Development Of Blisters Research Articles

Application of biomedical cell products in the treatment of congenital epidermolysis bullosa

Congenital epidermolysis bullosa is a phenotypically and genetically heterogeneous group of genodermatoses, which which is clinically manifested by the development of blisters on the skin and mucous membranes after mechanical injury. The presence of long-term erosive and ulcerative defects in patients with congenital epidermolysis bullosa reduces the quality of patients` life and also leads to malignancy of the lesions, as a result of constant stimulation of regenerative processes.Currently, there are a lot of publications describing the use of skin substitutes, three-dimensional tissue-engineered structures based on auto- and allogeneic cells that promote rapid epithelization of wounds in patients with congenital epidermolysis bullosa. The most prospective and at the same time the least studied direction of congenital epidermolysis bullosa treatment is the use of a combined skin equivalent created on the basis of keratinocytes and fibroblasts, which mixes the advantages of epidermal and dermal grafts.

Coronavirus-disease-2019-associated Stevens–Johnsons syndrome in a 15-year-old boy: a case report and review of the literature

BackgroundStevens–Johnson syndrome (SJS) is a life-threatening condition characterized by high fever and severe mucocutaneous lesions, often triggered by drugs or infection. During the coronavirus disease 2019 pandemic, there was a marked increase in Stevens–Johnson syndrome cases, but relatively few cases were reported in children. The present article reports a pediatric case of Stevens–Johnson syndrome due to coronavirus disease 2019 infection and provides a review of the most relevant literature.Case presentationA previously healthy 15-year-old Han Chinese boy from China presented to the hospital with oral ulcers, conjunctival hyperemia, and widespread maculopapular rash. He had a history of fever 9 days prior and tested positive for coronavirus disease 2019 infection. Upon admission, his rash and mucosal lesions worsened, with the development of blisters on the fingertips of both hands, ocular pain, photophobia, and erosive lesions on the genital mucosa with exudation. He was diagnosed with Stevens–Johnson syndrome and received treatment with methylprednisolone, intravenous immunoglobulin, and dermatological and mucosal care. The patient’s condition was managed, and the dosage of high-dose intravenous methylprednisolone was tapered down, followed by a transition to oral prednisolone. He was discharged without sequelae.ConclusionWe should be aware that coronavirus disease 2019 infection is associated with the development of Stevens–Johnson syndrome in children and may lead to a wide spectrum of dermatologic presentations. Although Stevens–Johnson syndrome is a relatively rare condition, given its potentially serious consequences, it is crucial to identify it as early as possible and to take appropriate preventive and therapeutic measures to reduce complications and improve the quality of life for patients.

Mucous membrane pemphigoid of the oral cavity and Genitalia: A case report

Mucous membrane pemphigoid (MMP) encompasses a diverse array of chronic autoimmune conditions characterized by the development of blisters predominantly affecting mucous membranes in various regions of the body. Commonly impacted areas include the mouth, mucosal linings of the eyes, throat, genitalia, and nasal passages. While MMP typically manifests in older women, with peak incidence occurring between 50 and 70 years of age, rare instances have been observed in children. Symptoms of MMP often entail recurrent blister formation, subsequent rupture, and potential scarring, with complications possibly affecting the eyes and throat. This article presents a unique case involving a 70-year-old female presenting with lesions localized to the oral and vaginal mucosa. A comprehensive discussion on histopathological examination findings and treatment modalities is provided. Notably, the absence of ocular involvement in this case distinguishes it from typical presentations of MMP.

Blister formation in acute compartment syndrome: Unraveling the underlying predictors.

