Psoriasis was first recognized as a disease confined to the skin and subsequently associated with a form of arthritis (“arthritic psoriasis”); it is now believed to be a chronic autoimmune disease with systemic inflammation [Ashton 2021].
The disease has been attributed to a complex interaction between immunological, genetic, cellular, and environmental factors [Dopytalska 2021]. The latter include obesity, alcohol, certain medications, biomechanical stress, and various infectious agents forming microbiota.
The skin disease was recognised in ancient times but not clearly distinguished from leprosy. In his Atlas of Skin Diseases (1841), Austrian physician and dermatologist Ferdinand Ritter von Hebra made a clear distinction between them.
In 1860, French physician and dermatologist Pierre Antoine Ernest Bazin connected psoriasis to a form of arthritis. Charles Bourdillon provided a detailed description of psoriatic arthritis in his doctoral thesis, Psoriasis Arthropathies (1888).
The characteristic red, itchy, scaly patches on the skin are due to cells in the epidermis (outer layer of the skin) multiplying at ten times their normal rate. Activated T cells (lymphocytes) accumulate in the epidermis and dermis. They have been likened to soldiers who search out and destroy the targeted invaders.
Cytokines are released from a cascade of autoimmune reactions, which drive the whole process and result in the skin being inflamed. They are small protein molecules that tell cells what to do. Their function is to regulate and mediate inflammatory and immune responses.
Cytokines may be seen as “good” when stimulating the immune system to fight a foreign pathogen or attack tumours. But they can also be seen as “bad” when their expression causes inflammatory diseases, such as rheumatoid arthritis, Crohn’s disease, and psoriasis [Ramani et al. 2015].
People with psoriasis can also develop clinical depression and “cardiometabolic syndrome” (consisting of insulin resistance, impaired glucose tolerance, blood lipid abnormalities and hypertension) [Griffiths et al. 2021].
The majority of people who develop psoriatic arthritis have a previous history of the skin disease. They share several immune-inflammatory pathways, with key roles for the cytokines Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-17 & Interleukin (IL)-23. Interleukins initially derived their name from being released by white blood cells. However, many other cell types can also release them.
The latest class of biologics, known as Janus kinase (JAK) inhibitors have a unique mode of action in that they interrupt signalling between the cytokines responsible for the inflammatory response in psoriasis. JAK inhibitors (such as tofacitinib) may be especially beneficial in the management of psoriatic arthritis.
Treatment for psoriatic disease (affecting skin and joints) now utilises genetically engineered antibodies to molecules (including cytokines), known to be important players in these conditions. They were introduced early in the 21st century.
The current medical armamentarium includes PUVA (psoralen and ultraviolet A) therapy and topical Vitamin D analogues for the skin manifestations, whereas methotrexate, cyclosporin A, apremilast, and an array of biological agents are used for controlling severe skin and joint manifestations. Their names and respective targets are listed in Table 1.
TABLE I. Biological agents in the treatment of psoriatic disease
certolizumab pegol (Cimzia)
|IL-12 & IL-23|
|abatacept (Orencia)||T-cell (CD-80 or CD-86)|
|tofacitinib (Xeljanz)||Janus kinase 1 & 3.|
NOTE: The Pharmaceutical Benefits Scheme subsides these agents for eligible adult patients with severe psoriatic arthritis being treated by a rheumatologist or an immunologist.
Early intervention with biologics may slow the process of persistent inflammation. However, it is unknown whether the early introduction of biologics might play a disease-modifying role by preventing the progression from skin involvement to the involvement of joints and other musculoskeletal tissues. But clinical trials of guselkumab, secukinmab and other drugs show sustained effectiveness out to five years [Gisondi et al. 2022].
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Armamentarium consists of the medicines, equipment, and techniques available to a medical practitioner.
Cytokines are a group of immune system proteins that affect the actions of other cells.
Lymphocytes are one of several different types of white blood cells.
Microbiota consists of a wide variety of bacteria, viruses, fungi, and other microorganisms present in a singular local environment, such as the human digestive tract. The microbiome refers to the habitat of the whole human body and includes its microorganisms, genomes, and the surrounding environmental conditions.
Tumor Necrosis Factor (TNF) is a substance in our bodies that helps fight off infections and abnormal cells, like cancer cells. It makes sure harmful things don’t spread and cause harm. Sometimes, our bodies can produce too much TNF and it can start to attack healthy cells, causing inflammation and even damage to our organs. This can lead to diseases like rheumatoid arthritis or Crohn’s disease. Drugs that block TNF can help control these diseases, but too much blocking can also weaken our ability to fight infections.
Interleukin is a type of protein made by cells in the body that helps regulate the immune system. It acts like a messenger, transmitting signals between different types of immune cells to coordinate their response to invading bacteria, viruses, or other foreign substances. In simple terms, interleukins help the immune system work properly and effectively fight off disease.
Article written by John Quintner Physician in Rheumatology and Pain Medicine (retired)
Ashton WD. The History of Psoriasis, Part II. 2021. Available at: https://www.papaa.org/learn-about-psoriasis-and-psoriatic-arthritis/common-questions/the-history-of-psoriasis/part-two-the-history-of-psoriasis/
Dopytalska K, Ciechanowicz P, Wisniewski K, et al. The role of epigenetic factors in psoriasis. Int J Mol Sci 2021;22:9294. doi: 10.3390/ijms22179294.
Gisondi P, Bellinato F, Targha G, et al. Biological disease-modifying antirheumatic drugs may mitigate the risk of psoriatic arthritis in patients with chronic plague psoriasis. Ann Rheum Dis 2022;81:68-73. doi: 10.1136/annrheumdis-2021-219961.
Griffiths EM, Armstrong AW, Guidjonsson JE, Barker JNWN. Psoriasis. Lancet 2021;397(10281):1301-1315. doi: 10.1016/s0140-6736(20)32549-6.
Ramani T, Auletta CS, Weinstock D, et al. Cytokines: the good, the bad, and the deadly. Int J Toxicol 2015;34(4):355-365. doi: 10.1177/1091581815584918.
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