-
Dermatology Reports Nov 2009Hailey-Hailey disease (HHD) and Darier's disease (DD) are caused by mutations in Ca(2+)-ATPases with the end result of desmosomal disruption and suprabasal acantholysis....
Hailey-Hailey disease (HHD) and Darier's disease (DD) are caused by mutations in Ca(2+)-ATPases with the end result of desmosomal disruption and suprabasal acantholysis. Tight junctions (TJ) are located in the granular cell layer in normal skin and contribute to the epidermal barrier. Aberrations in the epidermal differentiation, such as in psoriasis, have been shown to lead to changes in the expression of TJ components. Our aim was to elucidate the expression and dynamics of the TJ proteins during the disruption of desmosomes in HHD and DD lesions. Indirect immunofluorescence and avidin-biotin labeling for TJ, desmosomal and adherens junction proteins, and subsequent analyses with the confocal laser scanning microscope were carried out on 14 HHD and 14 DD skin samples. Transepidermal water loss (TEWL) was measured in normal and lesional epidermis of nine HHD and eight DD patients to evaluate the function of the epidermal barrier in HHD and DD skin. The localization of TJ proteins claudin-1, claudin-4, ZO-1, and occludin in perilesional HHD and DD epidermis was similar to that previously described in normal skin. In HHD lesions the tissue distribution of ZO-1 expanded to the acantholytic spinous cells. In agreement with previous findings, desmoplakin was localized intracellularly. In contrast claudin-1 and ZO-1 persisted in the cell-cell contact sites of acantholytic cells. TEWL was increased in the lesional skin. The current results suggest that TJ components follow different dynamics in acantholysis of HHD and DD compared to desmosomal and adherens junction proteins.
PubMed: 25386233
DOI: 10.4081/dr.2009.e1 -
Advanced Biology Jan 2021It is becoming increasingly clear that mechanical stress in adhesive junctions plays a significant role in dictating the fate of cell-cell attachment under physiological...
It is becoming increasingly clear that mechanical stress in adhesive junctions plays a significant role in dictating the fate of cell-cell attachment under physiological conditions. Targeted disruption of cell-cell junctions leads to multiple pathological conditions, among them the life-threatening autoimmune blistering disease pemphigus vulgaris (PV). The dissociation of cell-cell junctions by autoantibodies is the hallmark of PV, however, the detailed mechanisms that result in tissue destruction remain unclear. Thus far, research and therapy in PV have focused primarily on immune mechanisms upstream of autoantibody binding, while the biophysical aspects of the cell-cell dissociation process leading to acantholysis are less well studied. In work aimed at illuminating the cellular consequences of autoantibody attachment, it is reported that externally applied mechanical stress mitigates antibody-induced monolayer fragmentation and inhibits p38 MAPK phosphorylation activated by anti-Dsg3 antibody. Further, it is demonstrated that mechanical stress applied externally to cell monolayers enhances cell contractility via RhoA activation and promotes the strengthening of cortical actin, which ultimately mitigates antibody-induced cell-cell dissociation. The study elevates understanding of the mechanism of acantholysis in PV and shifts the paradigm of PV disease development from a focus solely on immune pathways to highlight the key role of physical transformations at the target cell.
Topics: Cell Adhesion; Desmoglein 3; Humans; Keratinocytes; Pemphigus; Stress, Mechanical
PubMed: 33724731
DOI: 10.1002/adbi.202000159 -
Oncology Letters Oct 2017Herein is described a unique case of esophageal cancer mimicking acantholytic squamous cell carcinoma (SCC). The patient succumbed to the disease within one month of...
Herein is described a unique case of esophageal cancer mimicking acantholytic squamous cell carcinoma (SCC). The patient succumbed to the disease within one month of diagnosis. Autopsy revealed a 10-cm esophageal tumor, characterized by prominent acantholysis-like areas composed of discohesive cancer cells, along with nested growth of SCC. These discohesive cancer cells focally exhibited pagetoid extension into adjacent esophageal epithelium, comprised ~60% of the esophageal tumor volume and had widely metastasized to the lungs, chest wall, liver, spleen, right adrenal gland, bones and lymph nodes. No metastases of SCC were observed. SCC cells were immunohistochemically positive for keratin 5/6 and E-cadherin and were negative for mucin and carcinoembryonic antigen (CEA). However, the discohesive cancer cells exhibited negativity for keratin 5/6, positivity for mucin and CEA, and diminished or no immunostaining for E-cadherin. Thus, these discohesive cells represented true adenocarcinomatous differentiation rather than acantholytic SCC cells. It was concluded that this tumor was an esophageal adenosquamous carcinoma with 'pseudo'-acantholytic adenocarcinoma components, which should be considered as a rare but distinctive type of aggressive cancer.
