What Is Axial Spondyloarthritis?

Overview

Axial spondyloarthritis (AxSpa) is an umbrella term for two types of inflammatory arthritis: non-radiographic axial spondyloarthritis (nr-AxSpa) and ankylosing spondylitis (AS). AxSpa is a progressive and chronic condition characterised by persistent lower back pain, joint pain, and fatigue.¹ It affects approximately 1 in 200 adults in the UK.¹ Despite its high prevalence, patients struggle with delayed diagnosis, which leads to reduced quality of life and a higher risk of developing clinical complications. 

Causes of axial spondyloarthritis

The exact causes for AxSpa are not known, however, it is expected that, as with most auto-immune disorders, both genetics and environmental triggers play important roles. AS, especially, seems to run in families, with an 82-fold increased risk of recurrence in siblings of AS patients compared to the general population.² 

One gene that has long been associated with AxSpa and AS is HLA-B27. This is one of many human leukocyte antigen (HLA) genes normally present in our genetic code. Their role is to aid in the presentation of antigens (molecules that activate immune response) to T cells (cells that mediate the immune response). Up to 90 % of patients with spondyloarthritis may present the HLA-B27 gene, however, healthy individuals can also carry the gene. The frequency of HLA-B27 varies across populations, thus diagnosis should not rely solely on the presence of this gene. 

Types of spondyloarthritis

There are two main types of axial spondyloarthritis: non-radiographic axial spondyloarthritis (nr-AxSpa) and ankylosing spondylitis (AS). Both share the same core symptoms of pain and stiffness in the spine and joints, as well as fatigue. However, in AS, the prolonged inflammatory activity leads to the formation of bone fusions in the spine and sacroiliac joints, which are observable on X-ray. It is estimated that approximately 26 % of patients with nr-AxSpa progress to AS over 15 years.³ A common misconception is that nr-AxSpa is a “milder form” of AS, however, the severity of symptoms is about the same in both conditions, the only difference being that in patients with nr-AxSpa, the inflammation doesn’t cause changes in radiographic exams. 

Signs and symptoms

Image generated on Microsoft Powerpoint

AxSpa involves a complex array of symptoms, such as:

• Persistent lower back pain for more than 3 months
• Pain that worsens with rest and improves with exercise
• Pain in the buttocks (sacroiliac joints)
• Waking up during the night due to pain
• Pain and stiffness in the spine, including lower back, neck, and sacroiliac joints
• Sacroiliitis
• Pain, stiffness, and inflammation in peripheral joints, such as knees, wrists, ankles, shoulders, elbows, ribs, and fingers, and toes (dactylitis)
• Early morning stiffness and pain, which tend to improve during the day
• Enthesitis (inflammation where the tendons and ligaments attach to the bone)
• Tendonitis, including Achilles tendonitis
• Bone fusions in the spine and sacroiliac joints (in patients with AS) 
• Uveitis
• Inflammatory bowel disease
• Psoriasis
• Fatigue, often also associated with anaemia
• Brain fog
• Low-grade fever and night sweats

Most patients with AxSpa experience some of these symptoms intermittently from their late teens until their late twenties and may experience a gradual worsening of symptoms over months or years until diagnosis. Increased severity of symptoms can usually be kept under control with the use of medication, adequate exercise, and a healthy diet, however, most patients exhibit flare-ups. Learning what triggers flare-ups can be beneficial for AxSpa patients and help to avoid severe and frequent symptoms. 

Diagnosis

AxSpa diagnosis can be challenging, especially due to a lack of awareness among healthcare professionals on the prevalence and presentation of AxSpa, which leads to delayed diagnosis for many patients, especially women.⁴ Reliable diagnosis relies on an ensemble of evidence from multiple tests, as well as clinical evaluation and family history. 

Blood tests

Blood tests used to diagnose and monitor AxSpa include:

• PCR test for HLA-B27 detection
• Quantification of inflammation markers, such as:
  • C reactive protein (CRP)
  • Erythrocyte sedimentation rate (ESR)
  • Plasma viscosity (PV)

Image tests

Image tests are important for the visualisation of inflammatory activity in the spine and sacroiliac joints. In AS, the main diagnostic criteria is the presence of bone fusions in the sacroiliac joints and/or spine, which can be detected by X-ray. In nr-AxSpa patients, the indicated diagnostic test is a magnetic resonance imaging (MRI) of the sacroiliac joints. Some evidence exists indicating that an MRI of the thoracic spine as well as the sacroiliac joints can be beneficial in the diagnosis of active spondyloarthritis.⁵

Clinical evaluation

The Bath Indices are also important diagnostic and monitoring tools and are used as part of the criteria for the administration of anti-TNF medication to patients. They consist of 4 different indices that assess the functional impairment and disease activity of AS and nr-AxSpa patients. The indices are:

• Bath AS Metrology Index (BASMI)
• Bath AS Functional Index (BASFI)
• Bath AS Disease Activity Index (BASDAI)
• Bath AS Patient Global Score (BAS-G)

Treatment and management

Unfortunately, AxSpa does not have a cure and tends to progress if left untreated. Adequate management strategies should be individualised and aim to reduce symptom severity, reduce overall inflammation, and increase quality of life. Often a combination of medication and non-pharmacological intervention provides the best results.

