RARE DISEASE
Bullous pemphigoid
Bullous pemphigoid
Bullous pemphigoid
Drug discovery
8
drugs
With orphan designations
Overview
Bullous Pemphigoid (BP) is a chronic autoimmune blistering disease characterized by IgG/IgE autoantibodies targeting hemidesmosomal proteins BP180/BP230, leading to subepidermal separation, pruritus, and tense blisters. Diagnosis combines clinical presentation (urticarial plaques, flexural blisters), histopathology (eosinophil-rich subepidermal cleavage), and immunofluorescence (linear basement membrane IgG/C3 deposits). Treatment centers on corticosteroids and immunosuppressants, with emerging biologics targeting IL-4/IL-13, IgE, and complement pathways. Mortality rates remain elevated due to comorbidities and treatment-related complications [1][5][6].
Population
Primarily affects adults >70 years (median age 66–83), with incidence rising to 190–312 cases/million/year in those >80; rarely occurs <50 [2][12][14].
Incidence has increased 1.9- to 4.3-fold since 2000, linked to aging populations, neurocognitive disorders (e.g., dementia), and drug triggers (e.g., DPP-4 inhibitors) [2][5][10].
Burden
Mortality: 23% 1-year mortality, rising to 27–72% in frail elderly, driven by infections, thromboembolism, and comorbidities (stroke, diabetes) [4][15][17].
Quality of life: Severe pruritus, pain, and depression/anxiety rates of 31–38%; prolonged hospitalizations (+2.6 days vs. controls) [4][7][16].
Economic impact: High healthcare utilization (mean 7.3 hospital days) and costs from long-term immunosuppression [4][12][19].
Therapies
First-line: High-potency topical corticosteroids (e.g., clobetasol) or oral prednisone (0.5 mg/kg/day), tapered with steroid-sparing agents (doxycycline, methotrexate, azathioprine) [1][8][18].
Refractory cases: Biologics (rituximab, omalizumab) and targeted therapies (dupilumab, bertilimumab) show promise in clinical trials [3][13][17].
Adjuncts: Wound care, infection prevention, and monitoring for steroid toxicity (osteoporosis, diabetes) [1][6][16].
Categories: rare skin diseases
Research Papers
1,220 drug discovery papers about Bullous pemphigoid, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,220 drug discovery papers about Bullous pemphigoid, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-02 | Factors associated with prolonged hospital stay in patients with autoimmune bullous diseases treated at an in-patient dermatology service.
Bullous diseases carry a great burden and are often linked to high healthcare costs. Patients with -bullous diseases are more vulnerable to infections and organ damage due to an incompetent skin barrier. To determine the demographic, clinical and laboratory factors associated with prolonged hospital stay in patients with autoimmune bullous diseases. This was a cross-sectional study, with a follow-up cohort, including all dermatology consultations in a university hospital between 2017 and 2022 to identify patients with autoimmune bullous disease. Duration of stay and other variables were obtained from the patients' medical records. A total of 83 patients were included in the study, of whom the majority had bullous pemphigoid (n = 45; 54%). There was significant metabolic comorbidity with hypertension (n = 51; 61%), diabetes (n = 31; 37%) and dyslipidaemia (n = 31; 37%). Fifty-eight per cent of patients had a prolonged hospital stay (>10 days). Among the associated variables, mucosal involvement, eosinophilia, in-hospital antibiotics and the absence of dipetidyl peptidase-4 (DPP4) inhibitor use stood out. Most patients with bullous diseases have prolonged hospital stays. The evaluation of mucous membranes, blood count and a basic chemical panel can help identify patients at greater risk of prolonged hospital stays. In addition, the use of DPP4 inhibitors and their rapid discontinuation could affect this outcome.
2026-07-29 | Treatment patterns for bullous pemphigoid in older adults: A population-based study.
Bullous pemphigoid (BP) is a chronic autoimmune blistering disease that disproportionately affects older adults and is associated with substantial morbidity, mortality, and treatment-related risks. Despite an expanding therapeutic landscape, real-world prescribing patterns in this population remain poorly characterized. To evaluate medication prescribing patterns among older adults with BP and assess the feasibility of using national claims data to characterize treatment exposures relevant to drug safety and risk stratification. We conducted a retrospective cohort study using Medicare fee-for-service claims data (2016-2020). Adults aged 65 years or older with BP were identified using ICD-10 codes. Prescription drug event data were linked to outpatient claims to capture medication use. Treatments were categorized into topical corticosteroids (by potency), oral immunomodulators and antibiotics, and biologic therapies. Descriptive analyses were performed to evaluate prescribing distributions. Among 10,959 patients with BP and 78,468 outpatient claims, we identified 19,663 prescriptions. Oral immunomodulators and antibiotics comprised 67.5% of prescriptions, followed by topical corticosteroids (32.5%) and biologics (0.04%). Prednisone accounted for 62.9% of oral prescriptions, followed by doxycycline (20.2%) and mycophenolate (6.0%). Among topical steroids, medium-potency agents were most common (40.6%), followed by super high-potency (38.2%). Biologic use was rare, with dupilumab accounting for most prescriptions. Systemic corticosteroids remain the predominant therapy for BP in older adults, with substantial variability in topical steroid use and minimal uptake of biologics. These findings highlight gaps in treatment optimization and support the need for risk-informed, steroid-sparing strategies in this high-risk population.
2026-07-27 | Effect and length of doxycycline administration in elderly patients with bullous pemphigoid.
Bullous pemphigoid (BP) is the most common autoimmune blistering disease and primarily affects the elderly. Systemic corticosteroids and immunosuppressive drugs are the standard treatment, but side effects often restrict their use. Doxycycline has been proposed as an alternative, but there is limited long-term, real-world data on its efficacy and tolerability. We aimed to evaluate the effectiveness and length of doxycycline treatment in BP patients. This retrospective, single-center study analyzed data from patients with a confirmed BP diagnosis treated with doxycycline. The comprehensive dataset included information on disease severity, concomitant therapies, and treatment response. Treatment duration was analyzed using the Kaplan-Meier method. The cohort comprised 102 patients with a mean age of 79 (range 51-95) years. A clinical response (an improvement of 1 or 2 on the PGA score, which ranges from 2 to -2) was observed in 85 patients (83.3 %), many of whom received combination therapy with other drugs (67.7 %). The median length of doxycycline treatment was 122.7 weeks. Adverse events, mainly of gastrointestinal origin, were rare, non-serious and manageable. Doxycycline proved to be an effective and well-tolerated long-term treatment for elderly patients with BP, when used either as monotherapy or in combination.
2026-07-18 | STING Drives CD4+T Cell Differentiation via JAK-STAT Signalling in Bullous Pemphigoid.
Bullous pemphigoid (BP) is an autoimmune blistering disease with an increasing incidence in recent years; however, the underlying immune regulatory mechanisms remain largely unclear. As a critical signalling hub linking innate and adaptive immunity, stimulator of interferon genes (STING) has recently been implicated in the pathogenesis of various autoimmune diseases and may regulate tissue inflammation and immune homeostasis through modulation of CD4+ T cell responses. In this study, we found that STING expression was significantly increased in lesional skin tissues from patients with BP compared with healthy controls. Transcriptomic analysis further revealed that differentially expressed genes in peripheral blood CD4+ T cells from BP patients were primarily enriched in the JAK-STAT signalling pathway, T cell activation and differentiation, and type I interferon (IFN-I)-related pathways. Pharmacological inhibition of STING markedly attenuated the aberrant activation of these signalling pathways. Moreover, qRT-PCR analysis confirmed that the mRNA levels of STING1, JAK1, and CXCR5 were significantly elevated in BP patients, whereas treatment with the STING inhibitor C176 suppressed the expression of these molecules. Collectively, our findings suggest that STING may contribute to BP immunopathogenesis by regulating the JAK-STAT signalling axis and promoting abnormal CD4+ T cell activation and differentiation, providing new insights into the molecular mechanisms underlying BP and identifying potential therapeutic targets.
2026-06-29 | Real-World Outcomes of Stapokibart-Based Combination Therapy for Bullous Pemphigoid: A Single-Center Retrospective Cohort.
