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Experimental Dermatology Jan 2024Pyodermatitis pyostomatitis vegetans is a rare inflammatory condition, affecting the skin and/or mucous membrane. Some cases include both skin and mucous involvement,... (Review)
Review
Pyodermatitis pyostomatitis vegetans is a rare inflammatory condition, affecting the skin and/or mucous membrane. Some cases include both skin and mucous involvement, whereas others develop either skin or mucous lesions only. The typically affected areas are the scalp, face, trunk and extremities, including the flexural areas and umbilicus. Clinical features show erosive granulomatous plaques, keratotic plaques with overlying crusts and pustular lesions. Among mucous lesions, oral mucosa is most frequently involved, and gingival erythema, shallow erosions, cobblestone-like papules on the buccal mucosa or upper hard palate of the oral cavity are also observed. Some of the lesions assume a 'snail track' appearance. Although there are several similarities between pyodermatitis pyostomatitis vegetans and other diseases, that is pyoderma gangrenosum, pemphigus vegetans and pemphigoid vegetans, the histopathological features of pyodermatitis pyostomatitis vegetans are unique in that epidermal hyperplasia, focal acantholysis and dense inflammatory infiltrates with intraepidermal and subepidermal eosinophilic microabscesses are observed. Direct immunofluorescence findings are principally negative. Activated neutrophils are supposed to play an important role in the pathogenesis of pyodermatitis pyostomatitis vegetans. The expression of IL-36 and neutrophil extracellular traps (NETs) was observed in the lesional skin, and additionally, eosinophil extracellular traps (EETs) was detected in pyodermatitis pyostomatitis vegetans. A possible pathogenic role of NETs and EETs in the innate immunity and autoinflammatory aspects of pyodermatitis pyostomatitis vegetans was discussed.
Topics: Humans; Pemphigus; Pyoderma; Stomatitis; Extracellular Traps; Neutrophils; Erythema; Organic Chemicals
PubMed: 37694984
DOI: 10.1111/exd.14931 -
Journal of Drugs in Dermatology : JDD Aug 2023Kresch M, Guénin S, Mubasher A, et al. Talquetamab-induced Grover’s disease. J Drugs Dermatol. 2023;22(8):828-829. doi:10.36849/JDD.7170.
Kresch M, Guénin S, Mubasher A, et al. Talquetamab-induced Grover’s disease. J Drugs Dermatol. 2023;22(8):828-829. doi:10.36849/JDD.7170.
Topics: Humans; Acantholysis; Ichthyosis
PubMed: 37556510
DOI: 10.36849/jdd.7170 -
Frontiers in Immunology 2023Pemphigus vulgaris (PV) is an acquired autoimmune blistering disease characterized by the production of autoantibodies targeting desmosomal cadherins, primarily...
Pemphigus vulgaris (PV) is an acquired autoimmune blistering disease characterized by the production of autoantibodies targeting desmosomal cadherins, primarily desmoglein 1 and desmoglein 3, leading to acantholysis. The etiology of PV is multifactorial, including genetic susceptibility. This retrospective study aimed to evaluate the association of HLA class II alleles and PV and to examine the impact of PV-associated HLA class II alleles on the concentration of anti-desmoglein antibodies. The study group included 30 patients in whom the diagnosis of PV was confirmed by histopathological analysis, immunofluorescence findings, and ELISA testing for detecting antibodies against desmoglein 1 and desmoglein 3. HLA class II alleles were typed by polymerase chain reaction with sequence-specific primers (PCR-SSP). The control group consisted of 190 healthy volunteer blood donors. Data analysis revealed a significantly higher frequency of HLA class II alleles in our population of patients with PV, including HLA-DRB1*04:02, HLA-DRB1*14:54, HLA-DQB1*03:02, HLA-DQB1*05:03, HLA- DQA1*03:01, and HLA-DQA1*01:04, as well as a significantly lower frequency of HLA-DQA1*05:01 compared to the control group. We have also investigated the influence of risk alleles for PV, recognized in almost all study populations, HLA-DRB1*04:02 and HLA-DQB1*05:03, on the concentration of antibodies against desmogleins 1 and 3 in relation to the presence of these alleles. The results showed significantly higher levels of antibodies directed against desmoglein 3 among patients with DRB1*04:02 compared to patients without this allele. No difference was found for anti-desmoglein 1 antibodies. Regarding DQB1*05:03 allele, statistical analysis showed no differences in the concentration of anti-desmoglein antibodies in patients carrying this allele versus those without it.
