Authors: P Joly, B Horvath, Α Patsatsi...

BACKGROUND

Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, pemphigus was almost always fatal. Due to its rarity, only few randomized controlled therapeutic trials are available. Recently, rituximab has been approved as first-line treatment for moderate and severe pemphigus vulgaris in Europe and the United States.

OBJECTIVES

The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology (EADV) has initiated a throughout update of the guideline for the management of patients with pemphigus.

RESULTS

The guidelines for the management of pemphigus were updated, and the degree of consent among all task force members was included. The final version of the guideline was consented by the European Dermatology Forum (EDF) and several patient organizations.

Topics: Academies and Institutes; Dermatology; Europe; Guidelines as Topic; Humans; Pemphigus; Venereology

PubMed: 32830877
DOI: 10.1111/jdv.16752

Review

Authors: Ali M Malik, Sarah Tupchong, Simo Huang...

Clinicians may encounter a variety of skin conditions that present with vesiculobullous lesions in their everyday practice. Pemphigus vulgaris, pemphigus foliaceus, IgA pemphigus, and paraneoplastic pemphigus represent the spectrum of autoimmune bullous dermatoses of the pemphigus family. The pemphigus family of diseases is characterized by significant morbidity and mortality. Considering the risks associated with a delayed diagnosis or misdiagnosis and the potential for overlap in clinical features and treatment, evaluation for suspected pemphigus disease often requires thorough clinical assessment and laboratory testing. Diagnosis is focused on individual biopsies for histopathology and direct immunofluorescence. Additional laboratory methods used for diagnosis include indirect immunofluorescence and enzyme-linked immunosorbent assay. Recent advancements, including anti-CD20 therapy, have improved the efficacy and reduced the morbidity of pemphigus treatment. This contribution presents updates on the pathophysiology, clinical features, diagnostic work-up, and medical management of pemphigus. Improved strategies for diagnosis and clinical assessment are reviewed, and newer treatment options are discussed.

Topics: Autoimmune Diseases; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Indirect; Humans; Pemphigus; Skin Diseases, Vesiculobullous

PubMed: 34684117
DOI: 10.3390/medicina57101080

Review

Authors: Michael Kasperkiewicz, Christoph T Ellebrecht, Hayato Takahashi...

Pemphigus is a group of IgG-mediated autoimmune diseases of stratified squamous epithelia, such as the skin and oral mucosa, in which acantholysis (the loss of cell adhesion) causes blisters and erosions. Pemphigus has three major subtypes: pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus. IgG autoantibodies are characteristically raised against desmoglein 1 and desmoglein 3, which are cell-cell adhesion molecules found in desmosomes. The sites of blister formation can be physiologically explained by the anti-desmoglein autoantibody profile and tissue-specific expression pattern of desmoglein isoforms. The pathophysiological roles of T cells and B cells have been characterized in mouse models of pemphigus and patients, revealing insights into the mechanisms of autoimmunity. Diagnosis is based on clinical manifestations and confirmed with histological and immunochemical testing. The current first-line treatment is systemic corticosteroids and adjuvant therapies, including immunosuppressive agents, intravenous immunoglobulin and plasmapheresis. Rituximab, a monoclonal antibody against CD20 B cells, is a promising therapeutic option that may soon become first-line therapy. Pemphigus is one of the best-characterized human autoimmune diseases and provides an ideal paradigm for both basic and clinical research, especially towards the development of antigen-specific immune suppression treatments for autoimmune diseases.

