Ankylosing Spondylitis

Slide 1 · Ankylosing Spondylitis

Inflammatory axial skeletal disease • morphology • diagnosis • clinical implications

Sacroiliac inflammation • cartilage injury • bony ankylosis

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Place ankylosing spondylitis within the seronegative spondyloarthritis group.

Connect enthesis/joint inflammation to cartilage damage, new bone, and spinal rigidity.

Interpret clinical, laboratory, and imaging evidence without overreliance on one test.

Compare key differentials and identify major clinical management principles.

Slide 3 · Core disease definition

Inflammation + skeletal fusion

Chronic inflammatory disease with prominent sacroiliac and spinal involvement.

Articular cartilage damage coexists with progressive bony ankylosis.

Lower back pain and loss of spinal mobility are the characteristic clinical consequences.

Slide 4 · The seronegative spondyloarthritis family

Shared group features

RF absence • enthesis involvement • sacroiliac/vertebral disease

Structural outcome

Bone proliferation may progress to ankylosis

Group feature: Rheumatoid factor is absent by definition of the classic seronegative pattern.

The enthesis is a prominent site of pathology, unlike synovium-dominant rheumatoid arthritis.

Sacroiliac/vertebral involvement and new bone formation are recurring themes.

Slide 5 · Predominantly axial anatomical distribution

Schematic axial anatomy

Sacroiliac joints link the spine with the pelvis.

Vertebral apophyseal (facet) joints are characteristic sites.

Peripheral joints can also be involved; Axial predominance does not mean axial exclusivity.

Slide 6 · Sacroiliac joints: Why their involvement matters

Inflammation in these joints produces a recognizable axial disease distribution.

Sacroiliac involvement links lower-back symptoms to objective anatomical pathology.

The sacroiliac region is a major focus of radiographic and MRI assessment.

Sacroiliac interfaces

Slide 7 · Vertebral apophyseal joints

Schematic axial anatomy

These synovial joints connect adjacent vertebrae posteriorly.

Articular damage followed by osseous fusion restricts segmental movement.

Accumulated fusion across spinal segments contributes to a rigid spinal column.

Slide 8 · Enthesis: A characteristic lesion site

An enthesis is the attachment of a tendon, ligament, or related structure to bone.

Spondyloarthropathies prominently affect ligamentous/tendinous attachments.

Local inflammation and subsequent bone formation help explain painful insertion sites and stiffness.

Bone

Tendon / ligament

Inflamed insertion

Schematic • not a histology image

Slide 9 · Axial and peripheral musculoskeletal disease

SACROILIAC

Axial

VERTEBRAL

Axial

HIP / KNEE / SHOULDER

Peripheral

Axial: Sacroiliac and vertebral joints are defining sites.

Peripheral: The hips, knees, and shoulders may be involved.

The full distribution should be elicited rather than assuming only back symptoms.

Slide 10 · Articular cartilage destruction

Joint inflammation

Cartilage damage

Reduced joint movement

Inflammation can injure articular cartilage in affected joints.

Loss of a smooth articular surface alters joint function.

Cartilage destruction is only one component; Later new bone can also limit movement.

Slide 11 · Ankylosis: Pathological endpoint

Inflammatory injury

Repair with new bone

Bony fusion → rigidity

Ankylosis denotes pathological joint immobility from fusion.

Bony ankylosis can occur in sacroiliac and vertebral apophyseal joints.

Fusion may reduce mobility even when symptoms fluctuate.

Slide 12 · A distinctive paradox: Damage and new bone

Destructive

Cartilage damage

Inflammatory joint lesions

Proliferative

New bone formation

Osseous ankylosis

Inflammatory injury produces destructive changes.

The structural response may also include abnormal bone proliferation.

Consequently, decreased flexibility can reflect fused structures, not merely ongoing painful inflammation.

Slide 13 · Disease as an inflammation-to-fusion sequence

Inflammation

Structural remodeling

Ankylosis / immobility

Persistent or recurrent inflammatory lesions can precede structural damage.

New bone formation may bridge previously mobile structures.

Clinical stiffness can progressively become fixed immobility.

Slide 14 · Typical age at presentation

Usually begins in young people

Presentation most often during the second and third decades.

An early-onset chronic back-pain pattern should prompt consideration of inflammatory causes.

Age is supportive context, not sufficient evidence for an individual diagnosis.

Slide 15 · Inflammatory versus mechanical back pain

Inflammatory pattern

Improves with movement • may worsen at rest/night

Mechanical pattern

Often more load-related • requires other explanations

Inflammatory pain often improves with exercise and does not reliably improve with rest.

Mechanical pain is more likely to be activity-provoked, although overlap exists.

