What is Ankylosing Spondylitis?
Ankylosing spondylitis (AS) is a chronic, inflammatory rheumatic disease that primarily affects the axial skeleton, particularly the spine and sacroiliac joints. It is a type of seronegative spondyloarthritis, meaning it does not present with rheumatoid factor in the blood. AS is characterized by inflammation, pain, and progressive stiffness that can lead to spinal fusion in severe cases. This condition typically begins in late adolescence or early adulthood and disproportionately affects men more than women.
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Table of Contents
Causes of Ankylosing Spondylitis
Ankylosing spondylitis (AS) is a chronic, immune-mediated inflammatory disease primarily affecting the axial skeleton. While the precise cause remains unknown, extensive research points to a combination of genetic, immunological, and environmental factors that contribute to its development.
A. Genetic Factors
Genetics plays a pivotal role in the pathogenesis of AS. The human leukocyte antigen B27 (HLA-B27) gene is the most significant genetic factor associated with AS. Approximately 90–95% of Caucasian patients with AS are HLA-B27 positive. However, not all individuals with this gene develop the disease, indicating that other genetic and environmental cofactors are also involved.
HLA-B27 is thought to contribute to disease development through several mechanisms:
✔ Misfolding in the endoplasmic reticulum, causing cellular stress and immune activation.
✔ Altered antigen presentation, leading to inappropriate immune responses.
✔ Molecular mimicry, where microbial peptides resemble self-antigens and trigger autoimmunity.
In addition to HLA-B27, other genes have been implicated. These include:
✔ ERAP1 (Endoplasmic Reticulum Aminopeptidase 1) – involved in antigen processing and HLA-B27 presentation.
✔ IL-23R (Interleukin-23 Receptor) – associated with the regulation of Th17 cells, which play a central role in inflammation.
Numerous other loci have been identified through genome-wide association studies (GWAS), many of which influence innate immune signaling and inflammation pathways.
B. Immunological Factors
AS involves an aberrant immune response, particularly in the innate immune system and Th17/IL-17 inflammatory pathway. Although it has autoimmune features, AS is increasingly seen as a condition that straddles both autoimmune and autoinflammatory spectrums.
Key immune-related contributors include:
✔ Overactivation of Th17 cells, leading to excessive production of IL-17, a proinflammatory cytokine.
✔ Increased levels of TNF-alpha, which drive inflammation and promote tissue damage and bone formation.
✔ Presence of chronic inflammation at sites where tendons and ligaments attach to bone (entheses), a hallmark of the disease.
These immunological imbalances result in both destructive and excessive bone-forming processes, contributing to the stiffness and eventual fusion of the spine characteristic of advanced AS.
C. Environmental Triggers
While genetic susceptibility is crucial, environmental factors may act as triggers in genetically predisposed individuals. One significant area of research focuses on the role of infections, particularly gastrointestinal and genitourinary infections, in initiating immune responses that cross-react with host tissues.
A commonly discussed pathogen is Klebsiella pneumoniae, which shares peptide sequences similar to HLA-B27. This phenomenon, known as molecular mimicry, may incite an autoimmune reaction, particularly in those who are HLA-B27 positive.
Another key environmental factor is gut microbiota imbalance. Studies have shown that patients with AS often have altered intestinal microbiota and increased intestinal permeability. This condition, sometimes referred to as “leaky gut,” allows microbial antigens to enter the bloodstream, triggering systemic inflammation. This observation supports the concept of a gut-joint axis, where immune responses in the gut influence joint inflammation.
In addition, mechanical stress at the entheses (attachment sites of tendons and ligaments) may play a role in disease initiation or exacerbation by promoting microtrauma and local inflammation.
Risk Factors of Ankylosing Spondylitis
Several demographic, genetic, and lifestyle factors have been associated with an increased risk of developing ankylosing spondylitis. These include:
1. HLA-B27 Positivity: The most significant risk factor. However, only a small percentage of HLA-B27-positive individuals actually develop AS, indicating that additional risk factors are necessary for disease expression.
2. Family History: A positive family history of AS or other spondyloarthritides significantly increases the risk due to shared genetic markers, particularly HLA-B27.
3. Age of Onset: AS typically begins in late adolescence or early adulthood, most commonly between 15 and 40 years of age. Juvenile-onset forms may initially present with peripheral joint involvement before axial symptoms become apparent.
4. Sex: AS is more common in males, who also tend to have more severe axial disease and radiographic progression. Females may present with milder or more atypical symptoms, leading to delayed diagnosis.