Topics: Humans; Pemphigus; Desmoglein 3; Retrospective Studies; Croatia; HLA-DRB1 Chains; Autoantibodies; Autoimmune Diseases
PubMed: 37529044
DOI: 10.3389/fimmu.2023.1200992 -
Journal of Translational Autoimmunity Dec 2023Endemic pemphigus foliaceus and endemic pemphigus vulgaris are autoimmune dermatologic disorders endemic to the Peruvian Amazon.
BACKGROUND
Endemic pemphigus foliaceus and endemic pemphigus vulgaris are autoimmune dermatologic disorders endemic to the Peruvian Amazon.
OBJECTIVE
To determine the ultrastructural skin alterations of three healthy subjects with anti DSG-1 antibodies in areas endemic to pemphigus foliaceus and pemphigus vulgaris in the Peruvian Amazon.
PATIENTS AND METHODS
Case series carried out from data of three clinically healthy subjects positive to anti DSG-1 antibodies, from Peru. This study consists of a sub-analysis of data gathered in a previous study.
RESULTS
Ultrastructural results are presented from the skin biopsies of three clinically healthy patients positive to -desmoglein 1 (DSG-1) antibodies. High Resolution Optical Microscopy (HROM) showed the absence of acantholysis. Transmission Electron Microscopy (TEM) showed the widening of intercellular space between keratinocytes, the presence of vacuoles in intercellular space with granular material and cytoplasmic vacuolization, loss of desmosome structure, loss of normal distribution among tonofilaments and lateral separation among cells in the stratum basale.
CONCLUSION
According to our results, healthy subjects that present -desmoglein 1 antibodies can develop ultrastructural alterations that are visible through transmission electron microscopy but not through conventional optical microscopy.
PubMed: 37520889
DOI: 10.1016/j.jtauto.2023.100208 -
International Journal of Molecular... Jul 2023The mucosal-dominant variant of pemphigus vulgaris (MPV) is an autoimmune disease characterized by oral mucosal blistering and circulating pathogenic IgG antibodies...
The mucosal-dominant variant of pemphigus vulgaris (MPV) is an autoimmune disease characterized by oral mucosal blistering and circulating pathogenic IgG antibodies against desmoglein 3 (Dsg3), resulting in life-threatening bullae and erosion formation. Recently, microRNAs (miRNAs) have emerged as promising players in the diagnosis and prognosis of several pathological states. For the first time, we have identified a different expression profile of miRNAs isolated from plasma-derived exosomes (P-EVs) of MPV patients positive for antibodies against Dsg3 (Dsg3-positive) compared to healthy controls. Moreover, a dysregulated miRNA profile was confirmed in MPV tissue biopsies. In particular, a strong downregulation of the miR-148a-3p expression level in P-EVs of MPV patients compared to healthy controls was demonstrated. Bioinformatics prediction analysis identifies metalloproteinase-7 (MMP7) as a potential miR-148a-3p target. An in vitro acantholysis model revealed that the miR-148a-3p expression level was dramatically downregulated after treatment with Dsg3 autoantibodies, with a concomitant increase in MMP7 expression. The increased expression of MMP7 leads to the disruption of intercellular and/or extracellular matrix adhesion in an in vitro cellular model of MPV, with subsequent cell dissociation. Overexpression of miR-148a-3p prevented cell dissociation and regressed MMP7 upregulation. Our findings suggest a pivotal role of P-EV cargo in regulating molecular mechanisms involved in MPV pathogenesis and indicate them as potential MPV therapeutic targets.
Topics: Humans; Pemphigus; Down-Regulation; Matrix Metalloproteinase 7; Desmoglein 3; Autoantibodies; MicroRNAs; Blister; Mouth Mucosa
PubMed: 37511259
DOI: 10.3390/ijms241411493 -
The American Journal of Dermatopathology Sep 2023Acantholysis is a microscopic finding describing the breakdown of desmosomes of keratinocytes and the formation of intraepithelial clefts after the loss of cohesion of...
Acantholysis is a microscopic finding describing the breakdown of desmosomes of keratinocytes and the formation of intraepithelial clefts after the loss of cohesion of keratinocytes. It can be observed in keratinocytic neoplasms, typically actinic keratoses and squamous cell carcinomas, and defines the acantholytic variants of these entities. Acantholysis has so far been reported in only 4 cases of basal cell carcinomas (BCCs), mainly of the superficial type. A case of an otherwise typical nodular BCC showing features of acantholysis is presented here. Because BCCs are keratinocytic neoplasms, the finding of acantholysis in them is not totally surprising; however, the reason why it is only very exceptionally observed in BCCs is unclear.