Bullous pemphigoid (BP) affects older adults and treatment is often limited by corticosteroid toxicity. Evidence for stapokibart in BP is limited. To describe the clinical outcomes and safety of stapokibart-based combination therapy in BP. We retrospectively reviewed consecutive BP patients who received stapokibart-based combination therapy at Peking Union Medical College Hospital between October 2024 and October 2025, and had a follow-up period of at least four months. Stapokibart was administered as 600 mg loading dose, followed by 300 mg every two weeks. Outcomes included time to disease control, time to Bullous Pemphigoid Disease Area Index (BPDAI) activity score of 0, complete remission (CR) on minimal therapy, adverse events, and changes in BPDAI activity, pruritus numeric rating scale (NRS), anti-BP180 titers, eosinophil counts, and concomitant corticosteroid exposure throughout the follow-up period. Twelve patients were enrolled, with a median age of 77.5 years and a median follow-up period of 216.5 days. All received concomitant Tripterygium glycoside, and 7/12 (58.3%) also received oral corticosteroids at stapokibart initiation. All patients achieved disease control, with a median time of 14.5 days. Eleven out of 12 patients (91.7%) reached disease control within four weeks. BPDAI activity score of 0 was reached in all patients (median 65.5 days). Seven patients (58.3%) achieved CR on minimal therapy (median 176.0 days among responders). During follow-up, BPDAI activity, pruritus NRS, eosinophil counts, anti-BP180 titers, and prednisone dosages all decreased. One patient reported temporary fatigue and later developed herpes zoster. No patients stopped treatment throughout the study. Stapokibart-based combination therapy was associated with rapid short-term disease control and clinical improvement in this small retrospective BP cohort. Given the limited sample size and frequent concomitant therapy, these preliminary findings require confirmation in larger controlled studies.
cell therapies
2026-05-07 | Regulatory T cells in bullous pemphigoid: biological characteristics, dysfunction, and pathogenic roles.
Bullous pemphigoid (BP) is an autoimmune blistering disorder that predominantly affects the elderly. Its pathogenesis involves the disruption of the basement membrane zone (BMZ), driven by pathogenic autoantibodies and a pronounced inflammatory response. Current first-line therapies, primarily based on glucocorticoids and immunosuppressants, are limited by substantial side effects and frequent disease recurrence. Regulatory T cells (Tregs) play a central role in maintaining immune homeostasis and peripheral tolerance, exerting control over effector immune cells through transcriptional regulation, surface markers, and diverse immunosuppressive mechanisms. Accumulating evidence indicates that numerical reduction and functional impairment of Tregs are critical to the breakdown of immune tolerance in BP. Treg dysfunction leads to the aberrant activation of Th2, Th17, and follicular helper T (Tfh) cells, which in turn promotes the production of anti-BP180/BP230 autoantibodies and disrupts the regulation of inflammatory cells such as neutrophils and eosinophils. These events collectively result in BMZ degradation and blister formation. Multiple factors, including age-related immunosenescence, genetic predisposition, pharmacological exposures, and environmental stimuli, can further compromise Treg function, thereby contributing to BP pathogenesis. A deeper understanding of Treg-driven mechanisms in BP provides a rational basis for developing targeted therapeutic strategies.
2025-12-19 | O01 Infantile bullous pemphigoid: when autoimmunity hides an immunodeficiency.
Infantile bullous pemphigoid (BP) can be an early manifestation of ZAP-70 deficiency, a rare combined immunodeficiency (CID) characterised by defective T-cell signalling and a propensity to multiple autoimmune manifestations.1 We describe two patients with BP subsequently diagnosed with ZAP-70 deficiency. Case 1: A female neonate presented at 14 days with severe seborrhoeic dermatitis. From 3 months she was repeatedly admitted with severe respiratory infections. Investigations revealed normal full blood count (FBC), but profoundly reduced CD8+ lymphocytes. At 7 months she developed an extensive bullous eruption. Skin biopsy with direct and indirect immunofluorescence confirmed the diagnosis of BP, which was difficult to control and required multiple systemic treatments, including methylprednisolone, dapsone, dupilumab, intravenous immunoglobulin and rituximab. She developed immune-mediated thrombocytopenia and is currently being prepared for bone marrow transplantation (BMT) due to ZAP-70 deficiency. Case 2: A female infant presented at 3 months with bullae of the face and extremities. Skin biopsy with direct and indirect immunofluorescence confirmed BP, which responded to topical corticosteroids and erythromycin. At 9 months she developed recurrent severe respiratory infections requiring ventilation. Laboratory studies showed near-absent CD8+ lymphocytes and confirmed ZAP-70 deficiency. She underwent BMT in June 2024, with no recurrence of blistering. Conclusion: Infantile BP should prompt suspicion of an underlying CID. Assessment of lymphocyte subsets is essential, as ZAP-70 deficiency is characterised by profoundly reduced CD8+ lymphocytes, which may not be apparent on a standard FBC where total lymphocyte numbers can be normal. Early -diagnosis is essential, as BMT offers the only curative -treatment.
2025-11-03 | Adjuvant therapy of severe and/or refractory bullous pemphigoid with immunoadsorption - A prospective monocenter pilot study.
Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the Western world. While remission is achieved in the majority of BP patients by long-term use of corticosteroids with or without immunomodulants/immunosuppressants, national and international guidelines recommend adjuvant immunoadsorption (IA) in refractory patients. Here we investigated the safety and efficacy of IA in severe and/or refractory BP patients. 10 BP patients (3 women, 7 men; mean age 69.7 years; range 52-81 years) were treated with IA on three consecutive days (LigaSorb®, Fresenius Medical Care) combined with oral prednisolone (0.5 mg/kg BW per day, tapered), dapsone (1.5 mg/kg BW per day), and lesional mometasone furoate ointment. Within 2 and 6 months after IA, 50% and 90% of patients showed complete remission on therapy, respectively. In all patients, serum anti-BP180 IgG levels decreased significantly by an average of 89% and 73% immediately after the third IA and 4 weeks later, respectively. A total of 56 adverse events (AE) occurred during the 12-month follow-up. The majority of AE were of severity grade 2 (50%), 15 AE were classified as severe (grade 3-4). IA can be considered as a relatively safe and effective adjuvant therapy for patients with severe or refractory BP.
2025-06-22 | Can we cure bullous skin diseases?
Autoimmune bullous diseases (AIBDs), including pemphigus and pemphigoid, are featured as the presence of autoantibodies directed against structural proteins, resulting in severe blistering as well as considerable morbidity. Current treatments, including glucocorticoids, immunomodulators, and biologics, often fail to achieve sustained remission due to high relapse rates and significant adverse effects. This review explores the pathophysiology of AIBDs, focusing on autoreactive B and T cells, inflammatory mediators, and immune dysregulation. Existing therapeutic limitations are then analyzed, and emerging treatment options, such as chimeric antigen receptor-T therapy, regulatory T cell-based interventions, and tolerogenic vaccines, are discussed as potential curative approaches. Additionally, preventive measures, such as genetic screening and environmental risk management, are considered. By integrating novel immunotherapies and immune modulation techniques through a three-step approach - disease control, pathogenic cell elimination, and induction of immune tolerance - we may move closer toward achieving sustained remission and potentially curing of AIBDs.
2025-05-15 | Autoimmune bullous diseases: pathogenesis and clinical management.
Autoimmune bullous diseases (AIBDs) represent a heterogeneous group of immune-mediated disorders characterized by life-threatening blistering of the skin and mucous membranes. This Review synthesizes current understanding of AIBD pathogenesis, clinical phenotypes, diagnostic approaches, and therapeutic strategies, emphasizing recent advancements and translational opportunities. At the core of AIBDs is autoantibody-mediated disruption of structural proteins in the epidermis or basement membrane zone, particularly at desmosomal and hemidesmosomal junctions. Key subtypes, including pemphigus, paraneoplastic pemphigus, pemphigoid, and IgA-related diseases, are distinguished by their target antigens, clinical manifestations, and immunopathological profiles. Diagnostic workflows rely on direct immunofluorescence, and serological assays, yet subtype differentiation remains challenging due to overlapping features. Traditional therapies, such as systemic corticosteroids and immunosuppressants, have improved outcomes but are limited by toxicity. Recent breakthroughs highlight targeted interventions, including B-cell depletion with rituximab, cytokine modulation via dupilumab, and JAK inhibitors for inflammatory pathways. Innovative strategies like chimeric autoantibody receptor T-cell (CAART) therapy further address refractory cases by eliminating autoreactive B cells. Additionally, the Review underscores the emerging role of inflammation-driven mechanisms and the necessity of multidisciplinary care, given AIBDs' associations with malignancies, autoimmune comorbidities. Despite progress, challenges persist in early diagnosis, personalized therapy optimization, and understanding antigen-specific immune responses. Future directions include refining diagnostic biomarkers, exploring novel targets, and developing precision medicine approaches.
proteins
2026-04-26 | Treg cells as potential therapeutic targets for bullous pemphigoid: A review.
