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Frontiers in Immunology 2019Autoimmune bullous dermatoses (AIBDs) are a group of rare chronic inflammatory skin diseases, which clinically manifest as blisters and erosions of the skin and/or... (Review)
Review
Autoimmune bullous dermatoses (AIBDs) are a group of rare chronic inflammatory skin diseases, which clinically manifest as blisters and erosions of the skin and/or mucosa. Immunologically, AIBDs are characterized and caused by autoantibodies targeting adhesion molecules in the skin and mucosa. According to the histological location of the blistering, AIBDs are classified into the following two main subtypes: pemphigus (intraepidermal blistering) and pemphigoid (subepidermal blistering). Most AIBDs were potentially life-threatening diseases before the advent of immunosuppressive drugs, especially systemic steroid therapies, which suppress pathogenic immunological activity. Although there have been recent advancements in the understanding of the pathogenesis of AIBDs, glucocorticosteroids and/or adjuvant immunosuppressive drugs are still needed to control disease activity. However, the long-term use of systemic immunosuppression is associated with major adverse events, including death. Based on the growing understanding of AIBD pathogenesis, novel treatment targets have emerged, some of which are currently being evaluated in clinical trials. Within this article, we review the current clinical trials involving pemphigus and pemphigoid and discuss the rationale that lead to these trials. Overall, we aim to foster insights into translational research in AIBDs to improve patient care.
Topics: Clinical Trials as Topic; Humans; Pemphigoid, Bullous; Pemphigus
PubMed: 31130959
DOI: 10.3389/fimmu.2019.00978 -
Journal of Investigative Medicine High... 2021Bullous pemphigoid (BP) is the most prevalent autoimmune blistering skin disease in the Western world affecting mainly the elderly population. The diagnosis is based on...
Bullous pemphigoid (BP) is the most prevalent autoimmune blistering skin disease in the Western world affecting mainly the elderly population. The diagnosis is based on clinical assessment along with specific immunopathologic findings on skin biopsy. Risk factors include genetic factors, environmental exposures, and several infections including hepatitis B, hepatitis C, , , and cytomegalovirus. A variety of drugs have been associated with BP including but not limited to dipeptidyl peptidase-4 inhibitors, loop diuretics, spironolactone, and neuroleptics. Associated neurologic disorders (dementia, Parkinson's disease, bipolar disorder, previous stroke history, and multiple sclerosis) have also been described. Common clinical presentation consists of extremely pruritic inflammatory plaques that resemble eczematous dermatitis or urticaria, followed by formation of tense bullae with subsequent erosions. Typical distribution involves the trunk and extremities. Mucosa is typically spared affecting only 10% to 30% of patients. Several unusual clinical presentations of BP have been described such as nonbullous forms with erythematous excoriated papules, plaques, and nodules. Other reported findings include urticarial lesions, prurigo-like nodules, multiple small vesicles resembling dermatitis herpetiformis or pompholyx, vegetating and purulent lesions localized in intertriginous areas, and even exfoliative erythroderma. Recognition and management of such cases can present a diagnostic challenge to clinicians. In this article, we describe another variant which to our knowledge is the first case to present with a cellulitis-like presentation in a patient with a known history of BP.
Topics: Aged; Blister; Cellulitis; Humans; Pemphigoid, Bullous; Skin
PubMed: 33847152
DOI: 10.1177/23247096211008585 -
Frontiers in Immunology 2023Bullous pemphigoid is an autoimmune blistering disorder that primarily occurs in elderly patients. Reports indicate that BP coexists with various hematological diseases,... (Review)
Review
Bullous pemphigoid is an autoimmune blistering disorder that primarily occurs in elderly patients. Reports indicate that BP coexists with various hematological diseases, including acquired hemophilia A, hypereosinophilic syndrome, aplastic anemia, autoimmune thrombocytopenia, and hematological malignancies. Early identification of these comorbidities contributes to a better control and reduced mortality. This article details the atypical clinical manifestations of BP when associated with hematological diseases, specific diagnostic strategies, underlying mechanistic connections, and possible treatments. Cross-reactivity between autoantibodies and exposed abnormal epitopes, shared cytokines and immune cells, together with genetic susceptibility are the most common connections between BP and hematological diseases. Patients were most often successfully treated with oral steroids combined with medications specifically targeting the hematological disorders. However, the individual comorbidities require specific considerations.
