-
Actas Dermo-sifiliograficas 2005Pemphigus is an infrequent, organ-specific, autoimmune bullous disease, which affects the skin, mucous membranes and appendages. Histopathologically, it is characterized... (Review)
Review
Pemphigus is an infrequent, organ-specific, autoimmune bullous disease, which affects the skin, mucous membranes and appendages. Histopathologically, it is characterized by acantholysis. Pemphigus has classically been divided into two major groups, pemphigus vulgaris and pemphigus foliaceus, with their respective clinical variants pemphigus vegetans and pemphigus erythematosus. In recent years, new variants of pemphigus have been described: paraneoplastic pemphigus, IgA pemphigus and pemphigus herpetiformis. This article reviews the epidemiology, etiopathogenesis, clinical symptoms, diagnosis, treatment and prognosis of pemphigus. Advances in molecular biology techniques have made it possible to more precisely identify the different antigens against which antibodies are directed, and to fine-tune ELISA diagnostic techniques. Treating pemphigus vulgaris and foliaceus with general steroids has modified their prognosis; it is estimated that mortality in recent decades is less than 10 %. Managing the clinical complications that appear during the evolution of the pemphigus has contributed to reducing morbidity and mortality.
Topics: Humans; Paraneoplastic Syndromes; Pemphigus
PubMed: 16476253
DOI: 10.1016/s0001-7310(05)73090-8 -
Frontiers in Immunology 2019Pemphigus encompasses a heterogeneous group of autoimmune blistering diseases, which affect both mucous membranes and the skin. The disease usually runs a... (Review)
Review
Pemphigus encompasses a heterogeneous group of autoimmune blistering diseases, which affect both mucous membranes and the skin. The disease usually runs a chronic-relapsing course, with a potentially devastating impact on the patients' quality of life. Pemphigus pathogenesis is related to IgG autoantibodies targeting various adhesion molecules in the epidermis, including desmoglein (Dsg) 1 and 3, major components of desmosomes. The pathogenic relevance of such autoantibodies has been largely demonstrated experimentally. IgG autoantibody binding to Dsg results in loss of epidermal keratinocyte adhesion, a phenomenon referred to as acantholysis. This in turn causes intra-epidermal blistering and the clinical appearance of flaccid blisters and erosions at involved sites. Since the advent of glucocorticoids, the overall prognosis of pemphigus has largely improved. However, mortality persists elevated, since long-term use of high dose corticosteroids and adjuvant steroid-sparing immunosuppressants portend a high risk of serious adverse events, especially infections. Recently, rituximab, a chimeric anti CD20 monoclonal antibody which induces B-cell depletion, has been shown to improve patients' survival, as early rituximab use results in higher disease remission rates, long term clinical response and faster prednisone tapering compared to conventional immunosuppressive therapies, leading to its approval as a first line therapy in pemphigus. Other anti B-cell therapies targeting B-cell receptor or downstream molecules are currently tried in clinical studies. More intriguingly, a preliminary study in a preclinical mouse model of pemphigus has shown promise regarding future therapeutic application of Chimeric Autoantibody Receptor T-cells engineered using Dsg domains to selectively target autoreactive B-cells. Conversely, previous studies from our group have demonstrated that B-cell depletion in pemphigus resulted in secondary impairment of T-cell function; this may account for the observed long-term remission following B-cell recovery in rituximab treated patients. Likewise, our data support the critical role of Dsg-specific T-cell clones in orchestrating the inflammatory response and B-cell activation in pemphigus. Monitoring autoreactive T-cells in patients may indeed provide further information on the role of these cells, and would be the starting point for designating therapies aimed at restoring the lost immune tolerance against Dsg. The present review focuses on current advances, unmet challenges and future perspectives of pemphigus management.