Bullous pemphigoid (BP) is an autoimmune disease characterized by Bullous pemphigoid antigen 180(BP180) and Bullous pemphigoid antigen 230(BP230) autoantibodies production. Regulatory T cells (Tregs) are key cells for the maintenance of immune tolerance. Increasing evidence suggests that Treg dysfunction leads to autoantibody production and skin rashes in mice and humans, making immunomodulatory therapies targeting Tregs a potential therapeutic strategy for BP. Low-dose Interleukin-2 treatment and adoptive cell therapy are promising methods to modulate Tregs' numbers and function. Herein, we review the immunological mechanisms underlying BP pathogenesis, with an emphasis on the protective role of Treg cell-mediated immune tolerance in BP. Furthermore, we explore the potential therapeutic applications of Treg-based therapies for BP, providing novel insights into patient management.
2025-07-31 | Galectin-9: diverse roles in skin disease.
Galectin-9 (Gal-9) is a multifunctional immunomodulatory molecule involved in cell growth, differentiation, adhesion, communication, and death. Galectin-9 mediates its physiological functions through interactions with multiple membrane receptors, including T-cell immunoglobulin mucin-domain containing-3 (Tim-3), immunoglobulin E, and the hyaluronan receptor CD44. In recent years, Gal-9 has been extensively studied in autoimmune diseases, tumor microenvironments, and viral infections. The circulating levels of this lectin demonstrate clinical correlation with disease progression in both acute and chronic infectious conditions. In addition, Gal-9 can potentially be a reliable, sensitive, and noninvasive biomarker of disease severity in many skin diseases. However, there has not been a review of Gal-9 studies in patients with dermatosis. This review summarizes recent advances in understanding Gal-9's immunomodulatory mechanisms in chronic spontaneous urticaria pathophysiology, systemic lupus erythematosus, atopic dermatitis, melanoma, systemic sclerosis, herpes simplex virus infection, bullous pemphigoid, psoriasis, vitiligo, maculopapular exanthema, and skin grafting to provide a reference for future research. Gal-9 is an important regulator of immune homeostasis whose level changes significantly in many skin diseases, and validation was performed in a mouse model using exogenous Gal-9. Ongoing studies are necessary to clarify the pathophysiology of Gal-9, identify the potential of Gal-9 as a new biomarker, and develop new therapeutic approaches for skin diseases.
2025-05-27 | A Closer Look at the Dermatological Profile of GLP-1 Agonists.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in treating type 2 diabetes and obesity, offering established metabolic and cardiovascular benefits. Emerging evidence suggests these agents also exert direct dermatologic effects. This systematic review categorizes these effects and explores their role in inflammatory skin diseases. A comprehensive literature search was performed across EMBASE, PubMed, Web of Science, and Google Scholar for studies published from 2014 to 2025. Inclusion criteria were English-language, peer-reviewed original research involving human subjects that linked GLP-1RAs to dermatologic effects. Animal and in vitro studies were excluded. PRISMA guidelines were followed. Fifty-one studies met inclusion criteria. Thirty-four reported adverse effects, including hypersensitivity, injection-site reactions, pruritus, urticaria, angioedema, and immune-mediated conditions like bullous pemphigoid. Seventeen studies described beneficial outcomes, such as improvements in psoriasis, reduced hidradenitis suppurativa flares, enhanced wound healing, anti-aging potential, and decreased inflammation. GLP-1RAs showed cytokine modulation in psoriasis, though their role in hidradenitis suppurativa remains uncertain. Cosmetic concerns, such as "Ozempic Face" due to rapid weight loss, were also noted. GLP-1RAs have a broad spectrum of dermatologic effects, from immunomodulatory benefits to adverse cutaneous reactions. Their impact on inflammatory skin disorders suggests a novel therapeutic avenue. However, adverse reactions and aesthetic changes warrant vigilance. Future research should focus on mechanistic studies, long-term safety, and identifying biomarkers to predict dermatologic responses, ultimately guiding personalized treatment approaches.
2025-04-27 | Analysis of rare events in healthcare intervention using department of defense data: intravenous immune globulin therapy for bullous pemphigoid.
Rare events data have proven difficult to explain and predict. Standard statistical procedures can sharply underestimate the probability of rare events, such as intravenous immune globulin therapy (IVIg) for bullous pemphigoid. This retrospective cross-sectional study used Department of Defense TRICARE data to determine factors associated with IVIg therapy among bullous pemphigoid patients. We used prior and weighted correction methods for logit regression to solve rare event bias. We identified 2,720 individuals diagnosed with bullous pemphigoid from 2019 to 2022, of which 14 were treated with IVIg. Patients who received IVIg therapy were younger (65.07 vs. 75.85, P =.0016) and more likely to be female (13 vs. 1, P =.0036). The underestimation with the standard regression model for event probabilities ranged from 11% to 102% using the prior correction method and from 15% to 107% using the weighted correction method. Rare events are low-frequency, high-severity problems that can have significant consequences. Rare diseases and rare therapies are individually unique but collectively contribute to substantial health and social needs. Therefore, correct estimation of the events is the first step toward assessing the burden of rare diseases and the pricing of their therapies.
2025-03-17 | Lipopolysaccharide-binding protein functions as factor VIII inhibitor in bullous pemphigoid associated with acquired hemophilia A.
Bullous pemphigoid (BP) represents an autoimmune blistering disorder that may coexist with acquired hemophilia A (AHA), a rare autoimmune condition arising from the formation of circulating autoantibodies directed against factor VIII (FVIII). The underlying pathomechanisms of BP-AHA remain elusive. This study conducted a retrospective analysis of data from 196 BP patients admitted to our hospital. We have collected serum samples from a recently admitted BP-AHA patient and healthy controls to isolate, screen and identify the potential FVIII inhibitors. The expression and function of lipopolysaccharide-binding protein (LBP) in BP-AHA were further validated by a series of biochemical experiments. The retrospective analysis showed that the activated partial thromboplastin time (APTT) values of seven patients exceeded 33.8 s (normal value) in 196 BP patients. FVIII: C (%) and FVIII inhibitors in the plasma of partial prolonged-APTT patients were significantly altered compared with control group or non-prolonged-APTT group. LBP was identified as a potential inhibitory protein of FVIII. Consistently, a notable alteration in LBP expression was observed in the plasma of BP patients with prolonged-APTT. Moreover, the amount of LBP bound to FVIII in the BP-AHA patient was notably higher than that in control group, which was also markedly reversed after treatment. In vitro experiments finally confirmed that exogenous LBP directly bound to FVIII and significantly inhibited FVIII activity. In conclusion, the incidence of AHA in BP patients may be substantially underestimated, which needs more vigilance towards indicators such as APTT, LBP, and FVIII. LBP emerges as an inhibitory protein of FVIII, indicating the potential involvement in the progression of BP-AHA.
antibodies
2026-08-13 | Transforming the treatment of autoimmune skin diseases: a journey through biologic therapies.
Autoimmune blistering diseases and autoimmune connective tissue diseases with prominent skin involvement are increasingly managed with biologic and targeted therapies. We review the evidence supporting these approaches and their practical positioning. We performed a PubMed/MEDLINE literature review (inception to February 2026) on biologic therapies for pemphigus, pemphigoid spectrum disorders, LABD, EBA, cutaneous lupus erythematosus, and dermatomyositis, including selected non-biologic small molecules, focusing on validated cutaneous outcomes. Evidence is strongest for B-cell depletion in pemphigus (including dose-optimization strategies) and for IL-4/IL-13 pathway blockade in BP, with additional data for anti-IgE therapy in selected BP phenotypes. In CLE, the most consistent cutaneous datasets involve pDC/type I interferon-axis modulation and BAFF inhibition, largely derived from systemic lupus cohorts; TYK2 inhibition has shown controlled benefit in CLE. In dermatomyositis, CDASI-based evidence is strongest for IVIg, with anti-IFNβ therapy and the TYK2/JAK1 inhibitor brepocitinib (positive in a phase 3 trial) showing cutaneous benefit; other biologics show limited trial signals. Biologic/targeted therapies should be positioned by disease phenotype and evidence strength, prioritizing steroid-sparing strategies in pemphigus and BP and using CLASI/CDASI-anchored outcomes to interpret lupus and dermatomyositis data. Evidence for rare AIBDs remains mostly case-level and should be framed accordingly.