Topics: Humans; Aged; Pemphigoid, Bullous; Autoimmune Diseases; Blister; Autoantibodies; Hemophilia A
PubMed: 36969223
DOI: 10.3389/fimmu.2023.1155181 -
Experimental Dermatology Dec 2017Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease that clinically demonstrates tense blisters with widespread erythema, histologically... (Review)
Review
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease that clinically demonstrates tense blisters with widespread erythema, histologically demonstrates subepidermal blistering and immunologically demonstrates the presence of circulating autoantibodies against hemidesmosomal molecules. Complement activation has long been regarded as necessary for the generation of the BP. However, certain evidence has recently come to support non-complemental blistering mechanisms. The story of BP blistering mechanisms is a complicated one. This review mainly focuses on a specific blistering mechanism that highlights the role of complements in BP blistering.
Topics: Animals; Autoantigens; Blister; Complement System Proteins; Humans; Non-Fibrillar Collagens; Pemphigoid, Bullous; Collagen Type XVII
PubMed: 28418613
DOI: 10.1111/exd.13367 -
Frontiers in Immunology 2022Pemphigoid diseases are autoimmune chronic inflammatory skin diseases, which are characterized by blistering of the skin and/or mucous membranes, and circulating and... (Review)
Review
Pemphigoid diseases are autoimmune chronic inflammatory skin diseases, which are characterized by blistering of the skin and/or mucous membranes, and circulating and tissue-bound autoantibodies. The well-established pathomechanisms comprise autoantibodies targeting various structural proteins located at the dermal-epidermal junction, leading to complement factor binding and activation. Several effector cells are thus attracted and activated, which in turn inflict characteristic tissue damage and subepidermal blistering. Moreover, the detection of linear complement deposits in the skin is a diagnostic hallmark of all pemphigoid diseases. However, recent studies showed that blistering might also occur independently of complement. This review reassesses the importance of complement in pemphigoid diseases based on current research by contrasting and contextualizing data from , murine and human studies.
Topics: Animals; Autoantibodies; Blister; Complement System Proteins; Humans; Mice; Pemphigoid, Bullous; Skin
PubMed: 36059476
DOI: 10.3389/fimmu.2022.973702 -
Frontiers in Immunology 2023Autoimmune blistering diseases such as bullous pemphigoid (BP) and pemphigus vulgaris (PV) are complex, multifactorial, and polygenic diseases, whose exact pathogenesis... (Review)
Review
Autoimmune blistering diseases such as bullous pemphigoid (BP) and pemphigus vulgaris (PV) are complex, multifactorial, and polygenic diseases, whose exact pathogenesis is difficult to pinpoint. Research aimed at elucidating the associated epidemiologic risk factors of these two diseases has been hampered by their rare disease status. Further, a lack of centralization and standardization of available data makes the practical application of this information challenging. In order to collate and clarify the available literature we comprehensively reviewed 61 PV articles from 37 different countries and 35 BP articles from 16 different countries addressing a range of disease relevant clinical parameters including age of onset, sex, incidence, prevalence, and HLA allele association. The reported incidence of PV ranged from 0.098 to 5 patients per 100,000 people, while BP ranged from 0.21 to 7.63 patients per 100,000. Prevalence of PV ranged from 0.38 to 30 per 100,000 people and BP ranged from 1.46 to 47.99 per 100,000. The mean age of onset in patients ranged from 36.5 to 71 years for PV and 64 to 82.6 years for BP. Female-to-male ratios ranged from 0.46 to 4.4 in PV and 1.01 to 5.1 in BP. Our analysis provides support for the reported linkage disequilibrium of HLA DRB1*0402 (an allele previously shown to be associated with PV) and DQB1*0302 alleles in Europe, North America, and South America. Our data also highlight that HLA DQB1*0503 (also known to be associated with PV) appears in linkage disequilibrium with DRB1*1404 and DRB1*1401, mainly in Europe, the Middle East, and Asian countries. The HLA DRB1*0804 allele was only associated with PV in patients of Brazilian and Egyptian descent. Only two HLA alleles were reported as associated with BP more than twice in our review, DQB1*0301 and DQA1*0505. Collectively, our findings provide detailed insights into the variation of disease parameters relevant to PV and BP that can be expected to inform future work aimed at unraveling the complex pathogenesis of these conditions across the globe.
Topics: Humans; Male; Female; Adult; Middle Aged; Aged; Pemphigus; HLA-DRB1 Chains; Pemphigoid, Bullous; Genetic Predisposition to Disease; Haplotypes; Epidemiologic Factors; Autoimmune Diseases; Brazil
PubMed: 37180132
DOI: 10.3389/fimmu.2023.1159351 -
The Journal of Investigative Dermatology Apr 2020For many years, The Journal of Investigative Dermatology (JID) has been a leader in our understanding of many aspects of the major autoimmune blistering skin diseases,... (Review)
Review
For many years, The Journal of Investigative Dermatology (JID) has been a leader in our understanding of many aspects of the major autoimmune blistering skin diseases, pemphigus and bullous pemphigoid. The purpose of this review is to highlight and summarize those advances by discussing the respective articles, published in the JID from 2015 to 2019. Seminal articles from elsewhere in the literature that set the stage for those advances, or that are "classics" in the area, are also included to provide context and a more complete picture.