Topics: Adoptive Transfer; Adrenal Cortex Hormones; Animals; Autoantibodies; Cell Adhesion; Desmoglein 1; Desmoglein 3; Disease Models, Animal; Epidermis; Humans; Immunoglobulin G; Keratinocytes; Mice; Pemphigus; Rituximab
PubMed: 31293582
DOI: 10.3389/fimmu.2019.01418 -
Indian Journal of Dermatology,... 2022
Review
Topics: Acantholysis; Diagnosis, Differential; Humans; Ichthyosis; Skin; Skin Diseases
PubMed: 34245536
DOI: 10.25259/IJDVL_1028_20 -
Dermatopathology (Basel, Switzerland) Feb 2024Galli-Galli disease (GGD) is a rare genodermatosis that exhibits autosomal dominant inheritance with variable penetrance. GGD typically manifests with erythematous... (Review)
Review
Galli-Galli disease (GGD) is a rare genodermatosis that exhibits autosomal dominant inheritance with variable penetrance. GGD typically manifests with erythematous macules, papules, and reticulate hyperpigmentation in flexural areas. A distinct atypical variant exists, which features brown macules predominantly on the trunk, lower limbs, and extremities, with a notable absence of the hallmark reticulated hyperpigmentation in flexural areas. This review includes a detailed literature search and examines cases since GGD's first description in 1982. It aims to synthesize the current knowledge on GGD, covering its etiology, clinical presentation, histopathology, diagnosis, and treatment. A significant aspect of this review is the exploration of the genetic, histopathological, and clinical parallels between GGD and Dowling-Degos disease (DDD), which is another rare autosomal dominant genodermatosis, particularly focusing on their shared mutations in the and genes. This supports the hypothesis that GGD and DDD may be different phenotypic expressions of the same pathological condition, although they have traditionally been recognized as separate entities, with suprabasal acantholysis being a distinctive feature of GGD. Lastly, this review discusses the existing treatment approaches, underscoring the absence of established guidelines and the limited effectiveness of various treatments.
PubMed: 38390850
DOI: 10.3390/dermatopathology11010008 -
Frontiers in Immunology 2018Pemphigus vulgaris (PV) is a potentially life-threatening mucocutaneous autoimmune blistering disease. Patients develop non-healing erosions and blisters due to... (Review)
Review
Pemphigus vulgaris (PV) is a potentially life-threatening mucocutaneous autoimmune blistering disease. Patients develop non-healing erosions and blisters due to cell-cell detachment of keratinocytes (acantholysis), with subsequent suprabasal intraepidermal splitting. Identified almost 30 years ago, desmoglein-3 (Dsg3), a Ca-dependent cell adhesion molecule belonging to the cadherin family, has been considered the "primary" autoantigen in PV. Proteomic studies have identified numerous autoantibodies in patients with PV that have known roles in the physiology and cell adhesion of keratinocytes. Antibodies to these autoantibodies include desmocollins 1 and 3, several muscarinic and nicotinic acetylcholine receptor subtypes, mitochondrial proteins, human leukocyte antigen molecules, thyroid peroxidase, and hSPCA1-the Ca/Mn-ATPase encoded by ATP2C1, which is mutated in Hailey-Hailey disease. Several studies have identified direct pathogenic roles of these proteins, or synergistic roles when combined with Dsg3. We review the role of these direct and indirect mechanisms of non-desmoglein autoantibodies in the pathogenesis of PV.
Topics: Animals; Autoantibodies; Desmoglein 3; Desmosomes; Epitopes; Humans; Keratinocytes; Mice; Pemphigus; Pemphigus, Benign Familial
PubMed: 29915578
DOI: 10.3389/fimmu.2018.01190 -
Journal of Cellular Physiology Jul 2022Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterized by cell-cell detachment (or acantholysis) and blister formation. While the... (Review)
Review
Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterized by cell-cell detachment (or acantholysis) and blister formation. While the signaling mechanisms that associate with skin/mucosal blistering are being elucidated, specific treatment strategies targeting PV-specific pathomechanisms, particularly kinase signaling, have yet to be established. Hence, the aim of this review was to systematically evaluate molecules in the class of kinases that are essential for acantholysis and blister formation and are therefore candidates for targeted therapy. English articles from PubMed and Scopus databases were searched, and included in vitro, in vivo, and human studies that investigated the role of kinases in PV. We selected studies, extracted data and assessed risk of bias in duplicates and the results were reported according to the methodology outlined by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The risk of bias assessment was performed on in vivo studies utilizing SYRCLE's risk of bias tool. Thirty-five studies were included that satisfied the pathogenicity criterion of kinases in PV, the vast majority being experimental models that used PV sera (n = 13) and PV-IgG (n = 22). Inhibition of kinase activity (p38MAPK, PKC, TK, c-Src, EGFR, ERK, mTOR, BTK, and CDK2) was achieved mostly by pharmacological means. Overall, we found substantial evidence that kinase inhibition reduced PV-associated phosphorylation events and keratinocyte disassociation, prevented acantholysis, and blocked blister formation. However, the scarce adherence to standardized reporting systems and the experimental protocols/models used did limit the internal and external validity of these studies. In summary, this systematic review highlighted the pathogenic intracellular events mediated by kinases in PV acantholysis and presented kinase signaling as a promising avenue for translational research. In particular, the molecules identified and discussed in this study represent potential candidates for the development of mechanism-based interventions in PV.
