1. ¹Department of Pathology, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, Illinois, USA
2. ²Department of Medicine, Division of Dermatology, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, Illinois, USA
3. ³Department of Surgery, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, Illinois, USA
4. ⁴Division of Dermatology, Evanston Northwestern Healthcare, Skokie, Illinois, USA
5. ⁵Department of Pathology, University of Chicago, Chicago, Illinois, USA

Correspondence: Dr Brian J. Nickoloff, Skin Cancer Research Program, Cardinal Bernardin Cancer Center, Building 112, Room 301, 2160 S. First Avenue, Maywood, Illinois 60153, USA. E-mail: bnickol@lumc.edu

Received 16 January 2006; Revised 20 March 2006; Accepted 21 March 2006.

Abstract

Following injury, skin establishes a balance between too little inflammation increasing risk of infection, and excessive inflammation contributing to delayed wound healing and scarring. Mounting evidence indicates both initiation and termination of inflammation involve active mechanisms. Not only does inflammation itself seem to be a paradox because inflammatory responses are both essential and potentially detrimental, but one chronic inflammatory skin disease (e.g. psoriasis) presents additional paradoxes. While plaques share several factors with wound healing, two understudied and puzzling aspects include why do not inflamed plaques more frequently transform?; and why do not plaques result in scarring? To get at these questions, we review responses involved in wound repair. Oral mucosa was probed because, like fetal skin, wound repair is characterized by its rapidity, low inflammation, and scarless resolution. Active roles for macrophages as both initiators and terminators of inflammation are highlighted. Therapeutic implications are discussed regarding psoriasis and pyoderma gangrenosum. Based on biochemical and immunohistochemical considerations linking psoriatic plaques to hard palate, a novel metaplastic model is presented. We hypothesize saliva and chronic trauma contribute to a constitutive epithelial program where keratinocyte proliferation is more intense prior to differentiation, accompanied by keratin 16 expression in hard palate, thereby resembling plaques. Rather than viewing psoriasis as a nonspecific response to inflammation, we postulate a metaplastic switch by which prepsoriatic skin is converted to a distinct adult tissue type resembling hard palate. In summary, many lessons can be learned by focusing on complex processes involved in regulation of inflammation, tissue repair, and remodeling.