• antibody titers
• clinical phenotype
• desmoglein
• disease activity
• pemphigus vulgaris
• risk factors

• Humans
• Pemphigus/immunology
• Pemphigus/blood
• Pemphigus/therapy
• Male
• Female
• Middle Aged
• Autoantibodies/blood
• Autoantibodies/immunology
• Registries
• Adult
• Prospective Studies
• Risk Factors
• Aged
• Remission Induction
• Biomarkers
• Desmogleins/immunology
• China
• Desmoglein 1/immunology

• Humans
• Antibodies, Monoclonal, Humanized/therapeutic use
• Keratoderma, Palmoplantar/drug therapy
• Pemphigoid, Bullous/drug therapy
• Pemphigoid, Bullous/diagnosis
• Treatment Outcome
• Female
• Male
• Aged
• Dermatologic Agents/therapeutic use
• Skin/pathology
• Skin/drug effects

• Nikolsky sign
• Wickham striae
• oral mucosal lesion
• pemphigoid

• autoimmune blistering skin disease
• autoimmune skin disorders
• clinical presentation of pv
• pemphigus vulgaris
• treatment choices

• FAERS
• Janus kinase inhibitor
• Tofacitinib
• pemphigus
• pharmacovigilance

• Humans
• Female
• Adult
• Middle Aged
• Janus Kinase Inhibitors/adverse effects
• Antirheumatic Agents/adverse effects
• Pemphigus/chemically induced
• Pemphigus/drug therapy
• Treatment Outcome
• Pyrroles/adverse effects
• Arthritis, Rheumatoid/drug therapy

• autoimmune
• bibliometric analysis
• dermatology
• immunology
• pemphigoid diseases

Autoimmune skin diseases are a group of disorders that arise due to the dysregulated immune system attacking self-antigens, causing multiple tissue and organ lesions. With disease progression, the physical and psychological health of patients may be seriously damaged. High-frequency ultrasound is non-invasive, reproducible, and suitable for visualizing the fine structure of external organs. The usage of high-frequency ultrasound has increased in recent years in the auxiliary diagnosis and monitoring of various skin diseases; it serves as a promising tool for dermatological disease assessment. This review summarizes the characteristics of high-frequency ultrasound imaging in common autoimmune skin diseases, including systemic lupus erythematosus, scleroderma, psoriasis, dermatomyositis, and pemphigus/pemphigoid. The objective of this review is to provide new ideas and strategies for dermatologists to diagnose and track the prognosis of autoimmune skin diseases.

• Autoimmune Diseases/diagnostic imaging
• Humans
• Lupus Erythematosus, Systemic/complications
• Pemphigus/complications
• Skin Diseases/diagnostic imaging
• Skin Diseases/etiology
• Ultrasonography/adverse effects

Molecular mechanisms underlying auto-antibody-induced acantholysis in pemphigus vulgaris are subject of current research to date. To decipher the discrepancy between ubiquitous antibody binding to the epidermal desmosomes, but discontinuous disease manifestation, we were able to identify Ultraviolet A (UVA) as a cofactor for acantholysis. UVA induces interleukin (IL)-1 secretion in keratinocytes, mirroring innate immune system activation. In an in vitro keratinocyte dissociation assay increased fragmentation was observed when UVA was added to anti-Desmoglein 3 Immunoglobulins (anti-Dsg3 IgG). These results were confirmed in skin explants where UVA enhanced anti-Dsg3-mediated loss of epidermal adhesion. The UVA-mediated effect was blocked in vitro by the pan-caspase-inhibitor zVAD-fmk. Thus, we introduce UVA as a caspase-dependent exogenous cofactor for acantholysis which suggests that local innate immune responses largely contribute to overt clinical blister formation upon autoantibody binding to epidermal cells in pemphigus vulgaris.

• Acantholysis/metabolism
• Caspases
• Humans
• Immunity, Innate
• Immunoglobulin G
• Pemphigus

• Deutsche Forschungsgemeinschaft

• delayed diagnosis
• oral ulcer
• pemphigus vulgaris

• IgA pemphigus
• autoimmune bullous dermatoses
• bullous pemphigoid
• dermatitis herpetiformis
• epidermolysis bullosa acquisita
• mucous membrane pemphigoid
• paraneoplastic pemphigus
• pemphigus foliaceus
• pemphigus vulgaris

Pemphigus vulgaris is an autoimmune bullous dermatosis which if occurred during pregnancy may result in neonatal complications. In this study we report a 41 years old woman with pemphigus vulgaris that triggered by pregnancy in first trimester of pregnancy followed by the premature birth of a healthy neonate.