5. Ethnicity: The prevalence of AS is closely tied to the prevalence of HLA-B27 in the population. It is more common in northern Europeans and less common in East Asians, Africans, and Pacific Islanders.
6. Smoking: Smoking is associated with:
✔ Increased disease susceptibility
✔ Greater disease severity and progression
✔ Poorer response to treatment
✔ Elevated risk of complications, especially lung involvement
7. Associated Inflammatory Conditions: Patients with the following conditions are more likely to develop AS or related forms of spondyloarthritis:
✔ Psoriasis
✔ Inflammatory bowel disease (IBD)
✔ Reactive arthritis
Pathophysiology of Ankylosing Spondylitis
Ankylosing spondylitis (AS) is a chronic, immune-mediated inflammatory disorder that primarily affects the axial skeleton. Its pathophysiology is complex, involving a combination of genetic susceptibility, immune system dysregulation, enthesitis, and abnormal bone remodeling. These interconnected mechanisms lead to both tissue damage and pathological new bone formation, ultimately resulting in spinal stiffness and fusion.
1. Initiation at the Entheses
The primary site of inflammation in AS is the enthesis, the location where ligaments, tendons, and joint capsules attach to bone. This differs from rheumatoid arthritis, which primarily targets synovial joints.
✔ In AS, microtrauma or mechanical stress at the entheses is believed to trigger an inflammatory response.
✔ This enthesitis leads to the recruitment of immune cells, including macrophages, T cells, and innate lymphoid cells, which release pro-inflammatory cytokines.
✔ Inflammatory changes at the enthesis can extend into adjacent bone, forming osteitis (inflammation of bone marrow) and soft tissues.
This early phase is often asymptomatic or may present subtly as intermittent stiffness and pain in young adults.
2. Role of the Immune System
The immune system plays a central role in perpetuating inflammation in AS, particularly through the involvement of innate immune pathways and T-helper 17 (Th17) cells.
Key Immune Mediators:
✔ TNF-alpha (Tumor Necrosis Factor-alpha): One of the most prominent pro-inflammatory cytokines in AS, driving inflammation at the entheses and stimulating osteoclast-mediated bone resorption.
✔ IL-17 (Interleukin-17): Produced primarily by Th17 cells, IL-17 promotes recruitment of neutrophils and amplifies inflammation. It also contributes to bone destruction and new bone formation.
✔ IL-23: Supports the survival and expansion of Th17 cells, enhancing the IL-17 pathway.
✔ Macrophages and Dendritic Cells: Involved in antigen presentation and cytokine production at the sites of inflammation.
This immune dysregulation is distinct from classic autoimmune diseases because AS lacks traditional autoantibodies such as rheumatoid factor or anti-CCP.
3. Genetic Influence (HLA-B27 and Beyond)
The HLA-B27 gene is strongly associated with AS and contributes to pathogenesis in several ways:
✔ Misfolding Hypothesis: Misfolded HLA-B27 molecules accumulate in the endoplasmic reticulum, causing cellular stress and activating the unfolded protein response (UPR), which promotes inflammation.
✔ Arthritogenic Peptide Hypothesis: HLA-B27 presents self or microbial peptides to cytotoxic T cells, which then trigger an immune response against self-tissues.
✔ Homodimer Formation: HLA-B27 can form cell-surface homodimers that activate natural killer (NK) cells and other immune cells.
In addition to HLA-B27, variants in genes such as ERAP1 (which trims peptides for MHC presentation) and IL-23R further modulate immune responses and predispose individuals to AS.
4. Chronic Inflammation and Bone Erosion
Prolonged inflammation leads to bone erosion, particularly at the edges of the vertebral bodies and sacroiliac joints. This process involves:
✔ Activation of osteoclasts, the bone-resorbing cells, by inflammatory cytokines such as TNF-alpha and IL-1.
✔ Disruption of normal bone homeostasis, resulting in structural damage and weakening of the affected bone.
These inflammatory lesions can often be detected on MRI before they become apparent on plain X-rays.
5. Pathological New Bone Formation
One of the defining features of AS is the simultaneous occurrence of bone destruction and new bone formation, which ultimately leads to ankylosis (fusion) of the spine.
✔ After inflammation subsides, repair mechanisms trigger osteoblast activation at the entheses and vertebral margins.
✔ New bone forms in the form of syndesmophytes, which are bony outgrowths that extend vertically along the spine.
✔ Over time, these syndesmophytes can bridge adjacent vertebrae, resulting in the classic “bamboo spine” seen in advanced AS on radiographs.
Importantly, this new bone formation is not simply a consequence of inflammation, as it can continue even after inflammation is controlled, suggesting that separate pathways drive this process.
