State of the art management of oral pemphigus vulgaris

Document Type : Type A: State-of-the-Art research papers.

Authors

1 Horus University in Egypt

2 Mansoura University

Abstract

Background Pemphigus, which is one of vesiculobullous diseases that affect the oral mucosa and skin, is caused by antibody-mediated autoimmune reaction to desmogleins desmosomal transmembrane glycoproteins and leads to acantholysis.

Objective Because early diagnosis and effective treatment minimize the morbidity of pemphigus vulgaris (PV), this review highlights the recent advances and management of oral lesions of PV disease.
Results Recent therapeutic modalities include combining anti-CD20 with corticosteroids. Adjunctive therapies that have proven effective in reducing the indicated dosage of corticosteroids include rituximab intravenous immunoglobulin and cyclosporin.

Advances in Knowledge A computational bootstrapping of the clinicopathological picture of PV was conducted to provide a state-of-the-art view on the validity of following each treatment modality. Although all profiles are deficient in providing data for many items, corticosteroid therapy is the most investigated modality before and after receiving a treatment course.
 

Keywords

Full Text

1. Introduction

Pemphigus, which etymologically means blister, is potentially life-threatening autoimmune mucocutaneous diseases that erode the epithelium of the mucosa, skin, or both. IgG autoantibodies attack keratinocyte cell surfaces of intercellular junctions and cause destruction of epithelial cell-to-cell adhesion (acantholysis) [1-3]. Pemphigus affects 0.1%-5.5% of the population each year. Pemphigus vulgaris (PV) and pemphigus foliaceus occur more frequently than erythematosus pemphigus, vegetans pemphigus, IgA pemphigus, drug-induced pemphigus and paraneoplastic pemphigus. PV is the most common type of pemphigus and accounts for more than 80% of cases. PV tends to affect Ashkenazi Jews, Mediterranean and South Asian ethnic groups [4-8]. Because oral manifestations of pemphigus vulgaris appear at an early stage of the disease, their diagnostic value cannot be overemphasized. However, challenges are always observed when oral pemphigus vulgaris is concomitant with desquamative gingivitis [9-11]. This article views the contemporary understanding of PV, the effectiveness of its novel therapeutic modalities and recommendations for managing PV and its oral manifestation.

 

2. Pathophysiology

Key players of causing PV are desmoglein 3 (Dsg 3) and desmoglein 1(Dsg 1), which are part of the cadherin family of cell–cell adhesion molecules that are found in desmosomes. Dsg 1 and Dsg 3 are transmembrane adhesion molecules of desmosomes where they are specialized in facilitating epidermal keratinocyte cohesion and bind to intercellular molecules of the desmosomal plaque. In patients with PV, blisters are found superior to the basal cell layer and either erode the cutaneous membrane or oral mucosa with flaccid blisters [12-14].

Although Dsg 3 is found throughout the oral mucosa, it can be only detected in basal and immediate suprabasal layers of the epidermis. In contrast, Dsg 1 is found throughout the epidermis but more intensely detected in the superficial oral mucosa and weakly detected in the deep layers [17]. Therefore, antibodies against Dsg 3 are elevated in oral pemphigus vulgaris, but antibodies against Dsg 1 are higher in cutaneous PV [18]. Immune complex deposits (often IgGs) bind to desmosomal transmembrane proteins of keratinocytes in PV, which are two major autoantigens [19-20]. Moreover, desmoglein 4 and other non-desmoglein antigens, like the human 𝛼-9-acetylcholine receptor that regulates keratinocyte adhesion and keratinocyte annexin-like molecules binding acetylcholine (pemphaxin and catenin), may influence its etiopathogenesis [21-24]. Antigen presenting cells (APCs), via the action of their human leukocyte antigen (HLA) class II molecules, activate autoreactive T cells and B cells and pathogenic B cells and T cells and also induce antibody production [25].

 

 

 

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