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Anais Brasileiros de Dermatologia 2021A 55-year-old male presented with an eight-month history of erythematous papules and plaques with demarcated areas of spared skin on his trunk, upper extremities, neck,...
A 55-year-old male presented with an eight-month history of erythematous papules and plaques with demarcated areas of spared skin on his trunk, upper extremities, neck, and face. Grover's disease is a rare, acquired disorder of unknown origin, which is classically characterized by the appearance of erythematous papules on the upper trunk that are usually transient. As in the present case, there are reports of atypical disease, with facial involvement, pityriasis rubra pilaris-like lesions, and a more chronic course.
Topics: Acantholysis; Humans; Ichthyosis; Male; Middle Aged; Pityriasis Rubra Pilaris; Skin
PubMed: 33589293
DOI: 10.1016/j.abd.2020.06.011 -
Dermatopathology (Basel, Switzerland) May 2022Pemphigus is a chronic blistering disorder caused by autoantibodies that target desmosomal proteins in the epidermis. Acantholysis may be absent, and pemphigus may...
Pemphigus is a chronic blistering disorder caused by autoantibodies that target desmosomal proteins in the epidermis. Acantholysis may be absent, and pemphigus may present only with spongiosis and vesiculation, thereby leading to a misdiagnosis of eczema. Herein, we conducted a retrospective, observational, single-center study to establish a pattern of spongiosis in cases of pemphigus confirmed by direct immunofluorescence. Immunopathologically diagnosed pemphigus specimens from 2001 to 2020 were retrieved, and specimens with spongiosis were analyzed for the following features: vesiculation, acantholysis, spongiosis, inflammatory cells in the epidermis, and inflammation in the dermis. Cases of spongiotic dermatitis were used as control. Out of 99 immunopathologically diagnosed pemphigus specimens, 41 samples with spongiosis were identified. About one quarter of the specimens did not have acantholysis. Spongiosis in the middle to lower thirds of the perilesional epidermis (p = 0.030), exocytosis with either neutrophils or eosinophils (p = 0.016), dermal infiltrates composed of lymphocytes, eosinophils, and neutrophils (p = 0.012), and absence of Langerhans cell microabscesses (p < 0.001) were more common in pemphigus than control. Spongiosis in pemphigus may mimic eczema in patients without acantholysis. The subtle histological findings in this study provide diagnostic clues and suggest that further immunofluorescence should be performed to confirm pemphigus diagnosis.
PubMed: 35645233
DOI: 10.3390/dermatopathology9020022 -
The Kaohsiung Journal of Medical... Jan 2013Desmosomes in keratinocytes are the most important intercellular adhering junctions that provide structural strength for the epidermis. These junctions are connected... (Review)
Review
Desmosomes in keratinocytes are the most important intercellular adhering junctions that provide structural strength for the epidermis. These junctions are connected directly with desmosomal cadherin proteins. Desmosomal cadherins are divided into four desmogleins (Dsgs), Dsg1-4, and three desmocollins (Dscs), Dsc1-3, all of which are involved in desmosomal adhesion by homo- and/or heterophilic binding between Dsgs and Dscs in a Ca(2+)-dependent manner. Cadherins are present on the cell surface and anchor keratin intermediate filaments (KIFs) to their inner cytoplasmic surface to generate an intracellular KIF-skeletal scaffold through several associate proteins, including plakoglobin, plakophillin, and desmoplakins. As such, the desmosomal contacts between adjacent cells generate an intercellular KIF scaffold throughout the whole epidermal sheet. However, despite these critical roles in maintaining epidermal adhesion and integrity, desmosomes are not static structures. Rather, they are dynamic units that undergo regular remodeling, i.e., assembly and disassembly, to allow for cell migration within the epidermis in response to outside-in signaling during epidermal differentiation. Recently, two cell-cell adhesion states controlled by desmosomes have been recognized, including "stable hyperadhesion (Ca(2+)-independent)" and "dynamic weak-adhesion (Ca(2+)-dependent)" conditions. These conditions are mutually reversible through cell signaling events involving protein kinase C (PKC) and epidermal growth factor receptor. Pemphigus vulgaris (PV) is an autoimmune bullous disease caused by anti-Dsg3 antibodies. Binding of these antibodies to Dsg3 causes endocytosis of Dsg3 from the cell surface and results in the specific depletion of Dsg3 from desmosomes, an event linked to acantholysis in the epidermis. This binding of anti-Dsg3 antibody to Dsg3 in epidermal keratinocytes activates PKC, to generate the "weak-adhesion (Ca(2+)-dependent)" state of desmosomes. The weak-adhesion desmosomes appear to be the susceptible desmosomal state and a prerequisite for Dsg3 depletion from desmosomes, pivotal and specific events leading to PV blistering. These observations allow us to propose a concept for pemphigus blistering disorders as a "desmosome-remodeling impairment disease" involving a mechanism of Dsg3 nonassembly and depletion from desmosomes through PV immunoglobulin G-activated intracellular signaling events.