Topics: Acantholysis; Autoantibodies; Blister; Humans; Immunoglobulin G; Keratinocytes; Pemphigus; Phosphorylation
PubMed: 35616233
DOI: 10.1002/jcp.30784 -
Indian Journal of Pathology &... Mar 2024Darier disease (DD) is a rare genodermatosis. Literature on this topic is overwhelmingly dominated by case reports with rare clinical presentations, which have mentioned...
Darier disease (DD) is a rare genodermatosis. Literature on this topic is overwhelmingly dominated by case reports with rare clinical presentations, which have mentioned the histopathologic features briefly. The aim of this study was to document the histopathology of DD. Skin biopsies diagnosed as Darier disease based on clinicopathologic correlation over 12 years were reviewed for various epidermal and dermal features. There were 16 patients included, who most commonly presented in the third decade, with slight female predilection. The most common clinical presentation was hyperpigmented, hyperkeratotic, papules and plaques (91%), with 69% affecting the trunk. In addition to the classic suprabasal acantholytic clefts, we noted some unusual features: absence of parakeratosis (19%), a cornoid lamella-like pattern (62%), follicular acantholysis (13%) and multiple foci of involvement within a single biopsy (63%). Features such as the presence of dyskeratotic cells and minimal dermal lymphocytic infiltrates were concordant with previous literature. The limitation of this study was the small sample size. To conclude, pathologists must be aware of the variations in histopathology of Darier's disease, especially when challenged with atypical clinical presentations. The Darier-like pattern is met within several acantholytic diseases, and clinicopathologic correlation has the last word in arriving at a diagnosis.
PubMed: 38563701
DOI: 10.4103/ijpm.ijpm_610_23 -
Biology Feb 2023The importance of acetylcholine (ACh) in keratinocyte adhesion and acantholysis has been investigated over the last three decades, particularly in the pathophysiology of... (Review)
Review
The importance of acetylcholine (ACh) in keratinocyte adhesion and acantholysis has been investigated over the last three decades, particularly in the pathophysiology of autoimmune blistering dermatoses. Pemphigus vulgaris (PV) is an autoimmune blistering skin disease where autoantibody-mediated suprabasilar intraepidermal splitting causes flaccid blisters and non-healing erosions of the oral mucosa and sometimes also of the skin. Historically, acantholysis in PV was thought to be driven by anti-desmoglein (Dsg) antibodies. Herein, we describe the role of autoantibodies against keratinocyte muscarinic and nicotinic acetylcholine receptors, as well as the annexin-like molecule pemphaxin that also binds ACh, in the immunopathogenesis of PV. The identification of targets in this disease is important, as they may lead to novel diagnostic and therapeutic options in the future for this potentially deadly disease.
PubMed: 36979046
DOI: 10.3390/biology12030354 -
Clinical, Cosmetic and Investigational... 2016Benign familial chronic pemphigus or Hailey-Hailey disease is caused by an autosomal dominant mutation in the gene leading to suprabasilar acantholysis. The disease... (Review)
Review
Benign familial chronic pemphigus or Hailey-Hailey disease is caused by an autosomal dominant mutation in the gene leading to suprabasilar acantholysis. The disease most commonly affects intertriginous areas symmetrically. The chronic nature of the disease and multiple recurrences make the disease bothersome for patients and a treatment challenge for physicians. Treatments include topical and/or systemic agents and surgery including laser. This review summarizes the available treatment options.
PubMed: 27695354
DOI: 10.2147/CCID.S89483 -
The Pan African Medical Journal 2022Pemphigus vulgaris (PV) is an autoimmune mucocutaneous disorder of the oral cavity and is the most common subtype of pemphigus. The etiology remains obscure, although...
Pemphigus vulgaris (PV) is an autoimmune mucocutaneous disorder of the oral cavity and is the most common subtype of pemphigus. The etiology remains obscure, although the disease is characterized by autoantibodies directed against the desmoglein component of the keratinocytes. It manifests clinically as vesicle, bullae or erosions of skin and mucous membrane and histopathologically shows the presence of acantholysis. The presence of exclusive oral lesions initially increases the chances of misdiagnosing the disease as another condition, posing diagnostic, therapeutic and prognostic difficulties, consequently prompt diagnosis and treatment can prevent untoward consequences. Demonstration of IgG antibodies against desmoglein in Immunofluroscence confirms the diagnosis. In here we report a case of a 55-year-old female patient suffering from PV emphasizing the significance of clinical examination, pertinent investigations, treatment rendered and its outcome.
Topics: Acantholysis; Autoantibodies; Blister; Desmogleins; Female; Humans; Immunoglobulin G; Keratinocytes; Middle Aged; Pemphigus
PubMed: 36212921
DOI: 10.11604/pamj.2022.42.184.34184