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Journal of the European Academy of... Sep 2020Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of...
BACKGROUND
Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, pemphigus was almost always fatal. Due to its rarity, only few randomized controlled therapeutic trials are available. Recently, rituximab has been approved as first-line treatment for moderate and severe pemphigus vulgaris in Europe and the United States.
OBJECTIVES
The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology (EADV) has initiated a throughout update of the guideline for the management of patients with pemphigus.
RESULTS
The guidelines for the management of pemphigus were updated, and the degree of consent among all task force members was included. The final version of the guideline was consented by the European Dermatology Forum (EDF) and several patient organizations.
Topics: Academies and Institutes; Dermatology; Europe; Guidelines as Topic; Humans; Pemphigus; Venereology
PubMed: 32830877
DOI: 10.1111/jdv.16752 -
Medicina (Kaunas, Lithuania) Oct 2021Clinicians may encounter a variety of skin conditions that present with vesiculobullous lesions in their everyday practice. Pemphigus vulgaris, pemphigus foliaceus, IgA... (Review)
Review
Clinicians may encounter a variety of skin conditions that present with vesiculobullous lesions in their everyday practice. Pemphigus vulgaris, pemphigus foliaceus, IgA pemphigus, and paraneoplastic pemphigus represent the spectrum of autoimmune bullous dermatoses of the pemphigus family. The pemphigus family of diseases is characterized by significant morbidity and mortality. Considering the risks associated with a delayed diagnosis or misdiagnosis and the potential for overlap in clinical features and treatment, evaluation for suspected pemphigus disease often requires thorough clinical assessment and laboratory testing. Diagnosis is focused on individual biopsies for histopathology and direct immunofluorescence. Additional laboratory methods used for diagnosis include indirect immunofluorescence and enzyme-linked immunosorbent assay. Recent advancements, including anti-CD20 therapy, have improved the efficacy and reduced the morbidity of pemphigus treatment. This contribution presents updates on the pathophysiology, clinical features, diagnostic work-up, and medical management of pemphigus. Improved strategies for diagnosis and clinical assessment are reviewed, and newer treatment options are discussed.
Topics: Autoimmune Diseases; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Indirect; Humans; Pemphigus; Skin Diseases, Vesiculobullous
PubMed: 34684117
DOI: 10.3390/medicina57101080 -
Nature Reviews. Disease Primers May 2017Pemphigus is a group of IgG-mediated autoimmune diseases of stratified squamous epithelia, such as the skin and oral mucosa, in which acantholysis (the loss of cell... (Review)
Review
Pemphigus is a group of IgG-mediated autoimmune diseases of stratified squamous epithelia, such as the skin and oral mucosa, in which acantholysis (the loss of cell adhesion) causes blisters and erosions. Pemphigus has three major subtypes: pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus. IgG autoantibodies are characteristically raised against desmoglein 1 and desmoglein 3, which are cell-cell adhesion molecules found in desmosomes. The sites of blister formation can be physiologically explained by the anti-desmoglein autoantibody profile and tissue-specific expression pattern of desmoglein isoforms. The pathophysiological roles of T cells and B cells have been characterized in mouse models of pemphigus and patients, revealing insights into the mechanisms of autoimmunity. Diagnosis is based on clinical manifestations and confirmed with histological and immunochemical testing. The current first-line treatment is systemic corticosteroids and adjuvant therapies, including immunosuppressive agents, intravenous immunoglobulin and plasmapheresis. Rituximab, a monoclonal antibody against CD20 B cells, is a promising therapeutic option that may soon become first-line therapy. Pemphigus is one of the best-characterized human autoimmune diseases and provides an ideal paradigm for both basic and clinical research, especially towards the development of antigen-specific immune suppression treatments for autoimmune diseases.