PubMed: 29085501
DOI: 10.3892/ol.2017.6804 -
Revista Medica de Chile Apr 2013Pemphigus is an autoimmune bullous disease that involves skin and mucous membranes caused by autoantibodies against antigens on the surface of keratinocytes. We report a... (Review)
Review
Pemphigus is an autoimmune bullous disease that involves skin and mucous membranes caused by autoantibodies against antigens on the surface of keratinocytes. We report a 30-year-old mole presenting with a five months history of pruriginous alopecic and crusted lesions in the scalp, that extended posteriorly to the trunk and limbs. Mucous membranes were not involved. A skin biopsy was performed, showing extensive loss of epidermis and acantholysis. Immuno fluorescence was positive for C3 and intercellular and epidermic IgG. With the presumptive diagnosis of pemphigus vulgaris (PV) without mucous involvement, the patient was treated with prednisone, observing an excellent clinical response. There are only few cases published in the literature of PV without mucous involvement. Some authors refer to this subtype of PV as "Cutaneous pemphigus vulgaris".
Topics: Adult; Biopsy; Glucocorticoids; Humans; Male; Pemphigus; Prednisone; Scalp Dermatoses
PubMed: 23900375
DOI: 10.4067/S0034-98872013000400015 -
Dermatology Practical & Conceptual Jul 2017Grover's disease is a benign condition of unknown origin characterized clinically by an erythematous papulovesicular eruption and histopathologically by intraepidermal...
Grover's disease is a benign condition of unknown origin characterized clinically by an erythematous papulovesicular eruption and histopathologically by intraepidermal clefting and four different patterns of acantholysis: Darier-like, pemphigus-like, spongiotic, and Hailey-Hailey-like. A case of a 54-year-old female affected by Grover's disease and showing a Darier-like histopathological pattern is described. Polarized light dermoscopy (PLD) revealed the presence of polygonal, star-like shaped yellowish/brownish areas of various sizes surrounded by a thin whitish halo. Handheld reflectance confocal microscopy (RCM) showed the presence of intraepidermal dark spaces histopathologically corresponding to intraepidermal clefts, roundish, bright cells correlating to acantholytic keratinocytes, target-like cells with a dark center and a highly reflectant halo corresponding to dyskeratotic cells, and epidermal, polygonal, structureless areas reflecting hyperparakeratosis. In conclusion, the use of PLD and RCM combined with clinical presentation, personal/family history, and genetic evaluation may be useful for the non-invasive diagnosis of Darier-like Grover's disease.
PubMed: 29085721
DOI: 10.5826/dpc.0703a11 -
Dermatology Reports Sep 2020Warty Dyskeratoma (WD) is a rare condition consisting in single or multiple papular or nodular lesions of the skin or of the oral mucosamucosa. Histologically, a...
Warty Dyskeratoma (WD) is a rare condition consisting in single or multiple papular or nodular lesions of the skin or of the oral mucosamucosa. Histologically, a cupshaped epidermal invagination centred by a plug of epidermal hyperparakeratosis with suprabasal acantholysis and dyskeratosis is typically observed. A case of post-inflammatory WD, which was also observed by dermoscopy, is described. Dermoscopy showed an eight-shape whitish collarette surrounded by light brown pigmentation. A central white structureless area with an adjacent rosette were observed. Some small rust-coloured blood crusts were also observed in the centre of the lesion; no prominent vascular pattern was detected. The etiopathogenesis of this benign neoplasm could be multifactorial. Dermoscopy of WD is not specific but may help to ruling out other skin tumors.
PubMed: 33408834
DOI: 10.4081/dr.2020.8791 -
California Medicine Feb 1971Immunofluorescent techniques offer considerable promise in facilitating the diagnosis of pemphigus and other bullous diseases and also have provided a means for further... (Review)
Review
Immunofluorescent techniques offer considerable promise in facilitating the diagnosis of pemphigus and other bullous diseases and also have provided a means for further investigative studies of these diseases. The immunofluorescent findings have in part stimulated the use of immunosuppressive agents in the management of pemphigus. Their exact status is still undetermined but early experience appears favorable.
Topics: Acantholysis; Antigen-Antibody Reactions; Azathioprine; Biopsy; Complement Fixation Tests; Cyclophosphamide
PubMed: 5542167
DOI: No ID Found -
The Journal of Biological Chemistry Feb 2008The mechanisms mediating and regulating assembly and disassembly of intercellular junctions is a subject of intensive research. The IgG autoantibodies produced in...