6. Extra-Articular Involvement
AS is not confined to the axial skeleton. Inflammation may also affect extra-articular tissues, reflecting the systemic nature of the disease.
Common sites and mechanisms include:
✔ Eyes: Acute anterior uveitis is mediated by immune cells infiltrating the iris and ciliary body, possibly driven by shared antigenic pathways.
✔ Heart: Inflammation of the aortic root (aortitis) and conduction system can lead to aortic regurgitation and arrhythmias.
✔ Lungs: Upper lobe fibrosis may occur due to chronic inflammation of the thoracic cage.
✔ Gut: Subclinical intestinal inflammation is common, with overlapping features seen in inflammatory bowel disease.
These manifestations are also thought to be influenced by HLA-B27 and dysregulated immune responses.
The pathophysiology of ankylosing spondylitis involves a multi-step process beginning with enthesitis, driven by genetic susceptibility (especially HLA-B27) and immune dysregulation, particularly involving the Th17/IL-17 axis. This leads to chronic inflammation, bone erosion, and ultimately pathological new bone formation, resulting in progressive spinal stiffness and deformity.(alert-passed)
Symptoms and Clinical Features of Ankylosing Spondylitis
Ankylosing spondylitis (AS) is a chronic inflammatory disease that primarily affects the axial skeleton, especially the sacroiliac joints and spine. However, its manifestations extend beyond the axial structures to include peripheral joints, entheses, and various organ systems. Symptoms typically develop gradually and may be subtle in the early stages, often delaying diagnosis.
1. Axial Symptoms
The most characteristic presentation of AS involves chronic inflammation of the axial skeleton, particularly the sacroiliac joints and spine. These symptoms usually begin insidiously in young adults.
🔹 Key Axial Features: Chronic Low Back Pain: A central symptom of AS, typically beginning before the age of 45. It develops slowly and persists for more than three months.
🔹 Inflammatory Nature of Pain: Pain worsens with rest and improves with activity or exercise. Often most severe during the second half of the night or early morning.
🔹 Morning Stiffness: Lasts more than 30 minutes. Gradually improves with movement throughout the day.
🔹 Limited Spinal Mobility: Reduced range of motion in the lumbar spine and cervical spine. Difficulty bending, turning, or twisting the back.
🔹 Chest Wall Involvement: Inflammation of the costovertebral and costosternal joints may lead to reduced chest expansion, which can impair respiratory function over time.
Over the years, progressive spinal fusion can lead to postural abnormalities such as a stooped or kyphotic posture, particularly in the thoracic region.
2. Peripheral Joint Involvement
Although axial involvement is the hallmark of AS, many patients also develop peripheral arthritis, particularly early in the disease or in juvenile-onset cases.
Characteristics:
🔹 Asymmetrical oligoarthritis: Often affecting large joints such as the hips, knees, and ankles.
🔹 Hip and shoulder joints: These may be severely involved and can significantly impact function and mobility.
🔹 In some cases, peripheral arthritis may precede axial symptoms by several years.
3. Enthesitis (Inflammation of Entheses)
Enthesitis refers to inflammation at the sites where tendons, ligaments, or fascia attach to bone. It is a key feature of spondyloarthropathies, including AS.
Common Sites
✔ Achilles tendon insertion
✔ Plantar fascia (heel pain)
✔ Patellar tendon
✔ Costosternal junctions
Patients may experience localized pain, tenderness, and swelling at these sites, which may limit physical activity and walking.
4. Extra-Articular Manifestations
Ankylosing spondylitis is a systemic disease and may affect multiple organ systems beyond the joints. These extra-articular features can be the first sign of AS in some cases and often indicate more severe disease.
🔹 Common Extra-Articular Features
a. Ocular Involvement: Acute anterior uveitis (iritis) is the most common extra-articular manifestation. Symptoms include:
✔ Unilateral eye pain
✔ Redness
✔ Blurred vision
✔ Photophobia (sensitivity to light)
✔ Often recurrent and may alternate between eyes.
b. Cardiovascular Involvement: Less common but potentially serious. This includes:
✔ Aortitis (inflammation of the aortic root)
✔ Aortic regurgitation
✔ Conduction abnormalities (e.g., heart block)
✔ May lead to chest pain, heart murmur, or arrhythmias.
c. Pulmonary Involvement: In advanced cases, apical pulmonary fibrosis may develop. Restriction of chest wall movement due to spinal and costovertebral joint involvement can lead to reduced lung capacity.
d. Gastrointestinal Involvement: Subclinical intestinal inflammation is common. A subset of patients may develop inflammatory bowel disease (IBD), such as Crohn’s disease or ulcerative colitis.