Topics: Autoantibodies; Calcium; Cell Adhesion; Desmocollins; Desmogleins; Desmoplakins; Desmosomes; Epidermis; Gene Expression Regulation; Humans; Keratinocytes; Pemphigus; Plakophilins; Signal Transduction; gamma Catenin
PubMed: 23257250
DOI: 10.1016/j.kjms.2012.08.001 -
Dermatology Online Journal Dec 2012Pityriasis rubra pilaris (PRP) is an inflammatory condition of uncertain etiology. We present a case of PRP that demonstrates acantholysis on histopathologic...
Pityriasis rubra pilaris (PRP) is an inflammatory condition of uncertain etiology. We present a case of PRP that demonstrates acantholysis on histopathologic examination, which is a characteristic feature that increasingly is recognized to aid in the diagnosis. We also review the clinical presentations and treatment options for this condition.
Topics: Antibodies, Antinuclear; Blood Sedimentation; C-Reactive Protein; Female; Humans; Middle Aged; Pityriasis Rubra Pilaris; Rheumatoid Factor
PubMed: 23286804
DOI: No ID Found -
Dermatology Reports Jun 2020Warty dyskeratoma is an uncommon benign skin lesion, which is mostly limited to the head or neck and is rarely seen in other areas of the skin or mucous membranes....
Warty dyskeratoma is an uncommon benign skin lesion, which is mostly limited to the head or neck and is rarely seen in other areas of the skin or mucous membranes. Although it is clinically similar to many skin lesions, its distinctive histopathologic features help distinguish it from other identical lesions. Herein, we report a case of warty dyskeratoma in a very unusual site (lateral border of the tongue) in a 56-year-old woman.
PubMed: 32670533
DOI: 10.4081/dr.2020.8236 -
The Journal of Investigative Dermatology Jul 1985Pemphigus and bullous pemphigoid are autoimmune bullous diseases of the skin. Pemphigus, an intraepidermal blistering disease, is characterized by autoantibodies... (Review)
Review
Pemphigus and bullous pemphigoid are autoimmune bullous diseases of the skin. Pemphigus, an intraepidermal blistering disease, is characterized by autoantibodies reactive with antigens located in the intercellular spaces or on the surfaces of epidermal cells. These antibodies, which have recently been shown to activate complement, appear to be the cause of the basic pathologic process of pemphigus, acantholysis. The complement system and the plasminogen-plasmin system may be important mediators in the detachment of epidermal cells. Bullous pemphigoid, a subepidermal blistering disease, is characterized by autoantibodies reactive with an antigen located in the lamina lucida region of the basement membrane zone. These autoantibodies, which will avidly fix complement, appear to mediate subepidermal separation by attraction of a variety of inflammatory cells. Anaphylatoxins, released by activation of C4 and C3, or specific IgE antibodies, may activate mast cells with release of ECF-A attracting eosinophils. With activation of C5, C5a is released which could attract polymorphonuclear leukocytes. Antigen-specific lymphocytes, which can also contribute histamine releasing substances, may also be involved. The exact mechanism by which the epidermis separates from the dermis in bullous pemphigoid, however, remains unresolved.
Topics: Adolescent; Adult; Aged; Antibody-Dependent Cell Cytotoxicity; Antigen-Antibody Reactions; Autoantibodies; Cells, Cultured; Complement Activation; Complement System Proteins; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Neutrophils; Pemphigoid, Bullous; Pemphigus; Skin Diseases, Vesiculobullous
PubMed: 3891883
DOI: 10.1111/1523-1747.ep12275497 -
International Journal of Women's... Sep 2017Warty (follicular) dyskeratoma (WD) is a discrete nodular lesion that demonstrates the characteristic histopathologic findings of acantholysis and dyskeratosis. WDs most...
Warty (follicular) dyskeratoma (WD) is a discrete nodular lesion that demonstrates the characteristic histopathologic findings of acantholysis and dyskeratosis. WDs most commonly occur on the head and neck of adults. We present a case of WD that occurred on the mons pubis of a 53-year-old woman. Only a few other cases of WDs occurring on the vulva have been reported. WD most likely represents a tumor of the follicular infundibulum. Despite its name, there is no evidence that WD is caused by a human papillomavirus (HPV) infection. Although occurrences on the vulva are rare, they must be distinguished from HPV-induced squamous tumors when found in this area.
PubMed: 28831426
DOI: 10.1016/j.ijwd.2017.07.003 -
International Journal of Molecular... Sep 2021The chemical milieu, microbiota composition, and immune activity show prominent differences in distinct healthy skin areas. The objective of the current study was to...