• CD25
• CD4
• Foxp3
• Immunohistochemistry
• Pemphigus

Pemphigus represents a group of rare and severe autoimmune intra-epidermal blistering diseases affecting the skin and mucous membranes. These painful and debilitating diseases are driven by the production of autoantibodies that are mainly directed against the desmosomal adhesion proteins, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1). The search to define underlying triggers for anti-Dsg-antibody production has revealed genetic, environmental, and possible vaccine-driven factors, but our knowledge of the processes underlying disease initiation and pathology remains incomplete. Recent studies point to an important role of T cells in supporting auto-antibody production; yet the involvement of the myeloid compartment remains unexplored. Clinical management of pemphigus is beginning to move away from broad-spectrum immunosuppression and towards B-cell-targeted therapies, which reduce many patients’ symptoms but can have significant side effects. Here, we review the latest developments in our understanding of the predisposing factors/conditions of pemphigus, the underlying pathogenic mechanisms, and new and emerging therapies to treat these devastating diseases.

• acantholysis
• caspases
• kinases
• molecular pathways
• pemphigus vulgaris

• Acantholysis/metabolism
• Acantholysis/pathology
• Autoantibodies
• Blister
• Humans
• Pemphigus
• Signal Transduction
• p38 Mitogen-Activated Protein Kinases/metabolism

• Autoimmune blistering disease
• Biologic
• Efficacy
• Immunosuppression
• Pemphigus
• Rituximab
• Safety

Pemphigus represents a group of chronic inflammatory disorders characterized by autoantibodies that target components of desmosomes, leading to the loss of intercellular adhesion between keratinocytes and causing intraepithelial blistering. The pemphigus group consists of four main clinical types with several variants: pemphigus vulgaris (with pemphigus vegetans and pemphigus herpetiformis as variants), pemphigus foliaceus, paraneoplastic pemphigus and IgA pemphigus (with two clinical variants: intraepidermal neutrophilic IgA dermatosis and subcorneal pustular dermatosis). Genetic factors are involved in the pathogenesis, with HLA-DR4 (DRB1*0402) and HLA-DRw6 (DQB1*0503) allele more common in patients with pemphigus vulgaris, HLA class II DRB1*0344 and HLA Cw*1445 correlated with paraneoplastic pemphigus, and HLA-DRB1*04:01, HLA-DRB1*04:06, HLA-DRB1*01:01, HLA-DRB1*14, associated with a higher risk of developing pemphigus foliaceus. Autoantibodies are conducted against structural desmosomal proteins in the skin and mucous membranes, mainly desmogleins, desmocollins and plakins. Cell-mediated immunity may also play a role, especially in paraneoplastic pemphigus. Patients may present erythema, blisters, erosions, and ulcers that may affect the skin, as well as mucosal surfaces of the oral cavity, eyes, nose, leading to severe complaints including pain, dysphagia, and fetor. Oral mucosal postbullous erosive lesions are frequently the first sign of disease in pemphigus vulgaris and in paraneoplastic pemphigus, without skin involvement, making the diagnosis difficult. Treatment options classically include immunosuppressive agents, such as corticosteroids and corticosteroid-sparing agents such as azathioprine, mycophenolate mofetil, cyclophosphamide, methotrexate or dapsone. Newer therapies focus on blocking cell signaling events induced by pathogenic autoantibodies and/or targeting specific autoantibodies. The disease evolution is conditioned by the treatment with maximum doses of corticosteroids and the side effects associated with long-term immunosuppressive therapy, which is why patients need a multidisciplinary approach in following the treatment. In this review, we provide a comprehensive overview of the epidemiology, pathophysiology, clinical aspect, diagnosis and management of the main intraepidermal blistering diseases from the pemphigus group.

• IgA pemphigus
• paraneoplastic pemphigus
• pemphigus foliaceus
• pemphigus herpetiformis
• pemphigus vegetans
• pemphigus vulgaris

• ELISA
• IIF
• autoimmune bullous diseases
• pemphigoid
• pemphigus

• adhesion
• autoantibodies
• autoimmune blistering disease
• pemphigus
• signalling

• Autoimmunity
• CD4 T cells
• CD8 T cells
• Interleukin (IL)-21
• Resident memory

• Pemphigus foliaceus
• Relapse
• Seasonal variation
• Therapy
• Ultraviolet

• endoscopy
• esophagus
• pemphigus

• autoantibodies
• autoimmune dermatosis
• desmogleins
• pemphigus
• plasmapheresis

• atopic dermatitis
• bone
• dermatology
• eczema
• osteoporosis
• pemphigus
• psoriasis
• skeletal health
• skin
• skin diseases
• urticaria
• vitiligo