✔ Symptoms may include abdominal pain, diarrhea, or weight loss.
e. Renal Involvement: Rare but may occur secondary to amyloidosis or long-term NSAID use, leading to proteinuria or renal impairment.
5. Constitutional and Systemic Symptoms
Systemic symptoms may be present, especially during periods of active disease.
🔹 Fatigue: A common and often disabling symptom, unrelated to physical activity.
🔹 Fever and weight loss: Less common, usually associated with high disease activity.
🔹 Psychological effects: Chronic pain and reduced mobility may contribute to depression, anxiety, and social withdrawal.
6. Functional and Postural Changes
As AS progresses, chronic inflammation leads to structural changes in the spine and joints.
🔹 Ankylosis (fusion of vertebrae) results in loss of spinal flexibility.
🔹 Kyphosis of the thoracic spine causes a stooped posture, making it difficult to look forward or upward.
🔹 Hip involvement may lead to gait disturbances.
🔹 Loss of lumbar lordosis and a rigid spine increase the risk of vertebral fractures, even with minor trauma.
The symptoms and clinical features of ankylosing spondylitis are diverse, ranging from axial back pain and stiffness to peripheral joint involvement, enthesitis, and extra-articular manifestations involving the eyes, heart, lungs, and gastrointestinal tract. Early symptoms can be subtle, especially in young adults, and may be misdiagnosed as mechanical back pain.(alert-passed)
Long-Term Complications of Ankylosing Spondylitis
Ankylosing spondylitis (AS) is a chronic, progressive inflammatory disease primarily affecting the axial skeleton. Over time, untreated or poorly managed AS can lead to significant complications, many of which are irreversible. These long-term complications result from both ongoing inflammation and the body’s maladaptive repair responses, particularly new bone formation. Complications can be musculoskeletal, neurological, systemic, or psychosocial in nature, and they significantly impact the quality of life, functional independence, and overall health of affected individuals.
1. Spinal Fusion and Postural Deformities
One of the hallmark long-term consequences of AS is progressive spinal fusion (ankylosis). Chronic inflammation at the vertebral margins stimulates the formation of new bone (syndesmophytes), which eventually bridges adjacent vertebrae. This process reduces spinal flexibility and leads to a rigid spine.
As the disease advances, affected individuals may develop a fixed, stooped posture known as thoracic kyphosis. Loss of lumbar lordosis and a forward-flexed cervical spine can severely limit head movement, interfere with vision (e.g., difficulty looking straight ahead), and affect daily tasks such as driving or walking safely. Spinal rigidity also predisposes patients to a higher risk of spinal fractures, even with minor trauma, due to the brittle, inflexible nature of the ankylosed spine.
2. Reduced Chest Expansion and Pulmonary Complications
Chronic inflammation and ossification of the costovertebral and costosternal joints can impair chest wall mobility. This leads to reduced chest expansion and a restrictive lung pattern, especially in severe or advanced cases. Patients may experience shortness of breath, particularly during exertion.
In rare cases, long-standing disease can lead to apical pulmonary fibrosis, especially in the upper lobes of the lungs. This complication may be asymptomatic initially but can progress to cause chronic cough, reduced oxygenation, and respiratory impairment. The restricted pulmonary function also makes these individuals more vulnerable to respiratory infections.
3. Neurological Complications
Neurological complications can arise as a result of structural changes in the spine. Spinal fractures, particularly in the cervical region, are a significant concern in patients with severe spinal rigidity, and they can lead to spinal cord injury or paralysis.
Another potential complication is cauda equina syndrome, though it is rare. This occurs when inflammation or fibrosis around the lower spine compresses the nerve roots, leading to symptoms such as lower limb weakness, saddle anesthesia, bladder and bowel dysfunction, and severe back pain. Cauda equina syndrome requires urgent medical attention to prevent permanent neurological damage.
4. Hip and Joint Destruction
Although AS primarily affects the spine, hip joints are also frequently involved. Chronic inflammation in the hips can lead to joint space narrowing, cartilage destruction, and eventually complete joint ankylosis. This results in significant pain, stiffness, and reduced mobility, often necessitating total hip replacement surgery at a younger age than is typical in osteoarthritis patients.
Peripheral joints, such as the shoulders and knees, may also be affected in some patients, leading to chronic pain and functional limitations. The burden of joint involvement, particularly in the weight-bearing joints, contributes significantly to long-term disability.
