Ankylosing Spondylitis: Symptoms, Types, Causes and Treatment

Ankylosing spondylitis (AS) is a chronic, inflammatory rheumatic disease that primarily affects the spine and sacroiliac joints. It can lead to pain, reduced mobility, and significant impacts on quality of life. Understanding this condition is crucial for early diagnosis, effective management, and improving patient outcomes. This article provides a comprehensive overview of AS, exploring its symptoms, types, causes, and treatment options, all grounded in recent research.

Symptoms of Ankylosing Spondylitis

Living with ankylosing spondylitis means coping with symptoms that may start subtly but can progress to cause significant discomfort and disability. Recognizing these symptoms early is key to timely intervention and better disease management.

Symptom	Description	Impact	Source
Back Pain	Chronic, worse at night, improves with exercise	Sleep disturbance, reduced mobility	2 8
Morning Stiffness	Lasts >30 minutes, especially upon waking	Difficulty starting daily activity	2 8
Fatigue	Persistent, often severe	Decreased quality of life	1 3 4
Spinal Rigidity	Reduced flexibility, loss of spinal mobility	Impaired function	2 8
Peripheral Pain	Involvement of hips, shoulders	Additional mobility limitations	8
Enthesitis	Inflammation at tendon/ligament insertions	Local pain, reduced function	8 12
Extra-articular	Uveitis, pulmonary, psychiatric symptoms	Visual, respiratory, mental impact	4 5 8

Table 1: Key Symptoms

Chronic Back Pain and Stiffness

The hallmark of AS is chronic back pain, which typically starts insidiously in early adulthood. This pain is often worse at night, waking individuals from sleep, and is not relieved by rest but improves with exercise. Morning stiffness lasting longer than 30 minutes is also characteristic, making it hard to get moving at the start of the day 2 8.

Fatigue: A Major and Overlooked Symptom

Fatigue is reported by up to 73% of patients with AS. It can be severe enough to overshadow pain and stiffness, significantly reducing quality of life. Fatigue is often linked to sleep disturbances, disease activity, and depression. Interestingly, it may occur independently of pain or stiffness in some patients 1 3 4.

Reduced Spinal Mobility

Over time, inflammation leads to reduced lateral mobility and flexion of the spine. This rigidity can cause a stooped posture and hinder everyday activities 2 8.

Peripheral and Extra-articular Manifestations

While the spine is primarily affected, AS can also involve hips, shoulders, and peripheral joints. Inflammation at entheses (sites where tendons and ligaments attach to bone) leads to localized pain and functional impairment 8 12. Extra-articular symptoms include eye inflammation (uveitis), reduced chest expansion due to spinal involvement, pulmonary complications, and psychiatric symptoms such as depression and anxiety 4 5 8.

Types of Ankylosing Spondylitis

AS is not a one-size-fits-all condition. It encompasses a spectrum of disease presentations, which can help guide diagnosis, monitoring, and therapeutic decisions.

Type	Key Features	Distinction	Source
Classical AS	Radiographic sacroiliitis, axial involvement	Visible on X-ray	6 8
Non-radiographic axial SpA	Clinical symptoms, MRI findings, no X-ray changes	Early or mild disease	6 7
Peripheral SpA	Peripheral joints and entheses involvement	Less spinal, more limb symptoms	6 8
Extra-articular AS	Eye, gut, lung, or psychiatric symptoms	Organ-specific manifestations	4 5 7 8

Table 2: Major Types of Ankylosing Spondylitis

Classical Ankylosing Spondylitis

This traditional form is defined by the presence of radiographic sacroiliitis—visible changes in the sacroiliac joints on X-ray—alongside clinical symptoms such as inflammatory back pain and stiffness. It often appears after years of subclinical disease progression 6 8.

Non-radiographic Axial Spondyloarthritis

Some patients exhibit all the classic symptoms of AS but lack X-ray evidence of sacroiliitis. Instead, MRI may reveal early inflammation. This "non-radiographic" form is considered part of the axial spondyloarthritis (SpA) spectrum and may progress to classical AS over time 6 7.

Peripheral Spondyloarthritis

A subset of patients primarily experience inflammation in the peripheral joints (such as hips and shoulders) and entheses, without prominent spinal involvement. This presentation is classified as peripheral SpA 6 8.

Extra-articular Manifestations

AS can extend beyond the joints, affecting organs such as the eyes (uveitis), lungs (fibrobullous disease), and even the gastrointestinal tract (subclinical colitis). Psychiatric symptoms—including depression and anxiety—are also more common in AS patients than in the general population 4 5 7 8.

Causes of Ankylosing Spondylitis

While the precise cause of AS remains elusive, research has revealed a complex interplay of genetic, immunological, and environmental factors.