• Blister/complications
• Blister/physiopathology
• Bone Remodeling/physiology
• Cytokines/physiology
• Dermatitis, Atopic/complications
• Dermatitis, Atopic/physiopathology
• Dermatologic Agents/adverse effects
• Humans
• Models, Biological
• Osteoporosis/chemically induced
• Osteoporosis/complications
• Osteoporosis/physiopathology
• Psoriasis/complications
• Psoriasis/physiopathology
• Skin Aging/physiology
• Skin Diseases/complications
• Skin Diseases/drug therapy
• Skin Diseases/physiopathology
• Skin Neoplasms/complications
• Skin Neoplasms/physiopathology
• Urticaria/complications
• Urticaria/physiopathology
• Vitamin D/physiology

• ELISA
• autoantibody
• autoimmune bullous dermatosis
• biochip
• indirect immunofluorescence
• pemphigoid
• pemphigus
• serology

• Alopecia
• Autoimmune blistering diseases
• Hair loss
• Pemphigoid
• Pemphigus
• Scalp
• Trichoscopy

• BTK inhibitors
• CAAR T-cell
• anti-CD 20 antibodies
• neonatal Fc receptor (FcRn)
• pemphigus
• rituximab

• Associations
• Autoimmune
• Bullous diseases
• Comorbidities
• Epidemiology
• Subepidermal

• atomic force microscopy
• cell adhesion
• desmosomal cadherin
• desmosome
• pemphigus

• Cadherins/metabolism
• Desmogleins/metabolism
• Desmosomes/metabolism
• Desmosomes/ultrastructure
• Humans
• Keratinocytes/metabolism
• Keratinocytes/ultrastructure
• Keratins/metabolism
• Microscopy, Atomic Force/methods
• Pemphigus/metabolism
• Pemphigus/pathology
• Protein Domains

Keratins are crucial for the anchorage of desmosomes. Severe alterations of keratin organization and detachment of filaments from the desmosomal plaque occur in the autoimmune dermatoses pemphigus vulgaris and pemphigus foliaceus (PF), which are mainly caused by autoantibodies against desmoglein (Dsg) 1 and 3. Keratin alterations are a structural hallmark in pemphigus pathogenesis and correlate with loss of intercellular adhesion. However, the significance for autoantibody-induced loss of intercellular adhesion is largely unknown. In wild-type (wt) murine keratinocytes, pemphigus autoantibodies induced keratin filament retraction. Under the same conditions, we used murine keratinocytes lacking all keratin filaments (KtyII k.o.) as a model system to dissect the role of keratins in pemphigus. KtyII k.o. cells show compromised intercellular adhesion without antibody (Ab) treatment, which was not impaired further by pathogenic pemphigus autoantibodies. Nevertheless, direct activation of p38MAPK via anisomycin further decreased intercellular adhesion indicating that cell cohesion was not completely abrogated in the absence of keratins. Direct inhibition of Dsg3, but not of Dsg1, interaction via pathogenic autoantibodies as revealed by atomic force microscopy was detectable in both cell lines demonstrating that keratins are not required for this phenomenon. However, PF-IgG shifted Dsg1-binding events from cell borders toward the free cell surface in wt cells. This led to a distribution pattern of Dsg1-binding events similar to KtyII k.o. cells under resting conditions. In keratin-deficient keratinocytes, PF-IgG impaired Dsg1-binding strength, which was not different from wt cells under resting conditions. In addition, pathogenic autoantibodies were capable of activating p38MAPK in both KtyII wt and k.o. cells, the latter of which already displayed robust p38MAPK activation under resting conditions. Since inhibition of p38MAPK blocked autoantibody-induced loss of intercellular adhesion in wt cells and restored baseline cell cohesion in keratin-deficient cells, we conclude that p38MAPK signaling is (i) critical for regulation of cell adhesion, (ii) regulated by keratins, and (iii) targets both keratin-dependent and -independent mechanisms.

• atomic force microscopy
• desmoglein
• desmosome
• keratin
• p38MAPK

Pemphigus vulgaris is an autoimmune bullous disorder characterized by the production of autoantibodies against the intercellular space of the epithelium. It has rarely been reported in association with inflammatory bowel disease. Ulcerative colitis is one of the forms of inflammatory bowel disease. A 62-year-old woman who had been treated for ulcerative colitis for 16 years developed pruritic bullae on the skin of her face and body. Histological findings and direct immunofluorescence examination of the skin showed pemphigus vulgaris. She was treated with systemic steroids, mesalazine, and azathioprine. Her cutaneous lesions have remained in remission and her ulcerative colitis has remained well-controlled. The relationship between pemphigus vulgaris and ulcerative colitis is unclear. An autoimmune response has been suspected in the pathogenesis of ulcerative colitis. Pemphigus vulgaris is also associated with an autoimmune mechanism. To our knowledge, this is the first case of ulcerative colitis associated with pemphigus vulgaris reported in Korea. The association may be causal.

