in a patient with chronic lymphocytic leukemia (CLL) that transformed into diffuse large B-cell lymphoma (DLBCL) and GvHD due to HSCT. The review yielded 15 publications that met the eligibility criteria. Including our case, a total of 16 cases were analyzed. Results: Nearly all patients (14/16) in this review had chronic GvHD due to their HSCT. Twelve patients were males, and six were of Japanese origin. The mean age for BP diagnosis was 38 years (a range of 5–67). On average, BP developed one year post-HSCT. The most common treatment for BP in these patients was prednisolone, with the majority experiencing complete resolution of symptoms. Conclusions: BP following HSCT is an exceptionally rare condition with an unclear underlying mechanism. Full article

Background/Objectives: Cutaneous side effects are the most common immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) and affect 70–90% of patients. Besides diverse types of exanthema, rare skin toxicity includes bullous dermatoses in 0.3% of cases. Systemic steroids are the first-line treatment for immune-related bullous pemphigoid (irBP); however, some cases are corticosteroid-resistant. IrBP is one of the irAEs most frequently chronic and associated with long-term steroid use. However, steroids may interfere with tumor response. Therefore, alternative treatment strategies for irBP are desperately needed. Dupilumab, a monoclonal antibody blocking the receptor binding of interleukin-4 (IL-4) and interleukin-13 (IL-13), has been successfully used to treat spontaneous forms of bullous pemphigoid (BP). In this study, we analyzed the gene expression profiles of BP and irBP. Patients and Methods: A retrospective multicenter study evaluated the gene expression profiles of irBP and BP in comparison to healthy controls. Gene expression analyses of skin biopsies were performed using NanoString technology from patients with BP (n = 17), irBP (n = 19), and healthy skin (n = 24) after the patients had consented to participate in this study, and differentially expressed genes (DEGs) were determined using Rosalind software. Results: Compared to healthy skin, BP showed 167 DEGs, and irBP revealed 99 DEGs. Some of the DEGs from irBP and BP vs. healthy skin overlapped. Specifically, IL-4- and IL-13-associated genes were upregulated in both irBP and BP compared to healthy skin. Interestingly, expression profiles of BP vs. irBP also showed 13 DEGs. Conclusions: These findings suggest a possibility for therapeutic efficacy of IL-4 and IL-13 inhibitors in the treatment of irBP. Full article

Bullous pemphigoid (BP) is a rare autoimmune disease, primarily affecting elderly individuals, that significantly impacts the patient’s quality of life. In contrast, psoriasis vulgaris (PV) is a common, chronic, immune-mediated skin condition recognized as a systemic T-cell-mediated disorder. We aim to present the case of a patient suffering from a dermatologic association of BP and PV, which unveiled hepatitis C viral infection as a potential trigger and led to complex therapeutic challenges. A literature review is also included, exploring previous cases of overlapping BP and PV, along with a discussion of the unique pathogenic mechanisms and an analysis of the available therapeutic options. The patient, a 53-year-old male with a seven-year history of PV, presented with tense bullae overlying the psoriatic papules and plaques, with a generalized distribution. The presence of hepatitis C infection was considered a potential trigger for the concurrent presentation of BP and PV. Recent GWASs have demonstrated a potential causal relationship between PV and the subsequent development of BP, suggesting shared genetic susceptibility and immune pathways. However, the exact mechanisms driving this transition remain incompletely understood. Our case is particularly relevant as it exemplifies how environmental triggers—such as chronic hepatitis C infection—together with chronic cutaneous inflammation may act as cofactors in this process, possibly through the ‘epitope spreading’ phenomenon. This case underlines the importance of identifying triggering factors in patients with overlapping autoimmune diseases and reinforces the need for future research to further elucidate the pathogenic link between genotype and phenotype, in order to improve personalized therapeutic strategies. Full article

