1. Layers of the host defense system
The host defense system of the skin is mainly composed of the following three layers: (1) barrier of the skin, (2) innate immunity, and (3) acquired immunity . In general, these layers are aligned in this order chronologically, functionally, and phylogenetically. A disorder in a specific layer can arise from defects in the superior layer. Each layer has unique roles to protect the body against specific infectious agents and external/internal dangers. Inflammation is defined as a series of protective and regenerative responses of the body. Therefore, inflammatory skin diseases are originally a result of these protective and regenerative responses of the skin against infections and dangers. If primarily causative infections and dangers are ruled out, the dermatitis is due to hereditary or acquired disorder in a specific layer of the host defense system.
Descriptive dermatology of the morphological phenomena of skin has been developed for more than two thousand years. Despite recent and ongoing progress in immunology, innate immunity, and the skin barrier, inflammatory skin diseases have not yet been fully classified in terms of the defects in each layer of the host defense system.
In this review, we propose a new algorithm to understand the pathology of inflammatory skin diseases in terms of the specific roles of each three layer in host defense system of the skin (Box). We describe the disorder of these layers in reverse order from acquired immunity to barrier, for the better understanding (see Section 5).
A number of hereditary diseases have been identified as a genetic lack of the specific molecules that are essential in acquired immunity. Many of them are associated with a variety of cutaneous infections and inflammation. For example, X-linked agammaglobulinemia (XLA) develops furunculosis, impetigo, and atopic-like eczematous eruptions. X-linked lymphoproliferative (XLP) disease is highly accompanied by infectious mononucleosis due to Epstein–Barr virus (EBV) infection. Chronic mucocutaneous candidiasis (CMCC) is composed of heterogeneous diseases, some of which have molecular defects in the acquired immunity, such as defects in the autoimmune regulator (AIRE) gene (see Section 2.3.1) . Acquired immunodeficiency syndrome (AIDS) patients are highly susceptible to fungal and herpes virus infection, such as human herpes virus 8 (HHV8), and patients develop repetitive and severe herpes and Kaposi’s sarcoma in the skin.