Blisters are a common complication of orthopedic trauma and can cause surgery delay and increase the risk of infection. This study aims to identify risk factors for blisters in patients with acute compartment syndrome (ACS). Our study collected data from 206 ACS patients admitted to 2 hospitals between November 2013 and January 2021. Patients were divided into 2 groups: the blister group (BG) and the control group (CG), based on the presence or absence of blisters. We conducted univariate analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis to identify any significant differences in demographics, comorbidities, and admission laboratory test results between the 2 groups. Our study found that the incidence of blisters in ACS patients was 21.8% (45 out of 206). Univariate analysis identified several factors that were significantly associated with blister formation. Logistic regression analysis showed that patients who developed ACS in the winter or spring (P = .007, OR = 2.690, 95% CI [1.308-5.534]), patients who received a referral (the process whereby patients are transferred between medical facilities for further evaluation and treatment attempts prior to admission to our hospital) (P = .009, OR = 4.235, 95% CI [1.432-12.527]), and patients with higher PLR (P = .036, OR = 1.005, 95% CI [1.000-1.009]) were independent risk factors for blisters. Additionally, a history of drinking (P = .039, OR = 0.027, 95% CI [0.046-0.927]) was found to be a protective factor for blister formation in these patients. Moreover, ROC curve analysis showed that a PLR value of 138 was the cutoff point for predicting the development of blisters in ACS patients. Our study identified seasonal factors (refer to these months like winter or spring), referral, and patients with higher PLR as independent risk factors, and a history of drinking as a protective factor for blister formation in ACS patients. These findings allow clinicians to individualize the evaluation of blister risk and perform early targeted therapies.

АНАЛИЗ КЛИНИЧЕСКОГО СЛУЧАЯ ВУЛЬГАРНОЙ ПУЗЫРЧАТКИ, АССОЦИИРОВАННОЙ С ХРОНИЧЕСКОЙ ВЭБ-ИНФЕКЦИЕЙ (ГЛОССИТА, ОБУСЛОВЛЕННОГО ВЭБ)

Background. One of the autoimmune diseases is pemphigus, a chronic malignantly occurring autoimmune dermatosis accompanied by the development of blisters on the skin and mucous membranes. Isolated lesions of the SOPR occur in 10–20% of cases, complicating differential diagnosis. Numerous studies have proven the role of herpes virus infection as an aggravating factor in the course of true acantholytic pemphigus. The aim of the study was to determine the features of the clinical course of vulgar pemphigus against the background of reactivation of chronic EBV infection (glossitis caused by EBV). The clinical case of a patient with a diagnosis of “Vulgar pemphigus. Glossitis caused by the Epstein-Barr virus”. The anamnesis of the disease was carefully collected, a clinical and laboratory examination was performed with a cytological examination of a smear taken from a LITTER, a general blood test with an expanded leukocyte formula, C-reactive protein. In order to diagnose the viral load, PCR diagnostics was performed on the DNA of the herpes virus 1, 2, 4, 5 types in saliva, on the DNA of EBV in the blood, quantitatively. Specific antibodies of Ig classes M and G to EBV were determined by the ELISA method. Results. Due to the lifelong persistence of EBV in the structures of the oral cavity, its reactivation leads not only to chronic pastoral infection and the local development of the corresponding glossitis, but also, first of all, to a decrease in the level of local immunity. This fact aggravates the course of pemphigus, shortens the period of absence of relapse. The appointment of antiviral therapy at the first visit allowed to stabilize the symptoms caused by EBV, which led to positive dynamics in the course of pemphigus against the background of average dosages of prednisone in a shorter time. Conclusions. With clinical and laboratory confirmation of chronic EBV infection (glossitis caused by EBV), it is recommended to include antiviral and immunocorrective drugs, systemically and topically, in the complex treatment of pemphigus erythematosus.

Staphylococcal scalded skin syndrome in neonate: Another face of CA-MRSA.