Autoimmune blistering diseases (AIBDs) involve autoantibodies targeting proteins in the epidermal/epithelial desmosome (pemphigus) or basement membrane zone (pemphigoid). Despite widespread antigen distribution, lesions exhibit a scattered involvement pattern. This study maps the frequency/severity of AIBD lesions on various body parts and investigates whether differential antigen expression contributes to specific predilection sites. We analyzed affected sites presenting blisters/erosions, erythematous/urticarial lesions, and mucosal lesions in bullous pemphigoid (BP-cohort 1, n = 65; BP-cohort 2, n = 119), pemphigus vulgaris (PV, n = 67), and pemphigus foliaceus (PF, n = 20) patients. To assess antigen expression, we conducted indirect immunofluorescence (IF) staining of 11 AIBD antigens from 13 anatomical sites of 10 body donors without AIBD. In BP, blisters/erosions and erythematous/urticarial lesions predominantly affected arms and legs, while PV/PF patients exhibited frequent involvement of buccal mucosa and back, respectively. IF staining identified significant regional differences in BP180, BP230, and integrin β4 expression, although these variations did not correlate with a higher lesion frequency/severity. Other antigens showed consistent expression across all regions. Our findings suggest that predilection sites for BP and PV/PF are largely unaffected by regional variations in antigen expression but may be influenced by factors like microbiota, mechanical stress, sunlight exposure, local immunity, or genetics. Full article

The COVID-19 pandemic has encouraged the rapid development and licensing of vaccines against SARS-CoV-2. Currently, numerous vaccines are available on a global scale and are based on different mechanisms of action, including mRNA technology, viral vectors, inactive viruses, and subunit particles. Mass vaccination conducted worldwide has highlighted the potential development of side effects, including ones with skin involvement. This review synthesizes data from 62 manuscripts, reporting a total of 142 cases of autoimmune blistering skin diseases (AIBDs) following COVID-19 vaccination, comprising 59 cases of pemphigus and 83 cases of bullous pemphigoid. Among the 83 bullous pemphigoid cases, 78 were BP, with additional cases including 2 oral mucous membrane pemphigoid, 1 pemphigoid gestationis, 1 anti-p200 BP, and 1 dyshidrosiform BP. The mean age of affected individuals was 72 ± 12.7 years, with an average symptom onset of 11 ± 10.8 days post-vaccination. Notably, 59% of cases followed vaccination with BNT162b2 (Pfizer-BioNTech), 51.8% were new diagnoses, and 45.8% occurred after the second dose. The purpose of our review is to analyze the cases of pemphigus and bullous pemphigoid associated with COVID-19 vaccination and to investigate the pathogenetic mechanisms underlying the new development or flare-up of these diseases in association with vaccination. Our results show that the association between COVID-19 vaccines and AIBDs is a possible event. Full article

Background: Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of autoimmune blistering disease (AIBD), which can result in scarring and vision loss. The diagnosis of oMMP is challenging as patients often have undetectable levels of circulating autoantibodies by conventional assays. Likewise, the principal autoantigen in oMMP has been an area of debate. Methods: In this preliminary experiment, we performed Phage Immunoprecipitation Sequencing (PhIP-seq) on sera from patients with oMMP, as well as non-ocular MMP, bullous pemphigoid, and mucocutaneous-type pemphigus vulgaris. Results: We identified several autoantigens unique to oMMP relative to other AIBDs. We then cross-referenced these antigens against previously published single-nuclei datasets, as well as the International Mouse Phenotyping Consortium Database. Several protein hits identified in our study demonstrated enriched expression on the anterior surface epithelia, including TNKS1BP1, SEC16B, FNBP4, CASZ1, GOLGB1, DOT1L, PRDM 15, LARP4B, and RPL6. Likewise, a previous study of mouse knockout models of murine analogs CASZ1, HIP1, and ELOA2 reported that these mice showed abnormalities in terms of the ocular surface and development in the eyes. Notably, PhIP-seq failed to identify the canonical markers of AIBDs such as BP180, BP230, desmogleins 1 and 3, or integrin β4, indicating that the patient autoantibodies react with conformational epitopes rather than linear epitopes. Conclusions: oMMP patients demonstrate a unique autoantibody repertoire relative to the other AIBDs. Further validation of the identified autoantibodies will shed light on their potentially pathogenic role. Full article

