-
JCI Insight Mar 2017Despite the rising incidence of autoimmunity, therapeutic options for patients with autoimmune disease still rely on decades-old immunosuppressive strategies that risk... (Review)
Review
Despite the rising incidence of autoimmunity, therapeutic options for patients with autoimmune disease still rely on decades-old immunosuppressive strategies that risk severe and potentially fatal complications. Thus, novel therapeutic approaches for autoimmune diseases are greatly needed in order to minimize treatment-related toxicity. Such strategies would ideally target only the autoreactive immune components to preserve beneficial immunity. Here, we review how several decades of basic, translational, and clinical research on the immunology of pemphigus vulgaris (PV), an autoantibody-mediated skin disease, have enabled the development of targeted immunotherapeutic strategies. We discuss research to elucidate the pathophysiology of PV and how the knowledge afforded by these studies has led to the preclinical and clinical testing of targeted approaches to neutralize autoantibodies, to induce antigen-specific tolerance, and to specifically eliminate autoreactive B cells in PV.
Topics: Antigens; Autoantibodies; B-Lymphocytes; Humans; Immune Tolerance; Lymphocyte Depletion; Pemphigus
PubMed: 28289723
DOI: 10.1172/jci.insight.92021 -
Epidemiology and Factors Associated with Remission of Pemphigus Vulgaris and Foliaceus in Singapore.Annals of the Academy of Medicine,... Jun 2020Pemphigus is a chronic, relapsing immunobullous disease. There is limited data on the clinical course and prognostic factors of pemphigus in Asian patients.
INTRODUCTION
Pemphigus is a chronic, relapsing immunobullous disease. There is limited data on the clinical course and prognostic factors of pemphigus in Asian patients.
MATERIALS AND METHODS
We conducted a retrospective cohort study of all newly diagnosed pemphigus vulgaris (PV) and pemphigus foliaceus (PF) patients seen at the National Skin Centre from 1 January 2004 to 31 December 2009. Demographic and clinical data on comorbidities, treatment and remission were recorded. Mortality information was obtained from the National Registry of Diseases. Prognostic endpoint was overall remission at last visit.
RESULTS
Sixty- one patients (36 PV and 25 PF) were recruited. Among PV patients, higher initial prednisolone dose ( = 0.017) and the use of azathioprine ( = 0.028) were significantly associated with overall remission at last visit. However, higher desmoglein 1 antibody titres at diagnosis ( = 0.024) and the use of dapsone ( = 0.008) were negatively associated with overall remission at last visit. Among PF patients, only higher desmoglein 1 antibody titre at diagnosis ( = 0.041) was found to be associated with lower overall remission at last visit. There was no mortality during the 3-year follow-up period in both PV and PF.
CONCLUSION
Higher initial prednisolone dose and the use of azathioprine in PV desmoglein 1 antibody titre at diagnosis in PV and PF might be prognostic markers for achieving remission. Use of dapsone was associated with lower overall remission in PV, but this might be confounded because dapsone was used as an adjuvant therapy in recalcitrant cases. Owing to study methodology and limitations, further evaluation is needed for better prognostication of pemphigus.
Topics: Autoantibodies; Azathioprine; Humans; Pemphigus; Prednisolone; Retrospective Studies; Singapore
PubMed: 32712634
DOI: No ID Found -
ORL; Journal For Oto-rhino-laryngology... 2021Autoimmune bullous diseases are rare conditions characterized by blistering of the skin and mucous membranes. The 2 commonest forms are pemphigus vulgaris and bullous... (Review)
Review
BACKGROUND
Autoimmune bullous diseases are rare conditions characterized by blistering of the skin and mucous membranes. The 2 commonest forms are pemphigus vulgaris and bullous pemphigoid. The oral cavity or oropharynx may be the initial site of presentation or often the only site involved.
SUMMARY
These conditions are often misdiagnosed or overlooked leading to poorer patient outcomes. Due to the chronic nature of these conditions and the systemic effects of treatment, there is a significant associated morbidity and mortality. As such, an understanding of the fundamentals of autoimmune bullous diseases is vital to those working in otolaryngology. The mainstay of management in both conditions is topical and systemic corticosteroids. There is also a role for immunomodulating and non-steroidal anti-inflammatory drugs as adjunct or alternative therapies. Surgical intervention may be required to protect the airway. Often multimodality treatment is required involving multidisciplinary input from otolaryngologists, oral surgeons, dermatologists, and rheumatologists. This review article will highlight the aetiology, pathology, clinical features, investigations, and management of both pemphigus vulgaris and bullous pemphigoid including recent advances in management.