Staphylococcal scalded skin syndrome (SSSS), also known as Ritter's disease, in its severe form occurs predominantly in infants and children. It is caused by infection with group II (often phage group 71) Staphylococcus aureus. The foci of infection include nasopharynx, less commonly umbilicus, urinary tract, superficial abrasion, conjunctivae, and blood. Staphylococci are non-motile, non-spore-forming, catalase-positive, gram-positive cocci that appear predominantly as grape-like clusters. Although this organism is frequently a part of normal human microbial flora, it can cause significant opportunistic infections under certain conditions such as when extremes of age groups are involved, the presence of indwelling medical devices, and intravenous (iv) drug abuse. Staphylococcus aureus may cause a variety of infectious manifestations ranging from relatively benign skin infections to life-threatening systemic illnesses. SSSS caused by S. aureus strains produces exfoliative toxins which result in the development of blisters, erythema, and desquamation. Here, we present a case of an 11-day-old neonate who was diagnosed with SSSS. The causative agent responsible for this syndrome was identified as methicillin-resistant Staphylococcus aureus (MRSA). The molecular characterization of the gene Panton-Valentine leukocidin (PVL) was done by polymerase chain reaction (PCR) and was detected positive for PVL which is a distinctive virulence factor seen almost in all of the community-acquired MRSA strains. The patient was discharged after parenteral clindamycin therapy with almost complete resolution of symptoms.

Photogallery. Genodermatoses. Part I

Genodermatoses are skin diseases caused by the inheritance of a pathological gene responsible for the formation of a particular skin structure.
 Hereditary diseases can be monogenic, polygenic and chromosomal. Genodermatoses follow Mendelian inheritance (autosomal dominant, autosomal recessive or sex-linked). Some genodermatoses appear as a result of genetic mosaicism (parts of two different chromosomes exchange their fragments).
 Autosomal dominant disorder manifest in every generation in women and men with the same frequency. Recessive genodermatoses are usually more severe and rarer. In this case, both parents are carriers of the pathological gene, but are clinically (phenotypically) healthy. The risk of developing of autosomal recessive pathology increases highly in closely related marriages.
 We present a gallery of the hereditary dermatoses.
 Neurofibromatosis is a neurocutaneous syndrome characterized by the formation of benign tumors in the skin, soft tissues, nervous system and internal organs.
 Congenital epidermolysis bullosa is a group of genodermatoses with the development of intraepidermal blisters that arise spontaneously or as a result of minor trauma.
 Tuberous sclerosis (Bourneville–Pringle disease) is a hereditary disease characterized by hyperplasia of ectodermal and mesodermal derivatives, leading to disruption of embryonic differentiation. It damages the skin, central nervous system and other organs.
 Pseudoxanthoma elasticum is characterized by calcification of elastic fibers of the skin with damage to the vision organ, cardiovascular system and reproductive function.

On the Occurrence of Filiform Corrosion on Organic-Coated Carbon Steel Exposed to Cyclic Aging Test

Filiform corrosion (FFC) is one of the possible failure mechanisms of organic-coated steel. Beyond cathodic delamination, FFC causes paint detachment and the dramatic loss of the protective properties given by the applied paint. As both failure mechanisms occur during in-field exposure (depending on the environment), when assessing the performance of the protective paint by lab scale tests, we must be aware of the failure mechanism we induce with different accelerated aging cabinets. In this study, we investigate the effect of the prohesion test on the initiation and propagation of FFC. We highlight the concurrent development of FFC and cathodic blistering, which includes the change between the cathodic and anodic delamination front, during an accelerated aging procedure that cycles between saturated humidity and dry stages. The role of the presence of aggressive contaminants (Cl− and ) is discussed. According to our findings, cyclic aging tests seem to better stick to the failure mechanism occurring during in-field exposure, particularly due to the wet/dry cycles.

C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita.

