-
The Australasian Journal of Dermatology Aug 2017Autoantibodies to the desmosomal proteins desmoglein 1 and 3 cause pemphigus foliaceus and pemphigus vulgaris, which are characterised by keratinocyte dissociation... (Review)
Review
Autoantibodies to the desmosomal proteins desmoglein 1 and 3 cause pemphigus foliaceus and pemphigus vulgaris, which are characterised by keratinocyte dissociation (acantholysis) and intraepidermal blister formation. The passive transfer of pathogenic anti-desmoglein antibodies induces blisters in mice in vivo and the loss of keratinocyte adhesion in vitro. The pathogenetic mechanisms of acantholysis due to anti-desmoglein autoantibodies are not fully understood. However, recent studies have revealed that signalling-dependent and signalling-independent pathways are operative in the loss of cell adhesion. In this review, we focus on the pathomechanism of acantholysis due to autoantibodies to desmogleins and recent therapeutic approaches.
Topics: Acantholysis; Animals; Autoantibodies; Desmoglein 1; Desmoglein 3; Humans; MAP Kinase Signaling System; Pemphigus; p38 Mitogen-Activated Protein Kinases
PubMed: 28211055
DOI: 10.1111/ajd.12562 -
International Journal of Dermatology Aug 2021Dowling-Degos disease is a rare autosomal dominant genodermatosis. It is characterized by acquired reticulate hyperpigmentation over the flexures, comedone-like... (Review)
Review
Dowling-Degos disease is a rare autosomal dominant genodermatosis. It is characterized by acquired reticulate hyperpigmentation over the flexures, comedone-like follicular papules, and pitted perioral scars that usually develop during adulthood. Mutations in genes affecting melanosome transfer, and melanocyte and keratinocyte differentiation have been implicated in the pathogenesis of this disease. These genes include KRT5, POFUT1, POGLUT1 and, most recently, PSENEN. Dowling-Degos disease can be found in isolation or with other associated findings, most notably hidradenitis suppurativa. This condition belongs to a spectrum of conditions that all result in reticulate hyperpigmentation that at times are hard to distinguish from each other. The most closely linked entity is Galli-Galli, which is clinically indistinguishable from Dowling-Degos disease and can only be distinguished by the presence of acantholysis on microscopy. Unfortunately, Dowling-Degos disease is generally progressive and recalcitrant to treatment.
Topics: Acantholysis; Adult; Amyloid Precursor Protein Secretases; Fucosyltransferases; Glucosyltransferases; Humans; Hyperpigmentation; Keratin-5; Membrane Proteins; Skin Diseases, Genetic; Skin Diseases, Papulosquamous
PubMed: 33368260
DOI: 10.1111/ijd.15385 -
Journal of Translational Autoimmunity Dec 2019Bullous skin diseases are a group of dermatoses characterized by blisters and bullae in the skin and mucous membranes. The etiology and pathogenesis of bullous skin... (Review)
Review
Bullous skin diseases are a group of dermatoses characterized by blisters and bullae in the skin and mucous membranes. The etiology and pathogenesis of bullous skin diseases are not completely clear. The most common are pemphigus and bullous pemphigoid (BP). Autoantibodies play critical roles in their pathogenesis. Abnormalities in the adhesion between keratinocytes in patients with pemphigus leads to acantholysis and formation of intra-epidermal blisters. Anti-desmoglein autoantibodies are present both in the circulation and skin lesions of patients with pemphigus. The deficient adhesion of keratinocytes to the basement membrane in BP patients gives rise to subepidermal blisters. Autoantibodies against the components of hemidesmosome can be detected in BP patients. Many novel therapeutics based on knowledge of the pathogenesis have emerged in recent years.