Topics: Adrenal Cortex Hormones; Animals; Autoantibodies; Desmoglein 1; Desmoglein 3; Disease Models, Animal; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Mice; Pemphigus; Plasmapheresis; Treatment Outcome
PubMed: 28492232
DOI: 10.1038/nrdp.2017.26 -
Lancet (London, England) Sep 2019Pemphigus consists of a group of rare and severe autoimmune blistering diseases mediated by pathogenic autoantibodies mainly directed against two desmosomal adhesion... (Review)
Review
Pemphigus consists of a group of rare and severe autoimmune blistering diseases mediated by pathogenic autoantibodies mainly directed against two desmosomal adhesion proteins, desmoglein (Dsg)1 and Dsg3 (also known as DG1 and DG3), which are present in the skin and surface-close mucosae. The binding of autoantibodies to Dsg proteins induces a separation of neighbouring keratinocytes, in a process known as acantholysis. The two main pemphigus variants are pemphigus vulgaris, which often originates with painful oral erosions, and pemphigus foliaceus, which is characterised by exclusive skin lesions. Pemphigus is diagnosed on the basis of either IgG or complement component 3 deposits (or both) at the keratinocyte cell membrane, detected by direct immunofluorescence microscopy of a perilesional biopsy, with serum anti-Dsg1 or anti-Dsg3 antibodies (or both) detected by ELISA. Corticosteroids are the therapeutic mainstay, which have recently been complemented by the anti-CD20 antibody rituximab in moderate and severe disease. Rituximab induces complete remission off therapy in 90% of patients, despite rapid tapering of corticosteroids, thus allowing for a major corticosteroid-sparing effect and a halved number of adverse events related to corticosteroids.
Topics: Adrenal Cortex Hormones; Azathioprine; Desmoglein 1; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin G; Immunosuppressive Agents; Pemphigus; Rituximab; Treatment Outcome
PubMed: 31498102
DOI: 10.1016/S0140-6736(19)31778-7 -
Anais Brasileiros de Dermatologia Jul 2019Pemphigus vulgaris is a chronic autoimmune bullous dermatosis that results from the production of autoantibodies against desmogleins 1 and 3. It is the most frequent and...
Pemphigus vulgaris is a chronic autoimmune bullous dermatosis that results from the production of autoantibodies against desmogleins 1 and 3. It is the most frequent and most severe form of pemphigus, occurring universally, usually between 40 and 60 years of age. It usually begins with blisters and erosions on the oral mucosa, followed by lesions on other mucous membranes and flaccid blisters on the skin, which can be disseminated. There is a clinical variant, pemphigus vegetans, which is characterized by the presence of vegetating lesions in the large folds of the skin. Clinical suspicion can be confirmed by cytological examination, histopathological examination, and direct and indirect immunofluorescence tests. The treatment is performed with systemic corticosteroids, and immunosuppressive drugs may be associated, among them azathioprine and mycophenolate mofetil. More severe cases may benefit from corticosteroids in the form of intravenous pulse therapy, and recent studies have shown a beneficial effect of rituximab, an anti-CD20 immunobiological drug. It is a chronic disease with mortality around 10%, and septicemia is the main cause of death. Patients need long-term and multidisciplinary follow-up.
Topics: Adult; Autoantibodies; Desmosomes; Diagnosis, Differential; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Immunotherapy; Male; Middle Aged; Pemphigus; Skin; Surveys and Questionnaires
PubMed: 31365654
DOI: 10.1590/abd1806-4841.20199011 -
Annual Review of Pathology May 2016Pemphigus and bullous pemphigoid are autoantibody-mediated blistering skin diseases. In pemphigus, keratinocytes in epidermis and mucous membranes lose cell-cell... (Review)
Review
Pemphigus and bullous pemphigoid are autoantibody-mediated blistering skin diseases. In pemphigus, keratinocytes in epidermis and mucous membranes lose cell-cell adhesion, and in pemphigoid, the basal keratinocytes lose adhesion to the basement membrane. Pemphigus lesions are mediated directly by the autoantibodies, whereas the autoantibodies in pemphigoid fix complement and mediate inflammation. In both diseases, the autoantigens have been cloned and characterized; pemphigus antigens are desmogleins (cell adhesion molecules in desmosomes), and pemphigoid antigens are found in hemidesmosomes (which mediate adhesion to the basement membrane). This knowledge has enabled diagnostic testing for these diseases by enzyme-linked immunosorbent assays and dissection of various pathophysiological mechanisms, including direct inhibition of cell adhesion, antibody-induced internalization of antigen, and cell signaling. Understanding these mechanisms of disease has led to rational targeted therapeutic strategies.
Topics: Animals; Humans; Pemphigoid, Bullous; Pemphigus
PubMed: 26907530
DOI: 10.1146/annurev-pathol-012615-044313 -
Immunologic Research Apr 2018Pemphigus forms a group of rare autoimmune bullous diseases that affect the skin and mucous membranes. This group has a chronic course leading to high morbidity and... (Review)
Review
Pemphigus forms a group of rare autoimmune bullous diseases that affect the skin and mucous membranes. This group has a chronic course leading to high morbidity and mortality. It is characterized by the production of pathogenic autoantibodies directed against different proteins of the desmosome, leading histologically to intraepidermal cleavage, and clinically to vesicles and erosions on the epithelium of the mucous membranes and/or the skin. The diagnosis of the subtype of pemphigus is based on clinical features, the level of histologic cleavage, and the identification of the antigens recognized by circulating autoantibodies by immunoserological analyses. The epidemiological features of pemphigus vary considerably in different regions of the world. Observational studies examining comorbidities and associations among patients with pemphigus are scarce and sometimes inconclusive. The prognosis, mortality, and clinical outcomes in pemphigus have undergone dramatic change throughout the years. This review provides a brief overview about the different subtypes of pemphigus: pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, pemphigus herpetiformis, and IgA pemphigus. In addition, it summarizes the most recent understanding of the epidemiology, mortality data, and comorbidities of this group of organ-specific autoimmune diseases.