• Autoimmunity
• Colitis, ulcerative
• Pemphigus

Pemphigus is an autoimmune blistering skin disease caused primarily by autoantibodies against desmoglein (Dsg)1 and 3. Here, we characterized the mechanisms engaged by pemphigus IgG from patients with different clinical phenotypes and autoantibody profiles. All pemphigus vulgaris (PV) and pemphigus foliaceus (PF) IgG and AK23, a monoclonal mouse antibody against Dsg3, caused loss of cell cohesion, cytokeratin retraction and p38MAPK activation. Strong alterations in Dsg3 distribution were caused by mucosal (aDsg3 antibodies), mucocutaneous (aDsg1 + aDsg3) as well as atypical (aDsg3) PV-IgG. All PV-IgG fractions and AK23 compromised Dsg3 but not Dsg1 binding and enhanced Src activity. In contrast, rapid Ca²⁺ influx and Erk activation were induced by mucocutaneous PV-IgG and pemphigus foliaceus (PF) IgG (aDsg1) whereas cAMP was increased by mucosal and mucocutaneous PV-IgG only. Selective inhibition of p38MAPK, Src or PKC blocked loss of keratinocyte cohesion in response to all autoantibody fractions whereas Erk inhibition was protective against mucocutaneous PV-IgG and PF-IgG only. These results demonstrate that signaling patterns parallel the clinical phenotype as some mechanisms involved in loss of cell cohesion are caused by antibodies targeting Dsg3 whereas others correlate with autoantibodies against Dsg1. The concept of key desmosome regulators may explain observations from several experimental models of pemphigus.

Pemphigus is a group of immune-mediated bullous disorders, which often cause fragile blisters and extensive lesions of the skin or mucous membranes, such as in the mouth. This disease could be life-threatening in some cases. During pregnancy, its condition will become more complicated due to the change in the mother’s hormone level and the effect of drug therapy on both the mother and her fetus. Thus, it will be more difficult to identify the clinical manifestations and to establish the treatment plan. In this article, we present a comprehensive review of pemphigus and pregnancy by analyzing 47 cases of pemphigus reported between 1966 and 2014, with diagnosis before or during pregnancy. The aim of this study is to make a comprehensive review of pemphigus and pregnancy, provide organized and reliable information for obstetricians, dermatologists, physicians, and oral medicine specialists.

• Abortion, Spontaneous
• Adult
• Female
• Humans
• Immunoglobulins, Intravenous/therapeutic use
• Immunosuppressive Agents/therapeutic use
• Infant, Newborn
• Infant, Newborn, Diseases
• Pemphigus/complications
• Plasmapheresis
• Pregnancy
• Pregnancy Complications/diagnosis
• Pregnancy Complications/drug therapy
• Pregnancy Complications/therapy
• Pregnancy Outcome
• Young Adult

Pemphigus vulgaris are autoimmune blistering diseases that may result in significant morbidity and death. Immunosuppressive therapy of pemphigus vulgaris would predispose the patients to infections. The aim of this study was to assess the prevalence of S. aureus infection and PVL gene in patients with pemphigus admitted to dermatology clinic. Materials and Methods. This descriptive study was conducted on 196 pemphigus vulgaris patients (119 males, 77 females) admitted to dermatology clinic between 2014 and 2015. In this study, the diagnosis of pemphigus vulgaris was made by histology, immunofluorescence pattern of perilesional skin, and indirect immunofluorescence testing of serum. Data were collected through a questionnaire. Results. 59.1% of pemphigus vulgaris patients had S. aureus infection. 49 out of 116 were methicillin-resistant. PVL gene was detected in 25 out of 116 S. aureus positive patients. Conclusion. This is the first report of S. aureus infection in pemphigus patients in Iran. More than forty percent of isolates were methicillin-resistant S. aureus. PVL gene carried by methicillin-resistant S. aureus was high in this study.