5. Cardiovascular Complications
Cardiovascular disease is a major long-term concern in AS. Chronic systemic inflammation accelerates atherosclerosis, increasing the risk of ischemic heart disease and stroke.
More specifically, AS can cause aortitis, particularly of the ascending aorta, leading to aortic root dilation and aortic valve regurgitation. Patients may develop symptoms of heart failure such as dyspnea, palpitations, or fatigue. Additionally, cardiac conduction abnormalities, including atrioventricular (AV) block and bundle branch block, can occur due to inflammation and fibrosis around the heart’s conduction system.
These complications often develop silently and are frequently underdiagnosed, making cardiovascular screening an important component of long-term care in AS.
6. Ocular Complications
Recurrent anterior uveitis is the most common extra-articular complication of AS, occurring in up to 40% of patients. Although each episode is typically acute and self-limiting with treatment, recurrent inflammation can lead to cumulative damage to the eye.
Long-term ocular complications may include:
✔ Glaucoma
✔ Posterior synechiae (adhesions between the iris and lens)
✔ Cataracts
✔ Vision loss, particularly if treatment is delayed
Prompt diagnosis and management by an ophthalmologist are essential to prevent these long-term sequelae.
7. Renal and Gastrointestinal Complications
Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), which are often the first-line treatment for AS, can cause renal impairment, gastritis, peptic ulcers, and even gastrointestinal bleeding with long-term use.
Rarely, AS may be complicated by secondary amyloidosis, a condition in which chronic inflammation leads to the deposition of amyloid proteins in organs, particularly the kidneys. This can result in proteinuria, nephrotic syndrome, and eventual renal failure.
Patients with coexisting inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) may experience additional gastrointestinal complications, which can exacerbate systemic inflammation and reduce treatment response.
8. Psychological and Social Impact
The chronic pain, fatigue, physical limitations, and disfigurement associated with advanced AS can have profound psychological effects. Patients frequently report depression, anxiety, social isolation, and a diminished sense of well-being.
The disease often affects individuals in the prime of life, which may impair their ability to work, maintain relationships, or participate in daily activities. Long-term disability can lead to loss of employment, financial strain, and decreased quality of life, particularly in the absence of adequate medical and social support.
Ankylosing spondylitis, when left untreated or poorly controlled, can result in a wide range of long-term complications that affect the musculoskeletal system, vital organs, and emotional health. These include spinal fusion, joint destruction, respiratory compromise, cardiovascular and neurological damage, and significant psychosocial burden.(alert-passed)
Diagnosis of Ankylosing Spondylitis
Diagnosing Ankylosing Spondylitis (AS) can be challenging, particularly in its early stages, due to its gradual onset and the nonspecific nature of symptoms. A comprehensive evaluation that includes clinical history, physical examination, imaging studies, and laboratory investigations is essential. Early diagnosis is vital to initiate treatment that may delay or prevent irreversible structural changes and functional decline.
A. Patient History
A detailed patient history is crucial in the evaluation of suspected AS. Most patients develop symptoms between the ages of 15 and 40. The hallmark of AS is chronic back pain with inflammatory features. This pain typically has an insidious onset, persists for more than three months, and is characterized by improvement with physical activity and worsening during rest or at night. Patients often report morning stiffness lasting more than 30 minutes, which gradually improves with movement. A thorough inquiry should include associated symptoms such as fatigue, hip or shoulder pain, heel pain, and a history of uveitis (characterized by red, painful eyes and photophobia).
Family history plays an important role, as AS often occurs in individuals with a first-degree relative affected by spondyloarthropathies. Other conditions associated with AS, such as psoriasis or inflammatory bowel disease, should be investigated. Symptoms like diarrhea, abdominal pain, or skin rashes may provide important clues. Additionally, chest pain or difficulty breathing may be reported due to involvement of the costovertebral and costosternal joints.
B. Physical Examination
Physical examination in AS aims to assess spinal mobility, detect peripheral arthritis, and identify enthesitis. Several bedside tests help evaluate spinal involvement.
🔹 Spinal and Postural Assessment
• Schober’s Test: Assesses lumbar spine flexion. Mark a point 10 cm above and 5 cm below the lumbosacral junction. The distance should increase by at least 5 cm on forward flexion. Less increase suggests reduced lumbar mobility.
• Occiput-to-Wall Test: Patient stands with heels and back against the wall. Inability to touch the wall with the back of the head indicates thoracic kyphosis.
• Chest Expansion: Measured at the fourth intercostal space. A difference of less than 2.5 cm between full inspiration and expiration indicates reduced chest expansion.