Back-pain quality guides investigation; It does not establish ankylosing spondylitis alone.

Slide 16 · Inflammatory back pain: A recognizable pattern

Insidious onset and onset at a younger age support inflammatory back pain.

Improvement with exercise and lack of improvement with rest are informative.

Night pain that eases after getting up can be another clue.

Slide 17 · Pain during rest and overnight

Ask what happens after rest

Periods of immobility may increase perceived stiffness and pain.

Nocturnal pain can be particularly informative when relieved by rising or movement.

Symptom timing should be documented, not replaced by a generic “back pain” label.

Slide 18 · Spinal mobility is an objective clinical target

Axial lesions

Reduced segmental motion

Functional limitation

Longstanding axial inflammation and fusion restrict bending and rotation.

Examination includes lumbar/cervical movement in multiple planes.

Symptoms and measured restriction convey different, complementary information.

Slide 19 · Chest-wall mobility can be affected

Assess chest excursion and spinal motion

Spinal/chest-wall involvement may constrain rib movement.

Patients may report difficulty taking deep breaths when rib-associated joints are involved.

Chest expansion can be assessed alongside spinal flexibility.

Slide 20 · Peripheral joints are not exceptional

SACROILIAC

Axial

VERTEBRAL

Axial

HIP / KNEE / SHOULDER

Peripheral

Peripheral joint involvement in at least one-third of cases.

Hips, knees, and shoulders are named sites.

Peripheral arthritis can coexist with typical axial manifestations.

Slide 21 · Hip involvement and functional burden

Hip disease can compound disability beyond spinal stiffness.

Lower-limb joint symptoms should be evaluated in the full joint examination.

The presence of peripheral disease can influence treatment individualization.

Slide 22 · Knee and shoulder involvement

Peripheral inflammation need not follow the distribution of rheumatoid arthritis.

Document painful/swollen joints rather than inferring synovitis from reported pain alone.

Clinically significant peripheral disease contributes to the total disease burden.

Slide 23 · Enthesitis and peripheral manifestations

Enthesitis is inflammation at a tendon/ligament insertion.

Peripheral arthritis, enthesitis, and dactylitis are recognized axial-SpA-associated domains.

Peripheral examination helps identify disease that back-focused evaluation misses.

Bone

Tendon / ligament

Inflamed insertion

Schematic • not a histology image

Slide 24 · Beyond the skeleton

AXIAL

Spine / sacroiliac

PERIPHERAL

Joints / entheses

EXTRA-SKELETAL

Eye / skin / gut

Axial spondyloarthritis can be accompanied by uveitis.

Psoriasis and inflammatory bowel disease are other associated manifestations.

These findings affect differential diagnosis and management selection.

Slide 25 · Acute anterior uveitis

Eye pain + visual change merit prompt assessment

Eye pain, redness, and visual change may indicate uveitis.

Ocular inflammation requires clinical assessment; Do not attribute every red eye to axial SpA.

A history of uveitis strengthens the overall spondyloarthritis clinical context.

Slide 26 · Psoriasis and inflammatory bowel disease

Skin domain

Psoriasis and characteristic skin findings

Gut domain

Crohn disease or ulcerative colitis

Skin and bowel inflammatory disease can coexist with axial spondyloarthritis.

Ask about psoriasis, abdominal symptoms, and inflammatory bowel diagnoses.

The presence of these manifestations is relevant when selecting advanced therapies.

Slide 27 · HLA-B27: Powerful association

~90% HLA-B27 positivity (Robbins)

Approximately 90% of patients with ankylosing spondylitis as HLA-B27 positive.

HLA-B27 is an MHC class I allele.

Genetic association is strong, but the biological mechanism is not fully established.

Slide 28 · HLA-B27 is not diagnostic by itself

Genetic evidence

HLA-B27 association

Raises clinical probability

Diagnostic decision

Clinical pattern

Imaging + alternative causes

A positive result can occur without ankylosing spondylitis.

A negative result does not automatically exclude the disease.

Interpret the result together with symptoms, examination, inflammatory markers, and imaging.

Slide 29 · Genetic susceptibility is not destiny

HLA-B27 susceptibility

Additional factors

Disease in only some carriers

Having the HLA-B27 allele does not mean a person will develop the disease.

Other genetic and environmental factors may contribute.

Family and personal history are useful risk context, not a deterministic test.

Slide 30 · Known mechanism versus unanswered mechanism

Supported

HLA-B27 association

Inflammatory bone/joint lesions

Unresolved

Triggering antigen

Specific causal immune-cell response

The disease shows HLA association and inflammatory skeletal pathology.

