Psoriatic arthritis (PsA) is a type of inflammatory arthritis in which the immune system starts to target the body’s own joints. It is most commonly associated with psoriasis, which is a chronic autoimmune skin condition that causes increased growth and build-up of skin cells. It is estimated that around 10% of people with psoriasis develop PsA. It can develop before, during, or after the appearance of psoriasis. In most people, psoriasis appears several years before PsA. A small number of people with PsA do not have signs of psoriasis.

Symptoms

The symptoms of PsA will be different for everyone. The condition can affect different joints and tissues, although the joints of the fingers and toes are most commonly affected.

Common symptoms include:

  • Joint pain, swelling and stiffness:
    • Especially in the fingers and toes;
    • Painful swelling of fingers or toes is known as dactylitis or “sausage digits”.
  • Finger or toe nail changes:
    • Such as pitting, brittleness, thickening, colour change, separation from the skin;
    • Approximately 80% of people with PsA have nail symptoms.
  • Lower back pain and stiffness:
    • In some cases, the joints of the spine can become inflamed – this is known as spondylitis.
  • Pain where the tendons or ligaments attach to the bone:
    • Known as enthesitis;
    • Especially in the back of the heel or sole of the foot.
  • Psoriasis plaques:
    • Bumpy patches of red, flaky, scaly skin.
  • Eye redness and soreness.

For many people, the condition occurs in flares and can go into remission.

Psoriatic Arthritis

Diagnosis

Diagnosis relies mainly on symptom presentation and physical examination of the joints. If psoriasis is present, the severity and presence of certain symptoms may provide some indication of PsA. Because not everyone with PsA will have signs of psoriasis, it can be difficult to distinguish PsA from rheumatoid arthritis (RA), another inflammatory arthritis involving the immune system that affects the joints (you can read more about RA here). Rheumatologists are specialists in diagnosing and treating arthritic conditions such as PsA and RA.

There are no specific diagnostic tests for PsA, although the following may help:

  • Blood test results, such as an elevated erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP), which indicate increased inflammatory activity;
  • Medical imaging (i.e. X-ray, MRI, CT scan) to assess joint and bone abnormalities or erosion.

What Causes PsA?

We do not know exactly what causes PsA. We do know that it is a multifactorial autoimmune condition – multifactorial means that it involves many factors (i.e. genetic and environmental factors) that interact with each other, and autoimmune means that it involves an abnormal immune response in which the immune system targets healthy tissues, especially the joints. Why the immune system targets the body’s own tissue is not well understood.

Genetic Factors

Research has identified several genes that may increase the risk of developing PsA and/or contribute to the progression and severity of the condition.

The most strongly associated genetic factor is a Human Leukocyte Antigen (HLA) variant known as HLA-B27. There are many different HLA variants. Not everyone has the same HLA genes. You will inherit half from each parent. The HLA genes code for molecules that play important roles in regulating the immune response. HLA type A, B, and C genes code for molecules found on the surface of most cells. They act as markers that help your immune cells tell the difference between your body’s own tissues and foreign objects (e.g. viruses, bacteria, blood received via transfusion). People with the HLA-B27 variant have an increased risk of developing PsA. However, not everyone with PsA is HLA-B27 positive, and not everyone who is HLA-B27 positive will develop PsA. Other HLA variants have been linked to other autoimmune conditions.

Inflammatory Factors

Interleukins (ILs) are a family of proteins (known as cytokines and chemokines) with roles in regulating the immune / inflammation response. Some are pro-inflammatory and others are anti-inflammatory. They are produced by immune cells and may stimulate or inhibit other immune cells. Interleukins that are associated with PsA include IL-12B, IL-13, IL-17 and IL-23.