• Lateral Spinal Flexion and Cervical Rotation: Assessed to detect spinal stiffness.
• Posture Observation: Look for a stooped or kyphotic posture, reduced lumbar lordosis, or forward head carriage.
🔹 Peripheral Joint and Enthesis Examination
• Palpation for enthesitis: Especially at the Achilles tendon, plantar fascia, patella, and iliac crests.
• Peripheral joint swelling or tenderness: Hip involvement is common and can indicate more severe disease.
🔹 Extra-Articular Manifestations
• Eye Examination: Look for signs of anterior uveitis (conjunctival injection, photophobia).
• Cardiac Auscultation: Detect murmurs associated with aortic regurgitation.
• Lung Auscultation: In advanced disease, reduced breath sounds in the upper lobes may suggest apical fibrosis.
C. Laboratory Investigations
Laboratory findings in AS are supportive rather than diagnostic. Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may be elevated in active disease, although normal levels do not exclude the diagnosis. Testing for the HLA-B27 gene is particularly useful. HLA-B27 is positive in over 90% of Caucasian patients with AS, although its prevalence is lower in other populations. A positive HLA-B27 test strengthens the suspicion of AS, particularly in the context of typical symptoms and early imaging findings.
Other routine blood tests, such as a complete blood count, may reveal anemia of chronic disease. Liver and kidney function tests are usually done to monitor baseline organ function, especially before initiating therapy. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies are generally negative in AS, which helps distinguish it from rheumatoid arthritis.
D. Imaging Studies
Imaging plays a key role in diagnosing AS, especially in detecting sacroiliitis, which is a defining feature. Conventional X-rays of the pelvis, particularly anteroposterior views of the sacroiliac joints, may show bilateral and symmetric changes such as joint space narrowing, subchondral sclerosis, erosions, or eventual fusion. However, in the early stages, X-rays can be normal.
Magnetic Resonance Imaging (MRI) is more sensitive in early disease and can detect active inflammation, including bone marrow edema and osteitis, before any structural changes appear on X-ray. This is especially helpful in diagnosing non-radiographic axial spondyloarthritis. MRI has become an important tool for early detection and is often preferred in patients with a high clinical suspicion of AS but normal X-rays.
While computed tomography (CT) scans can show more detailed bony changes, including erosions and ankylosis, they involve higher radiation exposure and are less sensitive to inflammation compared to MRI.
F. Diagnostic and Classification Criteria
The diagnosis of ankylosing spondylitis (AS) involves a combination of clinical evaluation, imaging findings, laboratory tests, and the application of specific classification criteria. These criteria are essential for standardizing diagnosis in clinical practice and research, especially in the early or atypical stages of the disease. The most commonly used systems are the Modified New York Criteria and the more recently established Assessment of SpondyloArthritis International Society (ASAS) criteria.
⏩ Modified New York Criteria (1984)
The Modified New York Criteria have historically been the standard for diagnosing radiographic ankylosing spondylitis, where structural changes in the sacroiliac joints are visible on plain radiographs.
🔹 Clinical Criteria: A patient must fulfill at least one of the following:
1. Low back pain and stiffness for more than 3 months, which improves with exercise but is not relieved by rest.
2. Limitation of motion of the lumbar spine in both the sagittal (forward bending) and frontal (side bending) planes.
3. Reduced chest expansion relative to normal values for age and sex.
🔹 Radiological Criterion: Definite sacroiliitis on X-ray: this is defined as at least bilateral grade 2 sacroiliitis or unilateral grade 3 or 4 sacroiliitis.
🔹 Diagnosis: Definite AS is diagnosed when the radiologic criterion is present, plus at least one clinical criterion.
While these criteria are specific for established disease, they may miss early or non-radiographic cases where structural damage has not yet occurred.
⏩ ASAS Criteria for Axial Spondyloarthritis (2009)
To address the limitations of the Modified New York Criteria, the ASAS (Assessment of SpondyloArthritis International Society) developed new criteria for axial spondyloarthritis (axSpA). These include both radiographic (AS) and non-radiographic axSpA, allowing earlier diagnosis before irreversible structural changes.
The ASAS criteria apply to patients with:
🔹 Back pain for ≥3 months, and
🔹 Age of onset <45 years.