2026-08-10 | Sitagliptin-associated Bullous Pemphigoid Complicated by Secondary Candidiasis, Urosepsis, and Gastrointestinal Bleeding in an Elderly Diabetic Woman.
Bullous pemphigoid (BP) is the most common autoimmune blistering disease in older adults and is increasingly associated with dipeptidyl peptidase-4 (DPP-4) inhibitors used in type 2 diabetes mellitus. Sitagliptin-associated BP is uncommon and may be complicated by secondary infections and multisystem involvement. A 74-year-old female with type 2 diabetes mellitus and hypertension presented with generalized weakness, burning micturition, abdominal pain, painful blistering skin lesions, and oral erosions. She had been receiving sitagliptin 100 mg once daily for approximately 2 years before symptom onset. Skin biopsy demonstrated a subepidermal bulla with eosinophilic infiltrates, suggestive of BP. Sitagliptin was discontinued after admission. The hospital course was complicated by bilateral pyelonephritis with multidrug-resistant urosepsis requiring bilateral double-J stenting, oral candidiasis caused by Candida albicans, recurrent gastrointestinal bleeding, and tubulovillous adenoma with high-grade dysplasia. Persistent dermatologic disease with markedly elevated immunoglobulin E levels necessitated omalizumab therapy, resulting in gradual improvement. Sitagliptin-associated BP should be considered in elderly diabetic patients presenting with blistering disorders after prolonged gliptin exposure. Early diagnosis, withdrawal of the suspected drug, histopathological confirmation, and multidisciplinary management are essential for favorable outcomes.
2026-08-02 | Bullous pemphigoid in patients who are frail: a case complicated by cerebral nocardiosis and Pneumocystis jirovecii pneumonia.
Bullous pemphigoid (BP) is the most common autoimmune blistering disorder in older patients and is typically managed with long-term immunosuppressive therapy tailored to the patient's comorbidities and overall health. Patients who are frail with concurrent haematological malignancies represent a particularly vulnerable population due to their impaired immunity and treatment-related immunosuppression. We report the case of an 85-year-old man with mantle cell lymphoma, previously treated with rituximab and ibrutinib, who developed BP confirmed by histology, direct immunofluorescence, indirect immunofluorescence and enzyme-linked immunosorbent assay. Initial disease control was achieved with systemic corticosteroids and methotrexate. Subsequently, he developed a subcutaneous thoracic nodule consistent with panniculitis, followed by cerebral nocardiosis and Pneumocystis jirovecii pneumonia. Despite successful remission of BP, his clinical course was complicated by life-threatening infections requiring prolonged hospitalization. This case highlights the delicate balance between controlling autoimmune disease and preventing severe opportunistic infections in older, frail patients with haematological malignancies. Current BP guidelines should be refined by integrating better frailty assessment, infection prophylaxis and tailored immunosuppressive strategies.
2026-07-24 | Shared Mechanistic Pathways in Bullous Pemphigoid, Chronic Spontaneous Urticaria, Prurigo Nodularis, and Chronic Prurigo of Unknown Origin: Implications for Targeted Therapies.
Bullous pemphigoid, chronic spontaneous urticaria, prurigo nodularis, and chronic prurigo of unknown origin are distinct chronic skin diseases with a high disease burden and an ongoing need for safe and effective therapies. Advances in our understanding of disease mechanisms have highlighted convergent type 2-associated neuroimmune pathways that may contribute to chronic itch and skin lesions across these conditions. In bullous pemphigoid, autoantibody binding of two dermal-epidermal junction proteins followed by complement system activation shapes the local immune environment to favor T helper cell 2 polarization and perpetuation of type 2 inflammation. In chronic spontaneous urticaria, mast cell activation and downstream mediators, including type 2 cytokines, may contribute to amplification of inflammation and itch. In prurigo nodularis, chronically activated itch sensory neurons induce an itch-scratch cycle with T-cell activation in parallel to mast cell degranulation, resulting in neurogenic inflammation that sustains the itch-scratch cycle. The pathogenesis of chronic prurigo of unknown origin is not well understood, but evidence to date points to interactions between skin barrier defects and immune and neural dysregulation triggering T helper cell 2 polarization. In this review, we discuss the role of type 2 inflammation in bullous pemphigoid, chronic spontaneous urticaria, prurigo nodularis, and chronic prurigo of unknown origin, and how this understanding is currently translated into new targeted therapeutic options.
2026-07-24 | Pembrolizumab-Induced Bullous Pemphigoid: Navigating Diagnostic Challenges and Treatment Resistance.
Immune checkpoint inhibitors (ICIs), including the programmed cell death protein-1 (PD-1) inhibitor pembrolizumab, have revolutionized metastatic urothelial carcinoma management but are frequently associated with cutaneous immune-related adverse events, including drug-induced bullous pemphigoid (DIBP). We present the case of an 81-year-old man with PD-L1-negative metastatic high-grade papillary urothelial carcinoma with a generalized, pruritic, bullous eruption following treatment with pembrolizumab. Histopathology and direct immunofluorescence confirmed bullous pemphigoid (BP). This case underscores the diagnostic challenges of DIBP. Clinicians must maintain a high index of suspicion and consider early transition to steroid-sparing agents such as rituximab in refractory cases. Timely dermatologic referral and close multidisciplinary coordination are essential.
other
2023-05-23 | The Essential Role of microRNAs in Inflammatory and Autoimmune Skin Diseases—A Review
The etiopathogenesis of autoimmune skin diseases is complex and still not fully understood. The role of epigenetic factors is emphasized in the development of such diseases. MicroRNAs (miRNAs), a group of non-coding RNAs (ncRNAs—non-coding RNAs), are one of the important post-transcriptional epigenetic factors. miRNAs have a significant role in the regulation of the immune response by participating in the process of the differentiation and activation of B and T lymphocytes, macrophages, and dendritic cells. Recent advances in research on epigenetic factors have provided new insights into the pathogenesis and potential diagnostic and therapeutic targets of many pathologies. Numerous studies revealed a change in the expression of some microRNAs in inflammatory skin disorders, and the regulation of miRNA expression is a promising therapeutic goal. This review presents the state of the art regarding changes in the expression and role of miRNAs in inflammatory and autoimmune skin diseases, including psoriasis, atopic dermatitis, vitiligo, lichen planus, hidradenitis suppurativa, and autoimmune blistering diseases.
2022-07-19 | Exacerbation of Autoimmune Bullous Diseases After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination: Is There Any Association?
Background and Aim There have been concerns regarding the potential exacerbation of autoimmune bullous diseases (AIBDs) following vaccination against COVID-19 during the pandemic. In the current study, vaccine safety was evaluated in patients with AIBDs. Methods In this study, patients with AIBDs were contacted via face-to-face visits or phone calls. Patient demographics, vaccine-related information, pre- and post-vaccine disease status, and complications were recorded. The exacerbation was considered either relapse in the remission/controlled phase of the disease or disease worsening in the active phase. The univariate and multivariate logistic regression tests were employed to determine the potential risk factors of disease exacerbation. Results Of the patients contacted, 446 (74.3%) reported receiving at least one dose of vaccine injection (54.7% female). Post-vaccine exacerbation occurred in 66 (14.8%) patients. Besides, there were 5 (1.1%) patients with AIBD diagnosis after vaccination. According to the analysis, for every three patients who received vaccines during the active phase of the disease one experienced disease exacerbation. The rate of disease exacerbation increased by three percent with every passing month from the last rituximab infusion. Active disease in the past year was another risk factor with a number needed to harm of 10. Conclusion Risk of AIBD exacerbation after the COVID-19 vaccine is not high enough to prevent vaccination. This unwanted side effect, can be reduced if the disease is controlled at the time of vaccination.
2021-06-09 | MicroRNAs in pemphigus and pemphigoid diseases.