Inflammatory epidermolysis bullosa acquisita (EBA) is characterized by a neutrophilic response to anti-type VII collagen (COL7) antibodies resulting in the development of skin inflammation and blistering. The antibody transfer model of EBA closely mirrors this EBA phenotype. To better understand the changes induced in neutrophils upon recruitment from peripheral blood into lesional skin in EBA, we performed single-cell RNA-sequencing of whole blood and skin dissociate to capture minimally perturbed neutrophils and characterize their transcriptome. Through this approach, we identified clear distinctions between circulating activated neutrophils and intradermal neutrophils. Most strikingly, the gene expression of multiple C-type lectin receptors, which have previously been reported to orchestrate host defense against fungi and select bacteria, were markedly dysregulated. After confirming the upregulation of Clec4n, Clec4d, and Clec4e in experimental EBA as well as in lesional skin from patients with inflammatory EBA, we performed functional studies in globally deficient Clec4e-/- and Clec4d-/- mice as well as in neutrophil-specific Clec4n-/- mice. Deficiency in these genes did not reduce disease in the EBA model. Collectively, our results suggest that while the upregulation of Clec4n, Clec4d, and Clec4e is a hallmark of activated dermal neutrophil populations, their individual contribution to the pathogenesis of EBA is dispensable.

Hyalinosis cutis ET mucosae

A 16-year-old male was brought to the Dermatology OPD with complaints of generalized progressive thickening of the skin since one year of life and development of blisters after trauma. There was a history of difficulty in swallowing, protrusion of tongue, hoarseness of voice, and diffuse loss of hair. Similar findings were also present in the younger sister.

DP17 A very rare presentation of linear IgA disease during pregnancy

Abstract We present a very rare immunobullous dermatosis, linear IgA disease (LAD), that developed during pregnancy, to highlight its clinical features, management and important safety considerations for the neonate. During her first pregnancy, a 32-year-old Japanese woman of 27 weeks’ gestation developed an intensely itchy blistering rash on her limbs, trunk and face without periumbilical predilection. The blisters were tense, clustering in an annular configuration, with subsequent development of blistering and erosions involving the oral and genital mucosae. Medications included a pregnancy multivitamin only. A lesional skin biopsy revealed a subepidermal blister containing neutrophils and eosinophils. Direct immunofluorescence of perilesional skin demonstrated linear deposition of IgA along the basement membrane zone. Linear IgA disease was diagnosed. Initial treatment consisted of erythromycin and daily clobetasol ointment. Owing to inadequate symptom control and blister progression, dapsone 50 mg daily was initiated with prompt improvement in her condition and cessation of new blistering. A postpartum flare necessitated a dose increase to 75 mg daily. Her baby’s glucose-6-phosphate dehydrogenase (G6PD) level was found to be normal at birth. She proceeded to breastfeed her son, and monitoring of his haemoglobin level was normal. Although her clinical presentation initially raised the possibility of pemphigoid gestationis (PG), there was no periumbilical involvement, and the morphology of blistering in conjunction with mucosal involvement was more suggestive of LAD. The immunofluorescence results also helped to distinguish LAD from PG. The new onset of LAD during pregnancy is very unusual and has been rarely reported (Ikkaku N, Tateishi N, Oda Y et al. Linear immunoglobulin A bullous dermatosis developing during late pregnancy. J Dermatol 2017; 44:e44–5). Pre-existing LAD typically improves during pregnancy, although postpartum flares are recognized. Pemphigoid gestationis has been associated with an increased risk of prematurity and intrauterine growth restriction, but this has not been reported with LAD during pregnancy, possibly due to its rarity. Both the diagnosis of LAD and its mainstay treatment—dapsone—have important potential implications for the neonate. As for other immunobullous diseases, transplacental transfer of pathogenic antibodies may result in transient, usually mild, neonatal blistering. Although dapsone can be safely used during pregnancy and breastfeeding, the risk of neonatal haemolysis and methemoglobinaemia necessitates the assessment of the G6PD level and haemoglobin monitoring in the neonate. Multidisciplinary input from the dermatology, obstetric and paediatric teams is crucial to ensure appropriate counselling and care of the affected mother and baby.

Epidemiology, prevention methods, and risk factors of foot blisters in French trail ultramarathons.