Topics: Adrenal Cortex Hormones; Animals; Autoantibodies; Desmoglein 1; Desmoglein 3; Disease Models, Animal; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Mice; Pemphigus; Plasmapheresis; Treatment Outcome

PubMed: 28492232
DOI: 10.1038/nrdp.2017.26

Review

Authors: Christoph M Hammers, John R Stanley

Pemphigus and bullous pemphigoid are autoantibody-mediated blistering skin diseases. In pemphigus, keratinocytes in epidermis and mucous membranes lose cell-cell adhesion, and in pemphigoid, the basal keratinocytes lose adhesion to the basement membrane. Pemphigus lesions are mediated directly by the autoantibodies, whereas the autoantibodies in pemphigoid fix complement and mediate inflammation. In both diseases, the autoantigens have been cloned and characterized; pemphigus antigens are desmogleins (cell adhesion molecules in desmosomes), and pemphigoid antigens are found in hemidesmosomes (which mediate adhesion to the basement membrane). This knowledge has enabled diagnostic testing for these diseases by enzyme-linked immunosorbent assays and dissection of various pathophysiological mechanisms, including direct inhibition of cell adhesion, antibody-induced internalization of antigen, and cell signaling. Understanding these mechanisms of disease has led to rational targeted therapeutic strategies.

Topics: Animals; Humans; Pemphigoid, Bullous; Pemphigus

PubMed: 26907530
DOI: 10.1146/annurev-pathol-012615-044313

Authors: Adriana Maria Porro, Camila Arai Seque, Maria Carolina Corsi Ferreira...

Pemphigus vulgaris is a chronic autoimmune bullous dermatosis that results from the production of autoantibodies against desmogleins 1 and 3. It is the most frequent and most severe form of pemphigus, occurring universally, usually between 40 and 60 years of age. It usually begins with blisters and erosions on the oral mucosa, followed by lesions on other mucous membranes and flaccid blisters on the skin, which can be disseminated. There is a clinical variant, pemphigus vegetans, which is characterized by the presence of vegetating lesions in the large folds of the skin. Clinical suspicion can be confirmed by cytological examination, histopathological examination, and direct and indirect immunofluorescence tests. The treatment is performed with systemic corticosteroids, and immunosuppressive drugs may be associated, among them azathioprine and mycophenolate mofetil. More severe cases may benefit from corticosteroids in the form of intravenous pulse therapy, and recent studies have shown a beneficial effect of rituximab, an anti-CD20 immunobiological drug. It is a chronic disease with mortality around 10%, and septicemia is the main cause of death. Patients need long-term and multidisciplinary follow-up.

Topics: Adult; Autoantibodies; Desmosomes; Diagnosis, Differential; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Immunotherapy; Male; Middle Aged; Pemphigus; Skin; Surveys and Questionnaires

PubMed: 31365654
DOI: 10.1590/abd1806-4841.20199011

Authors: Dedee F Murrell, Sandra Peña, Pascal Joly...

BACKGROUND

Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management.

OBJECTIVE

We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations.

METHODS

A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus.

RESULTS

The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion.

LIMITATIONS

Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available.

CONCLUSIONS

We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.

Topics: Academies and Institutes; Administration, Intravenous; Antigens, CD20; Combined Modality Therapy; Consensus; Delphi Technique; Dermatology; Drug Therapy, Combination; Europe; Glucocorticoids; Humans; Immunologic Factors; Pemphigus; Plasmapheresis; Practice Guidelines as Topic; Rituximab; Severity of Illness Index

PubMed: 29438767
DOI: 10.1016/j.jaad.2018.02.021

Review

Authors: Pedro Mendes-Bastos, Ana Brasileiro, Pavel Kolkhir...

Bruton's tyrosine kinase (BTK), a member of the Tec kinase family, is critically involved in a range of immunological pathways. The clinical application of BTK inhibitors for B-cell malignancies has proven successful, and there is strong rationale for the potential benefits of BTK inhibitors in some autoimmune and allergic conditions, including immune-mediated dermatological diseases. However, the established risk-to-benefit profile of "first-generation" BTK inhibitors cannot be extrapolated to these emerging, non-oncological, indications. "Next-generation" BTK inhibitors such as remibrutinib and fenebrutinib entered clinical development for chronic spontaneous urticaria (CSU); rilzabrutinib and tirabrutinib are being studied as potential treatments for pemphigus. Promising data from early-phase clinical trials in CSU suggest potential for these agents to achieve strong pathway inhibition, which may translate into measurable clinical benefits, as well as other effects such as the disruption of autoantibody production. BTK inhibitors may help to overcome some of the shortcomings of monoclonal antibody treatments for immune-mediated dermatological conditions such as CSU, pemphigus, and systemic lupus erythematosus. In addition, the use of BTK inhibitors may improve understanding of the pathophysiological roles of mast cells, basophils, and B cells in such conditions.

