Pathogenesis of cutaneous lupus

Cutaneous lupus erythematosus (CLE) is a potentially disfiguring autoimmune disease that can manifest only in the skin or can be present as part of a diverse range of potentially life-threatening and debilitating symptoms in patients with lupus erythematosus (LE). Although disease symptoms similar to LE were first documented by Hippocrates in the year 400 BC, physicians are still challenged regarding the classification and diagnosis of cutaneous lupus today, largely because of the inherent overlap and high heterogeneity of displayed features. The clinical expression of LE is predisposed by underlying genetics working together with environmental factors to elicit an abnormal immune response that skews the patient into a loss of immunologic self-tolerance. Overall, it is becoming increasingly clear that the skin is significant in LE in terms of clinical presentation and consequent disability as well as of critical importance for disease induction. To enable an understanding of the importance of potential trigger mechanisms of CLE in the overall management of the disease, this chapter describes ultraviolet (UV) light, medications, and smoking as three of the well-established initiators of the disease. We further revise our current understanding of pathomechanisms such as cell death, inflammation, and immunomodulation that serve as central drivers of the disease and bridge the gap between innate and adaptive immune systems. The important roles of humoral and cellular factors as well as participation of soluble cytokines and chemokines in disease initiation, amplification, and target tissue damage as orchestrated events in the autoimmune reaction are considered based on what is known regarding systemic lupus erythematosus (SLE).