Topics: Humans; Acantholysis; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Keratinocytes; Skin Neoplasms
PubMed: 37506275
DOI: 10.1097/DAD.0000000000002499 -
Blocking soluble Fas Ligand ameliorates pemphigus: PC111 efficacy in ex-vivo human pemphigus models.Frontiers in Immunology 2023Pemphigus is a life-threatening, chronic, autoimmune bullous disease affecting both the skin and the mucous membranes. Based on the mainstream concept that blister...
Pemphigus is a life-threatening, chronic, autoimmune bullous disease affecting both the skin and the mucous membranes. Based on the mainstream concept that blister formation occurs upon binding of autoantibodies to their antigen proteins (desmoglein1, DSG1 and desmoglein3, DSG3), current therapies mostly aim to suppress the immune system. To avoid the severe side effects associated with the chronic use of immunosuppressive treatments, we have developed PC111, a fully human monoclonal antibody targeting human Fas ligand (FasL). We have provided a number of and evidences showing that soluble FasL induces keratinocyte apoptosis followed by acantholysis. An anti-murine FasL prevents blister formation in the pemphigus neonatal mouse model. To confirm the mechanism of action (MoA) and the efficacy of PC111 in a human pemphigus context, we used the keratinocyte dissociation assay and two independent Human Skin Organ Cultures (HSOC) pemphigus models. PC111 reduced acantholysis , as shown by the dose-dependent reduction of fragments in the monolayer cultures. In the first HSOC model, normal human skin was subcutaneously injected with a scFv antibody fragment directed against DSG1 and DSG3, resulting in a severe acantholysis (70-100%) after 24 hours. PC111 inhibited blister formation to around 50% of control. In the second model, normal human skin was injected with a mixture of pemphigus patients' autoantibodies resulting in a less severe acantholysis (20-30%). PC111 significantly suppressed blister formation to more than 75% up to 72 hours. These results confirm PC111 MoA and demonstrates the efficacy of the anti-FasL antibody also in a pemphigus setting.
Topics: Humans; Animals; Mice; Pemphigus; Fas Ligand Protein; Blister; Acantholysis; Autoantibodies
PubMed: 37503332
DOI: 10.3389/fimmu.2023.1193032 -
The Journal of Dermatology Nov 2023Pemphigus is an autoimmune blistering disease with two major subtypes, pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Although most patients with PV show oral...
Pemphigus is an autoimmune blistering disease with two major subtypes, pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Although most patients with PV show oral lesions, cutaneous type PV (C-PV) is a rare subtype clinically characterized by predominant cutaneous involvement with no or subtle mucosal lesions. Patients with PF present with only skin involvement; they do not have mucosal lesions. Serologically, autoantibodies against desmoglein (Dsg) 3 and Dsg1 are observed in C-PV whereas PF is associated with anti-Dsg1 antibodies only. Herein, we describe three cases of pemphigus presenting with predominant skin lesions and no mucosal involvement despite high anti-Dsg 3 autoantibody levels in chemiluminescent enzyme immune assays (CLEIAs). In addition, anti-Dsg 1 autoantibodies were positive in patients 2 and 3, but negative in patient 1 based on CLEIAs. Histological examination of the skin showed suprabasal acantholysis in patients 1 and 2, and blister formation in the upper epidermis in patient 3. Histopathology of the oral membrane in patients 1 and 2 showed subtle acantholysis in the suprabasal layer. Thus, we diagnosed patients 1 and 2 as having cutaneous type PV and patient 3 as having PF. Ethylenediaminetetraacetic acid-treated enzyme-linked immunosorbent assay demonstrated a low proportion of anti-Dsg3 autoantibodies recognizing Ca -dependent epitopes, antibodies against which are thought to be the main contributor to acantholysis. Thus, along with Dsg1 antibodies, weak anti-Dsg3 antibodies could induce acantholysis in the skin, but they are insufficient to induce mucosal lesions.
Topics: Humans; Pemphigus; Autoantibodies; Acantholysis; Desmoglein 1; Mucous Membrane; Enzyme-Linked Immunosorbent Assay; Blister
PubMed: 37485682
DOI: 10.1111/1346-8138.16907