Topics: Autoantibodies; Autoimmunity; Humans; Pemphigoid, Bullous; Pemphigus
PubMed: 32200875
DOI: 10.1016/j.jid.2019.11.005 -
ORL; Journal For Oto-rhino-laryngology... 2021Autoimmune bullous diseases are rare conditions characterized by blistering of the skin and mucous membranes. The 2 commonest forms are pemphigus vulgaris and bullous... (Review)
Review
BACKGROUND
Autoimmune bullous diseases are rare conditions characterized by blistering of the skin and mucous membranes. The 2 commonest forms are pemphigus vulgaris and bullous pemphigoid. The oral cavity or oropharynx may be the initial site of presentation or often the only site involved.
SUMMARY
These conditions are often misdiagnosed or overlooked leading to poorer patient outcomes. Due to the chronic nature of these conditions and the systemic effects of treatment, there is a significant associated morbidity and mortality. As such, an understanding of the fundamentals of autoimmune bullous diseases is vital to those working in otolaryngology. The mainstay of management in both conditions is topical and systemic corticosteroids. There is also a role for immunomodulating and non-steroidal anti-inflammatory drugs as adjunct or alternative therapies. Surgical intervention may be required to protect the airway. Often multimodality treatment is required involving multidisciplinary input from otolaryngologists, oral surgeons, dermatologists, and rheumatologists. This review article will highlight the aetiology, pathology, clinical features, investigations, and management of both pemphigus vulgaris and bullous pemphigoid including recent advances in management.
Topics: Autoimmune Diseases; Humans; Mouth; Pemphigoid, Bullous; Pemphigus; Pharynx
PubMed: 33902048
DOI: 10.1159/000515229 -
Frontiers in Immunology 2023Bullous pemphigoid (BP) is an autoimmune disease that mainly occurs in the elderly, severely affecting their health and life quality. Traditional therapy for BP is... (Review)
Review
Bullous pemphigoid (BP) is an autoimmune disease that mainly occurs in the elderly, severely affecting their health and life quality. Traditional therapy for BP is mainly based on the systemic use of corticosteroids, but long-term use of corticosteroids results in a series of side effects. Type 2 inflammation is an immune response largely mediated by group 2 innate lymphoid cells, type 2 T helper cells, eosinophils, and inflammatory cytokines, such as interleukin (IL)-4, IL-5 and IL-13. Among patients with BP, the levels of immunoglobulin E and eosinophils are significantly increased in the peripheral blood and skin lesions, suggesting that the pathogenesis is tightly related to type 2 inflammation. To date, various targeted drugs have been developed to treat type 2 inflammatory diseases. In this review, we summarize the general process of type 2 inflammation, its role in the pathogenesis of BP and potential therapeutic targets and medications related to type 2 inflammation. The content of this review may contribute to the development of more effective drugs with fewer side effects for the treatment of BP.
Topics: Aged; Humans; Pemphigoid, Bullous; Immunity, Innate; Lymphocytes; Autoimmune Diseases; Drug-Related Side Effects and Adverse Reactions; Inflammation
PubMed: 36875098
DOI: 10.3389/fimmu.2023.1115083 -
Experimental Dermatology Dec 2017Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering skin disease and is characterized by the presence of autoantibodies directed against the... (Review)
Review
Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering skin disease and is characterized by the presence of autoantibodies directed against the hemidesmosomal proteins BP180 and BP230 that can be detected in the skin and serum of BP patients. Histologically, the dermal infiltration of eosinophils is obvious. The objective of this review was to present evidence that eosinophils play a key role in the pathogenesis of BP. Eosinophils, together with cytokines and chemokines regulating their production, recruitment and activation, are abundantly present in lesional skin, in blisters and in peripheral blood of patients with BP. Recently, using a cryosection model, eosinophils were demonstrated to induce dermal-epidermal separation in the presence of BP antibodies. Thus, eosinophils and their products, as well as mediators regulating their function, present promising targets for the treatment of BP.
Topics: Animals; Eosinophils; Humans; Immunoglobulin E; Molecular Targeted Therapy; Pemphigoid, Bullous
PubMed: 28833620
DOI: 10.1111/exd.13416