Topics: Autoimmune Diseases; Humans; Mouth; Pemphigoid, Bullous; Pemphigus; Pharynx
PubMed: 33902048
DOI: 10.1159/000515229 -
Acta Dermato-venereologica Nov 2019Pemphigus is an autoimmune skin disease characterized by blistering and erosions of the skin and mucous membranes. Pemphigus is rare in Northern and Western Europe but...
Pemphigus is an autoimmune skin disease characterized by blistering and erosions of the skin and mucous membranes. Pemphigus is rare in Northern and Western Europe but its incidence is higher around the Mediterranean Sea. The most common type worldwide is pemphigus vulgaris. The aim of this study was to investigate the incidence of pemphigus subtypes in Northern Finland between 1985 and 2017. A total of 46 patients diagnosed with pemphigus at the Department of Dermatology of Oulu University Hospital were found the female/male ratio was 1.7. In contrast to many other countries it was found that in Northern Finland the superficial pemphigus subtypes were the most common: erythematosus or foliaceus (65%) followed by pemphigus vulgaris (26%). Over the past 4 decades the annual incidence of pemphigus in Finland has increased from 0.76 to 2.8 cases per million persons.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Erythema; Female; Finland; Humans; Incidence; Infant; Infant, Newborn; Male; Middle Aged; Pemphigus; Sex Distribution; Time Factors; Young Adult
PubMed: 31396635
DOI: 10.2340/00015555-3280 -
Journal of Autoimmunity Dec 2008Pemphigus encompasses a group of organ specific, antibody mediated autoimmune diseases of the skin characterized by keratinocyte detachment that leads to the development... (Review)
Review
Pemphigus encompasses a group of organ specific, antibody mediated autoimmune diseases of the skin characterized by keratinocyte detachment that leads to the development of blisters and erosions, which can become life-threatening. The pathogenic autoantibodies recognize desmogleins, which are members of the desmosomal cadherin family of cell adhesion molecules. Desmoglein 3 is targeted in pemphigus vulgaris while desmoglein 1 is targeted in pemphigus foliaceus and its endemic form, Fogo Selvagem. This review will briefly define the salient features of pemphigus and the proposed steps in pathogenesis. We will then summarize the most recent advances in three important areas of investigation: (i) epidemiologic, genetic, and immunologic features of Fogo Selvagem, (ii) molecular mechanisms of injury to the epidermis, and (iii) novel therapeutic strategies targeting specific steps in disease pathogenesis. The advances in each of these three seemingly separate areas contribute to the overall understanding of the pemphigus disease model. These recent advancements also underscore the dynamic interplay between the treatment of patients in a clinical setting and basic science research and have led to an integrative understanding of disease pathogenesis and treatment, allowing pemphigus to serve as a paradigm of human autoimmunity.
Topics: Animals; Autoantibodies; Autoimmunity; B-Lymphocytes; Desmoglein 1; Desmoglein 3; Endemic Diseases; Humans; Pemphigus; Skin; T-Lymphocytes
PubMed: 18838249
DOI: 10.1016/j.jaut.2008.08.003 -
International Journal of Molecular... Nov 2017Paraneoplastic pemphigus is a rare autoimmune skin disease that is always associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the earliest... (Review)
Review
Paraneoplastic pemphigus is a rare autoimmune skin disease that is always associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the earliest manifestations shown by paraneoplastic pemphigus patients. The pathogenesis of paraneoplastic pemphigus is not yet completely understood, although some immunological aspects have been recently clarified. Because of its rarity, several diagnostic criteria have been proposed. Besides, several diagnostic procedures have been used for the diagnosis, including indirect immunofluorescence, direct immunofluorescence, and ELISA. We reviewed the most recent literature, searching on PubMed "paraneoplastic pemphigus". We included also papers in French, German, and Spanish. We found 613 papers for "paraneoplastic pemphigus". Among them, 169 were review papers. Because of its varying clinical features, paraneoplastic pemphigus still represents a challenge for clinicians. Furthermore, diagnosis and management of paraneoplastic pemphigus requires close collaboration between physicians, including dermatologist, oncologist, and otorhinolaryngologist.
