-
Cureus Jan 2023Pemphigus vulgaris (PV) represents damage to epidermal keratinocytes, resulting in acantholysis due to the production of autoantibodies against desmoglein-1 and...
Pemphigus vulgaris (PV) represents damage to epidermal keratinocytes, resulting in acantholysis due to the production of autoantibodies against desmoglein-1 and desmoglein-3. Autoimmune blistering disorders such as pemphigus vulgaris or bullous pemphigoid that develop following coronavirus disease 2019 (COVID-19) have been reported in several studies. Herein, we report a case of PV onset following COVID-19 infection in a 17-year-old female, demonstrating --the potential pathogenic capacity of SARS-CoV-2 to develop PV.
PubMed: 36819405
DOI: 10.7759/cureus.33897 -
The Journal of Investigative Dermatology May 2004
Review
Topics: Acantholysis; Animals; Humans; Pemphigus; Skin
PubMed: 15140250
DOI: 10.1111/j.0022-202X.2004.22438.x -
Vaccines Jan 2022Pemphigus vulgaris (PV) is a chronic, life-altering autoimmune disease due to the production of anti-desmoglein antibodies causing the loss of cell-cell adhesion in...
Pemphigus vulgaris (PV) is a chronic, life-altering autoimmune disease due to the production of anti-desmoglein antibodies causing the loss of cell-cell adhesion in keratinocytes (acantholysis) and blister formation in both skin and mucous membranes. The dispase-based keratinocyte dissociation assay (DDA) is the method of choice to examine the pathogenic effect of antibodies and additional co-stimuli on cell adhesion in vitro. Despite its widespread use, there is a high variability of experimental conditions, leading to inconsistent results. In this paper, we identify and discuss pitfalls in the application of DDA, including generation of a monolayer with optimized density, appropriate culturing conditions to obtain said monolayer, application of mechanical stress in a standardized manner, and performing consistent data processing. Importantly, we describe a detailed protocol for a successful and reliable DDA and the respective ideal conditions for three different types of human keratinocytes: (1) primary keratinocytes, (2) the HaCaT spontaneously immortalized keratinocyte cell line, and (3) the recently characterized HaSKpw spontaneously immortalized keratinocyte cell line. Our study provides detailed protocols which guarantee intra- and inter-experimental comparability of DDA.
PubMed: 35214667
DOI: 10.3390/vaccines10020208 -
The Journal of Investigative Dermatology Jul 1989In organ culture experiments, the induction of pemphigus acantholysis is known to be blocked by the addition of serine proteinase inhibitors. Recently, nontoxic...
Proteinase inhibitors block formation of pemphigus acantholysis in experimental models of neonatal mice and skin explants: effects of synthetic and plasma proteinase inhibitors on pemphigus acantholysis.
In organ culture experiments, the induction of pemphigus acantholysis is known to be blocked by the addition of serine proteinase inhibitors. Recently, nontoxic synthesized low molecular weight proteinase inhibitors have been clinically available for the treatment of disseminated intravascular coagulation and pancreatitis. To determine if these drugs are useful aids to treat patients with pemphigus, we examined the effect of omega-guanidino ester analogues, i.e., 1) gabexate mesilate, 2) camostat mesilate, and 3) nafamostat mesilate, on experimental pemphigus acantholysis in both organ culture and neonatal BALB/c mice. Furthermore, the effect of plasma natural proteinase inhibitors (alpha-1-proteinase inhibitor) isolated from human plasma was similarly examined. Results revealed that synthesized low molecular weight inhibitors (drugs) were able to inhibit the induction of acantholysis in organ culture system, but had little or no effect on lesion formation in the neonatal mouse system. By contrast, alpha-1-proteinase inhibitor could completely inhibit acantholysis formation in mice. These findings implied a possible new therapeutic approach using proteinase inhibitors for patients with pemphigus.
