ARRA IMPACT REPORT:
Public Health Burden
Psoriasis is a chronic autoimmune disease with variable clinical features and triggers.
It is characterized by thick patches of inflamed, scaly, itchy skin, created by
abnormal, rapid, and excessive growth of keratinocytes, the cells that form the outermost
layer of skin (epidermis). Psoriasis is estimated to affect approximately 2.3
percent of the U.S population, with a higher incidence in Caucasians. Ten to 30
percent of psoriasis patients may subsequently develop psoriatic arthritis, a
potentially debilitating joint condition.
Understanding Disease Risk and Development
Family studies indicate a genetic basis for psoriasis and psoriatic arthritis; more than 19 susceptibility loci (gene regions) associated with these diseases have been identified by genome-wide scanning studies. The identification of additional disease susceptibility loci, and the study of microRNA—very short RNA molecules that regulate gene expression—in psoriasis patients are in progress. Researchers are using new technologies, computational systems, and experimental approaches, including the analysis of epigenetics—chemical modifications to the genome that play
a role in development, aging, health, and disease—to gain insights into the causes of these diseases that may guide the development of new treatments. Examples of ARRA-funded projects include the following:
- A nationwide consortium of psoriasis researchers, funded in part by NIAMS, has identified and confirmed the association of psoriasis cases with variants in the gene encoding a protein involved in immune regulation. These mutations were shown to increase the activation of a molecular pathway that leads to inflammation in psoriatic skin lesions, providing evidence for a causal link between the gene variants, enhanced inflammation, and psoriasis.1
- Recent research has revealed variations in microRNA expression in psoriatic skin lesions. Among the 1,001 microRNAs identified in a large cohort of psoriasis patients, 98 microRNAs, which are associated with inflammation and keratinocyte proliferation, were abnormally regulated. In addition, investigators found extensive epigenetic differences between diseased and healthy skin that correlate with reduced expression of nearby genes in psoriasis. This is the first comprehensive epigenetic study of an inflammatory skin disease.2
Developing evidence-based strategies for the control of psoriasis: A wide range of effective drugs for psoriasis has become available in recent years. However, some patients are not responsive to them, and there are reports of associated toxic side effects. In addition to these issues, dissatisfaction with treatment, underutilization of systemic therapies (a treatment that affects the whole body), and the inability to follow disease management recommendations have triggered extensive comparative effectiveness studies (direct comparisons of treatments to each other) in ways to treat psoriasis.
In one such ARRA-funded project, investigators at several institutions have established the first U.S.-based network to conduct studies on treatments for moderate-to-severe psoriasis in clinical practice. The Dermatology Clinical Effectiveness Research Network (DCERN) is collecting data on more than 1,000 people with psoriasis in Philadelphia, St. Louis, and Salt Lake City. DCERN is contributing to improvements in disease management decisions and patient care. Results from these studies include: comparable outcomes with the use of phototherapy or systemic drugs for moderate-to-severe psoriasis; the low risk of serious infections from an effective group of biologic therapies (treatments that use the immune system) for the disease; and improved understanding of why patients stop treatment.3 Overall, these studies add to the development of evidence-based strategies for the control of psoriasis.
Contributing NIH Institutes & Centers
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)