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Understanding Psoriasis Pathophysiology

Medically reviewed by Ariel D. Teitel, M.D., M.B.A.
Posted on May 5, 2021

The term pathophysiology comes from three Greek words. “Pathos” means suffering. “Physis” means nature or origin, and “logos” is the study of something. Pathophysiology looks at the processes in the body that explain why a condition develops and progresses. For example, the pathophysiology of psoriasis (a chronic inflammatory skin condition) includes the autoimmune attack that leads to inflammation, as well as the skin symptoms that develop as a result.

Psoriasis affects 2 percent to 3 percent of the world’s population. Psoriasis vulgaris, also known as chronic plaque psoriasis, is the most prevalent type of psoriasis. It is known for its red, scaly plaques. There are also more rare types of psoriasis, including erythrodermic, pustular, and guttate psoriasis. These types can be distinguished based on how the plaques look and where they appear. In psoriatic arthritis, a person’s joints are also affected. However, each type of psoriasis shares similar pathophysiology.

Understanding the pathophysiology of psoriasis can help people with psoriasis better understand some of the treatment options. It may also help you talk to other people about your condition, especially your doctors. This article reviews the basics of the skin, as well as the processes that lead to inflammation and to telltale signs of psoriasis.

Understanding the Normal Function of the Skin

Because psoriasis is an inflammatory skin disorder, an understanding of the skin and its cell types can also help in understanding the pathophysiology of psoriasis.

The skin is our largest organ. It consists of three layers:

  • The epidermis is the outermost layer (also called the cutaneous layer).
  • The dermis is the middle layer.
  • The subcutis is the inner layer (also called the hypodermis or subcutaneous layer).

Psoriasis primarily involves the epidermis and the dermis.

In the epidermis, we find several cell types:

  • Keratinocytes produce keratin, a protective and structural protein of the skin. They also participate in immune reactions.
  • Melanocytes provide color to the skin.
  • Langerhans cells are involved in the immune response.

In the dermis, there are several members of the immune cell family. These immune cells include dendritic cells, macrophages, and T lymphocytes (T cells), among others. The dermal immune cells react and begin an immune response when exposed to certain factors — invading germs, chemicals, ultraviolet (UV) light, or other irritating environmental factors. The cells begin the immune attack by producing compounds called cytokines. Cytokines help activate our immune system, and they promote inflammation. One of the main cytokines produced by the immune cells in the dermis is tumor necrosis factor-alpha (TNF-alpha).

The immune cells in the dermis — along with keratinocytes in the epidermis — also repair and rebuild the skin’s outer layer if it is damaged.

Pathophysiology of Psoriasis

Psoriasis develops when the immune system in our skin spins out of control or when there is an imbalance in the production of cytokines.

In people with psoriasis, TNF-alpha contributes to a proliferation (super growth) of keratinocytes, the primary type of cell found in the epidermis. This excess growth of skin cells results in the typical red, scaly lesions characteristic of psoriatic skin.

Although it may be obvious that the outer layer of the skin is affected, the development of psoriatic plaques is not restricted to inflammation in the epidermal layer. Psoriasis’ pathophysiology also involves many inflammatory mechanisms in the dermal layer of the skin. Other proinflammatory cytokines besides TNF-alpha are produced in plaque psoriasis, including:

  • Interleukin 23, which is produced by dendritic cells and macrophages in the dermis
  • Interleukin 17, which is synthesized by some of the T cells in the dermis

In other forms of psoriasis, there might be other pathophysiology involved:

  • In nail psoriasis and psoriatic arthritis, there are increased levels of cytokines such as TNF-alpha, nuclear factor kappa beta, interleukin 6, and interleukin 8.
  • In guttate psoriasis, antigens from infection with a streptococcal virus (strep throat) cause too many T cells to grow in the skin.
  • In pustular psoriasis, there is an increased level of the cytokines interleukin 1 beta, interleukin 36 alpha, and interleukin 36 gamma.

Treatment of Psoriasis

There are two main forms of therapy for this autoimmune condition that address the pathophysiology of psoriasis.

Topical therapy is applied directly on the skin. Topical therapy includes the use of corticosteroids, but also vitamin D3 analogs (such as calcipotriol) and a combination of calcipotriol and another drug called betamethasone dipropionate. Topical therapy is recommended for people with mild to moderate psoriasis. Vitamin D3 analogs reduce symptoms by keeping the growth and development of keratinocytes in check. They also work by inhibiting the activity of dermal T cells.

Systemic therapy includes phototherapy (light therapy), acitretin (a synthetic retinoid), methotrexate, and cyclosporine. When nothing works, another systemic therapy is highly potent biologics, which are administered by injection or by intravenous infusion.

Biologics may help people for whom traditional systemic therapies cause side effects, don’t work well enough, or aren’t suitable because of existing conditions or comorbidities. Unlike other therapies, biologics specifically target inflammation by inhibiting one of the proinflammatory cytokines. Currently, biologics target TNF-alpha, and interleukins 12, 23, and 17 (the main cytokines produced in chronic plaque psoriasis).

Biologics That Target TNF-Alpha

Biologics that inhibit TNF-alpha have been available for over a decade. They are considered the first generation of biologics. They are effective for both chronic plaque psoriasis and psoriatic arthritis. Currently, five drugs inhibit TNF-alpha: etanercept, infliximab, adalimumab, certolizumab, and golimumab.

Biologics That Target Interleukins 12 and 23

The cytokine interleukin 23 consists of two parts or subunits: p40 and p19.

Ustekinumab, which acts against the p40 subunit, was the first biologic to be approved for psoriasis vulgaris after TNF-alpha inhibitors. Ustekinumab is effective for chronic plaque psoriasis and psoriatic arthritis. Ustekinumab has few side effects.

Drugs that target p19, the other subunit of interleukin 23, are guselkumab, tildrakizumab, and risankizumab.

Biologics That Target Interleukin 17

Biologics that target interleukin 17 are ixekizumab and brodalumab. Ixekizumab has also proven effective for scalp and nail psoriasis, which tend to be resistant to conventional topical therapies. Common side effects of these biologics include colds, headache, upper respiratory tract infection, and joint pain.

Knowledge of Psoriasis’ Pathophysiology Is Still Developing

Although there is no cure yet for psoriasis, this inflammatory disease can be managed with proper treatment under the supervision of your dermatologist or health care provider. Our knowledge about the processes in the body that lead to psoriasis has greatly increased over the past few years — thanks to advances in dermatology.

However, many areas still need to be investigated and understood. There is a need for more information on the origin, inflammatory signals, and cause and progression of psoriasis. This information will ultimately allow experts to create more targeted and effective therapies that can help improve quality of life, especially for those with other existing comorbidities.

Talk With Others Who Understand

MyPsoriasisTeam is the social network for people with psoriasis and their loved ones. On MyPsoriasisTeam more than 92,000 members come together to ask questions, give advice, and share their stories with others who understand life with psoriasis.

Are you living with a form of psoriasis? Share your experience in the comments below or start a conversation by posting on MyPsoriasisTeam.

Posted on May 5, 2021
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Ariel D. Teitel, M.D., M.B.A. is the clinical associate professor of medicine at the NYU Langone Medical Center in New York. Review provided by VeriMed Healthcare Network. Learn more about him here.
Paz Etcheverry, Ph.D. has an M.S. in food science and nutrition from North Carolina State University and a Ph.D. in food science and technology from Cornell University. Learn more about her here.

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