Background and Objectives: Bullous pemphigoid (BP) is the most common autoimmune blistering disease affecting mainly elderly patients. Still, little is known about the pathogenesis of pruritus in BP or the factors that affect the clinical course of the disease. This study aimed to evaluate the factors influencing the clinical course of BP among older patients. Materials and Methods: A retrospective analysis of medical records of 55 patients with BP hospitalized in the dermatology department in 2015–2021 was conducted. The study focused on preliminary diagnosis, medical history, clinical examination (characteristics and location of cutaneous changes), laboratory investigation, and direct and indirect immunofluorescence. Results: Analysis of laboratory results in combination with the clinical course of BP showed that red blood cell count, hemoglobin, and hematocrit values were negatively associated with a risk of erosions and erythema, while MCHC values were positively correlated with a risk of associated pruritus. A correlation was found between neurological diseases and an increased risk of erosions. Conclusions: We have shown that age and neurological conditions, including stroke, affect the clinical course of BP. Further studies on a larger group of patients should be conducted to investigate the different factors affecting the clinical aspect of BP and to understand the relationship between them. Full article

Background: Bullous pemphigoid is an autoimmune bullous disease that frequently affects a large skin surface area, but it can also present in localized areas. It has been hypothesized that bullous pemphigoid affects the systemic functioning of different organs because inflammatory cells and cytokines circulate throughout numerous organs. Results: Recent clinical and experimental studies have revealed an association between bullous pemphigoid and systemic organ disorders. To avoid the emergence of systemic organ diseases, the significance of systemic treatment in cases of severe bullous pemphigoid should be emphasized. Conclusions: Here, we discuss the specific molecular processes underlying typical systemic organ inflammatory diseases associated with bullous pemphigoids. Full article

Bullous pemphigoid (BP) is the most common autoimmune bullous disease, whose main autoantigens are hemidesmosomal components BP180 and BP230. Although recent studies found no association between COVID-19 vaccines and BP, since mass vaccinations started, more than 90 vaccine-associated BP cases have been reported. To find an agreement among real-life clinical observations and recent epidemiologic data, we further investigated this topic. A total of 64 patients with BP onset in 2021 were demographically, clinically, and serologically characterized: 14 (21.9%) vaccine-associated patients (VA) developed BP within 5 weeks from the first/second vaccine dose. VA and vaccine-non-associated (VNA) patients had similar demographics and clinical and immunological characteristics. Noteworthy, the monthly distribution of BP onset during mass vaccinations paralleled vaccine administration to the elderly in the same catchment area. Additionally, in 2021, BP onsets in April–May and June–July significantly increased (p = 0.004) and declined (p = 0.027), respectively, compared to the three years before vaccination campaigns (2018–2020). Interestingly, VA and VNA patients showed statistically significant differences in the use of inhalers and diuretics. Our findings suggest that the COVID-19 vaccine may constitute an accelerating factor that, together with other triggering factors, could act in genetically predisposed individuals with possible sub-clinical autoreactivity against BP antigens, slightly accelerating BP onset. Full article

Immune checkpoint inhibitors (ICIs) activate T cells, causing immune-related adverse events (irAEs). Skin manifestations are common among irAEs, but ICI-associated bullous pemphigoid (BP) is rare. Inhibiting programmed death (PD)-1 signaling, in addition to causing epitope spreading, may disrupt B and T cell balance, causing excessive autoantibody production against the skin’s basement membrane, leading to BP. A 70-year-old woman developed late-onset multi-organ irAEs, including diarrhea, thyroid dysfunction, and BP, while receiving pembrolizumab, a PD-1 inhibitor. This highlights the long-term risk of irAEs, which can occur 2–3 years after starting ICIs. In cases of multi-organ irAE, C-reactive protein levels and neutrophil/lymphocyte ratio are often low. These characteristics were observed in our case. Few papers address multiple organ involvement, highlighting the need to consider irAEs in a multi-organ context. While it is known that drug-induced skin reactions worsen as blood eosinophil counts increase, in our case, the eosinophil count remained normal, suggesting that ICI-associated BP might have been controlled without discontinuing the ICI and through tapering of low-dose oral prednisone treatment. Additionally, in this case, significant CD4-positive T cell infiltration was observed in the immunostaining examination of the blisters, indicating that severe CD4-positive T cell infiltration induced by the ICI might have led to multi-organ involvement, including severe diarrhea. Few reports focus on blood eosinophil counts in BP cases or discuss CD4 and CD8 immunostaining in BP cases. Therefore, future research should explore the relationship between blood eosinophil counts, immunostaining results, and the prognosis of irAEs, including BP, in treatment courses. Full article