• Autoantibodies
• Immunosuppression
• Mucosal pemphigoid
• Pemphigus vulgaris
• Systemic therapy

Pemphigus vulgaris (PV) is an autoimmune epidermal blistering disease in which autoantibodies (IgG) are directed against the desmosomal cadherin desmoglein 3 (Dsg3). In order to better understand how PV IgG alters desmosome morphology and function in vivo, PV patient biopsies were analyzed by structured illumination microscopy (SIM), a form of super-resolution fluorescence microscopy. In patient tissue, desmosomal proteins were aberrantly clustered and localized to PV IgG-containing endocytic linear arrays. Patient IgG also colocalized with markers for lipid rafts and endosomes. Additionally, steady-state levels of Dsg3 were decreased and desmosomes were reduced in size in patient tissue. Desmosomes at blister sites were occasionally split, with PV IgG decorating the extracellular faces of split desmosomes. Desmosome splitting was recapitulated in vitro by exposing cultured keratinocytes both to PV IgG and to mechanical stress, demonstrating that splitting at the blister interface in patient tissue is due to compromised desmosomal adhesive function. These findings indicate that Dsg3 clustering and endocytosis are associated with reduced desmosome size and adhesion defects in PV patient tissue. Further, this study reveals that super-resolution optical imaging is powerful approach for studying epidermal adhesion structures in normal and diseased skin.

Pemphigus is an autoimmune disease in which IgG auto-antibodies (auto-ab) against the desmosomal cadherins desmoglein (Dsg) 3 and Dsg1 cause loss of epidermal keratinocyte adhesion. Aim of this study was to investigate cytokines derived from antigen-presenting cells (APC) and their relation to CD4⁺ T cell subpopulations and to the auto-ab response in pemphigus. In this regard, patients with pemphigus were compared to patients with myasthenia gravis (MG), an unrelated auto-ab–mediated autoimmune disease, and healthy controls. In pemphigus and MG, the plasma concentrations of the APC-derived immunomodulatory cytokine IL-27 were highly increased. Strikingly, IL-27 strongly correlated with Dsg-specific IgG auto-ab titers. T helper (Th) 17 cells were augmented in both pemphigus and MG patients while T follicular helper (Tfh) cells, which are essential in providing B cell help, were increased only in pemphigus along with increasing plasma concentrations of IL-21, a cytokine produced by Th17 and Tfh cells. Moreover, we could detect Dsg3-specific autoreactive T cells producing IL-21 upon ex vivo stimulation with Dsg3. These findings suggest that IL-27 and IL-21-producing T cells, are involved in the pathogenesis of pemphigus. The further characterization of IL-21-producing T cells and of the role of IL-27 will lead to a more defined understanding of the auto-ab response in pemphigus.

• Autoantibodies/blood
• Case-Control Studies
• Humans
• Immunoglobulin G/blood
• Interleukin-10/blood
• Interleukin-6/blood
• Interleukins/blood
• Pemphigus/blood
• Pemphigus/immunology
• Receptors, CXCR5/metabolism
• T-Lymphocytes, Helper-Inducer/immunology
• T-Lymphocytes, Helper-Inducer/metabolism

Pseudopemphigoid can cause a chronic cicatricial conjunctivitis that is clinically identical to the manifestations seen in mucous membrane pemphigoid, a disorder with a common clinical phenotype and multiple autoimmune links. For the purpose of this review, we will describe pseudopemphigoid as caused by topical drugs, the most common etiology with ocular manifestations, and as caused by the pemphigus disease, a more rare etiology. Specifically, we will discuss the ophthalmological features of drug-induced cicatricial conjunctivitis, pemphigus vulgaris, and paraneoplastic pemphigus. Other etiologies of pseudopemphigoid exist that will not be described in this review including autoimmune or inflammatory conditions such as lichen planus, sarcoidosis, granulomatosis with polyangiitis (Wegener’s granulomatosis), erythema multiforme (minor, major, and Stevens-Johnson syndrome), bullous pemphigoid, skin-dominated linear IgA bullous dermatosis, and skin-dominated epidermolysis bullosa acquisita. Prompt diagnosis of the underlying etiology in pseudopemphigoid is paramount to the patient’s outcome as certain diseases are associated with a more severe clinical course, increased ocular involvement, and differential response to treatment. A complete history and ocular examination may find early cicatricial changes in the conjunctiva that are important to note and evaluate to avoid progression to more severe disease manifestations. When such cicatricial changes are noted, proper diagnostic techniques are needed to help elucidate a diagnosis. Lastly, collaboration between ophthalmologists and subspecialists such as dermatologists, pathologists, immunologists, and others involved in the care of the patient is needed to ensure optimal management of disease.

• Pseudopemphigoid
• Mucous membrane pemphigoid
• Cicatricial conjunctivitis
• Pemphigus vulgaris
• Paraneoplastic pemphigus
• Drug-induced conjunctival cicatrization