Topics: Diagnosis, Differential; Humans; Immunologic Factors; Paraneoplastic Syndromes; Pemphigus
PubMed: 29186863
DOI: 10.3390/ijms18122532 -
Frontiers in Immunology 2019Paraneoplastic pemphigus (PNP) is a rare but life-threatening mucocutaneous disease mediated by paraneoplastic autoimmunity. Various neoplasms are associated with PNP.... (Review)
Review
Paraneoplastic pemphigus (PNP) is a rare but life-threatening mucocutaneous disease mediated by paraneoplastic autoimmunity. Various neoplasms are associated with PNP. Intractable stomatitis and polymorphous cutaneous eruptions, including blisters and lichenoid dermatitis, are characteristic clinical features caused by humoral and cell-mediated autoimmune reactions. Autoreactive T cells and IgG autoantibodies against heterogeneous antigens, including plakin family proteins and desmosomal cadherins, contribute to the pathogenesis of PNP. Several mechanisms of autoimmunity may be at play in this disease on the type of neoplasm present. Diagnosis can be made based on clinical and histopathological features, the presence of anti-plakin autoantibodies, and underlying neoplasms. Immunosuppressive agents and biologics including rituximab have been used for the treatment of PNP; however, the prognosis is poor due to underlying malignancies, severe infections during immunosuppressive treatment, and bronchiolitis obliterans mediated by autoimmunity. In this review, we overview the characteristics of PNP and focus on the immunopathology and the potential pathomechanisms of this disease.
Topics: Animals; Autoantibodies; Autoantigens; Autoimmunity; Biopsy; Disease Management; Disease Susceptibility; Humans; Mucous Membrane; Paraneoplastic Syndromes; Pemphigus; Prognosis; Skin; Symptom Assessment
PubMed: 31214197
DOI: 10.3389/fimmu.2019.01259 -
Italian Journal of Dermatology and... Apr 2021Originally described by Anhalt as paraneoplastic pemphigus in 1990, paraneoplastic autoimmune multiorgan syndrome (PAMS) is a potentially lethal blistering disease,...
Originally described by Anhalt as paraneoplastic pemphigus in 1990, paraneoplastic autoimmune multiorgan syndrome (PAMS) is a potentially lethal blistering disease, characterized by polymorphous clinical features, including mucocutaneous erosions, blisters, lichenoid papules, and erythemas. Several autoantibodies have been detected in serum of PAMS patients, including antiplakins, anti-alpha-2-macroglobulin like 1, and antidesmogleins autoantibodies. The mortality rate of PAMS is up to 90%. This is due on the one hand to the poor response to treatments and on the other hand to the delay in the diagnosis and to the prognosis of the underlying neoplasia.
Topics: Autoantibodies; Autoimmune Diseases; Humans; Neoplasms; Paraneoplastic Syndromes; Pemphigus
PubMed: 33070576
DOI: 10.23736/S2784-8671.20.06675-4 -
Dermatologic Clinics Jul 2011Pemphigus refers to a group of human autoimmune blistering diseases involving skin and/or mucous membranes. Endemic pemphigus foliaceus (EPF), or fogo selvagem is an... (Review)
Review
Pemphigus refers to a group of human autoimmune blistering diseases involving skin and/or mucous membranes. Endemic pemphigus foliaceus (EPF), or fogo selvagem is an organ-specific autoimmune blistering disease, first reported in the beginning of the 20th century in rural areas of Brazil. The disease follows the course of streams and creeks, and vanishes after urbanization of the endemic areas. The auto-antigen related to EPF is desmoglein 1, a 160 kDa glycoprotein of the desmossomal core, targeted by in situ and circulating IgG autoantibodies, mainly of the IgG4 subclass.
Topics: Endemic Diseases; Humans; Pemphigus; Skin
PubMed: 21605806
DOI: 10.1016/j.det.2011.03.014 -
Cytokine Jun 2015The immunomodulatory cytokine interleukin-10 (IL-10) plays beneficial but also potentially detrimental roles in inflammation, infection, and autoimmunity. Recent studies... (Review)
Review
The immunomodulatory cytokine interleukin-10 (IL-10) plays beneficial but also potentially detrimental roles in inflammation, infection, and autoimmunity. Recent studies suggest a regulatory role for IL-10-expressing B cells in the autoimmune blistering disease pemphigus vulgaris. Here we review the studies on IL-10 in pemphigus vulgaris and discuss the potential pathophysiological significance of these findings in comparison to prior studies of IL-10 in other human conditions. A better understanding of the complex roles of IL-10 in immune regulation may improve our understanding of pemphigus pathogenesis and treatment.
Topics: Animals; Homeostasis; Humans; Immunity; Interleukin-10; Models, Biological; Pemphigus
PubMed: 25464924
DOI: 10.1016/j.cyto.2014.11.002