Autoimmune blistering diseases are a heterogenous group of dermatological disorders characterized by blisters and erosions of the skin and/or mucous membranes induced by autoantibodies against structural proteins of the desmosome or the dermal-epidermal adhesion complex including the hemidesmosome. They consist of the two major disease groups, pemphigus and pemphigoid diseases (PPDs). The diagnosis is based on clinical findings, histopathology, direct immunofluorescence, and detection of circulating autoantibodies. The pathogenesis is not fully elucidated, prognostic factors are lacking, and to date, there is no cure for PPDs. MicroRNAs (miRNAs) represent small, non-coding RNAs that play a pivotal role in the posttranscriptional regulation of gene expression. Their dysfunction was highlighted to play a significant role in the pathogenesis of various diseases. Even though a link between miRNAs and autoimmune blistering diseases had been suggested, the research of their involvement in the pathogenesis of PPDs is still in its infancy. miRNAs hold promise for uncovering new layers in the pathogenesis of PPDs, in order to improve diagnosis and also to develop potential therapeutic options. In the current article, we provide an overview regarding current knowledge of miRNAs in terms of complex pathogenesis of PPDs, and, also, their potential role as biomarkers, predictive factors and therapeutic targets.
small molecules
2026-08-02 | Factors associated with prolonged hospital stay in patients with autoimmune bullous diseases treated at an in-patient dermatology service.
Bullous diseases carry a great burden and are often linked to high healthcare costs. Patients with -bullous diseases are more vulnerable to infections and organ damage due to an incompetent skin barrier. To determine the demographic, clinical and laboratory factors associated with prolonged hospital stay in patients with autoimmune bullous diseases. This was a cross-sectional study, with a follow-up cohort, including all dermatology consultations in a university hospital between 2017 and 2022 to identify patients with autoimmune bullous disease. Duration of stay and other variables were obtained from the patients' medical records. A total of 83 patients were included in the study, of whom the majority had bullous pemphigoid (n = 45; 54%). There was significant metabolic comorbidity with hypertension (n = 51; 61%), diabetes (n = 31; 37%) and dyslipidaemia (n = 31; 37%). Fifty-eight per cent of patients had a prolonged hospital stay (>10 days). Among the associated variables, mucosal involvement, eosinophilia, in-hospital antibiotics and the absence of dipetidyl peptidase-4 (DPP4) inhibitor use stood out. Most patients with bullous diseases have prolonged hospital stays. The evaluation of mucous membranes, blood count and a basic chemical panel can help identify patients at greater risk of prolonged hospital stays. In addition, the use of DPP4 inhibitors and their rapid discontinuation could affect this outcome.
2026-07-29 | Treatment patterns for bullous pemphigoid in older adults: A population-based study.
Bullous pemphigoid (BP) is a chronic autoimmune blistering disease that disproportionately affects older adults and is associated with substantial morbidity, mortality, and treatment-related risks. Despite an expanding therapeutic landscape, real-world prescribing patterns in this population remain poorly characterized. To evaluate medication prescribing patterns among older adults with BP and assess the feasibility of using national claims data to characterize treatment exposures relevant to drug safety and risk stratification. We conducted a retrospective cohort study using Medicare fee-for-service claims data (2016-2020). Adults aged 65 years or older with BP were identified using ICD-10 codes. Prescription drug event data were linked to outpatient claims to capture medication use. Treatments were categorized into topical corticosteroids (by potency), oral immunomodulators and antibiotics, and biologic therapies. Descriptive analyses were performed to evaluate prescribing distributions. Among 10,959 patients with BP and 78,468 outpatient claims, we identified 19,663 prescriptions. Oral immunomodulators and antibiotics comprised 67.5% of prescriptions, followed by topical corticosteroids (32.5%) and biologics (0.04%). Prednisone accounted for 62.9% of oral prescriptions, followed by doxycycline (20.2%) and mycophenolate (6.0%). Among topical steroids, medium-potency agents were most common (40.6%), followed by super high-potency (38.2%). Biologic use was rare, with dupilumab accounting for most prescriptions. Systemic corticosteroids remain the predominant therapy for BP in older adults, with substantial variability in topical steroid use and minimal uptake of biologics. These findings highlight gaps in treatment optimization and support the need for risk-informed, steroid-sparing strategies in this high-risk population.
2026-07-27 | Effect and length of doxycycline administration in elderly patients with bullous pemphigoid.
Bullous pemphigoid (BP) is the most common autoimmune blistering disease and primarily affects the elderly. Systemic corticosteroids and immunosuppressive drugs are the standard treatment, but side effects often restrict their use. Doxycycline has been proposed as an alternative, but there is limited long-term, real-world data on its efficacy and tolerability. We aimed to evaluate the effectiveness and length of doxycycline treatment in BP patients. This retrospective, single-center study analyzed data from patients with a confirmed BP diagnosis treated with doxycycline. The comprehensive dataset included information on disease severity, concomitant therapies, and treatment response. Treatment duration was analyzed using the Kaplan-Meier method. The cohort comprised 102 patients with a mean age of 79 (range 51-95) years. A clinical response (an improvement of 1 or 2 on the PGA score, which ranges from 2 to -2) was observed in 85 patients (83.3 %), many of whom received combination therapy with other drugs (67.7 %). The median length of doxycycline treatment was 122.7 weeks. Adverse events, mainly of gastrointestinal origin, were rare, non-serious and manageable. Doxycycline proved to be an effective and well-tolerated long-term treatment for elderly patients with BP, when used either as monotherapy or in combination.
2026-07-18 | STING Drives CD4+T Cell Differentiation via JAK-STAT Signalling in Bullous Pemphigoid.
Bullous pemphigoid (BP) is an autoimmune blistering disease with an increasing incidence in recent years; however, the underlying immune regulatory mechanisms remain largely unclear. As a critical signalling hub linking innate and adaptive immunity, stimulator of interferon genes (STING) has recently been implicated in the pathogenesis of various autoimmune diseases and may regulate tissue inflammation and immune homeostasis through modulation of CD4+ T cell responses. In this study, we found that STING expression was significantly increased in lesional skin tissues from patients with BP compared with healthy controls. Transcriptomic analysis further revealed that differentially expressed genes in peripheral blood CD4+ T cells from BP patients were primarily enriched in the JAK-STAT signalling pathway, T cell activation and differentiation, and type I interferon (IFN-I)-related pathways. Pharmacological inhibition of STING markedly attenuated the aberrant activation of these signalling pathways. Moreover, qRT-PCR analysis confirmed that the mRNA levels of STING1, JAK1, and CXCR5 were significantly elevated in BP patients, whereas treatment with the STING inhibitor C176 suppressed the expression of these molecules. Collectively, our findings suggest that STING may contribute to BP immunopathogenesis by regulating the JAK-STAT signalling axis and promoting abnormal CD4+ T cell activation and differentiation, providing new insights into the molecular mechanisms underlying BP and identifying potential therapeutic targets.
2026-06-29 | Real-World Outcomes of Stapokibart-Based Combination Therapy for Bullous Pemphigoid: A Single-Center Retrospective Cohort.
Bullous pemphigoid (BP) affects older adults and treatment is often limited by corticosteroid toxicity. Evidence for stapokibart in BP is limited. To describe the clinical outcomes and safety of stapokibart-based combination therapy in BP. We retrospectively reviewed consecutive BP patients who received stapokibart-based combination therapy at Peking Union Medical College Hospital between October 2024 and October 2025, and had a follow-up period of at least four months. Stapokibart was administered as 600 mg loading dose, followed by 300 mg every two weeks. Outcomes included time to disease control, time to Bullous Pemphigoid Disease Area Index (BPDAI) activity score of 0, complete remission (CR) on minimal therapy, adverse events, and changes in BPDAI activity, pruritus numeric rating scale (NRS), anti-BP180 titers, eosinophil counts, and concomitant corticosteroid exposure throughout the follow-up period. Twelve patients were enrolled, with a median age of 77.5 years and a median follow-up period of 216.5 days. All received concomitant Tripterygium glycoside, and 7/12 (58.3%) also received oral corticosteroids at stapokibart initiation. All patients achieved disease control, with a median time of 14.5 days. Eleven out of 12 patients (91.7%) reached disease control within four weeks. BPDAI activity score of 0 was reached in all patients (median 65.5 days). Seven patients (58.3%) achieved CR on minimal therapy (median 176.0 days among responders). During follow-up, BPDAI activity, pruritus NRS, eosinophil counts, anti-BP180 titers, and prednisone dosages all decreased. One patient reported temporary fatigue and later developed herpes zoster. No patients stopped treatment throughout the study. Stapokibart-based combination therapy was associated with rapid short-term disease control and clinical improvement in this small retrospective BP cohort. Given the limited sample size and frequent concomitant therapy, these preliminary findings require confirmation in larger controlled studies.
cell therapies
2026-05-07 | Regulatory T cells in bullous pemphigoid: biological characteristics, dysfunction, and pathogenic roles.