Blisters are a common running injury and are known to limit runners' performance. There have been many studies on the subject with contrasting results. It would therefore be useful to describe more clearly blister epidemiology, blister prevention methods, and risk factors of blister development. This study is a retrospective anonymous, post-race survey. Runners were contacted by email after races in France during the summer and autumn of 2021 and asked to fill-in an online survey about their experience with blisters and running experiences. Five hundred and thirty-three runners participated, of whom were 468 (88%) men and 47 women (12%), mean age 42±9.75. Sixty-one percent (N.=329) of runners applied blister prevention methods before the start of the race and 29% (N.=155) reported blisters at the end of the race. Most commonly used blisters prevention methods were: anti-friction cream 79% (N.=260), "anti-blister socks" 33% (N.=107), paper tape 13% (N.=44), and topical lemon application 11% (N.=36). Having a history of blisters in the past is strongly associated with blisters onset OR=15.950 (9.135-29.640; P<0.0001). Distances ran between 40 to 74 km appeared to be the less likely to cause blisters OR 0.188 (0.045-0.729; P=0.019). None of the studied blister prevention methods seemed to match the protective effect of running shorter distances. Having a history of previous blisters is a major risk factor for blister occurrence, while running shorter distances seems protective.

Factors affecting urticaria control in patients with chronic urticaria

Objective: Urticaria is a condition characterized by the development of blisters (hives), angioedema, or both. Acute urticaria is the appearance of rashes lasting 6 weeks or less, angioedema, or both. It is recommended to use the urticaria control test to evaluate disease control in patients with CSU. This study aimed to evaluate the factors affecting urticaria control in patients followed up with the diagnosis of chronic spontaneous urticaria. Material and Methods: Urticaria control results of children diagnosed with chronic urticaria were evaluated retrospectively and factors that could affect urticaria control were investigated. Results: Relationships between the urticaria control test and age, gender, onset time of the complaint, family history of atopy, and laboratory values such as anti-nuclear antibody (ANA) and c4 were examined. Conclusion: Although chronic urticaria has a mild course in children, parameters such as gender, age, and ANA positivity may affect the control of the disease.

Role of ADAM10 and ADAM17 in the Regulation of Keratinocyte Adhesion in Pemphigus Vulgaris.

The severe autoimmune blistering disease Pemphigus vulgaris (PV) is mainly caused by autoantibodies (IgG) against desmoglein (Dsg) 3 and Dsg1. The mechanisms leading to the development of blisters are not fully understood, but intracellular signaling seems to play an important role. Sheddases ADAM10 and ADAM17 are involved in the turnover of the desmosomal cadherin Dsg2 and ADAM10 has been shown to contribute to acantholysis in a murine pemphigus model. In the present study, we further examined the role of ADAM10 and ADAM17 both in keratinocyte adhesion and in the pathogenesis of PV. First, we found that inhibition of ADAM10 enhanced adhesion of primary human keratinocytes but not of immortalized keratinocytes. In dissociation assays, inhibition of ADAM10 shifted keratinocyte adhesion towards a hyperadhesive state. However, ADAM inhibition did neither modulate protein levels of Dsg1 and Dsg3 nor activation of EGFR at Y1068 and Y845. In primary human keratinocytes, inhibition of ADAM10, but not ADAM17, reduced loss of cell adhesion and fragmentation of Dsg1 and Dsg3 immunostaining in response to a PV1-IgG from a mucocutaneous PV patient. Similarly, inhibition of ADAM10 in dissociation assay decreased fragmentation of primary keratinocytes induced by a monoclonal antibody against Dsg3 and by PV-IgG from two other patients both suffering from mucosal PV. However, such protective effect was not observed in both cultured cells and ex vivo disease models, when another mucocutaneous PV4-IgG containing more Dsg1 autoantibodies was used. Taken together, ADAM10 modulates both hyperadhesion and PV-IgG-induced loss of cell adhesion dependent on the autoantibody profile.

How to decrease systemic corticosteroids in pemphigus patients under rituximab.

