Atopy of the Skin

Introduction

When atopy occurs in the skin, the medical term is atopic dermatitis or atopic eczema . In this chapter, a bird’s-eye view on major aspects of atopic dermatitis will be discussed, including the histology of inflammatory skin lesion, the skin surface abnormalities, the physiologic abnormalities of atopic dermatitis, and the altered immune milieu. The chapters that follow will expand the overview of atopic dermatitis with detailed delineation. This chapter, in fact, is the miniature representation of this entire book on clinical and basic sciences of atopic dermatitis.

Atopy of the skin under the microscope: histopathology

Historically, one of the earliest attempts by the medical community to understand the pathomechanism of disease is through a microscopic examination of disease tissue (histopathology), as it is an identification of what the disease is and what damages the disease causes at the tissue level. The basic process involves getting the disease tissue, preserving the tissue with formaldehyde (formalin), dehydrating the tissue in graded alcohol, embedding and hardening the tissue in paraffin, sectioning and placing thin sections of tissue on glass slides, rehydrating the tissue, and staining the tissue sections with routine combination stain of hematoxylin (for cell nucleus) and eosin (for cellular cytoplasm). After mounting the stained tissues with a coverslip, the tissues on slides can then be examined microscopically. Although not particularly high-tech compared to newer diagnostic methods, histopathology provides very important information regarding a particular disease, including tissues and level affected, structures and/or cells damaged, invading pathogens detected, inflammatory cells involved, cancerous cell type identified, and boundary of the cancerous tissue delineated. When needed, special stains other than hematoxylin/eosin are used to detect other components with better visualization. Giemsa stain is used to identify mast cells, periodic acid–Schiff (PAS) stain detects fungal elements, Gram stain reveals bacteria, Warthin-Starry stain labels spirochetes bacteria, and acid-fast stain identifies mycobacteria ( ). Besides these special staining techniques that utilize chemical stains, immunohistochemistry staining methods use antibody to identify certain cellular components for visualization after the sectioned tissues undergo certain antigen retrieval steps. These retrieval steps are necessary since formalin fixation disguises the antigenic epitope, and the unmasking steps are required to make these antigenic epitopes available for the antibody binding ( ). Tissues obtained for regular histopathology can also be specially preserved and processed for electron microscopic examination if indications for the more detailed examination arise ( ). We can apply molecular diagnostic methods to the tissue sections processed through the routine formalin-fixed paraffinized tissues as well ( ).

In the nonvesicular lesional skin of atopic dermatitis, one can commonly visualize a picture of inflammation with the following findings under the microscope ( Fig. 3.1 ). In the acute inflammatory lesion, the epidermis shows psoriasiform hyperplasia and intercellular edema. Epidermal and dermal white blood cell infiltrations are composed primarily of lymphocytes with occasional monocytes/macrophages, neutrophils, eosinophils, and basophils. Mast cells and Langerhans cells are present. We can also observe some vascular changes, including endothelial cell hypertrophy, rare endothelial mitosis, and large activated nuclei, suggesting a process of angiogenesis. In chronically inflamed lesion, the epidermis is visibly different from the acute lesion, with the presence of hyperkeratosis and dyskeratosis besides psoriasiform hyperplasia. Varying degrees of intercellular edema and a few lymphocytes are present. In the dermis there are a moderate number of lymphocytes and monocytes/macrophages. The number of mast cells significantly increases ( ). The thickness of the granular layer of the epidermis in atopic dermatitis lesion can be similar to that of normal individuals, unless atopic dermatitis occurs in a person who has filaggrin gene mutation with a corresponding reduction of granular cell layer ( ). More details of filaggrin mutation in atopic dermatitis are discussed in Chapter 5, Chapter 11 .

A bird's-eye view of the atopic skin surface