Topics: Acantholysis; Animals; Animals, Newborn; Fibrinolysin; Humans; Mice; Mice, Inbred BALB C; Organ Culture Techniques; Pemphigus; Plasminogen Activators; Protease Inhibitors; Skin; Skin Diseases
PubMed: 2526184
DOI: 10.1111/1523-1747.ep12277395 -
Case Reports in Women's Health Sep 2023Darier disease is an autosomal dominant disorder with hyperkeratotic papules affecting primarily seborrheic areas of the upper chest, back, forehead, scalp, nasolabial...
Darier disease is an autosomal dominant disorder with hyperkeratotic papules affecting primarily seborrheic areas of the upper chest, back, forehead, scalp, nasolabial folds, ears, and, less frequently, the oral mucosa. A typical eruption consists of keratotic and crusted skin-colored papules and plaques. Pruritus occurs in 80% of patients, and pain is rare. Lesions can be triggered by exposure to ultraviolet light, heat, or stress. Secondary infections of the lesions are a common complication. A definitive diagnosis is obtained by a biopsy showing histological features such as acantholysis, suprabasal clefts, and "corps rond and grains". Here we present a 37-year-old woman admitted to the gynecology department with pruritic lesions she had noticed on her vulva and perineum for three months. A vulvar biopsy led to the diagnosis of Darier disease. She was referred to the dermatology department and treated with oral acitretin since systemic retinoids are offered as the first-line treatment of the disease.
PubMed: 37753222
DOI: 10.1016/j.crwh.2023.e00545 -
Indian Journal of Dermatology 2022Pemphigus is a group of auto-immune blistering disorders, characterised clinically by mucocutaneous blisters and erosions and histopathologically by intra-epidermal...
BACKGROUND
Pemphigus is a group of auto-immune blistering disorders, characterised clinically by mucocutaneous blisters and erosions and histopathologically by intra-epidermal acantholysis. It was traditionally associated with high morbidity and mortality. The use of rituximab has brought upon a new dawn in the treatment of pemphigus.
AIM
A retrospective analysis to ascertain the efficacy, tolerance, adverse effect profile, remission, and relapse with the use of rituximab.
MATERIAL AND METHODS
A retrospective analysis of all diagnosed pemphigus patients who received rituximab therapy over a period of 3 years was performed. The patient's baseline characteristics, disease duration, clinical presentations, mucosal involvement, disease-severity assessment, and adverse events with rituximab were noted. The outcomes were evaluated based on the definitions of the disease-outcome parameters as early and late endpoints.
RESULTS
Of the 17 pemphigus patients, there were 14 females (82.4%) and three males (17.6%) with a mean age of 35.9 ± 16.5 years (range: 9-65 years). Pemphigus vulgaris (PV) was the predominant type in 11 (64.7%) patients. After rituximab infusion, the 17 patients attained the end of consolidation phase (ECP) within 15 days to 3 months, and the mean duration was 1.24 months. The complete remission (CR on/off) ranged from 0.5 to 35 months, and the mean duration of remission was 21.7 months. Within a median time of 4.2 months, almost 80% patients achieved CR on therapy. Nine (53%) patients were in CR without any therapy till the end of the study period, and eight (47%) were in remission while on minimal therapy.
CONCLUSION
Rituximab is an efficacious therapeutic agent for pemphigus and is better tolerated and safer to all the previous medications used in the treatment.