The precise antigen and pathogenic immune-cell population are unknown.

Do not portray a speculative single antigen-to-T-cell pathway as established fact.

Slide 31 · Immune pathogenesis: Calibrated interpretation

Genetic predisposition

Immune dysregulation (hypothesized)

Skeletal inflammation

Seronegative spondyloarthropathies are placed in an immune-mediated disease group.

Textbook discussion proposes T-cell responses to incompletely defined antigenic triggers.

This is a pathogenesis hypothesis, not proof of a specific microbial cause in ankylosing spondylitis.

Slide 32 · Inflammatory injury and structural remodeling

Active process

Pain and inflammation

Potentially changeable

Structural outcome

Ankylosis and rigidity

May be permanent

Axial lesions have both inflammatory and structural dimensions.

Cartilage loss and new bone formation can coexist in affected joints.

Clinical activity and accumulated irreversible damage are not identical constructs.

Slide 33 · Sacroiliitis is a core anatomical lesion

Inflammation affects the joints between sacrum and ilium.

Changes in sacroiliac joints can be detected structurally by radiographs.

MRI can provide evidence of early inflammatory disease before radiographic change is apparent.

Sacroiliac interfaces

Slide 34 · Progression from joint injury to fusion

Inflamed joint

Cartilage destruction

New bone bridging

Ankylosis

Joint inflammation damages the cartilage and adjacent structures.

Repair and abnormal bone proliferation may progressively reduce the joint space.

Extensive osseous bridging produces fixed ankylosis.

Slide 35 · Syndesmophytes: An imaging correlate

Spinal inflammation

New bone at margins

Bridging across segments

Syndesmophytes are new bone bridges associated with spinal spondyloarthritis.

Their presence indicates structural involvement beyond symptoms alone.

Accumulated bridging can contribute to the classic rigid spinal appearance.

Slide 36 · “Bamboo spine” is an advanced structural pattern

Late radiographic appearance ≠ required entry criterion

The term describes extensive spinal bridging and reduced segmental mobility.

It is not required to establish earlier axial spondyloarthritis.

Avoid using an advanced radiographic endpoint as the universal disease phenotype.

Slide 37 · Radiographs: What they reveal

PLAIN RADIOGRAPH

Structural abnormalities

MRI

Inflammation and structural lesions

Plain radiographs can demonstrate established structural sacroiliac changes.

Spinal structural damage can be followed over time when clinically appropriate.

Normal early radiographs cannot independently exclude inflammatory axial disease.

Slide 38 · MRI: What it adds

PLAIN RADIOGRAPH

Structural abnormalities

MRI

Inflammation and structural lesions

MRI evaluates inflammatory changes in sacroiliac joints and spine.

It can support earlier diagnosis when plain films have not yet shown structural lesions.

Findings require clinical interpretation; MRI alone is not a diagnostic shortcut.

Slide 39 · Structural damage is not synonymous with current activity

Inflammatory signal

Current clinical symptoms

CRP/MRI as indicated

Damage signal

Syndesmophytes/fusion

Structural radiographs

Radiographic bone bridging reflects accumulated structural change.

Pain and functional status do not always track radiographic findings precisely.

Inflammatory activity and established damage therefore deserve separate assessment.

Slide 40 · Laboratory tests: Supportive, not decisive

No single blood test diagnoses ankylosing spondylitis.

HLA-B27 is a susceptibility marker rather than a definitive disease marker.

Inflammatory markers may support activity assessment but must be interpreted contextually.

Slide 41 · Build the diagnosis from converging domains

History

Examination

Imaging + labs

Integrated clinical probability and differential diagnosis

History: Chronic inflammatory back pain and related clinical features.

Examination: Spinal/chest motion, joints, insertion sites, and extra-articular findings.

Objective evidence: Appropriate imaging and selective laboratory testing.

Explicitly evaluate alternative causes of symptoms.

Slide 42 · When referral for axial SpA is appropriate

Back pain ≥3 months + onset before age 45

Plus ≥1 supporting axial-SpA feature

At least one supportive feature is required in that referral approach.

Examples: Inflammatory back pain, HLA-B27, imaging changes, enthesitis, uveitis, or elevated inflammatory markers.

Slide 43 · Classification criteria are not clinical diagnosis

Classification

Research enrollment

Standardized inclusion rules

Diagnosis

Individual clinical judgment

Differential exclusion

Classification schemes create comparable groups for research.

Clinical diagnosis weighs pretest probability, disease pattern, imaging, and competing conditions.

ASAS–EULAR specifically cautions against diagnosing solely by research classification criteria.

