Axial Spondyloarthritis: Symptoms, Types, Causes and Treatment

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that primarily affects the spine and sacroiliac joints, leading to pain, stiffness, and functional limitations. Over recent years, greater awareness and advances in diagnostics have led to improved recognition and management of this impactful condition. In this article, we explore the symptoms, types, causes, and treatments of axial spondyloarthritis, drawing on the latest scientific research.

Symptoms of Axial Spondyloarthritis

Axial spondyloarthritis can manifest in a variety of ways, often making early recognition challenging. Understanding its core and associated symptoms is key to timely diagnosis and effective management.

Symptom	Description	Impact on Life	Source(s)
Back Pain	Chronic, inflammatory, often worse at night	Reduced mobility, poor sleep	2 3 4 5
Stiffness	Morning stiffness, improves with exercise	Limits daily activities	2 3 4
Fatigue	Persistent tiredness, not relieved by rest	Affects work/leisure	3
Extra-articular	Skin, bowel, eye involvement (e.g., HS, uveitis)	Additional health complications	1 2 3

Table 1: Key Symptoms of Axial Spondyloarthritis

Understanding the Range of Symptoms

Chronic Inflammatory Back Pain

• The hallmark of axSpA is persistent back pain, typically with an inflammatory character—worse at night, better with movement, and often starting before age 45. Unlike mechanical back pain, it improves with physical activity rather than rest. Over time, the pain may become more constant and disabling 2 4.

Stiffness and Reduced Mobility

• Morning stiffness is a classic feature, sometimes lasting for hours. This can limit daily functioning, making simple activities like getting out of bed or bending over challenging 2 3.

Fatigue and Quality of Life

• Many people with axSpA experience profound, chronic fatigue. This is not merely a consequence of poor sleep due to pain, but also a direct result of systemic inflammation. Fatigue can impair work performance, social life, and emotional wellbeing 3.

Extra-articular Manifestations

• AxSpA is more than a joint disease. It can involve other organs:
  • Skin: Conditions like hidradenitis suppurativa (HS) and psoriasis are more common in axSpA patients. HS, in particular, appears more prevalent and is linked to higher disease activity and poorer quality of life 1.
  • Eyes: Uveitis (eye inflammation) can cause redness, pain, and vision changes.
  • Bowel: Inflammatory bowel disease may be present.
• These manifestations can further worsen quality of life and complicate management 1 2 3.

Persistent Residual Symptoms

• Even with effective treatment, some patients continue to experience pain due to nociplastic (altered pain processing) or neuropathic (nerve-related) mechanisms, which contributes to ongoing symptoms and disability 5.

Types of Axial Spondyloarthritis

Axial spondyloarthritis exists on a spectrum, with key distinctions between its subtypes. Recognizing these types helps tailor diagnosis and treatment.

Type	Key Features	Diagnosis Basis	Source(s)
Non-radiographic axSpA	Symptoms without definite X-ray changes	MRI, HLA-B27, clinical	2 6 8 12
Radiographic axSpA	Clear structural changes (Ankylosing Spondylitis)	X-ray evidence of sacroiliitis	2 6 8 9

Table 2: Types of Axial Spondyloarthritis

Non-radiographic vs Radiographic Axial Spondyloarthritis

Non-radiographic Axial Spondyloarthritis

• Patients have classic symptoms of axSpA but do not show definitive sacroiliac joint changes on X-ray.
• Diagnosis relies on MRI (which detects early inflammation), genetic testing for HLA-B27, and specific clinical features 2 12.
• This type often affects more women and tends to show less structural damage at presentation, but the burden and response to therapy are similar to radiographic axSpA 12.

Radiographic Axial Spondyloarthritis (Ankylosing Spondylitis)

• This is the traditional form, where X-rays reveal clear changes in the sacroiliac joints and/or spine.
• It is more common in men, and structural changes accumulate over years, potentially leading to spinal fusion ("bamboo spine") 6 9.

Continuous Disease Spectrum

• Both forms share similar symptoms and extra-articular features. The distinction is mainly based on imaging findings, not on differences in disease severity or management needs 8 9.
• Importantly, the use of these terms is mostly for classification rather than distinct diagnosis, as patients may progress from non-radiographic to radiographic disease over time 8.

Causes of Axial Spondyloarthritis

While the exact causes of axSpA are still being unraveled, a combination of genetic, immunological, and environmental factors is known to play a role.

Factor	Contribution	Key Notes	Source(s)
Genetics	High heritability (>90%); HLA-B27 association	Strongest risk factor	6 9 12
Immune Pathways	TNF-α, IL-17, and IL-23 involvement	Drive inflammation	6 9 11 12
Environmental	Possible triggers (e.g., infections)	Not fully understood	6 9
Structural	Inflammation → bone formation/erosion	Leads to damage	6 9 10

Table 3: Causes and Pathogenesis of Axial Spondyloarthritis

Genetic Predisposition

HLA-B27 and Other Genes

• The strongest known risk factor is the presence of the HLA-B27 gene, found in the vast majority of patients. However, not everyone with HLA-B27 develops axSpA, indicating other genes and factors also contribute 6 9.
• Heritability is estimated at over 90%, suggesting a major genetic component 6.

