Psoriasis and inflammatory bowel disease: links and risks

Abstract

Psoriasis and the spectrum of inflammatory bowel diseases (IBD) are chronic, inflammatory, organotropic conditions. The epidemiologic coexistence of these diseases is corroborated by findings at the level of disease, biogeography, and intrafamilial and intrapatient coincidence. The identification of shared susceptibility loci and DNA polymorphisms has confirmed this correlation at a genetic level. The pathogenesis of both diseases implicates the innate and adaptive segments of the immune system. Increased permeability of the epidermal barrier in skin and intestine underlies the augmented interaction of allergens and pathogens with inflammatory receptors of immune cells. The immune response between psoriasis and IBD is similar and comprises phagocytic, dendritic, and natural killer cell, along with a milieu of cytokines and antimicrobial peptides that stimulate T-cells. The interplay between dendritic cells and Th17 cells appears to be the core dysregulated immune pathway in all these conditions. The distinct similarities in the pathogenesis are also reflected in the wide overlapping of their therapeutic approaches. Small-molecule pharmacologic immunomodulators have been applied, and more recently, biologic treatments that target proinflammatory interleukins have been introduced or are currently being evaluated. However, the fact that some treatments are quite selective for either skin or gut conditions also highlights their crucial pathophysiologic differences. In the present review, a comprehensive comparison of risk factors, pathogenesis links, and therapeutic strategies for psoriasis and IBD is presented. Specific emphasis is placed on the role of the immune cell species and inflammatory mediators participating in the pathogenesis of these diseases.

Keywords: Crohn’s disease; immune cells; inflammation; inflammatory bowel disease; psoriasis; ulcerative colitis.

Figure 1

The epithelial barrier in both diseases appears more permeable than normal. Notes: The increased rate of epithelial cell apoptosis in IBD and the acanthosis/parakeratosis in psoriasis are accompanied by a reduction in the structural complexity of the intercellular junctions. Thus, antigen and pathogen crossing-through is increased, resulting in binding to pattern recognition receptors (PRRs) and immune system activation. The dendritic cells are the main regulators of immune reaction, armored with a wide range of PRRs, including toll-like receptors and nod-like receptors (NLRs). Under inflammation, they produce cytokines, as IL-6 or IL-23, contributing to T helper-17 (Th17) cell formation. Macrophages have a complementary role in eliminating and displaying antigens to T-lymphocytes, besides producing cytokines to recruit other immune cells to the inflammation site. Tissue macrophages are also involved in the generation of T-regulatory cells. The IL-23/Th17 axis interaction with epithelial and synovial cells is one of the main events in the initiation and maintenance of the inflammation in both diseases. Abbreviation: IBDs, inflammatory bowel diseases.