How to decrease systemic corticosteroids in pemphigus patients under rituximab.

Rituximab - Progress but Still Not a Final Resolution for Pemphigus Patients: Clinical Report From a Single Center Study.

Pemphigus is a rare autoimmune disease characterized by the production of pathogenic autoantibodies against desmosomal adhesion proteins, desmoglein 1 and 3. The pathophysiological process leads to the development of blisters and erosions on mucosal and/or skin surfaces as the main clinical manifestation of the disease. Rituximab emerged as the first-line therapeutic option for pemphigus due to its ability to induce remission by depleting peripheral B lymphocytes. Our aim was to assess the efficacy of rituximab in the treatment of patients in Croatia. A single-center, retrospective study was conducted on 19 patients treated with rituximab following a rheumatoid arthritis dosing protocol between October 2015 and March 2021, with a mean follow-up of 24.1 months. After the first rituximab cycle, two patients achieved complete remission off therapy (10.5%), and six patients achieved complete remission on minimal therapy (31.6%). Partial remission was observed among ten patients (52.6%). Eight patients (44.4%) relapsed after the first rituximab cycle. The mean relapse time was 21 months. Seven patients received two rituximab cycles, and three patients received three cycles. Overall, 13 out of 19 patients experienced complete remission at some point during the study, while there were no non-responders after the rituximab treatment. No statistically significant associations were observed between age, sex, type of disease involvement and clinical remission, either on or off therapy. A steady decrease in anti-desmoglein 1 and anti-desmoglein 3 levels was measured among all patients following rituximab treatment. One patient experienced a treatment-related adverse event of infectious etiology (cellulitis). One patient died following the first rituximab cycle, with the cause of death likely not to be associated with the treatment. Rituximab is an effective disease-modifying agent in the treatment of pemphigus with the main benefit of reducing corticosteroid exposure and steroid-related side effects among pemphigus patients. However, a feature of rituximab therapy is high relapse rates and the need for repeated treatment cycles to achieve complete remission. Developing an optimal protocol for rituximab treatment and finding suitable markers for predicting relapse will improve the management of pemphigus patients.

Pemphigus-The Crux of Clinics, Research, and Treatment during the COVID-19 Pandemic.

Pemphigus is a rare autoimmune disease characterised by the production of pathogenic autoantibodies in response to different desmosome proteins. The pathophysiological process leads to the development of blisters and erosions on mucosal and/or skin surfaces. The classical clinical variants of pemphigus are pemphigus vulgaris and pemphigus foliaceus. A diagnostic delay is very common in pemphigus, especially among patients with mucosal involvement. However, in recent years we have witnessed considerably fewer patients with extensive mucocutaneous manifestations, since patients with oral lesions are referred to dermatologists to start the treatment much sooner than they had been previously. Among non-classical variants of pemphigus, unusual cases with discrepancies between autoantibody profiles and clinics challenge the “desmoglein compensation theory”. The identification of several other autoantigens that perform a role in the pathogenesis of different variants of pemphigus will progress immunodermatology towards an approach that will determine personalized pemphigus subtypes for each patient. Comorbidities among patients are primarily associated with the prolonged use of corticosteroids and other immunosuppressive agents. The SARS-CoV-2 pandemic raised concerns regarding the immunosuppressive effects of treatment and the risk of a more complicated COVID-19 infection, as well as on the ability to develop an adequate vaccine response.

A Case of Irritant Contact Dermatitis Mimicking as Localized Bullous Pemphigoid.

Introduction: 19 years old adult male a college going scholar presented to the Derm OPD, with complaints of multiple clear fluid filled lesions over left forearm around the hemodialysis fistula site. Patient gave history of applying thrombophob ointment over fistula site, which led to development of tense blisters filled with clear fluid that mimics localized bullous pemphigoid, where in appropriate and adequate investigations proved it to be a case of Irritant Contact Dermatitis. Thrombophob ointment which contains benzyl nicotinate and heparin applied over the hemodialysis fistula site leads to bullous lesions of Irritant Contact Dermatitis (ICD)which mimics as localized bullous pemphigoid over fistula site.&#x0D; Keywords: Hemodialysis fistula site,Irritant Contact Dermatitis, localized Bullous Pemphigoid.