Slide 44 · Historical modified New York criteria

Clinical components include chronic inflammatory back pain, restricted lumbar motion, and reduced chest expansion.

Radiographic component requires a specified grade of sacroiliitis.

This is a historical radiographic classification framework—not a substitute for specialist diagnosis.

Slide 45 · The axial spondyloarthritis spectrum

Axial spondyloarthritis

Non-radiographic axSpA

Radiographic axSpA / AS

Radiographic axial spondyloarthritis is conventionally termed ankylosing spondylitis.

Non-radiographic axial spondyloarthritis may have inflammatory disease without qualifying radiographic sacroiliitis.

The terms describe an imaging-defined spectrum, not a simple distinction between “real” and “unconfirmed” disease.

Slide 46 · Assess axial and peripheral compartments separately

Axial

Sacroiliac/spinal joints • spinal mobility

Peripheral

Hip/knee/shoulder arthritis • enthesitis

Axial symptoms include back stiffness, limited spinal flexibility, and sacroiliac pain.

Peripheral manifestations may include arthritis and enthesitis.

The relative burden of each compartment should guide assessment and follow-up.

Slide 47 · Inflammatory versus nonspecific mechanical back pain

Inflammatory clues

Insidious, younger onset; Movement relief; Night/rest pain

Other causes

Load-related pain, radicular causes, injury or infection require separate assessment

Age at onset, morning/rest symptoms, and response to movement can orient the differential.

Examining neurologic features and red flags remains important when presentations are atypical.

Neither an isolated symptom nor a normal early radiograph reliably settles the diagnosis.

Slide 48 · Ankylosing spondylitis versus rheumatoid arthritis

Ankylosing spondylitis

Axial/sacroiliac disease • entheses • bony ankylosis

Rheumatoid arthritis

Synovial inflammation • peripheral erosive arthropathy

Ankylosing spondylitis preferentially involves the sacroiliac and vertebral joints.

Rheumatoid arthritis is characteristically synovium-centered and erosive.

RF absence and enthesis-dominant pathology help orient the classic group distinction.

Slide 49 · Ankylosing spondylitis versus osteoarthritis

Ankylosing spondylitis

Inflammatory axial pattern • sacroiliitis • ankylosis

Osteoarthritis

Degenerative cartilage damage • mechanical joint symptoms

Osteoarthritis predominantly reflects cartilage/joint failure, unlike immune-mediated axial inflammation.

Ankylosing spondylitis is associated with seronegative axial inflammatory disease and new bone fusion.

Clinical pattern and imaging distribution are essential discriminators.

Slide 50 · Ankylosing spondylitis versus reactive arthritis

Ankylosing spondylitis

Chronic axial-predominant pattern

Reactive arthritis

Postinfectious onset • asymmetric peripheral arthritis

Reactive arthritis is temporally associated with gastrointestinal or genitourinary infection.

It often begins as asymmetric oligoarthritis of the lower extremities.

Sacroiliitis and inflammatory back pain can overlap; Clinical history may discriminate.

Slide 51 · Do not miss infectious arthritis

Acute hot joint: Investigate infection

Acute destructive monoarthritis needs a different, urgent diagnostic pathway.

A swollen, hot joint should not be attributed automatically to chronic spondyloarthritis.

That microbial arthritis may rapidly damage cartilage.

Slide 52 · Case 1: Early inflammatory back pain

A young adult reports insidious lower-back pain for months.

Symptoms are worse after rest and improve after movement.

Plain radiographs are not diagnostic.

What findings would increase or decrease the probability of axial SpA?

Slide 53 · Case 1: Integrate the evidence

History

Examination

Imaging + labs

Integrated clinical probability and differential diagnosis

Ask about morning stiffness, night pain, uveitis, psoriasis, bowel disease, and family history.

Examine spinal mobility and peripheral joints/entheses.

Consider HLA-B27, inflammation markers, and sacroiliac MRI as clinically appropriate.

Exclude competing diagnoses before labeling the patient.

Slide 54 · Case 2: Established structural disease

An adult has chronic back stiffness and progressive restriction in spinal movement.

Imaging demonstrates sacroiliac structural damage and extensive vertebral bridging.

Structural ankylosis explains fixed loss of flexibility.

Which findings reflect current inflammation, and which reflect accumulated damage?

Slide 55 · Case 2: Separate activity from damage

Activity

Pain/stiffness

Inflammatory assessment

Damage

Fusion/rigidity

Mobility and safety

Inflammatory pain and CRP changes reflect possible active disease.

Sacroiliac/spinal fusion reflects established structural damage.

Both domains inform care, but their management targets are not identical.

Slide 56 · Disease activity: More than pain intensity

Monitor pain, stiffness, function, clinical examination, and patient-reported outcomes.