Image of cytokines being released from immune cells by www.scientificanimations.com / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0)

[Image of cytokines being released from immune cells by www.scientificanimations.com / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0)]

Clinical & Environmental Factors

The following factors may also increase the risk, progression or severity of PsA:

  • Having severe psoriasis, presence of plaques, nail psoriasis;
  • Infection (viral or bacterial);
  • Obesity;
  • Injury or trauma to a joint;
  • Smoking;
  • Stress.

Current Treatment Options

Unfortunately, there is no cure for PsA. Effective, early treatment may reduce damage to the joints and hopefully send the condition into remission.

Pharmaceuticals

The following conventional medications are used to treat the symptoms or PsA:

  • Non-steroidal anti-inflammatory drugs (NSAIDs) may help to relieve joint pain, swelling and stiffness associated with inflammation (e.g. ibuprofen, naproxen, celecoxib).
  • Medicated creams or ointments containing corticosteroids (e.g. cortisone) help to reduce inflammation. Creams or ointments containing calcipotriol (a vitamin D3 derivative) are used to treat psoriasis symptoms.

Disease-modifying antirheumatic drugs (DMARDs)

DMARDs are drugs that aim to treat the underlying condition, not just the symptoms. They suppress the immune system in order to stop ongoing damaging inflammation. They are effective at slowing the progression of inflammatory arthritis conditions, therefore reducing damage to joints. Because they are immunosuppressants, there is a risk of severe side effects and they are not suitable for everyone. DMARDs are used to treat active, severe PsA that has not responded to conventional treatments.

DMARDs that are approved for the treatment of PsA in Australia include:

  • Methotrexate – an immunosuppressive drug that was originally developed to treat cancer, but that is also used to treat various arthritic conditions. It may reduce, delay or stop damage to the joints. The way it treats arthritis is different to how it treats cancer. It is thought that methotrexate works by causing an increase in adenosine levels, a molecule that can signal various anti-inflammatory effects within the joints.
  • Tumour necrosis factor (TNF) inhibitors – (e.g. etanercept, infliximab, golimumab, adalimumab, certolizumab) are biological DMARDs that block TNF/TNF-alpha, an inflammatory cell signalling protein (cytokine) that is increased in various arthritis conditions. TNF inhibitors may be able to stop joint damage and erosion.
  • Interleukin 17A inhibitors – (e.g. secukinumab, ixekizumab) biological DMARDs that inhibit the pro-inflammatory IL-17A cytokine. They have shown to be effective in treating arthritis, enthesitis and dactylitis.
  • Ustekinumab – a biological DMARD that treats psoriasis and PsA by inhibiting both IL-23 and IL-12 (pro-inflammatory cytokines).
  • Tofacitinib – an inhibitor of janus kinase (JAK) 1 and 3. JAKs are proteins with an important role in cell signalling. JAK inhibitors treat inflammation by inhibiting cytokine signalling in immune cells, therefore decreasing the production of pro-inflammatory cytokines.
  • Abatacept – a biological DMARD that inhibits inflammatory responses by T-cells. It is used to treat PsA when other DMARDs have not helped.
  • Cyclosporin – a natural immunosuppressant produced by certain strains of fungi. It is used to treat psoriasis. It treats skin inflammation by lowering the activity of T-cells in the skin and slowing down skin cell growth.
  • Apremilast – whether this drug can be classed as a DMARD is debatable. Apremilast is a phosphodiesterase 4 (PDE4) inhibitor. PDE4 is an enzyme in immune cells that when inhibited results in a decrease in pro-inflammatory molecules, such as TNF-alpha, IL-17 and IL-23.

Combinations of DMARDs are often used to treat active arthritic conditions.

Physical Therapy

Exercise can help to reduce joint inflammation and symptoms. Low impact activities are recommended (e.g. walking, swimming, hydrotherapy).

Ultraviolet Light therapy

UV light therapy (also known as phototherapy) is used to treat psoriasis as it slows down the skin cell production.