The diagnosis is made via two possible arms:
1. Imaging Arm: Sacroiliitis on imaging (X-ray or MRI) plus at least one SpA feature.
SpA features include:
✔ Inflammatory back pain
✔ Arthritis
✔ Enthesitis (heel)
✔ Uveitis
✔ Dactylitis (sausage digits)
✔ Psoriasis
✔ Crohn’s disease or ulcerative colitis
✔ Good response to NSAIDs
✔ Family history of spondyloarthritis
✔ HLA-B27 positivity
✔ Elevated CRP levels
2. HLA-B27 Arm: HLA-B27 positive plus two or more SpA features from the list above.
This system is particularly valuable for identifying non-radiographic axSpA, which can progress to AS over time. MRI, with its ability to detect early inflammatory changes in the sacroiliac joints (such as bone marrow edema), plays a crucial role in this early detection process.
Comparison and Utility
While the Modified New York Criteria are more specific and reflect later-stage disease, they often delay diagnosis until structural damage becomes visible on radiographs. The ASAS criteria, in contrast, are more sensitive, especially in early disease, and help clinicians initiate treatment before irreversible joint damage occurs. They are particularly helpful in evaluating younger patients with chronic back pain and no clear radiographic findings.
It's important to note that classification criteria are not meant to replace clinical judgment but rather serve as tools to support diagnosis and standardize research populations.
The diagnosis of ankylosing spondylitis requires a careful integration of clinical history, physical examination, laboratory testing, and imaging findings. Inflammatory back pain, limited spinal mobility, and sacroiliitis on imaging are central to diagnosis. Early detection is crucial, particularly with the availability of advanced imaging (like MRI) and classification criteria such as ASAS, which allow diagnosis even before irreversible structural damage occurs. A high index of suspicion in young adults with persistent back pain is essential to initiate timely management and prevent complications.(alert-passed)
Management of Ankylosing Spondylitis
The management of Ankylosing Spondylitis (AS) aims to reduce symptoms, maintain functional mobility, prevent structural damage, and improve the overall quality of life. A multidisciplinary approach that combines pharmacological treatment, physical therapy, lifestyle modifications, and patient education is most effective. Treatment is individualized based on disease activity, severity, comorbid conditions, and patient preferences.
1. Pharmacological Management
a. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
NSAIDs are the first-line pharmacological treatment for AS and are effective in relieving pain and stiffness by reducing inflammation. They may also slow radiographic progression in some patients.
Commonly used NSAIDs include:
✔ Naproxen
✔ Indomethacin
✔ Diclofenac
✔ Celecoxib (a selective COX-2 inhibitor)
Long-term use may be limited by gastrointestinal, renal, or cardiovascular side effects, so regular monitoring is essential.
b. Biologic Agents – TNF Inhibitors
For patients with inadequate response to NSAIDs, tumor necrosis factor (TNF) inhibitors are the next step. These biologics significantly reduce inflammation and halt disease progression.
Examples include:
✔ Etanercept
✔ Adalimumab
✔ Infliximab
✔ Certolizumab pegol
✔ Golimumab
c. IL-17 Inhibitors
For those who do not respond or cannot tolerate TNF inhibitors, interleukin-17 (IL-17) inhibitors are effective alternatives.
Agents such as:
✔ Secukinumab
✔ Ixekizumab
These biologics have shown efficacy in reducing disease activity and improving quality of life.
d. Analgesics and Corticosteroids
Analgesics like acetaminophen or opioids may be used for short-term pain relief when NSAIDs are insufficient, though their long-term use is discouraged.
Local corticosteroid injections may be helpful in patients with enthesitis or peripheral arthritis, but systemic corticosteroids are generally not effective for axial symptoms.
2. Physical Therapy and Rehabilitation
Physical therapy is a cornerstone of AS management and should be initiated early in the disease course. The goal is to preserve spinal mobility, maintain posture, and reduce stiffness.
Key components include:
✔ Daily exercise routines focusing on spinal extension and strengthening
✔ Posture training to prevent deformity
✔ Breathing exercises to maintain chest wall expansion
✔ Hydrotherapy and supervised rehabilitation programs for enhanced mobility
Patients are encouraged to remain physically active and avoid prolonged rest, which can exacerbate stiffness.
3. Lifestyle Modifications and Education
Patient engagement and lifestyle adaptation play a vital role in managing AS.
✔ Smoking cessation is strongly advised, as smoking worsens disease severity and spinal fusion.
✔ Maintaining a healthy weight helps reduce strain on joints.
✔ Ergonomic adjustments in the workplace and home environments can improve comfort and functionality.
✔ Patient education empowers individuals to manage their condition effectively, improving adherence and long-term outcomes.
Support groups and counseling may also benefit those struggling with the chronic nature of the disease.
4. Surgical Management
Surgery is rarely needed but may be considered in severe cases with significant deformity or joint destruction.
✔ Total hip arthroplasty may be indicated for advanced hip involvement.