Background: Bullous pemphigoid (BP) is an autoimmune disease characterized by the appearance of very pruritic subepidermal blisters. It appears mostly in the elderly and is associated with multiple comorbidities, which makes its management and treatment difficult. The purpose of this systematic review is to compile current information on published cases of BP treated with omalizumab (omalizumab) and dupilumab (dupilumab) in order to obtain information on clinical efficacy and safety data available. Methods: A literature search of all cases of BP treated with omalizumab/dupilumab published in the literature up to January 2024 was performed using the Pubmed database. After an exhaustive search, a total of 61 studies encompassing 886 patients met the inclusion criteria and were included in the review. Results: The majority of patients with BP treated with omalizumab/dupilumab presented a significant improvement in symptomatology, being very safe drugs with minimal side effects. The main limitation of the presented review is the quality of the included studies, most of them being case series or individual cases. The development of studies with a higher level of scientific evidence in the near future would be of great interest. Conclusions: Both omalizumab and dupilumab appear to be effective options for treating BP in patients refractory to other pharmacological therapies. They are drugs with a good safety profile and the adverse reactions associated with their use are infrequent and generally mild. Full article

Background: Cases of autoimmune bullous dermatosis (AIBD) have been reported following COVID-19 vaccination. Objective: We aimed to provide an overview of clinical characteristics, treatments, and outcomes of AIBDs following COVID-19 vaccination. Methods: We conducted a systematic review and searched the Embase, Cochrane Library, and Medline databases from their inception to 27 March 2024. We included all studies reporting ≥ 1 patient who developed new-onset AIBD or experienced flare of AIBD following at least one dose of any COVID-19 vaccine. Results: We included 98 studies with 229 patients in the new-onset group and 216 in the flare group. Among the new-onset cases, bullous pemphigoid (BP) was the most frequently reported subtype. Notably, mRNA vaccines were commonly associated with the development of AIBD. Regarding the flare group, pemphigus was the most frequently reported subtype, with the mRNA vaccines being the predominant vaccine type. The onset of AIBD ranged from 1 to 123 days post-vaccination, with most patients displaying favorable outcomes and showing improvement or resolution from 1 week to 8 months after treatment initiation. Conclusions: Both new-onset AIBD and exacerbation of pre-existing AIBD may occur following COVID-19 vaccination. Healthcare practitioners should be alert, and post-vaccination monitoring may be essential. Full article

Bullous pemphigoid (BP), the most common autoimmune blistering disease, is characterized by the presence of autoantibodies targeting BP180 and BP230 in the basement membrane zone. This leads to the activation of complement-dependent and independent pathways, resulting in proteolytic cleavage at the dermoepidermal junction and an eosinophilic inflammatory response. While numerous drugs have been associated with BP in the literature, causality and pathogenic mechanisms remain elusive in most cases. Dipeptidyl peptidase 4 inhibitors (DPP4i), in particular, are the most frequently reported drugs related to BP and, therefore, have been extensively investigated. They can potentially trigger BP through the impaired proteolytic degradation of BP180, combined with immune dysregulation. DPP4i-associated BP can be categorized into true drug-induced BP and drug-triggered BP, with the latter resembling classic BP. Antineoplastic immunotherapy is increasingly associated with BP, with both B and T cells involved. Other drugs, including biologics, diuretics and cardiovascular and neuropsychiatric agents, present weaker evidence and poorly understood pathogenic mechanisms. Further research is needed due to the growing incidence of BP and the increasing identification of new potential triggers. Full article