The mechanisms mediating and regulating assembly and disassembly of intercellular junctions is a subject of intensive research. The IgG autoantibodies produced in patients with the immunoblistering skin disease pemphigus vulgaris (PV) can induce keratinocyte (KC) dyshesion (acantholysis) via mechanisms that involve signaling kinases targeting intercellular adhesion molecules, thus providing a useful model to study the physiologic regulation of KC cohesion. Previous studies showed that activation of Src and protein kinase C are the earliest events in the PV IgG-induced intracellular phosphorylation cascades and that cholinergic agonists are effective for treating patients with pemphigus. In this study, we sought to elucidate the molecular mechanisms allowing cholinergic agonists to inhibit PV IgG-induced acantholysis and phosphorylation of KC adhesion molecules. The extent of acantholysis in KC monolayers correlated closely with the degree of PV IgG-induced phosphorylation of p120- and beta-catenins, with classic isoforms of protein kinase C mediating serine phosphorylation of beta-catenin and Src-tyrosine phosphorylation of p120-catenin. The M(1) muscarinic agonist pilocarpine blocked phosphorylation of both catenins, which could be abolised by the M(1) antagonist MT7. The alpha7 nicotinic agonist AR-R17779 inhibited phosphorylation of P120-cateinin. The alpha7 antagonist methyllycaconitine abolished the effect of AR-R17779. Okadaic acid abrogated protective effects of agonists on phosphorylation of beta-catenin, and pervanadate, on that of p120-catenin. Stimulation of KCs with pilocarpine significantly (p < 0.05) elevated both serine/threonine and tyrosine phosphatase activities in KCs. AR-R17779 both stimulated tyrosine phosphatase and decreased PV IgG-induced Src activity. Methyllycaconitine released Src activity in intact KCs and caused acantholysis. Thus, downstream signaling from M(1) abolished PV IgG-dependent catenin phosphorylation due to activation of both serine/threonine and tyrosine phosphatases, whereas alpha7 action involved both activation of tyrosine phosphatase and inhibition of Src. These findings identified novel paradigm of regulation of signaling kinases associated with cholinergic receptors and provided mechanistic explanation of therapeutic activity of cholinomimetics in PV patients.
Topics: Aconitine; Cell Adhesion; Cells, Cultured; Gene Expression Regulation; Humans; Immunoglobulin G; Keratinocytes; Models, Biological; Okadaic Acid; Pemphigus; Phosphorylation; Receptor, Muscarinic M1; Receptors, Nicotinic; alpha7 Nicotinic Acetylcholine Receptor; beta Catenin; src-Family Kinases
PubMed: 18073210
DOI: 10.1074/jbc.M704956200 -
International Journal of Clinical... 2017Pemphigus is a chronic mucocutaneous disease that initially manifests in the form of intraoral blisters which spread to other mucous membrane and skin. This study...
UNLABELLED
Pemphigus is a chronic mucocutaneous disease that initially manifests in the form of intraoral blisters which spread to other mucous membrane and skin. This study describes an unusual case of chronic generalized childhood pemphigus disease in an 11-year-old girl, who presented with multiple vesicles all over her body. Such a condition is seen more often in older people rather than children. It is crucial for dental professionals to be familiar with the diagnosis of bullous skin diseases in children and adolescents, especially in its initial stages in order to prevent the serious consequences and morbidity. The article highlights clinical presentation, histopathology, and successful management strategies useful for pediatric dental practice.
HOW TO CITE THIS ARTICLE
Patil RU, Anegundi RT, Gujjar KR, Indushekar KR. Childhood Occurrence of Pemphigus. Int J Clin Pediatr Dent 2017;10(2):196-200.
PubMed: 28890623
DOI: 10.5005/jp-journals-10005-1434 -
Translational Andrology and Urology Apr 2021Pseudoangiosarcomatous squamous cell carcinoma, also called pseudovascular, pseudoangiomatoid or adenoid pseudovascular carcinoma, is an uncommon and highly aggressive...
Pseudoangiosarcomatous squamous cell carcinoma, also called pseudovascular, pseudoangiomatoid or adenoid pseudovascular carcinoma, is an uncommon and highly aggressive variant of squamous cell carcinoma. Histologically, it is characterized by proliferation of atypical keratinocytes with acantholysis and formation of pseudovascular spaces, forming anastomosed channels lined with neoplastic cells that invade the dermis. These cells are positive for cytokeratin and negative for vascular markers such as CD31 and CD34. There are few reports of this variant in the literature. Skin, breast, lung and vulva involvement have been described, but to the best of our knowledge, no cases involving the penis has been described. This study aims to describe the first case of angiosarcomatous squamous cell carcinoma of the penis. The patient presented with a painful lesion in the penis associated with urinary retention. Macroscopic findings exhibited an ulcerative vegetating lesion that involving the entire glans and part of the penile body, as well as infiltration of penile structures and scrotal skin. Microscopy shows atypical proliferation of sarcomatous keratinocyte pattern mimicking vascular spaces. Human papilloma virus (HPV) biomarkers and polymerase chain reaction (PCR) were all negative. Advanced penile squamous cell carcinoma with aggressive lymph node metastasis. This report presents the first case of penile pseudoangiosarcomatous squamous cell carcinoma, as an important differential diagnosis.
PubMed: 33968668
DOI: 10.21037/tau-20-1234