✔ Corrective spinal osteotomy may be necessary in cases of disabling kyphosis (forward curvature of the spine).
✔ Spinal stabilization procedures may be performed following fractures in severely ankylosed spines.
These procedures should be conducted by experienced orthopedic teams familiar with the complexities of AS.
5. Monitoring and Follow-Up
Regular follow-up is essential to monitor disease activity, medication side effects, and functional status. Disease activity can be measured using tools like:
✔ Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
✔ Bath Ankylosing Spondylitis Functional Index (BASFI)
✔ C-reactive protein (CRP) and ESR levels as markers of inflammation
Imaging (such as MRI) may be repeated periodically to assess disease progression, particularly in non-radiographic axSpA.
Managing Ankylosing Spondylitis requires a comprehensive, patient-centered approach that balances pharmacological therapy, physical activity, lifestyle changes, and continuous monitoring. Early diagnosis and intervention are critical to improving prognosis and preserving long-term function. With proper management, many patients can lead active, productive lives despite the chronic nature of the disease.(alert-passed)
Prognosis of Ankylosing Spondylitis
The prognosis of ankylosing spondylitis (AS) varies widely among patients, influenced by factors such as disease severity, presence of extra-articular manifestations, and response to treatment. While AS is a chronic and progressive disease, advances in early diagnosis and modern therapies have significantly improved outcomes.
Disease Progression and Functional Outcome
AS generally follows a gradual and progressive course, with inflammation leading to structural damage primarily in the axial skeleton. Many patients experience fluctuating periods of disease activity, with episodes of increased pain and stiffness alternating with remission phases. Over time, chronic inflammation results in new bone formation and eventual fusion of spinal vertebrae, which can severely restrict mobility and posture.
Despite this, the rate of progression is highly variable. Some individuals may have a relatively mild course with limited structural damage and preserved function over many years, while others develop rapid spinal fusion and significant disability. Early onset of disease, high levels of inflammatory markers, and extensive peripheral joint involvement are generally associated with worse functional outcomes.
Impact on Quality of Life
The chronic pain, stiffness, and reduced mobility associated with AS can substantially affect patients’ quality of life. Physical limitations may interfere with occupational activities, daily living, and social participation. Fatigue, a common symptom, further impairs overall well-being. Psychological effects, including depression and anxiety, are also prevalent, especially in patients with long-standing or severe disease.
However, with appropriate treatment—including biologic therapies and physiotherapy—many patients maintain a good quality of life and continue to lead active lives. Patient education and support systems play an important role in coping with the disease’s challenges.
Extra-Articular and Systemic Complications
The presence of extra-articular manifestations such as uveitis, cardiovascular disease, and pulmonary fibrosis can influence prognosis. Acute anterior uveitis, though often treatable, may recur and lead to visual impairment if not managed properly. Cardiovascular complications, including aortic valve disease and conduction abnormalities, contribute to increased morbidity and mortality in AS patients. Pulmonary involvement, although less common, may cause restrictive lung disease that worsens respiratory function over time.
Comorbid conditions like osteoporosis also pose risks, especially due to spinal rigidity and increased fracture susceptibility. These systemic complications necessitate comprehensive monitoring to improve long-term outcomes.
Effect of Treatment on Prognosis
The advent of biologic therapies, particularly tumor necrosis factor (TNF) inhibitors and interleukin-17 (IL-17) blockers, has transformed the prognosis of AS. These agents effectively reduce inflammation, alleviate symptoms, and may slow radiographic progression. Early initiation of treatment is linked to better control of disease activity and preservation of spinal mobility.
Physical therapy remains fundamental for maintaining function and preventing deformity. Smoking cessation and lifestyle modifications contribute positively to disease control and overall health. With these advances, many patients experience a slower disease course and reduced disability compared to historical cohorts.
Mortality and Life Expectancy
While AS itself is rarely fatal, it is associated with a slightly increased mortality risk compared to the general population. This increased risk is primarily due to cardiovascular disease, infections, and complications related to systemic inflammation and long-term immunosuppressive therapy. Life expectancy for most patients with well-managed disease approaches that of the general population, especially when comorbidities are adequately controlled.
Ankylosing spondylitis is a chronic, variable disease with a prognosis influenced by multiple factors, including disease severity, presence of extra-articular features, and treatment effectiveness. Early diagnosis and comprehensive management can improve functional outcomes, quality of life, and reduce long-term complications. Although AS remains a lifelong condition, modern therapies and multidisciplinary care have substantially enhanced the prognosis for many patients.(alert-passed)
