The mechanism of skin damage

Introduction

Lupus erythematosus (LE) comprises a broad spectrum of chronic inflammatory autoimmune disorders that display many diverse symptoms. Localized cutaneous LE (CLE) and severe systemic LE (SLE) represent the two ends of the spectrum of LE. The various cutaneous manifestations of LE are divided into LE-specific and LE-nonspecific skin disease based on histopathological findings. The underlying cause of lupus like lesion is unknown but it is generally believed that the pathogenesis involves a genetic predisposition triggered by environmental factors. These environmental triggers include ultraviolet radiation (UVR), infection, hormones, and exposure to drugs and chemicals. To date, a growing body of literature indicates that the activation of intrinsic and extrinsic pathways of apoptosis by UVR and externalization of autoantigens initiate skin injury in LE. UVR can stimulate the immune response through the activation and recruitment of dendritic cells (DCs), B cells and effector T cells. During this process, the type 1 interferon (IFN-1) pathway play an important role in the interaction of immune cells. Under the influence of various cytokines (e.g., interleukins and tumor necrosis factor family) and chemokines, activated immune cells migrate into different layers of the dermis and epidermis, causing lupus like lesions.

In this chapter, we will focus on the clinical aspects associated with skin damage and elucidate the recent advance in the pathogenesis of skin lesions of LE.

Clinical aspects

The various cutaneous manifestations of LE can present as LE-specific or LE-nonspecific manifestations. According to the duration of the lesions, histological localization and pattern of the infiltrate and presence of mucin, LE-specific skin manifestations can be further subdivided into acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), intermittent CLE (ICLE), et al. (for information on the manifestations of different subsets of LE, see Chapter 41 ). The diagnosis of the so-called “LE-specific manifestations” relies on the presence of an interface dermatitis in which the epidermal/dermal junction seems to be the main target. While most of the LE-nonspecific manifestations, such as Degos’ like papules, livedo racemose and atrophie blanche are considered to be signs of thrombotic vasculopathy.

Histological findings of skin lesions are essentially identical for SLE and CLE. Direct histological examination of skin biopsies shows the appearance of characteristic skin changes, which are always organ-specific and meaningful for distinguishing LE from other dermatology diseases in the differential diagnosis. The most common histologic findings are abnormal keratinocytes distribution, perivascular and periappendageal lymphocytic infiltration, smudged appearance of the dermoepidermal junction and thickened basement membrane ( Fig. 37.1 ). Direct immunofluorescence (DIF) is another common test for LE skin lesion, and it is important for distinguishing SLE from CLE. DIF can detect the deposition of immunoglobulins and complement component C3 at the dermoepidermal junction and is also known as the “ lupus band test ” ( Fig. 37.2 ). Although positive findings in nonlesional, sun-protected skin strongly support a diagnosis of SLE, it is not exclusive as similar deposits can also be found in normal or sun-damage skin. What also need to be noted is that first, some uncommon manifestations of CLE, such as LE panniculitis (LEP) and chilblain LE (CHLE), have very little literature or have been shown to be negative in DIF studies. Second, different subsets of LE may share similar histological changes and in certain cases of LE, their skin will undergo a consequent epidermal and dermal transformation throughout the entire disease process. Thus the abundant dermatopathology experience is critical for the diagnosis of skin damage.

Pathogenesis of skin damage