Psoriasis Awareness Month 2020

I remember one of the first dates with the man who is now my husband. In the process of getting to know each other, as all couples do, I causally asked why he always wore pants. It could be 110^oF outside, and he still wouldn’t wear shorts. He told me that he wore pants to hide a condition known as psoriasis. Apparently, he developed the autoimmune disease after a huge life stressor at 18 years old. It initially showed up as a small patch on his lower leg, but over time had come to occupy nearly half of one of his shins. Having never heard of the disease before, and being the curious individual that I am, I berated him with questions. Thankfully he was a good sport!

Here are some of the things I learned at the time, and other things I wish I’d known.

An estimated 125 million individuals worldwide are affected by psoriasis. As with many other autoimmune diseases (diseases where the immune system mistakenly attacks itself), it is not clear what causes the immune system to initially malfunction. However, research has shown that, in those with psoriasis, white blood cells, known as T cells, mistakenly attack skin cells, which causes the skin-cell production process to go into overdrive. In healthy individuals, skin production occurs over the course of a month, where skin cells grow deep in the skin and slowly rise to the surface where they are sloughed off. In those with psoriasis, new skin cells are produced in a matter of days. The increased rate of skin cell production doesn’t allow sufficient time for older skin cells to fall off, resulting in a buildup of cells.

Although the exact cause of psoriasis hasn’t been pinpointed, scientists do know that the immune system and genetics play a role in its development. In those with a genetic predisposition for the disease, certain environmental factors may trigger psoriasis. Common triggers include: infections, weather (cold, dry conditions), injury to the skin, stress, smoking, heavy alcohol consumption, and certain medications.

In particular, there are five different types of psoriasis all characterized by abnormal skin, as outlined below:

1. Plaque — This is the most common form of psoriasis, encompassing approximately 80% of all cases. Plaque psoriasis presents as inflamed red patches covered with a silvery, white buildup of dead skin cells (known as plaque). Diseased skin is itchy and painful and can occur anywhere on the body, but commonly affects the scalp, knees, elbow, and lower back.

2. Guttate — Guttate psoriasis is the second most common form and occurs in about 10% of people. This form of psoriasis most commonly presents in childhood or young adulthood and is characterized by small, pink, dot-like lesions. These commonly present on the torso, arms, and legs.

3. Inverse — Areas of red, shiny, and inflamed skin are hallmarks of inverse psoriasis. This form of the disease is found in body folds, such as behind the knee, under the armpits or breasts, in the groin, or in the skinfolds around the genitals. Interestingly, many people with inverse psoriasis simultaneously have another form of psoriasis elsewhere on the body.

4. Pustular — Pustular psoriasis is a rare form of the disease that generally occurs in adults. This form is characterized by white pustules or pus-filled blisters surrounded by red, inflamed skin. It is often localized to small areas of the body, and presents on the hands or feet.

5. Erythrodermic — Erythrodermic psoriasis is a severe and very rare type of psoriasis. It presents as widespread, fiery redness over large sections of the body and causes the skin to come off in sheets. This form of psoriasis occurs in about 3% of people who have psoriasis, most commonly in those with unstable plaque psoriasis.

As a result of the easily distinguishable characteristics of psoriasis, diagnosis typically occurs after a simple physical examination, although a biopsy may also be utilized to confirm disease.

Unfortunately, there is no cure for psoriasis. However, there are several classes of medications capable of alleviating psoriatic symptoms, including topical, light, and systemic therapies.

Treatment typically begins with topical treatments, which are creams and ointments that are applied directly to the affected area. These include corticosteroids, retinoids, vitamin D analogues, anthralin, salicylic acid, and calcineurin inhibitors. Light therapy is another first-line therapy in which ultraviolet or natural light is used to kill the overactive white blood cells. Finally, if the above two treatment options are unsuccessful, oral or injected (systemic) medications, such as steroids, retinoids, methotrexate, cyclosporine, or various biologics may be utilized to relieve symptoms. Although systemic medications are often efficacious, they are used with caution because they have a much greater potential for severe side effects.

Below are articles published in ASBMB journals that showcase recent psoriasis research efforts.

Small molecule reduces T cell proliferation associated with psoriasis

Nck (noncatalytic region of tyrosine kinase) is involved in T cell proliferation in response to low-affinity autoantigens. Prior research has shown that inhibition of a specific protein–protein interaction known as Nck/CD3ε can improve psoriatic symptoms in a mouse model. In this work, published in the Journal of Biological Chemistry, researchers tested a small molecule, AX-024, that was previously identified as a potential target for autoimmune diseases, such as psoriasis, due to its ability to inhibit the Nck/CD3ε interaction. However, the combination of biophysical techniques and crystal structures reported in this article suggest that AX-024 is not, in fact, involved in modulating the Nck/CD3ε interaction and likely has other T cell targets.

Quantification of eicosanoids in skin inflammation

Eicosanoids have been identified as key players in inflammatory skin diseases, such as psoriasis. Specifically, these molecules are released in areas of inflammation and are responsible for local dysregulations. In this article in the Journal of Lipid Research, the authors develop a solid-phase extraction ultra-HPLC/MS/MS method to detect eicosanoids in a rat model of skin inflammation. They propose that directly monitoring inflammatory mediators in skin lesions may provide a better understanding of the effects of skin disease treatments.

Identification of a novel peptidome

Interactions between human leukocyte antigen (HLA) class I and endoplasmic reticulum aminopeptidase 1 (ERAP1) have been reported in some forms of psoriasis. In this Molecular & Cellular Proteomics article, the authors identified and investigated a novel subpeptidome and how it is regulated by ERAP1. They used CRISPR–Cas9 technology to generate an appropriate cell line in which to test various peptides. While the focus of this paper is the pathogenic role of ERAP1 and a particular HLA for Behcet’s disease, these methods and technologies could potentially be applied to study the pathogenesis of psoriasis as well.