Desmosomal dissolution in Grover's disease, Hailey‐Hailey's disease and Darier's disease

Abstract

Proteins involved in the formation of desmosomes and simpler adherens junctions were studied in three types of non-immune acantholytic diseases; specifically, four cases of Grover's disease (GD), one case of Hailey-Hailey's disease (HHD) and one case of Darier's disease (DD), and these were compared to two cases of immune-mediated acantholytic disease pemphigus vulgaris (PV). The proteins studied included: 1. The intracellular desmosomal proteins, desmoplakin I and II and plakoglobin; 2. The intercellular desmosomal proteins, desmoglein and CD44; and 3. vinculin, which is a major intracellular protein of the simpler aherens junctions. In GD, HHD and DD, immunostaining showed a loss of desmoplakin I and II and plakoglobin from the desmosomes, and a diffuse staining in the cytoplasm. In contrast, in pemphigus vulgaris, these proteins seemed intact and were localized to dot-like spots on the cell surface. Also, desmoglein, and CD44 were slightly affected in GD, and moderately affected in HHD and DD. Absence of desmosomal attachment plaques, the lack of labeling with desmoglein in the affected desmosomes and a diffusion of the labels into cytoplasm were demonstrated with electron microscopy using an immunogold technique. In PV, desmoglein III is one of the target antigens for the autoantibodies in this disease and was only partially preserved in a small number of lesional cells, while CD44 was mostly preserved. Vinculin was intact in GD, HHD and DD, but was lost in PV. This study, our previous work, and that of others, suggest that: 1. In GD, HHD and DD, the proteins of the desmosomal attachment plaque are primarily affected; 2. In PV, the intercellular glycoproteins are primarily involved; and 3. Simple adherens junctions are intact in GD, HHD and DD, but are damaged in PV.

Grover’s Disease Following Multiple Bilateral Blaschko Lines: A Rare Clinical Presentation with Genetic and Electron Microscopic Analyses

“…Although our present study is consistent with these observations, desmosomes were rather increased in number, which may indicate compensation of defective desmosomal function. Grover’s disease and Darier’s disease may share similar electron microscopic findings [17], but we were not able to find half-split desmosomes that were documented in Darier’s disease [21] as well as in pemphigus vulgaris and pemphigus foliaceus [22]. …”

“…The pathogenesis of Grover’s disease is presently unknown, and only a few studies have addressed desmosomal dissolution [17]. Electron microscopic observations previously indicated that the damage to the tonofibrils seemed to start proximal to their insertion into the desmosomes [18,19].…”

Eight Novel Mutations of <i>ATP2C1</i> Identified in 17 Chinese Families with Hailey-Hailey Disease

“…The patients were diagnosed by using the criteria described elsewhere [18, 19]. The disease is characterized by typical vesicular lesions, painful erosions and erythematous plaques occurring at sites of friction (neck, axillae, groin and perineum).…”

A Case of Acral Darier’s Disease

“…This gene encodes a sarco/endoplasmic reticulum CA 2+ -ATPase type 2 isoform pump [9, 10]. Alterations of the Ca 2+ pump may cause impaired desmosome assembly or altered anchorage of cyclokeratin filaments to the desmosomal plaques [10]explaining the dissolution of desmosome attachment plaque proteins and the breakdown of desmosome keratin filament complexes between keratinocytes [11, 12]. The most effective systemic therapy for managing the disease currently seems to be oral aromatic retinoids [13, 14].…”