Topics: Autoantibodies; Humans; Pemphigus; Prognosis
PubMed: 29479654
DOI: 10.1007/s12026-018-8986-7 -
Clinical and Experimental Dermatology Oct 2019Pemphigus diseases are cutaneous and mucous membrane blistering diseases, related to the key antigens of desmoglein 1 and 3. This article reviews the topic, including... (Review)
Review
Pemphigus diseases are cutaneous and mucous membrane blistering diseases, related to the key antigens of desmoglein 1 and 3. This article reviews the topic, including diagnosis, and provides the physician with guidance on the treatment of these difficult to control disorders.
Topics: Biopsy; Diagnosis, Differential; Fluorescent Antibody Technique, Direct; Humans; Maintenance Chemotherapy; Pemphigus; Practice Guidelines as Topic; Remission Induction; Skin
PubMed: 31378971
DOI: 10.1111/ced.14041 -
Autoimmunity Reviews Apr 2019Pemphigus diseases (PDs) and mucous membrane pemphigoid (MMP) are a group of immune-mediated mucocutaneous disorders clinically characterized by the formation of... (Review)
Review
Pemphigus diseases (PDs) and mucous membrane pemphigoid (MMP) are a group of immune-mediated mucocutaneous disorders clinically characterized by the formation of blisters, erosions and ulcers. The skin and mucous membranes are predominantly affected, with the oropharyngeal mucosa as the initially involved site. Ocular involvement is also a frequent feature of these diseases. Because of the considerable overlap in their clinical presentations, the diagnosis of PDs vs. MMP can be challenging. A recognition of their specific immunological and histopathologic features is crucial in the differential diagnosis. Treatment modalities include systemically administered corticosteroids, steroid-sparing immunosuppressive agents, and biologic therapies (rituximab, intravenous immunoglobulins, and anti-tumor necrosis factor agents). Topical, oral, conjunctival, or intralesional corticosteroids as well as anti-inflammatory drugs and antibiotics are prescribed as needed.
Topics: Adrenal Cortex Hormones; Diagnosis, Differential; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Pemphigoid, Benign Mucous Membrane; Pemphigoid, Bullous; Pemphigus; Rituximab
PubMed: 30738958
DOI: 10.1016/j.autrev.2019.02.005 -
Allergy Aug 2022Bruton's tyrosine kinase (BTK), a member of the Tec kinase family, is critically involved in a range of immunological pathways. The clinical application of BTK... (Review)
Review
Bruton's tyrosine kinase (BTK), a member of the Tec kinase family, is critically involved in a range of immunological pathways. The clinical application of BTK inhibitors for B-cell malignancies has proven successful, and there is strong rationale for the potential benefits of BTK inhibitors in some autoimmune and allergic conditions, including immune-mediated dermatological diseases. However, the established risk-to-benefit profile of "first-generation" BTK inhibitors cannot be extrapolated to these emerging, non-oncological, indications. "Next-generation" BTK inhibitors such as remibrutinib and fenebrutinib entered clinical development for chronic spontaneous urticaria (CSU); rilzabrutinib and tirabrutinib are being studied as potential treatments for pemphigus. Promising data from early-phase clinical trials in CSU suggest potential for these agents to achieve strong pathway inhibition, which may translate into measurable clinical benefits, as well as other effects such as the disruption of autoantibody production. BTK inhibitors may help to overcome some of the shortcomings of monoclonal antibody treatments for immune-mediated dermatological conditions such as CSU, pemphigus, and systemic lupus erythematosus. In addition, the use of BTK inhibitors may improve understanding of the pathophysiological roles of mast cells, basophils, and B cells in such conditions.
Topics: Agammaglobulinaemia Tyrosine Kinase; B-Lymphocytes; Humans; Pemphigus; Protein Kinase Inhibitors
PubMed: 35175630
DOI: 10.1111/all.15261