ASDAS incorporates a patient report and an objective inflammatory marker.

BASDAI is based on patient-reported symptoms and is not interchangeable with structural damage.

Slide 57 · Imaging is selective during follow-up

PLAIN RADIOGRAPH

Structural abnormalities

MRI

Inflammation and structural lesions

MRI may clarify uncertain inflammatory activity or symptom origin.

Routine serial MRI is not generally recommended by ASAS–EULAR for every visit.

Progressive radiographic damage evolves slowly; Imaging frequency must be justified.

Slide 58 · Management objectives

Control inflammation

Preserve function

Reduce long-term harm

Reduce pain and suppress inflammation.

Preserve mobility, function, posture, and participation.

Limit progressive structural damage when possible, while individualizing treatment to disease features.

Slide 59 · Exercise and posture are central

Regular exercise and physical therapy help maintain flexibility, mobility, and posture.

Nonpharmacologic care complements medicines rather than replacing indicated treatment.

Program choice should account for current symptoms, disability, and safety.

Slide 60 · NSAIDs as initial pharmacologic therapy

ASAS–EULAR recommends NSAIDs as first-choice pharmacologic treatment of axial symptoms.

Choice and use depend on clinical response, comorbidities, and adverse-effect risk.

Analgesic response does not, by itself, prove a specific diagnosis.

Slide 61 · Persistent high activity: Targeted therapy

Persistent active axSpA

Reassess inflammation

Consider targeted therapy

When activity remains high despite conventional measures, biologic or targeted synthetic therapy may be considered.

Guideline-supported options include TNF inhibitors, IL-17 inhibitors, and JAK inhibitors.

This is specialist-directed, individualized treatment—not a fixed sequence for every patient.

Slide 62 · Extra-musculoskeletal disease guides therapy

AXIAL

Spine / sacroiliac

PERIPHERAL

Joints / entheses

EXTRA-SKELETAL

Eye / skin / gut

Uveitis, psoriasis, and inflammatory bowel disease influence treatment choice.

No single drug class is automatically optimal for every extra-articular phenotype.

Collaboration with relevant specialists is part of individualized care.

Slide 63 · Long-term therapy needs monitoring

Follow-up should incorporate patient-reported outcomes, examination, and relevant tests.

Sustained remission may support cautious dose tapering rather than abrupt withdrawal of biological therapy.

Major treatment decisions require discussion of disease activity and adverse effects.

Slide 64 · A rigid spine has additional vulnerability

New pain after trauma in a fused spine requires assessment

Advanced fusion produces a long, inflexible spinal lever arm.

Structural rigidity complicates normal motion and increases concern when trauma occurs.

New pain after trauma in advanced ankylosis warrants appropriate clinical evaluation.

Slide 65 · Complications are not inevitable

Severity varies considerably between individuals.

Some patients have intermittent mild symptoms; Others develop major mobility limitations.

Early recognition and ongoing management can support sustained function.

Slide 66 · Integrated pathology-to-clinic map

Immune-mediated inflammation

Cartilage + bone changes

Stiffness / reduced mobility

Enthesis/joint inflammation → painful axial and peripheral manifestations.

Articular injury plus bone proliferation → spinal and sacroiliac ankylosis.

Clinical examination, imaging, and laboratory evidence must be integrated.

Slide 67 · Practice question: HLA-B27-positive back pain

A patient has HLA-B27 positivity but a nonspecific short history of back pain.

There is no suggestive examination, no defined inflammatory pattern, and no objective inflammation.

Question: Is HLA-B27 positivity sufficient to diagnose ankylosing spondylitis?

Choose the next step in clinical reasoning, not a label.

Slide 68 · Practice answer: Probability, not proof

A risk marker must never replace diagnosis

No. HLA-B27 is associated with disease but is not sufficient for diagnosis.

Clarify clinical features; Examine for other SpA domains and alternatives.

Use targeted investigation and specialist assessment where warranted.

Slide 69 · Five points to retain

Sacroiliac and vertebral joints define the axial distribution.

Cartilage destruction coexists with bony proliferation and ankylosis.

HLA-B27 association is strong but not diagnostic.

MRI and radiographs answer different inflammation-versus-damage questions.

Management aims to control inflammation while preserving mobility and function.

Slide 70 · Source references

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. Ch. 26, pp. 1091–1092.

NIAMS. Ankylosing Spondylitis; diagnosis and treatment resources (2023 review).

Ramiro et al. ASAS–EULAR axial spondyloarthritis management recommendations, 2022 update (2023).

ASAS early referral recommendations and ASAS handbook (historical criteria).