Psoriasis and the Immune System: More Confusing Than Teenage Slang

The immune system is one of the most complicated systems, as challenging to understand as the human brain, the economy, and teenage slang. When a complicated and interconnected system gets out of whack, terrible things can occur: autoimmune disorders, mental problems, supply chain problems, and …skibidi toilet. One particularly uncool immune condition is the skin disorder psoriasis. Psoriasis is a chronic inflammatory autoimmune disease with no cure ^[1]. It affects approximately 2-3% of Americans, although precise data on its prevalence are limited ^[1]. White Americans are at the highest risk, though there may be underreporting of cases among those with darker skin ^{[1, 2]}. Onset, much like our inability to keep up with cool lingo, us efore age 40 ^[2].

The word “psoriasis” is from the Greek word “psōra” meaning “itch,” a common symptom. Other symptoms include red, hardened, flaky, or peeling skin ^[1]. There are a few manifestations of psoriasis, but the most common variant is plaque psoriasis, with thick, shiny scales that are silvered, pink, red, or purple ^[1]. Psoriasis can be a major bummer for sufferers; it can be disabling, disfiguring, and lead to low self-esteem and depression ^{[1, 2]}. Psoriasis sufferers have increased rates of ^{[1, 3]}:

• Arthritis
• Eye problems
• Inflammatory bowel disease
• Cardiovascular and metabolic diseases, including
  • High blood pressure
  • Diabetes
  • High cholesterol
  • Stroke

Inside the body, psoriasis is a complicated immune disorder with genetic and environmental risk factors ^[4]. T helper immune cells (Th1 and Th17) become stimulated and release signaling molecules called interleukins (IL-17 and IL-23) which are then mediated by enzymes like tyrosine kinase 2 (TYK2) ^{[4, 5, 6]}. The outer layer of the skin is made primarily of keratinocytes. TYK2 and the interleukins tell the body to produce too many skin cells, which form the plaques characteristic of psoriasis ^{[4, 6]}. The end result is an immune response called inflammation and new cell growth on the skin to help fight an imagined threat. The chronic nature of psoriasis is due to keratinocytes producing molecules that activate T helper immune cells, making for a vicious cycle ^[4].

Cross-section of the skin, showing a growing psoriasis plaque. Signaling molecules include interleukins, interferons, and tumor necrosis factors. TYK2 is found inside of immune cells, T helper cells, and keratinocytes (skin cells)

Treating psoriasis is a real challenge. Obesity, smoking, stress, and infections can trigger psoriasis onset, exacerbate flare-ups, or contribute to its progression to long-lasting chronic psoriasis ^[1]. Targeting these factors may help reduce risk and severity ^[1]. Mild to moderate psoriasis can be treated using topical or light-based approaches. Topical creams, ointments, or lotions may contain corticosteroids, vitamin D, synthetic vitamin D, or medications that promote the shedding of dead skin cells called keratolytics ^{[3, 7]}. Light-based treatments, called phototherapy, are the strategic exposure of the skin to UV light, which slows the body’s production of skin cells ^{[3, 7]}. For moderate to severe psoriasis, UV light therapy may be combined with light-sensitizing medications, but long-term use comes with a risk of skin cancer. Current medical treatments for moderate to severe psoriasis are systemic, they affect the whole body. 

Biologics are complex drugs that can target specific systems in the body, including the immune system. These target the cytokines or other systems on the path of immune response and attempt to interrupt them ^[3]. Targeting the immune system directly is a tricky balancing act which can increase the chances of infections, blood disorders, and some types of cancer ^[5]. Clinical trials have found great effectiveness of biologic medication, with up to 80% success rates, though side effects must be monitored carefully ^{[3, 5]}. New medications which target the psoriasis pathway with fewer effects on the greater immune system are being developed currently and may be available in clinical trials. Now that’s rizz lit fam.

Creative Director Benton Lowey-Ball, BS, BFA

References:

[1] World Health Organization (WHO). (2016). Global report on psoriasis. https://www.who.int/publications/i/item/global-report-on-psoriasis

[2] Michalek, I. M., Loring, B., & John, S. M. (2017). A systematic review of worldwide epidemiology of psoriasis. Journal of the European Academy of Dermatology and Venereology, 31(2), 205-212. https://onlinelibrary.wiley.com/doi/abs/10.1111/jdv.13854

[3] Armstrong, A. W., & Read, C. (2020). Pathophysiology, clinical presentation, and treatment of psoriasis: a review. Jama, 323(19), 1945-1960. https://jamanetwork.com/journals/jama/article-abstract/2766169

[4] Zhou, X., Chen, Y., Cui, L., Shi, Y., & Guo, C. (2022). Advances in the pathogenesis of psoriasis: from keratinocyte perspective. Cell death & disease, 13(1), 81. https://pmc.ncbi.nlm.nih.gov/articles/PMC8786887/

[5] Fauny, M., Moulin, D., d'Amico, F., Netter, P., Petitpain, N., Arnone, D., ... & Peyrin-Biroulet, L. (2020). Paradoxical gastrointestinal effects of interleukin-17 blockers. Annals of the rheumatic diseases, 79(9), 1132-1138. https://www.sciencedirect.com/science/article/abs/pii/S0003496724012342

[6] Gorman JA, Hundhausen C, Kinsman M, et al. The TYK2-P1104A autoimmune protective variant limits coordinate signals required to generate specialized T cell subsets. Front Immunol. 2019 Jan 25;10:44. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00044/full

[7] Rendon, A., & Schäkel, K. (2019). Psoriasis pathogenesis and treatment. International journal of molecular sciences, 20(6), 1475. https://www.mdpi.com/1422-0067/20/6/1475