Bullous pemphigoid (BP) is an autoimmune blistering disorder that predominantly affects the elderly. Its pathogenesis involves the disruption of the basement membrane zone (BMZ), driven by pathogenic autoantibodies and a pronounced inflammatory response. Current first-line therapies, primarily based on glucocorticoids and immunosuppressants, are limited by substantial side effects and frequent disease recurrence. Regulatory T cells (Tregs) play a central role in maintaining immune homeostasis and peripheral tolerance, exerting control over effector immune cells through transcriptional regulation, surface markers, and diverse immunosuppressive mechanisms. Accumulating evidence indicates that numerical reduction and functional impairment of Tregs are critical to the breakdown of immune tolerance in BP. Treg dysfunction leads to the aberrant activation of Th2, Th17, and follicular helper T (Tfh) cells, which in turn promotes the production of anti-BP180/BP230 autoantibodies and disrupts the regulation of inflammatory cells such as neutrophils and eosinophils. These events collectively result in BMZ degradation and blister formation. Multiple factors, including age-related immunosenescence, genetic predisposition, pharmacological exposures, and environmental stimuli, can further compromise Treg function, thereby contributing to BP pathogenesis. A deeper understanding of Treg-driven mechanisms in BP provides a rational basis for developing targeted therapeutic strategies.
2025-12-19 | O01 Infantile bullous pemphigoid: when autoimmunity hides an immunodeficiency.
Infantile bullous pemphigoid (BP) can be an early manifestation of ZAP-70 deficiency, a rare combined immunodeficiency (CID) characterised by defective T-cell signalling and a propensity to multiple autoimmune manifestations.1 We describe two patients with BP subsequently diagnosed with ZAP-70 deficiency. Case 1: A female neonate presented at 14 days with severe seborrhoeic dermatitis. From 3 months she was repeatedly admitted with severe respiratory infections. Investigations revealed normal full blood count (FBC), but profoundly reduced CD8+ lymphocytes. At 7 months she developed an extensive bullous eruption. Skin biopsy with direct and indirect immunofluorescence confirmed the diagnosis of BP, which was difficult to control and required multiple systemic treatments, including methylprednisolone, dapsone, dupilumab, intravenous immunoglobulin and rituximab. She developed immune-mediated thrombocytopenia and is currently being prepared for bone marrow transplantation (BMT) due to ZAP-70 deficiency. Case 2: A female infant presented at 3 months with bullae of the face and extremities. Skin biopsy with direct and indirect immunofluorescence confirmed BP, which responded to topical corticosteroids and erythromycin. At 9 months she developed recurrent severe respiratory infections requiring ventilation. Laboratory studies showed near-absent CD8+ lymphocytes and confirmed ZAP-70 deficiency. She underwent BMT in June 2024, with no recurrence of blistering. Conclusion: Infantile BP should prompt suspicion of an underlying CID. Assessment of lymphocyte subsets is essential, as ZAP-70 deficiency is characterised by profoundly reduced CD8+ lymphocytes, which may not be apparent on a standard FBC where total lymphocyte numbers can be normal. Early -diagnosis is essential, as BMT offers the only curative -treatment.
2025-11-03 | Adjuvant therapy of severe and/or refractory bullous pemphigoid with immunoadsorption - A prospective monocenter pilot study.
Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the Western world. While remission is achieved in the majority of BP patients by long-term use of corticosteroids with or without immunomodulants/immunosuppressants, national and international guidelines recommend adjuvant immunoadsorption (IA) in refractory patients. Here we investigated the safety and efficacy of IA in severe and/or refractory BP patients. 10 BP patients (3 women, 7 men; mean age 69.7 years; range 52-81 years) were treated with IA on three consecutive days (LigaSorb®, Fresenius Medical Care) combined with oral prednisolone (0.5 mg/kg BW per day, tapered), dapsone (1.5 mg/kg BW per day), and lesional mometasone furoate ointment. Within 2 and 6 months after IA, 50% and 90% of patients showed complete remission on therapy, respectively. In all patients, serum anti-BP180 IgG levels decreased significantly by an average of 89% and 73% immediately after the third IA and 4 weeks later, respectively. A total of 56 adverse events (AE) occurred during the 12-month follow-up. The majority of AE were of severity grade 2 (50%), 15 AE were classified as severe (grade 3-4). IA can be considered as a relatively safe and effective adjuvant therapy for patients with severe or refractory BP.
2025-06-22 | Can we cure bullous skin diseases?
Autoimmune bullous diseases (AIBDs), including pemphigus and pemphigoid, are featured as the presence of autoantibodies directed against structural proteins, resulting in severe blistering as well as considerable morbidity. Current treatments, including glucocorticoids, immunomodulators, and biologics, often fail to achieve sustained remission due to high relapse rates and significant adverse effects. This review explores the pathophysiology of AIBDs, focusing on autoreactive B and T cells, inflammatory mediators, and immune dysregulation. Existing therapeutic limitations are then analyzed, and emerging treatment options, such as chimeric antigen receptor-T therapy, regulatory T cell-based interventions, and tolerogenic vaccines, are discussed as potential curative approaches. Additionally, preventive measures, such as genetic screening and environmental risk management, are considered. By integrating novel immunotherapies and immune modulation techniques through a three-step approach - disease control, pathogenic cell elimination, and induction of immune tolerance - we may move closer toward achieving sustained remission and potentially curing of AIBDs.
2025-05-15 | Autoimmune bullous diseases: pathogenesis and clinical management.
Autoimmune bullous diseases (AIBDs) represent a heterogeneous group of immune-mediated disorders characterized by life-threatening blistering of the skin and mucous membranes. This Review synthesizes current understanding of AIBD pathogenesis, clinical phenotypes, diagnostic approaches, and therapeutic strategies, emphasizing recent advancements and translational opportunities. At the core of AIBDs is autoantibody-mediated disruption of structural proteins in the epidermis or basement membrane zone, particularly at desmosomal and hemidesmosomal junctions. Key subtypes, including pemphigus, paraneoplastic pemphigus, pemphigoid, and IgA-related diseases, are distinguished by their target antigens, clinical manifestations, and immunopathological profiles. Diagnostic workflows rely on direct immunofluorescence, and serological assays, yet subtype differentiation remains challenging due to overlapping features. Traditional therapies, such as systemic corticosteroids and immunosuppressants, have improved outcomes but are limited by toxicity. Recent breakthroughs highlight targeted interventions, including B-cell depletion with rituximab, cytokine modulation via dupilumab, and JAK inhibitors for inflammatory pathways. Innovative strategies like chimeric autoantibody receptor T-cell (CAART) therapy further address refractory cases by eliminating autoreactive B cells. Additionally, the Review underscores the emerging role of inflammation-driven mechanisms and the necessity of multidisciplinary care, given AIBDs' associations with malignancies, autoimmune comorbidities. Despite progress, challenges persist in early diagnosis, personalized therapy optimization, and understanding antigen-specific immune responses. Future directions include refining diagnostic biomarkers, exploring novel targets, and developing precision medicine approaches.
proteins
2026-04-26 | Treg cells as potential therapeutic targets for bullous pemphigoid: A review.
Bullous pemphigoid (BP) is an autoimmune disease characterized by Bullous pemphigoid antigen 180(BP180) and Bullous pemphigoid antigen 230(BP230) autoantibodies production. Regulatory T cells (Tregs) are key cells for the maintenance of immune tolerance. Increasing evidence suggests that Treg dysfunction leads to autoantibody production and skin rashes in mice and humans, making immunomodulatory therapies targeting Tregs a potential therapeutic strategy for BP. Low-dose Interleukin-2 treatment and adoptive cell therapy are promising methods to modulate Tregs' numbers and function. Herein, we review the immunological mechanisms underlying BP pathogenesis, with an emphasis on the protective role of Treg cell-mediated immune tolerance in BP. Furthermore, we explore the potential therapeutic applications of Treg-based therapies for BP, providing novel insights into patient management.
2025-07-31 | Galectin-9: diverse roles in skin disease.
