Abstract

Background: Claudin-4 is a key component of tight junctions, which play an important role in the formation of the epidermal barrier, forming a circumferential network in the granular layer, serve as a gatekeeper of the paracellular pathway. The aim of this study is to illustrate claudin-4 immunohistochemical staining patterns of different acantholytic disorders (AD). Methods: We collected 22 AD cases, including 2 Hailey-Hailey, 1 Darier, 1 Grover, 5 acantholytic dermatoses, 11 pemphigus vulgaris (PV) including 6 mucosal PV, and 2 pemphigus diseases. For comparison, we included 5 cases of normal skin, 5 eczema, and 3 bullous pemphigoid. Results: Claudin-4 demonstrated weak-to-moderate expression in the stratum granulosum keratinocytes, surrounding hair follicles, and adnexal glands in all cases, confirming that claudin-4 is present in these tissues. Furthermore, claudin-4 exhibited moderate-to-strong membranous staining in disrupted keratinocytes of the acantholytic and bullous areas in 16/22 of the acantholytic cases (not seen in the six case of mucosal PV) and all 3 bullous pemphigoid cases. Conclusions:  This suggests that claudin-4 is upregulated in these conditions, which may be a compensatory response to the disrupted barrier function. This finding could shed light on the molecular mechanisms underlying disrupted barrier function in bullous disorders, independent of underlying disease mechanism.