The precise cause of psoriatic arthritis is not known, but research suggests that genetic and environmental factors that affect the immune system are responsible.

Psoriatic arthritis (PsA) is a chronic, painful condition of the joints. It most commonly occurs in people who already have psoriasis but can affect anyone of any age. In addition to joint pain and stiffness, people with PsA may experience:

  • scaly, inflamed patches of skin
  • swelling in the joints, fingers, or toes
  • fatigue
  • tender entheses, which are the areas where tendons and ligaments attach to bones
  • nail changes

This article explores the relationship between PsA and the immune system, including what this means for treatment and prevention.

A healthy immune system is the body’s natural defense against invaders that can make a person sick, such as bacteria, viruses, or fungi. For most people, there are checks and balances in place that help the immune system distinguish the body’s own tissues from foreign invaders. This ability is known as self-tolerance.

In some people, this ability becomes lost, which can lead to autoimmunity. Autoimmunity occurs when the immune system no longer recognizes the body as “self” and mistakenly generates inflammatory responses to healthy tissues.

PsA has autoimmune features, as it occurs when the immune system attacks tissues in the joints, entheses, and skin, leading to inflammation, swelling, and pain. Without treatment, it can cause permanent damage to the joints, affecting mobility and functionality.

Loss of self-tolerance is the basis of all autoimmune diseases. It is not always clear what causes the loss of self-tolerance, but experts believe a variety of factors may play a role, including:

  • genetics
  • injury or infection
  • gut dysregulation
  • hormones
  • chemical or pharmaceutical exposures

They think that in many cases, a person’s underlying genetics predispose them to the loss of self-tolerance. However, this does not fully occur until a secondary trigger causes the development of autoimmune responses.

Given the role of the immune system in the disease, immunosuppression is a cornerstone of PsA treatment. Doctors use several types of medications to treat PsA, including both broad and targeted immunosuppressants.

In most cases, doctors will begin by using a nonsteroidal anti-inflammatory drug (NSAID) or corticosteroid to control inflammation and reduce pain. These are generally effective in managing mild symptoms of PsA.

For more persistent or severe disease, a doctor may incorporate one or multiple disease-modifying antirheumatic drugs (DMARDs). These medications target the underlying causes of inflammation in the immune system.

There are three broad categories of DMARDs that can treat PsA:

  • conventional or synthetic DMARDs
  • biological DMARDs, or biologics
  • JAK inhibitors

Conventional DMARDs are broad immunosuppressants that work in a similar way to NSAIDs or corticosteroids. They tend to be more potent, though. Examples include methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide.

Biologics and JAK inhibitors provide a more targeted suppression of key immune molecules involved in the development of PsA.

Considerations and risks of immunosuppression

As PsA medications generally work by suppressing the immune system, people receiving this treatment may be more likely to develop serious infections.

Reports have suggested an increased likelihood of developing infections with all types of DMARDs that doctors use to treat PsA, but biologics may carry the highest risk. An analysis of records from 9,305 adults with psoriatic disease found that 190 serious infections occurred with biologic treatment.

Common infections that occur with PsA use include:

  • pneumonia
  • urinary tract infections (UTIs)
  • cellulitis
  • viral reactivation

Certain precautions can reduce the likelihood of developing a serious infection during PsA treatment. These include:

  • antiviral treatment for people with hepatitis B
  • delivering or updating vaccinations, including pneumococcal, influenza, and COVID-19
  • the discontinuation of certain DMARDs during active infections

If someone receiving treatment for PsA begins showing symptoms of illness, such as fever or cough, they should contact a doctor right away.

Although the first symptoms of PsA may appear in the skin and joints, autoimmunity can develop against other tissues in the body. People with psoriatic diseases, including PsA, are often prone to developing health complications related to tissue damage in other parts of the body.

Some of the most common immune-mediated complications of PsA include:

  • inflammatory bowel disease
  • autoimmune eye diseases
  • heart disease
  • metabolic diseases, such as diabetes
  • cancer

The treatment for PsA focuses on slowing disease progression, with the aim of protecting not only the joints and tendons, but also other organs that autoimmune responses may damage.

In addition to using medications according to the prescription, there are a number of ways that people with PsA can help support their immune system. Among these, diet and physical activity are the best-studied options.

A 2020 review of seven studies involving 468 participants found that a low inflammatory diet can help reduce inflammation in people with PsA, but the effects on joint symptoms were unclear.

One of the most commonly studied anti-inflammatory diets is the Mediterranean diet, which emphasizes fruits, vegetables, whole grains, legumes, and heart-healthy fats. Research has shown that among people with PsA, greater adherence to a Mediterranean diet correlates with lower disease activity.

Consistent with this finding, a 2017 study found that people with PsA who received supplements of omega-3 fatty acids — naturally present in fish and olive oil — had lower disease activity, less inflammation, and reduced use of NSAIDs after 24 weeks.

The National Psoriasis Foundation recommends that people with PsA consider a trial of vitamin D supplements to help support immune health.

It also advises adults with a body mass index (BMI) of 25 or higher to follow a calorie-restricted diet and increase their physical activity levels. Research has shown that weight loss in adults with PsA and obesity is associated with a reduction in disease activity, inflammation, and pain in the joints, entheses, and skin.

A person should seek advice from a healthcare professional before making any significant changes to their diet or exercise regimen.

Autoimmunity is the basis of PsA and other psoriatic diseases. It can lead to tissue damage not only in the joints and skin, but also throughout the body. The treatment of PsA focuses on the suppression of the immune system to slow disease progression and prevent complications from unchecked immune activity.

Alongside medical PsA treatment, lifestyle adjustments can help promote immune health. It is important to talk with a doctor about the best way to support the immune system in PsA.