Galectin-9 (Gal-9) is a multifunctional immunomodulatory molecule involved in cell growth, differentiation, adhesion, communication, and death. Galectin-9 mediates its physiological functions through interactions with multiple membrane receptors, including T-cell immunoglobulin mucin-domain containing-3 (Tim-3), immunoglobulin E, and the hyaluronan receptor CD44. In recent years, Gal-9 has been extensively studied in autoimmune diseases, tumor microenvironments, and viral infections. The circulating levels of this lectin demonstrate clinical correlation with disease progression in both acute and chronic infectious conditions. In addition, Gal-9 can potentially be a reliable, sensitive, and noninvasive biomarker of disease severity in many skin diseases. However, there has not been a review of Gal-9 studies in patients with dermatosis. This review summarizes recent advances in understanding Gal-9's immunomodulatory mechanisms in chronic spontaneous urticaria pathophysiology, systemic lupus erythematosus, atopic dermatitis, melanoma, systemic sclerosis, herpes simplex virus infection, bullous pemphigoid, psoriasis, vitiligo, maculopapular exanthema, and skin grafting to provide a reference for future research. Gal-9 is an important regulator of immune homeostasis whose level changes significantly in many skin diseases, and validation was performed in a mouse model using exogenous Gal-9. Ongoing studies are necessary to clarify the pathophysiology of Gal-9, identify the potential of Gal-9 as a new biomarker, and develop new therapeutic approaches for skin diseases.
2025-05-27 | A Closer Look at the Dermatological Profile of GLP-1 Agonists.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in treating type 2 diabetes and obesity, offering established metabolic and cardiovascular benefits. Emerging evidence suggests these agents also exert direct dermatologic effects. This systematic review categorizes these effects and explores their role in inflammatory skin diseases. A comprehensive literature search was performed across EMBASE, PubMed, Web of Science, and Google Scholar for studies published from 2014 to 2025. Inclusion criteria were English-language, peer-reviewed original research involving human subjects that linked GLP-1RAs to dermatologic effects. Animal and in vitro studies were excluded. PRISMA guidelines were followed. Fifty-one studies met inclusion criteria. Thirty-four reported adverse effects, including hypersensitivity, injection-site reactions, pruritus, urticaria, angioedema, and immune-mediated conditions like bullous pemphigoid. Seventeen studies described beneficial outcomes, such as improvements in psoriasis, reduced hidradenitis suppurativa flares, enhanced wound healing, anti-aging potential, and decreased inflammation. GLP-1RAs showed cytokine modulation in psoriasis, though their role in hidradenitis suppurativa remains uncertain. Cosmetic concerns, such as "Ozempic Face" due to rapid weight loss, were also noted. GLP-1RAs have a broad spectrum of dermatologic effects, from immunomodulatory benefits to adverse cutaneous reactions. Their impact on inflammatory skin disorders suggests a novel therapeutic avenue. However, adverse reactions and aesthetic changes warrant vigilance. Future research should focus on mechanistic studies, long-term safety, and identifying biomarkers to predict dermatologic responses, ultimately guiding personalized treatment approaches.
2025-04-27 | Analysis of rare events in healthcare intervention using department of defense data: intravenous immune globulin therapy for bullous pemphigoid.
Rare events data have proven difficult to explain and predict. Standard statistical procedures can sharply underestimate the probability of rare events, such as intravenous immune globulin therapy (IVIg) for bullous pemphigoid. This retrospective cross-sectional study used Department of Defense TRICARE data to determine factors associated with IVIg therapy among bullous pemphigoid patients. We used prior and weighted correction methods for logit regression to solve rare event bias. We identified 2,720 individuals diagnosed with bullous pemphigoid from 2019 to 2022, of which 14 were treated with IVIg. Patients who received IVIg therapy were younger (65.07 vs. 75.85, P =.0016) and more likely to be female (13 vs. 1, P =.0036). The underestimation with the standard regression model for event probabilities ranged from 11% to 102% using the prior correction method and from 15% to 107% using the weighted correction method. Rare events are low-frequency, high-severity problems that can have significant consequences. Rare diseases and rare therapies are individually unique but collectively contribute to substantial health and social needs. Therefore, correct estimation of the events is the first step toward assessing the burden of rare diseases and the pricing of their therapies.
2025-03-17 | Lipopolysaccharide-binding protein functions as factor VIII inhibitor in bullous pemphigoid associated with acquired hemophilia A.
Bullous pemphigoid (BP) represents an autoimmune blistering disorder that may coexist with acquired hemophilia A (AHA), a rare autoimmune condition arising from the formation of circulating autoantibodies directed against factor VIII (FVIII). The underlying pathomechanisms of BP-AHA remain elusive. This study conducted a retrospective analysis of data from 196 BP patients admitted to our hospital. We have collected serum samples from a recently admitted BP-AHA patient and healthy controls to isolate, screen and identify the potential FVIII inhibitors. The expression and function of lipopolysaccharide-binding protein (LBP) in BP-AHA were further validated by a series of biochemical experiments. The retrospective analysis showed that the activated partial thromboplastin time (APTT) values of seven patients exceeded 33.8 s (normal value) in 196 BP patients. FVIII: C (%) and FVIII inhibitors in the plasma of partial prolonged-APTT patients were significantly altered compared with control group or non-prolonged-APTT group. LBP was identified as a potential inhibitory protein of FVIII. Consistently, a notable alteration in LBP expression was observed in the plasma of BP patients with prolonged-APTT. Moreover, the amount of LBP bound to FVIII in the BP-AHA patient was notably higher than that in control group, which was also markedly reversed after treatment. In vitro experiments finally confirmed that exogenous LBP directly bound to FVIII and significantly inhibited FVIII activity. In conclusion, the incidence of AHA in BP patients may be substantially underestimated, which needs more vigilance towards indicators such as APTT, LBP, and FVIII. LBP emerges as an inhibitory protein of FVIII, indicating the potential involvement in the progression of BP-AHA.
antibodies
2026-08-13 | Transforming the treatment of autoimmune skin diseases: a journey through biologic therapies.
Autoimmune blistering diseases and autoimmune connective tissue diseases with prominent skin involvement are increasingly managed with biologic and targeted therapies. We review the evidence supporting these approaches and their practical positioning. We performed a PubMed/MEDLINE literature review (inception to February 2026) on biologic therapies for pemphigus, pemphigoid spectrum disorders, LABD, EBA, cutaneous lupus erythematosus, and dermatomyositis, including selected non-biologic small molecules, focusing on validated cutaneous outcomes. Evidence is strongest for B-cell depletion in pemphigus (including dose-optimization strategies) and for IL-4/IL-13 pathway blockade in BP, with additional data for anti-IgE therapy in selected BP phenotypes. In CLE, the most consistent cutaneous datasets involve pDC/type I interferon-axis modulation and BAFF inhibition, largely derived from systemic lupus cohorts; TYK2 inhibition has shown controlled benefit in CLE. In dermatomyositis, CDASI-based evidence is strongest for IVIg, with anti-IFNβ therapy and the TYK2/JAK1 inhibitor brepocitinib (positive in a phase 3 trial) showing cutaneous benefit; other biologics show limited trial signals. Biologic/targeted therapies should be positioned by disease phenotype and evidence strength, prioritizing steroid-sparing strategies in pemphigus and BP and using CLASI/CDASI-anchored outcomes to interpret lupus and dermatomyositis data. Evidence for rare AIBDs remains mostly case-level and should be framed accordingly.
2026-08-10 | Sitagliptin-associated Bullous Pemphigoid Complicated by Secondary Candidiasis, Urosepsis, and Gastrointestinal Bleeding in an Elderly Diabetic Woman.
Bullous pemphigoid (BP) is the most common autoimmune blistering disease in older adults and is increasingly associated with dipeptidyl peptidase-4 (DPP-4) inhibitors used in type 2 diabetes mellitus. Sitagliptin-associated BP is uncommon and may be complicated by secondary infections and multisystem involvement. A 74-year-old female with type 2 diabetes mellitus and hypertension presented with generalized weakness, burning micturition, abdominal pain, painful blistering skin lesions, and oral erosions. She had been receiving sitagliptin 100 mg once daily for approximately 2 years before symptom onset. Skin biopsy demonstrated a subepidermal bulla with eosinophilic infiltrates, suggestive of BP. Sitagliptin was discontinued after admission. The hospital course was complicated by bilateral pyelonephritis with multidrug-resistant urosepsis requiring bilateral double-J stenting, oral candidiasis caused by Candida albicans, recurrent gastrointestinal bleeding, and tubulovillous adenoma with high-grade dysplasia. Persistent dermatologic disease with markedly elevated immunoglobulin E levels necessitated omalizumab therapy, resulting in gradual improvement. Sitagliptin-associated BP should be considered in elderly diabetic patients presenting with blistering disorders after prolonged gliptin exposure. Early diagnosis, withdrawal of the suspected drug, histopathological confirmation, and multidisciplinary management are essential for favorable outcomes.
2026-08-02 | Bullous pemphigoid in patients who are frail: a case complicated by cerebral nocardiosis and Pneumocystis jirovecii pneumonia.
