The Complicated Pathogenesis of Psoriasis

Psoriasis is an autoimmune disease that affects 7.5 million people in the United States and roughly 100 million worldwide. While its main manifestation is in unsightly, often irritating skin lesions, many patients also experience painful psoriatic arthritis. Additionally, psoriasis often comes with a wide range of other chronic conditions, including Type 2 diabetes, cardiovascular disease and depression.

What Causes Psoriasis?

Psoriasis is a heterogenous condition characterized by the excessive growth and aberrant differentiation of keratinocytes, which are the cells that make up a majority of the outer layer of skin. It involves a complex pathogenesis attributed to multiple factors, including genetic, immunological and environmental influences. At its core, psoriasis is caused by the dysregulated interactions of the innate and adaptive immune system within skin epithelium and connective tissue.

What Are the Genetics Behind Psoriasis?

Psoriasis involves at least nine different genes, with 50 genetic loci having been identified in association with psoriasis risk thus far. Many of its associated single nucleotide polymorphisms (SNPs) are also linked to other autoimmune disorders, such as inflammatory bowel disease and ankylosing spondylitis. These genes include those that code for and regulate the proteins that are involved in nuclear factor kappa B (NF-ƙB) signaling, the interleukin (IL)-23/IL-17 axis, innate immune signaling and the type I interferon pathway. Additionally, gene variants in IL-23 receptor (IL-23R) may have a protective effect against psoriasis.

What Role Do T Helper Cells Play in Psoriasis?

It appears that psoriasis develops through activation and proliferation of T helper cells, specifically Th-17 cells. Activation of these cells in turn triggers keratinocytes to produce the clinical hallmarks of psoriasis within the skin:

  • Erythema
  • Scaling
  • Induration

Environmental triggers known to precipitate onset of and exacerbate psoriasis include emotional stress, injury to the skin, infection (especially streptococcal), and certain drugs, including lithium, beta blockers, antimalarials, nonsteroidal anti-inflammatory drugs and tetracycline antibiotics.

What Treatment Options Are Available for Psoriasis?

The newest and most effective psoriasis treatments are those that target the immune component of psoriasis. Further research into their action may provide insight for managing other autoimmune disorders. To find out about specific developments in psoriasis therapies, be sure to review our dermatology webinar.