PubMed: 36578732
DOI: 10.4103/ijd.ijd_169_22 -
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 -
Clinical and Experimental Immunology Jan 1997Epidermal blister formation is the hallmark of three cutaneous autoimmune diseases: pemphigus foliaceous (PF), pemphigus vulgaris (PV) and bullous pemphigoid (BP). In PF... (Review)
Review
Epidermal blister formation is the hallmark of three cutaneous autoimmune diseases: pemphigus foliaceous (PF), pemphigus vulgaris (PV) and bullous pemphigoid (BP). In PF and PV, blistering is due to acantholysis (cell-cell detachment) in the subcorneal and suprabasal epidermal layers, respectively, while BP is characterized by detachment of the basal epidermal cells from the underlying dermis. For several years, we have focused our research efforts on elucidating the pathogenic mechanisms operating in these bullous diseases. Early studies performed by our research group and others revealed that in all three diseases, the patients produce autoantibodies that bind to target antigens located on the surface of cells that are undergoing detachment. Thus it was hypothesized that these anti-epidermal autoantibodies played a role in initiating blister formation. We recognized that elucidating the normal mechanisms of epidermal cell-cell and cell-dermis adhesion would help us understand the abnormal epidermal cell detachment seen in these patients. We hypothesized that under normal conditions these adhesive mechanisms in the epidermis are complex and dynamic and mediated by the interaction of cell surface molecules unique to each layer of the epidermis. Also, we postulated that PV, PF and BP autoantibodies may cause cell detachment by impairing the function of their respective epidermal cell surfaces. Support for this hypothesis has come from recent studies which showed that PV and PF autoantibodies recognize distinct, yet related, desmosomal glycoproteins in the cadherin family of calcium-dependent adhesion molecules. The epidermal antigen in PV is desmoglein-3 (dsg3), while in PF it is desmoglein-1 (dsg1). These anti-epidermal autoantibodies have been shown to be pathogenic in passive transfer experiments. Neonatal mice injected with these antibodies develop intraepidermal blisters characteristic of the corresponding human disease. Autoantibodies in BP react with BP180 and BP230, two major components of the hemidesmosome, a cell structure involved in dermal-epidermal adhesion. Recent passive transfer mouse model studies performed in our laboratory have shown that anti-BP180 antibodies can induce subepidermal blistering in the experimental animals. Moreover, the pathogenic mechanism was shown to be dependent on complement activation and recruitment of neutrophils to the dermal-epidermal junction. In conclusion, desmosomal glycoproteins are the targets of autoimmune injury in PV and PF. The anti-epidermal autoantibodies may cause intraepidermal blisters by impairing the function of dsg1 and dsg3. In BP the hemidesmosome is the target. It appears that antiBP180 antibodies cause subepidermal blister formation by triggering a complement- and neutrophil-mediated inflammatory process.
Topics: Animals; Autoantibodies; Autoimmunity; Desmosomes; Humans; Mice; Pemphigoid, Bullous; Pemphigus; Skin
PubMed: 9020929
DOI: No ID Found -
Actas Dermo-sifiliograficas Mar 2017
Topics: Acantholysis; Aged; Dermatologic Agents; Genital Diseases, Male; Humans; Keratinocytes; Keratosis; Male; Scrotum; Tacrolimus
PubMed: 27328825
DOI: 10.1016/j.ad.2015.10.021 -
BMC Dermatology Jul 2019Hidradenitis suppurativa is one member of the follicular occlusion triad: acne conglobata, hidradenitis suppurativa, and dissecting cellulitis of the scalp. The presence...
BACKGROUND
Hidradenitis suppurativa is one member of the follicular occlusion triad: acne conglobata, hidradenitis suppurativa, and dissecting cellulitis of the scalp. The presence of acantholysis and desmoglein autoantibodies in hidradenitis suppurativa is rare.
CASE PRESENTATION
We report a case of 68-year-old male with a diagnosis of gluteal hidradenitis suppurativa co-presenting pemphigus-like findings including acantholysis and positive desmoglein autoantibodies.
CONCLUSION
To our knowledge, comorbidity of gluteal hidradenitis suppurativa and pemphigus-like findings has not been reported before. This case implies a relationship between two different conditions; the follicular occlusion triad and pemphigus, highlighting a potential induction of pemphigus-like lesion by chronic inflammatory process.
Topics: Acantholysis; Acne Conglobata; Aged; Autoantibodies; Buttocks; Desmoglein 1; Desmoglein 3; Diagnosis, Differential; Hidradenitis Suppurativa; Humans; Male; Pemphigus; Skin
PubMed: 31337387
DOI: 10.1186/s12895-019-0091-7