Bullous pemphigoid (BP) is the most common autoimmune blistering disorder in older patients and is typically managed with long-term immunosuppressive therapy tailored to the patient's comorbidities and overall health. Patients who are frail with concurrent haematological malignancies represent a particularly vulnerable population due to their impaired immunity and treatment-related immunosuppression. We report the case of an 85-year-old man with mantle cell lymphoma, previously treated with rituximab and ibrutinib, who developed BP confirmed by histology, direct immunofluorescence, indirect immunofluorescence and enzyme-linked immunosorbent assay. Initial disease control was achieved with systemic corticosteroids and methotrexate. Subsequently, he developed a subcutaneous thoracic nodule consistent with panniculitis, followed by cerebral nocardiosis and Pneumocystis jirovecii pneumonia. Despite successful remission of BP, his clinical course was complicated by life-threatening infections requiring prolonged hospitalization. This case highlights the delicate balance between controlling autoimmune disease and preventing severe opportunistic infections in older, frail patients with haematological malignancies. Current BP guidelines should be refined by integrating better frailty assessment, infection prophylaxis and tailored immunosuppressive strategies.
2026-07-24 | Shared Mechanistic Pathways in Bullous Pemphigoid, Chronic Spontaneous Urticaria, Prurigo Nodularis, and Chronic Prurigo of Unknown Origin: Implications for Targeted Therapies.
Bullous pemphigoid, chronic spontaneous urticaria, prurigo nodularis, and chronic prurigo of unknown origin are distinct chronic skin diseases with a high disease burden and an ongoing need for safe and effective therapies. Advances in our understanding of disease mechanisms have highlighted convergent type 2-associated neuroimmune pathways that may contribute to chronic itch and skin lesions across these conditions. In bullous pemphigoid, autoantibody binding of two dermal-epidermal junction proteins followed by complement system activation shapes the local immune environment to favor T helper cell 2 polarization and perpetuation of type 2 inflammation. In chronic spontaneous urticaria, mast cell activation and downstream mediators, including type 2 cytokines, may contribute to amplification of inflammation and itch. In prurigo nodularis, chronically activated itch sensory neurons induce an itch-scratch cycle with T-cell activation in parallel to mast cell degranulation, resulting in neurogenic inflammation that sustains the itch-scratch cycle. The pathogenesis of chronic prurigo of unknown origin is not well understood, but evidence to date points to interactions between skin barrier defects and immune and neural dysregulation triggering T helper cell 2 polarization. In this review, we discuss the role of type 2 inflammation in bullous pemphigoid, chronic spontaneous urticaria, prurigo nodularis, and chronic prurigo of unknown origin, and how this understanding is currently translated into new targeted therapeutic options.
2026-07-24 | Pembrolizumab-Induced Bullous Pemphigoid: Navigating Diagnostic Challenges and Treatment Resistance.
Immune checkpoint inhibitors (ICIs), including the programmed cell death protein-1 (PD-1) inhibitor pembrolizumab, have revolutionized metastatic urothelial carcinoma management but are frequently associated with cutaneous immune-related adverse events, including drug-induced bullous pemphigoid (DIBP). We present the case of an 81-year-old man with PD-L1-negative metastatic high-grade papillary urothelial carcinoma with a generalized, pruritic, bullous eruption following treatment with pembrolizumab. Histopathology and direct immunofluorescence confirmed bullous pemphigoid (BP). This case underscores the diagnostic challenges of DIBP. Clinicians must maintain a high index of suspicion and consider early transition to steroid-sparing agents such as rituximab in refractory cases. Timely dermatologic referral and close multidisciplinary coordination are essential.
other
2023-05-23 | The Essential Role of microRNAs in Inflammatory and Autoimmune Skin Diseases—A Review
The etiopathogenesis of autoimmune skin diseases is complex and still not fully understood. The role of epigenetic factors is emphasized in the development of such diseases. MicroRNAs (miRNAs), a group of non-coding RNAs (ncRNAs—non-coding RNAs), are one of the important post-transcriptional epigenetic factors. miRNAs have a significant role in the regulation of the immune response by participating in the process of the differentiation and activation of B and T lymphocytes, macrophages, and dendritic cells. Recent advances in research on epigenetic factors have provided new insights into the pathogenesis and potential diagnostic and therapeutic targets of many pathologies. Numerous studies revealed a change in the expression of some microRNAs in inflammatory skin disorders, and the regulation of miRNA expression is a promising therapeutic goal. This review presents the state of the art regarding changes in the expression and role of miRNAs in inflammatory and autoimmune skin diseases, including psoriasis, atopic dermatitis, vitiligo, lichen planus, hidradenitis suppurativa, and autoimmune blistering diseases.
2022-07-19 | Exacerbation of Autoimmune Bullous Diseases After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination: Is There Any Association?
Background and Aim There have been concerns regarding the potential exacerbation of autoimmune bullous diseases (AIBDs) following vaccination against COVID-19 during the pandemic. In the current study, vaccine safety was evaluated in patients with AIBDs. Methods In this study, patients with AIBDs were contacted via face-to-face visits or phone calls. Patient demographics, vaccine-related information, pre- and post-vaccine disease status, and complications were recorded. The exacerbation was considered either relapse in the remission/controlled phase of the disease or disease worsening in the active phase. The univariate and multivariate logistic regression tests were employed to determine the potential risk factors of disease exacerbation. Results Of the patients contacted, 446 (74.3%) reported receiving at least one dose of vaccine injection (54.7% female). Post-vaccine exacerbation occurred in 66 (14.8%) patients. Besides, there were 5 (1.1%) patients with AIBD diagnosis after vaccination. According to the analysis, for every three patients who received vaccines during the active phase of the disease one experienced disease exacerbation. The rate of disease exacerbation increased by three percent with every passing month from the last rituximab infusion. Active disease in the past year was another risk factor with a number needed to harm of 10. Conclusion Risk of AIBD exacerbation after the COVID-19 vaccine is not high enough to prevent vaccination. This unwanted side effect, can be reduced if the disease is controlled at the time of vaccination.
2021-06-09 | MicroRNAs in pemphigus and pemphigoid diseases.
Autoimmune blistering diseases are a heterogenous group of dermatological disorders characterized by blisters and erosions of the skin and/or mucous membranes induced by autoantibodies against structural proteins of the desmosome or the dermal-epidermal adhesion complex including the hemidesmosome. They consist of the two major disease groups, pemphigus and pemphigoid diseases (PPDs). The diagnosis is based on clinical findings, histopathology, direct immunofluorescence, and detection of circulating autoantibodies. The pathogenesis is not fully elucidated, prognostic factors are lacking, and to date, there is no cure for PPDs. MicroRNAs (miRNAs) represent small, non-coding RNAs that play a pivotal role in the posttranscriptional regulation of gene expression. Their dysfunction was highlighted to play a significant role in the pathogenesis of various diseases. Even though a link between miRNAs and autoimmune blistering diseases had been suggested, the research of their involvement in the pathogenesis of PPDs is still in its infancy. miRNAs hold promise for uncovering new layers in the pathogenesis of PPDs, in order to improve diagnosis and also to develop potential therapeutic options. In the current article, we provide an overview regarding current knowledge of miRNAs in terms of complex pathogenesis of PPDs, and, also, their potential role as biomarkers, predictive factors and therapeutic targets.
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Drug Discovery Landscape
8 orphan drug designations for Bullous pemphigoid, including 1 approved therapy.
8 orphan drug designations for Bullous pemphigoid, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
rituximab | antibodies | FDA | 2025-10-16 | — | ODDIFACT SAS |
Nomacopan | proteins | EMA | 2020-06-26 | — | Akari Malta Limited |
nomacopan | combination | FDA | 2019-09-12 | — | Akari Therapeutics Plc |
dupilumab [Dupixent] | antibodies | FDA | 2019-08-21 | 2025-06-18 | Regeneron Pharmaceuticals, Inc. |
Bertilimumab | antibodies | EMA | 2018-08-24 | — | IQVIA RDS Ireland Limited |
bertilimumab | antibodies | FDA | 2018-08-17 | — | Alexion Pharmaceuticals, Inc. |
humanized IgG4 Monoclonal Antibody against total complement component 1, subcomponent s (C1s) | antibodies | FDA | 2017-08-17 | — | Recordati Rare Diseases Inc. |
Dimethyl fumarate | small molecules | EMA | 2016-07-14 | — | Novalis Investments S.L |
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