Topics: Agammaglobulinaemia Tyrosine Kinase; B-Lymphocytes; Humans; Pemphigus; Protein Kinase Inhibitors

PubMed: 35175630
DOI: 10.1111/all.15261

Review

Authors: Massimo Petruzzi, Fedora Della Vella, Nicola Squicciarini...

Autoimmune diseases (ADs) affect about 5% of the general population, causing various systemic and/or topical clinical manifestations. The oral mucosa is often affected, sometimes as the only involved site. The misdiagnosis of oral ADs is an underreported issue. This narrative review focuses on diagnostic delay (DD) in oral ADs (oral lichen planus [OLP], oral Pemphigus Vulgaris, mucous membrane pemphigoid, oral lupus erythematosus, orofacial granulomatosis, oral erythema multiforme [EM], and Sjogren syndrome). Extensive literature research was conducted via MEDLINE, Embase and Google Scholar databases for articles reporting the time spent to achieve the correct diagnosis of oral ADs. Only 16 studies reported DD in oral ADs. Oral autoimmune vesiculobullous diseases are usually diagnosed after 8 months from the initial signs/symptoms, the Sjogren Syndrome diagnosis usually requires about 73 months. No data exist about the DD in OLP, oral lupus erythematosus, orofacial granulomatosis, and oral EM. The diagnosis of oral ADs can be difficult due to the non-specificity of their manifestations and the unawareness of dentists, physicians, and dental and medical specialists about these diseases. This can lead to a professional DD and a consequential treatment delay. The delay can be attributed to the physicians or/and the healthcare system (Professional Delay) or the patient (Patient's Delay).

Topics: Humans; Delayed Diagnosis; Sjogren's Syndrome; Granulomatosis, Orofacial; Autoimmune Diseases; Mouth Diseases; Pemphigus; Lupus Erythematosus, Systemic; Lichen Planus, Oral

PubMed: 36565434
DOI: 10.1111/odi.14480

Review

Authors: Frank A Santoro, Eric T Stoopler, Victoria P Werth...

Pemphigus vulgaris and paraneoplastic pemphigus are 2 subtypes of pemphigus that involve the oral mucosa. These autoimmune blistering disorders have antibodies targeted against proteins of keratinocyte adhesion, thereby causing acantholysis. Clinical findings include oral erosions and flaccid cutaneous bullae and erosions. Further malignancy workup in patients with suspected paraneoplastic pemphigus is warranted. Retrospective uncontrolled studies suggest that immunosuppressive agents reduce mortality in pemphigus vulgaris and cohort uncontrolled studies of rituximab, a monoclonal antibody against CD20, suggest it is an effective treatment for refractory patients. Ongoing studies will define its role in early disease.

Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal; Diagnosis, Differential; Humans; Mouth Mucosa; Mouth Neoplasms; Pemphigus; Severity of Illness Index

PubMed: 24034068
DOI: 10.1016/j.cden.2013.06.002

Review

Authors: Jeanette Kaae, Rikke Bech, Elisabeth Hjardem Taudorf...

This review finds that topical corticosteroids and systemic corticosteroids are the mainstays of initial treatment for bullous pemphigoid and pemphigus diseases. Additional immunomodulatory therapies such as methotrexate, azathioprine and mycophenolatmofetil should be added early during treatment to minimize the adverse effects of chronic corticosteroid therapy and to augment improvement in the disease. Rituximab is a first-line immunomodulatory treatment for moderate to severe pemphigus disease.

Topics: Autoimmune Diseases; Azathioprine; Glucocorticoids; Humans; Methotrexate; Pemphigus; Rituximab; Skin Diseases, Vesiculobullous

PubMed: 36254827
DOI: No ID Found