The chemical milieu, microbiota composition, and immune activity show prominent differences in distinct healthy skin areas. The objective of the current study was to compare the major permeability barrier components (stratum corneum and tight junction (TJ)), investigate the distribution of (corneo)desmosomes and TJs, and measure barrier function in healthy sebaceous gland-rich (SGR), apocrine gland-rich (AGR), and gland-poor (GP) skin regions. Molecules involved in cornified envelope (CE) formation, desquamation, and (corneo)desmosome and TJ organization were investigated at the mRNA and protein levels using qRT-PCR and immunohistochemistry. The distribution of junction structures was visualized using confocal microscopy. Transepidermal water loss (TEWL) functional measurements were also performed. CE intracellular structural components were similarly expressed in gland-rich (SGR and AGR) and GP areas. In contrast, significantly lower extracellular protein levels of (corneo)desmosomes (DSG1 and CDSN) and TJs (OCLN and CLDN1) were detected in SGR/AGR areas compared to GP areas. In parallel, kallikrein proteases were significantly higher in gland-rich regions. Moreover, gland-rich areas were characterized by prominently disorganized junction structures ((corneo)desmosomes and TJs) and significantly higher TEWL levels compared to GP skin, which exhibited a regular distribution of junction structures. According to our findings, the permeability barrier of our skin is not uniform. Gland-rich areas are characterized by weaker permeability barrier features compared with GP regions. These findings have important clinical relevance and may explain the preferred localization of acantholytic skin diseases on gland-rich skin regions (e.g., Pemphigus foliaceus, Darier's disease, and Hailey-Hailey disease).
Topics: Acantholysis; Adult; Aged; Epidermis; Female; Humans; Male; Middle Aged; Permeability; Sebaceous Glands; Tight Junctions
PubMed: 34638769
DOI: 10.3390/ijms221910428 -
Frontiers in Medicine 2022Pemphigus is a chronic autoimmune skin blistering disease, characterized by acantholysis and by the production of autoantibodies directed against the structural...
Pemphigus is a chronic autoimmune skin blistering disease, characterized by acantholysis and by the production of autoantibodies directed against the structural desmosomal proteins desmoglein 1 (DSG1) and/or DSG3. Model systems allow the identification and testing of new therapeutic targets. Here, we evaluated ultrastructural desmosomal morphology in the human skin organ culture (HSOC) model injected with either anti-desmoglein (DSG) 1/3 single-chain variable fragment (scFv, termed Px4-3), Staphylococcus aureus exfoliative toxin (ETA) as a reference and positive control, and normal human IgG as a negative control. Each experimental condition was evaluated in abdominal skin biopsies from five different donors. After 24 h of incubation, we processed the samples for histological and ultrastructural electron microscopy analyses. We found that Px4-3 or ETA induced a loss of desmosomes and increased interdesmosomal widening, similar to patient skin biopsies and other pemphigus models. Thus, we propose the HSOC pemphigus model as an attractive tool to unravel novel therapeutic targets.
PubMed: 36452895
DOI: 10.3389/fmed.2022.997387 -
The Journal of Dermatology Jan 2015Pemphigus are organ-specific autoimmune diseases, where autoantibodies (mainly immunoglobulin [Ig]G) directed against epidermal targets (glycoproteins of the desmosomal... (Review)
Review
Pemphigus are organ-specific autoimmune diseases, where autoantibodies (mainly immunoglobulin [Ig]G) directed against epidermal targets (glycoproteins of the desmosomal core) are detected. Endemic pemphigus foliaceus or fogo selvagem (FS) is one of the variants of pemphigus foliaceus pemphigus foliaceus that shares the same clinical and immunopathological features of the classic non-endemic pemphigus foliaceus form, including pathogenic IgG (mainly IgG4) autoantibodies directed against the ectodomain of desmoglein 1 (Dsg1), that lead to acantholysis. Pathogenesis of FS is complex, involving genetic, environmental and immunological factors. Human leukocyte antigen (HLA)-DRB1 alleles DRB1*0404, *1402, *1406 or *0102 have been previously identified as risk factors for FS (relative risk, >14). Individuals exposed to hematophagous insects are more susceptible to develop the disease. Non-pathogenic anti-Dsg1 antibodies of the IgG1 subclass, directed against the extracellular 5 domain of Dsg1, are detected in patients in the preclinical stage of the disease, and also in healthy controls living in endemic areas. In counterpart, patients with FS show pathogenic anti-Dsg1 IgG4 autoantibodies that bind the pathogenic extracellular 1 and 2 domains of Dsg1, emphasizing the intramolecular epitope-spreading hypothesis. A possible explanation for the development of the autoimmune process would be antigenic mimicry, initiated by environmental stimuli in those genetically predisposed individuals. Characterization of the pathogenesis of FS will allow the development of specific therapeutic targets, and the elucidation of other autoimmune processes.
Topics: Brazil; Endemic Diseases; Humans; Pemphigus
PubMed: 25558948
DOI: 10.1111/1346-8138.12675