Pharmacological treatment

Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAIDs, such as ibuprofen, naproxen, and eterocoxib, are often the first line of treatment for AxSpa. They are frequently used with other medications and contribute to reducing inflammation and pain.

Corticosteroids 

Not to be confused with anabolic steroids, corticosteroids such as prednisone, prednisolone, methylprednisolone, and betamethasone, can be used for short-term management of AxSpa flares. These can be administered as tablets or injections. Tablets are often more effective however they present a higher risk of side effects. Injections can be administered directly in the affected joint or intramuscularly. Many patients find that steroids are effective in reducing pain and inflammation, however, they should not be used for long periods of time due to an increased risk of side effects.

Disease-modifying anti-rheumatic drugs (DMARDs)

DMARDs are helpful for patients who experience important peripheral joint pain (i.e., knees, elbows, shoulders, ankles, fingers, etc), although there is no evidence that they also improve spine (axial) pain. The most commonly used DMARDs in AxSpa include methotrexate and sulfasalazine.

Biologic therapy

Biologics are medications containing antibodies that selectively target and neutralise important immuno-modulating molecules. The currently approved targets for biological therapy in axSpa are tumour necrosis factor-alpha (TNF-ɑ) and interleukin 17 (IL-17). Biologics are the main treatment option for patients with high disease activity who haven’t responded well to other therapies. They are strong immunosuppressants, and the main side effects related to long-term use include an increased risk of infections. Biologics usually come in the form of injection pens that are self-administered by the patients. Usually, patients that classify for biologic therapy will start with anti-TNFɑ treatment, such as adalimumab, and monitor their response to it for 3 to 6 months. In case no improvement is observed during that time, patients will usually try other biologics. The most commonly used anti-TNFɑ medications are adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab. Anti-IL17 medication includes secukinumab, ixekizumab, and bimekizumab. 

Non-pharmacological treatment

Physical activity

An adequate exercise routine is one of the best treatments for patients with AxSpa. Exercise improves flexibility, maintains muscle strength, increases range of movement, and improves posture, among many other benefits.⁶ However, it is extremely important that AxSpa patients proceed with care when exercising in order to avoid strains that could trigger flare-ups. Finding a balance between exercising healthily and avoiding injury is one of the most important aspects of AxSpa management. For this reason, low-impact exercises adapted to patients with AxSpa are preferred, including:

• Swimming 
• Cycling
• Walking 
• Yoga
• Physiotherapy

A consistent routine of exercises is also important to improve cardiovascular health, which is particularly important in AxSpa due to patients being at increased risk of cardiovascular diseases.⁷

Diet

Unfortunately, studies investigating the effect of diet in AxSpa are scarce, yet some conclusions can be taken from research involving other types of inflammatory arthritis, like rheumatoid arthritis (RA). General recommendations revolve around keeping a healthy body mass index (BMI), eating plenty of fruits, vegetables, and fibre, and avoiding ultra-processed foods. Other potentially beneficial measures are:

• Adhering to a Mediterranean diet^8-11
• Limiting salt and refined sugar intake¹²
• Supplementation with long-chain omega-3 fatty acids - eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)^13-16
• Supplementation with vitamin D^12,17

Keeping a healthy gut by regular consumption of probiotic foods^18-21

Emotional wellbeing

Dealing with a progressive, chronic, painful condition such as AxSpa can severely impact patients’ emotional well-being and conditions such as depression and anxiety are common among axSpa patients.²² Furthermore, increasing evidence has shown that depression and anxiety increase disease activity, decrease quality of life and work productively, and negatively impact patients’ response to treatment.²⁴ Thus, it is of great importance that patients take care of their minds as well as their bodies and that healthcare providers consistently screen AxSpa patients for anxiety and depression, in order to provide adequate therapies.²³

Summary

AxSpa is an umbrella term that encompasses AS and nr-AxSpa. These are autoimmune, chronic, progressive conditions that cause pain and stiffness in the spine and joints, as well as fatigue and several other symptoms. Although no definitive cure exists, symptoms and disease progression can be controlled with a combination of medication and non-pharmacological approaches. Pharmacological treatment relies mostly on analgesics for pain control, and anti-inflammatory and immunosuppressive medication, such as NSAIDs, DMARDs, corticosteroids, and biologic therapy. Non-pharmacological treatment involves adequate physical activities of low impact and a healthy diet. Furthermore, the emotional distress caused by AxSpa leads to the high incidence of depression and anxiety in these patients, and therefore, holistic approaches should be considered to include emotional, as well as, physical well-being support.