Immune and Inflammatory Pathways

TNF-α and Interleukin-17

• Inflammation in axSpA is driven by immune system messengers, particularly tumor necrosis factor alpha (TNF-α) and interleukin-17 (IL-17). These cytokines promote inflammation in the joints and surrounding tissues 6 9 11 12.
• Recent research has identified the IL-23/IL-17 axis as a crucial pathway, although blocking IL-23 has not been effective clinically, highlighting the complex immunology involved 12.

Environmental and Structural Factors

Environmental Triggers

• While genetics lay the groundwork, environmental factors such as infections may act as triggers, especially in genetically predisposed individuals. The exact triggers remain unclear, and research is ongoing 6 9.

Inflammation Leads to Damage

• Chronic inflammation can lead to the formation of new bone (osteoproliferation) as well as bone erosion, resulting in long-term structural changes and disability. The interplay between inflammation and bone formation is not yet fully understood 6 9 10.

Treatment of Axial Spondyloarthritis

The goal of axSpA treatment is to reduce symptoms, control inflammation, prevent structural damage, and improve quality of life. Modern therapy is multifaceted, combining lifestyle, medication, and sometimes surgical options.

Treatment Type	Use/Indication	Notes/Examples	Source(s)
Non-pharmacological	First-line for all patients	Exercise, education, physiotherapy	2 13 15
NSAIDs	First-line drug therapy	Ibuprofen, naproxen	2 6 9 13 15
Biologics	For high disease activity despite NSAIDs	TNF inhibitors, IL-17 inhibitors	2 6 9 12 13
JAK inhibitors	When other biologics fail or are not tolerated	Upadacitinib	2 16
Other	Surgery, analgesics (limited), DMARDs (rarely)	For severe or refractory cases	13 15

Table 4: Treatment Modalities in Axial Spondyloarthritis

Non-pharmacological Management

Exercise and Physical Therapy

• Regular exercise is essential to maintain mobility, reduce stiffness, and improve function. Physiotherapy and patient education are cornerstones of management, often with measurable benefits on symptoms and quality of life 2 13 15.

Pharmacological Therapies

NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)

• NSAIDs are the first-line drug treatment. They reduce pain and stiffness and may slow disease progression in some patients. Continuous rather than on-demand use may be preferred in patients with active inflammation, although risks must be considered 2 6 9 13 15.

Biologic Therapies

• If NSAIDs are insufficient, biologic disease-modifying antirheumatic drugs (bDMARDs) are recommended:
  • TNF inhibitors (e.g., etanercept, adalimumab) and IL-17 inhibitors (e.g., secukinumab) are both highly effective 2 6 9 12 13.
  • These agents target the key cytokines driving inflammation, leading to symptom control and improved function.
  • IL-17 inhibitors are especially useful for patients with contraindications to TNF inhibitors or specific extra-articular features 12.

Janus Kinase (JAK) Inhibitors

• Newer oral agents, such as upadacitinib, show promise for patients with non-radiographic axSpA, especially when standard biologics fail or are not tolerated. They work by blocking intracellular signaling involved in inflammation 2 16.

Other Treatment Strategies

Analgesics and DMARDs

• Conventional synthetic DMARDs (e.g., methotrexate) and systemic glucocorticoids have limited roles in axSpA, especially for axial symptoms 13 15.
• Analgesics may be used for pain management but do not address underlying inflammation 13.

Surgical Interventions

• In rare, severe cases (e.g., spinal fractures, advanced deformity), surgery may be considered 13.

Monitoring and Treatment Targets

• Regular monitoring of disease activity (using ASDAS, BASDAI) and shared decision-making between patient and clinician are essential.
• The treatment target is remission or low disease activity to prevent progression and optimize quality of life 13 14.

Conclusion

Axial spondyloarthritis is a complex and variable disease, but advances in research and treatment have greatly improved patient outcomes. Early recognition and a personalized, multi-pronged approach are essential for optimal management.

Key Points Covered:

• Symptoms: Chronic inflammatory back pain, stiffness, fatigue, and extra-articular features such as skin and eye involvement are common and impact quality of life 1 2 3 4 5.
• Types: AxSpA includes non-radiographic and radiographic forms (ankylosing spondylitis), representing a continuous spectrum 2 6 8 9 12.
• Causes: Genetics (especially HLA-B27), immune pathways (TNF-α, IL-17), and unclear environmental factors underlie axSpA 6 9 11 12.
• Treatment: A combination of non-pharmacological measures, NSAIDs, biologic agents (TNF and IL-17 inhibitors), and new therapies like JAK inhibitors offers effective management for most patients 2 6 9 12 13 15 16.

By staying informed and proactive, individuals with axial spondyloarthritis can achieve better symptom control and improved quality of life.