Emerging Treatments

There are many new drugs undergoing clinical trials for PsA, especially DMARDs. The following drugs are currently in Phase III clinical trials for PsA:

  • Guselkumab – an IL-23 inhibitor that is approved for treatment of severe plaque psoriasis. It is being trialed in PsA and has so far shown to be effective.
  • Risankizumab – another IL-23 inhibitor that is approved for treatment of severe plaque psoriasis. It is currently approved for PsA only in Japan. Clinical trials in patients with active PsA who have not responded to or can’t tolerate other biologics are ongoing.
  • Bimekizumab – an IL-17 inhibitor currently being trialled in patients with active PsA who haven’t responded to TNF-alpha inhibitors. Recent clinical trial data indicates that it is effective and safe.
  • Upadacitinib – a selective JAK-1 inhibitor that is approved for the treatment of rheumatoid arthritis. It may cause less side effects than other JAK inhibitors as it only inhibits JAK-1. Recent clinical trial results show it is effective in the treatment of PsA in patients who haven’t responded to or are intolerant to other DMARDs.

Clinical Trials

Genesis Research Services conducts clinical trials for a range of arthritic conditions, including psoriatic arthritis. To view currently recruiting studies or register your interest for future studies, click here or call us on (02) 4985 1860.


References & Resources:

Journal Articles:

  1. Chimenti MS, et al. “An update on pathogenesis of psoriatic arthritis and potential therapeutic targets”. Expert Reviews in Clinical Immunology 2019; [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pubmed/31177868
  2. Coates LC and Helliwell PS. “Psoriatic arthritis: state of the art review”. Clinical Medicine 2017; 17(1): 65-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297592/ (free)
  3. Merola JF, Espinoza LR and Fleischmann R. “Distinguishing rheumatoid arthritis from psoriatic arthritis”. RMD Open 2018; 4(2): e000656. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109814/ (free)
  4. Ogdie A and Weiss P. “The Epidemiology Psoriatic Arthritis”. Rheumatic Disease Clinics of North America 2015; 41(4): 545-568.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610151/ (free)
  5. Raychaudhuri SP, et al. “Management of psoriatic arthritis: Early diagnosis, monitoring of disease severity and cutting edge therapies”. Journal of Autoimmunity 2017; 76: 21-37. https://www.ncbi.nlm.nih.gov/pubmed/27836567
  6. Ritchlin CT, Colbert RA and Gladman DD. “Psoriatic Arthritis”. The New England Journal of Medicine 2017; 376(10): 957-970. https://www.ncbi.nlm.nih.gov/pubmed/28273019
  7. Scher, et al. “Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition.” Nature Reviews Rheumatology 2019; 15(3): 153-166. https://www.ncbi.nlm.nih.gov/pubmed/30742092
  8. Sritheran D and Leung YY. “Making the next steps in psoriatic arthritis management: current status and future directions”. Therapeutic Advances in Musculoskeletal Disease 2015; 7(5): 173-186. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572364/ (free)
  9. Veale DJ and Fearon U. “What makes psoriatic and rheumatoid arthritis so different?” RMD Open 2015; 1(1): e000025. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613157/ (free)

Websites:

  1. Arthritis Australia: “Psoriatic arthritis”. Accessed 23/06/2020: https://arthritisaustralia.com.au/types-of-arthritis/psoriatic-arthritis/ (see the downloadable information sheet and booklet)
  2. Arthritis Foundation: “What is Psoriatic Arthritis?” Accessed 23/06/2020: https://www.arthritis.org/about-arthritis/types/psoriatic-arthritis/what-is-psoriatic-arthritis.php
  3. Leavitt M. “Nail changes, PsA symptoms go hand in hand”. National Psoriasis Foundation Accessed 23/06/2020: https://www.psoriasis.org/advance/nail-changes-psa-symptoms-go-hand-in-hand
  4. NIH: U.S. National Library of Medicine: “Psoriatic arthritis”. Genetics Home Reference 2019. Accessed 23/06/2020: https://ghr.nlm.nih.gov/condition/psoriatic-arthritis