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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 -
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 -
Journal of the American Academy of... Mar 2020Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of...
BACKGROUND
Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management.
OBJECTIVE
We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations.
METHODS
A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus.
RESULTS
The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion.
LIMITATIONS
Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available.
CONCLUSIONS
We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.
Topics: Academies and Institutes; Administration, Intravenous; Antigens, CD20; Combined Modality Therapy; Consensus; Delphi Technique; Dermatology; Drug Therapy, Combination; Europe; Glucocorticoids; Humans; Immunologic Factors; Pemphigus; Plasmapheresis; Practice Guidelines as Topic; Rituximab; Severity of Illness Index
PubMed: 29438767
DOI: 10.1016/j.jaad.2018.02.021 -
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 -
International Journal of Molecular... Mar 2020Skin manifestations of systemic disease and malignancy are extremely polymorphous. Clinicians should be familiarized with paraneoplastic dermatoses in order to perform... (Review)
Review
Skin manifestations of systemic disease and malignancy are extremely polymorphous. Clinicians should be familiarized with paraneoplastic dermatoses in order to perform an early diagnosis of the underlying neoplasm. Lack of familiarity with cutaneous clues of internal malignancy may delay diagnosis and treatment of cancer. In this review, we described several paraneoplastic dermatoses and discussed extensively two paradigmatic ones, namely paraneoplastic pemphigus and paraneoplastic dermatomyositis.
Topics: Cytokines; Dermatomyositis; Erythema; Humans; Neoplasms; Paraneoplastic Syndromes; Pemphigus; Pyoderma Gangrenosum; Skin; Skin Diseases; Sweet Syndrome
PubMed: 32245283
DOI: 10.3390/ijms21062178 -
Frontiers in Immunology 2020Myasthenia gravis (MG) is a prototypical autoantibody mediated disease. The autoantibodies in MG target structures within the neuromuscular junction (NMJ), thus... (Review)
Review
Myasthenia gravis (MG) is a prototypical autoantibody mediated disease. The autoantibodies in MG target structures within the neuromuscular junction (NMJ), thus affecting neuromuscular transmission. The major disease subtypes of autoimmune MG are defined by their antigenic target. The most common target of pathogenic autoantibodies in MG is the nicotinic acetylcholine receptor (AChR), followed by muscle-specific kinase (MuSK) and lipoprotein receptor-related protein 4 (LRP4). MG patients present with similar symptoms independent of the underlying subtype of disease, while the immunopathology is remarkably distinct. Here we highlight these distinct immune mechanisms that describe both the B cell- and autoantibody-mediated pathogenesis by comparing AChR and MuSK MG subtypes. In our discussion of the AChR subtype, we focus on the role of long-lived plasma cells in the production of pathogenic autoantibodies, the IgG1 subclass mediated pathology, and contributions of complement. The similarities underlying the immunopathology of AChR MG and neuromyelitis optica (NMO) are highlighted. In contrast, MuSK MG is caused by autoantibody production by short-lived plasmablasts. MuSK MG autoantibodies are mainly of the IgG4 subclass which can undergo Fab-arm exchange (FAE), a process unique to this subclass. In FAE IgG4, molecules can dissociate into two halves and recombine with other half IgG4 molecules resulting in bispecific antibodies. Similarities between MuSK MG and other IgG4-mediated autoimmune diseases, including pemphigus vulgaris (PV) and chronic inflammatory demyelinating polyneuropathy (CIDP), are highlighted. Finally, the immunological distinctions are emphasized through presentation of biological therapeutics that provide clinical benefit depending on the MG disease subtype.
Topics: Animals; Antibodies, Bispecific; Autoantibodies; B-Lymphocytes; Humans; Immunoglobulin G; LDL-Receptor Related Proteins; Mice; Myasthenia Gravis; Pemphigus; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Receptors, Nicotinic
PubMed: 32547535
DOI: 10.3389/fimmu.2020.00776 -
JID Innovations : Skin Science From... Mar 2021Pemphigus is an epidemiologically heterogeneous group of autoimmune bullous diseases comprising pemphigus vulgaris (PV), pemphigus foliaceus, paraneoplastic pemphigus,... (Review)
Review
Pemphigus is an epidemiologically heterogeneous group of autoimmune bullous diseases comprising pemphigus vulgaris (PV), pemphigus foliaceus, paraneoplastic pemphigus, IgA pemphigus, and pemphigus herpetiformis. Recently, our knowledge about the frequency of pemphigus, which is highly variable between different populations, has considerably expanded, and the first non-HLA genes associated with PV have been identified. In addition, a variety of comorbidities, including other autoimmune diseases, hematological malignancies, and psoriasis, have been described in this variant. Here, initial data about the impact of COVID-19 on this fragile patient population are discussed and perspectives for future epidemiological studies are outlined.
PubMed: 34909708
DOI: 10.1016/j.xjidi.2021.100004