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  • Immunologic/inflammatory skin diseases result from inappropriate and frequently exaggerated responses to endogenous skin constituents or external stimuli and are orchestrated by leukocytes and nonleukocytes.

  • Disease pathogenesis is often incompletely understood, but select experimental models and skin diseases have provided insight into the pathogenesis of human immunologic/inflammatory skin diseases.

  • This chapter provides examples where disease pathogenesis is reasonably well understood and describes contemporary approaches that have resulted in improved understanding and, in some instances, improved therapy.


The skin is a physical barrier that is vital for the maintenance of organismal homeostasis. It experiences, and reacts to, a constant barrage of external insults including environmental changes (heat extremes, changes in humidity, sunlight exposure, etc), allergens, toxic chemicals, and pathogenic microbes. In addition to keratinocytes, Merkel cells, melanocytes, fibroblasts, adipocytes, and vascular cells, recent studies document that skin harbors a community of resident leukocytes whose composition and activation status is tuned by commensal microbes. In aggregate, these leukocytes and nonleukocytes constitute a critically important immunologic interface between organism and other.

Immune responses involving skin are highly orchestrated. Appropriate immune responses are directed exclusively (or primarily) against external agents, they are sufficiently (but not excessively) vigorous and they are time-limited. Correspondingly, there are multiple mechanisms that promote and suppress immune and inflammatory reactions in skin. Inappropriate or dysregulated local or systemic responses against self-antigens, foreign antigens, or microbes that are associated with, or enter via, skin may result in skin diseases. Examples include allergic and inflammatory skin diseases, autoimmune diseases, and drug reactions. Selected examples of each of these disease categories will be discussed. Ultimately, detailed understanding of mechanisms that cause immunologic/inflammatory skin diseases will facilitate development of less toxic, more effective therapies.


Allergic contact dermatitis (ACD) is a common inflammatory skin condition caused by repeated exposures to haptens, typically low-molecular-weight chemicals and metals, which interact with endogenous proteins to form immunogenic (complete) antigens after entering skin. ACD can be acute or chronic, depending on the nature, dose, and frequency of allergen exposure. For example, after sensitization to urushiol (a lipid component of poison ivy sap), individuals predictably develop acute ACD after reexposure. In contrast, occupational ACD commonly results from long-term exposure to low doses of metal ions such as nickel or chromium. Topical or systemic corticosteroids are commonly prescribed for ACD, but avoiding reexposure to the relevant allergen is crucial for effective treatment. However, it is not uncommon for the offending allergen to be difficult to identify, particularly in patients with occupational ACD.

Individual susceptibility and/or familial predisposition to ACD has been observed in studies where haptens were used to sensitize human volunteers in controlled experiments. However, evidence suggesting that genetic susceptibility to ACD is important is not strong. HLA haplotype associations have been reported, but results of different studies are conflicting. Polymorphisms ...

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