Factor	Role in AS	Notable Details	Source
Genetics	HLA-B27 and other gene associations	Strongest risk factor	9 10 11 12
Immune Response	Abnormal cytokine activity, IL-17/23 axis	Drives inflammation	7 10 11 12
Microbiota	Gut inflammation, biomechanical triggers	May initiate immune response	7 10
Environmental	Unknown triggers, biomechanical stress	Potential contributors	7 10

Table 3: Major Causes and Risk Factors

Genetic Risk Factors

AS is highly heritable, with over 90% of patients expressing the HLA-B27 gene. However, not everyone with HLA-B27 develops AS, indicating the influence of additional genetic and environmental factors. Recent genome-wide studies have identified other susceptibility genes involved in immune regulation 9 10 11 12.

Immune System Dysfunction

Abnormal activity in the IL-17/23 cytokine pathway is central to AS pathogenesis. These cytokines promote inflammation at the entheses and axial skeleton. While tumor necrosis factor-alpha (TNF-α) is a key mediator of inflammation, it is not directly involved in bone erosion or new bone formation 7 10 11 12.

Microbiota and Environmental Triggers

Changes in the gut microbiome and subclinical gut inflammation are increasingly recognized as possible triggers for AS. Biomechanical stress at sites of high mechanical load (entheses) may also initiate or exacerbate immune responses 7 10.

Other Factors

Although AS is considered an autoimmune disease, the exact mechanisms remain under investigation. The interplay between innate and adaptive immunity, microbiota, and environmental factors is complex and not fully understood 10 11 12.

Treatment of Ankylosing Spondylitis

Managing AS requires a comprehensive, multidisciplinary approach. While no cure exists, significant advances have improved symptom control and quality of life.

Treatment Type	Key Approaches	Benefits/Limitations	Source
NSAIDs	First-line, reduce pain and stiffness	Symptomatic relief only	8 13 15 16
DMARDs	Methotrexate, sulfasalazine, etc.	Limited efficacy for axial	8 13 16
Biologics (anti-TNF, IL-17)	Etanercept, adalimumab, secukinumab	Target inflammation, effective	8 13 14 15
Physical Therapy	Exercise, physiotherapy, education	Maintains function	13 15 16
Corticosteroids	Local/systemic therapy	For short-term control	13 16
Surgery	For severe spinal or joint damage	Last-resort, restores mobility	13 16

Table 4: Main Treatment Approaches

Non-steroidal Anti-inflammatory Drugs (NSAIDs)

NSAIDs are the mainstay of treatment, effectively reducing pain and stiffness. However, they only provide symptomatic relief and do not alter disease progression. Long-term use requires monitoring for side effects 8 13 15 16.

Disease Modifying Anti-Rheumatic Drugs (DMARDs)

Traditional DMARDs, such as methotrexate and sulfasalazine, may benefit peripheral joint involvement but have limited efficacy on spinal symptoms 8 13 16.

Biologic Therapies

The advent of biologic drugs has revolutionized AS treatment. Anti-TNF agents (etanercept, adalimumab) and IL-17 inhibitors (secukinumab) target specific inflammatory pathways and can provide rapid, sustained relief even in patients unresponsive to NSAIDs. These agents may also impact extra-articular symptoms, though their effect on pulmonary manifestations is unclear 8 13 14 15.

Physical Therapy and Exercise

A structured exercise program and physiotherapy are essential components of AS management. Regular movement helps maintain spinal flexibility and function, though the optimal regimen is still debated 13 15 16.

Corticosteroids and Surgery

Systemic and local corticosteroids can be used for short-term control of severe inflammation. Surgical intervention may be necessary for individuals with advanced spinal fusion or severe joint damage 13 16.

Addressing Extra-articular and Psychiatric Symptoms

Management of extra-articular complications—such as uveitis or pulmonary fibrosis—often requires specialist care. Psychiatric symptoms, including depression and anxiety, are common and should be addressed as part of a holistic treatment plan 4 5 13.

Conclusion

Ankylosing spondylitis is a complex, multifaceted disease. From early symptoms to advanced management techniques, understanding its full spectrum is vital for both patients and healthcare providers.

Main Points:

• AS most commonly presents as chronic back pain, morning stiffness, fatigue, and reduced spinal mobility. Extra-articular symptoms can also occur.
• Disease types range from classical, radiographic AS to non-radiographic and peripheral forms, with potential organ involvement.
• The causes involve a mix of genetics (notably HLA-B27), immune system dysfunction, and environmental factors, including gut microbiota.
• Treatment is multidisciplinary: first-line NSAIDs, biologics for refractory cases, physical therapy, DMARDs for peripheral involvement, and targeted management of extra-articular symptoms.
• Early diagnosis and intervention are crucial to prevent irreversible damage and maintain quality of life.

By staying informed and proactive, individuals with ankylosing spondylitis can work with their healthcare team to manage symptoms, slow disease progression, and maintain an active, fulfilling life.