PubMed: 32743502
DOI: 10.1016/j.jtauto.2019.100014 -
Annales de Dermatologie Et de... Nov 2017
Review
Topics: Acantholysis; Autoimmune Diseases; Humans; Keratosis, Seborrheic; Paraneoplastic Syndromes; Pemphigus; Precancerous Conditions; Skin Diseases, Genetic; Skin Diseases, Infectious; Skin Diseases, Vesiculobullous; Skin Neoplasms
PubMed: 28784249
DOI: 10.1016/j.annder.2017.05.002 -
American Journal of Clinical Dermatology Dec 2020Pemphigus vulgaris (PV) is a severe chronic autoimmune blistering disease that affects the skin and mucous membranes. It is characterized by suprabasal acantholysis due... (Review)
Review
Pemphigus vulgaris (PV) is a severe chronic autoimmune blistering disease that affects the skin and mucous membranes. It is characterized by suprabasal acantholysis due to disruption of desmosomal connections between keratinocytes. Autoantibodies against desmosomal cadherins, desmoglein 3 and 1, have been shown to induce disease. Certain human leukocyte antigen (HLA) types and non-HLA foci confer genetic susceptibility. Until the discovery of corticosteroids in the 1950s, PV was 75% fatal. Since then, multiple PV treatments, such as systemic corticosteroids and adjunctive therapy with immunosuppressive medications (mycophenolate mofetil, azathioprine, cyclophosphamide, cyclosporine, methotrexate, gold, and others) have been introduced; however, none have led to long-term remissions and many have undesired adverse effects. Our growing understanding of the pathophysiologic mechanisms in PV is leading to development of new targeted therapies, such as intravenous immunoglobulin, anti-CD20 monoclonal antibodies, inhibitors of Bruton tyrosine kinase and neonatal Fc receptors, and adoptive cellular transfer, that may result in lasting control of this life-threatening disease.
Topics: Agammaglobulinaemia Tyrosine Kinase; Antibodies, Monoclonal; Antigens, CD20; Autoantibodies; Combined Modality Therapy; Drug Therapy, Combination; Genetic Predisposition to Disease; HLA Antigens; Histocompatibility Antigens Class I; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Immunotherapy, Adoptive; Molecular Targeted Therapy; Pemphigus; Plasmapheresis; Receptors, Fc; Remission Induction; Signal Transduction; Treatment Outcome
PubMed: 32860200
DOI: 10.1007/s40257-020-00544-w -
Seminars in Diagnostic Pathology May 2017Several dermatoses are typified by the formation of spaces (blisters; bullae) within or beneath the epidermis. These may be acellular or filled with particular species... (Review)
Review
Several dermatoses are typified by the formation of spaces (blisters; bullae) within or beneath the epidermis. These may be acellular or filled with particular species of inflammatory cells. Etiological categories include infectious, immune-mediated, genetic, drug-related, and idiopathic lesions. Examples of such disorders include impetigo, Herpes virus infections, pemphigus, bullous pemphigoid and pemphigoid gestationis, epidermolysis bullosa acquisita, IgA-related dermatoses, inherited epidermolysis bullosa variants, Hailey-Hailey disease, and porphyria cutanea tarda. Other conditions manifest microscopic acantholysis within the surface epithelium but are not associated with clinical bullae, such as Darier disease and Grover disease. Finally, both infectious and non-infectious causes exist for the development of neutrophilic pustules in the epidermis, as seen in pustular psoriasis, Sneddon-Wilkinson disease (subcorneal pustular dermatosis), and acute generalized exanthematous pustulosis. This review considers the clinical and histological features of all of these diseases.
Topics: Humans; Skin Diseases, Vesiculobullous
PubMed: 28108048
DOI: 10.1053/j.semdp.2016.12.001 -
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 -
Clinics in Dermatology 2015Hailey-Hailey disease, also called benign familial pemphigus, is a late-onset blistering disorder that affects the flexures. There are typically painful erosions and... (Review)
Review
Hailey-Hailey disease, also called benign familial pemphigus, is a late-onset blistering disorder that affects the flexures. There are typically painful erosions and cracks in affected areas. Lesions generally begin between 20 and 40 years of age. In two third of all cases, positive family history is detected. In pathogenesis, there is a defect in keratinocyte adhesion due to ATP2 C1 gene mutation. The result of the desmosomal decomposition is acantholysis. Menstruation, pregnancy, skin infections, physical trauma, excessive sweating and exposure to ultraviolet radiation are important triggering factors. Histopathologic changes are suprabasal acantholysis and formation of intraepidermal bullae. In the epidermis, a partial acantholysis that looks like broken bricks is observed.
Topics: Adrenal Cortex Hormones; Adult; Age Distribution; Age of Onset; Anti-Infective Agents; Biopsy, Needle; Cryotherapy; Female; Humans; Immunohistochemistry; Incidence; Intertrigo; Laser Therapy; Male; Pemphigus, Benign Familial; Pregnancy; Recurrence; Risk Assessment; Severity of Illness Index; Sex Distribution; Treatment Outcome; Young Adult
PubMed: 26051060
DOI: 10.1016/j.clindermatol.2015.04.006