27005 Proteomics analysis of blister fluid from patients with bullous pemphigoid

Bullous pemphigoid (BP) is an autoimmune disorder characterized by the development of pruritic lesions and/or blisters. Previous research analyzing the blister fluid from BP patients shows proinflammatory cytokines/chemokines, typically at a higher concentration than in serum. We explored the blister fluid proteome of 8 patients with BP to assess the intraepidermal microenvironment. TMT-labeled proteomics identified a total of 339 proteins. Using gene names for these proteins, Gene Ontology was used for analysis, demonstrating marked enrichment of exocytosis pathways, immune response, and platelet degranulation. In light of an abundance of exosomal proteins, we depleted exosomes using ultracentrifugation, to determine which proteins were exosome-bound and increase sensitivity for soluble proteins. Differential protein analysis was performed between these samples. Notable findings in BP blister fluid proteome include eosinophil degranulation proteins (EPX, ECP, EDN, MBP) at greater abundance than neutrophil-related proteins (neutrophil gelatinase-associated lipocalin, myeloperoxidase, neutrophil defensin 3). We identified IgM/IgA/IgG/IgE, 16 SERPIN-family protease inhibitors, heat shock proteins (HSP90AA1, HSP90AB1, HSP90B1, HSPA1b, HSPA5, HSPA8, HSPB1), neutrophil inflammasome mediators (lipopolysaccharide-binding protein, CD14), clotting factors (factors 2,5,9,10-13 (A1,B), VWF, tissue factor, fibrinogen), and complement mediators (C1-9). Neutrophil elastase, MMP9, ECP, and eosinophil derived neurotoxin appear to be bound or contained in fluid exosomes. The results demonstrate the players that may be responsible for the inflammatory/proteolytic environment in BP. Exosomal proteins appear to be derived from eosinophils, keratinocytes, and neutrophils, suggesting that exosomes likely contribute to the propagation of the inflammatory response. The extent of clotting factor presence in fluid confirms prior studies identifying coagulation activation in BP.

Autoreactive T cells in pemphigus: perpetrator and target.

Pemphigus vulgaris (PV) is an autoimmune blistering disease, in which autoantibodies against epidermal cadherins, such as desmoglein (Dsg)1 and Dsg3, lead to the development of blisters and erosions on the skin and mucous membranes. Autoreactive CD4+ T cells are essential for the induction and perpetuation of the disease by interaction with B cells producing autoantibodies. PV has a strong genetic association with certain human leucocyte antigen (HLA) alleles with HLA-DRB1*04:02 and LA-DQB1*05:03 being the most prevalent in patients. Recently, genome-wide association studies have provided a new approach to identify single nucleotide polymorphisms, alongside the known association with HLA alleles. Loss of tolerance against Dsgs and other autoantigens is a critical event in the pathogenesis of PV. Epitope spreading contributes to the progression of PV, leading to an extension of the Dsg-specific autoimmune response to other molecular epitopes of autoantigens, such as desmocollins or muscarinic receptors. Alterations in CD4+CD25+ FoxP3+ regulatory T cells are thought to contribute to the development of PV representing a suitable target for therapeutic interventions. Several CD4+ T-cell subsets and cytokines are involved in the pathogenesis of PV, while Th2 cells are the extensively studied population. Recently, other T cell subsets like T follicular helper cells and Th17 have gained attention as new potential players in PV pathogenesis. The involvement of local autoantibody production in the lesional skin of PV patients in tertiary lymphoid organs is currently discussed but not yet clarified. In this study, we reviewed the current knowledge about the development, characteristics and function of autoreactive T cells in pemphigus and present current new T cell-targeted therapeutic approaches.