Every condition I give I want defination aetiology type predisposing factors pathogenesis clinical feature with sign diagnosis or investigation and complications
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Ankylising spondylitis
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"ankylosing spondylitis"[MeSH Terms] AND diagnosis
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Ankylosing Spondylitis (AS)
1. Definition
Ankylosing spondylitis (AS) is a chronic, progressive, inflammatory seronegative spondyloarthropathy primarily affecting the axial skeleton - particularly the sacroiliac (SI) joints and spine - characterised by enthesitis (inflammation at sites of tendon/ligament insertion), leading to progressive ankylosis (bony fusion) of spinal joints. It is classified as radiographic axial spondyloarthritis (r-AxSpA) by the Assessment of SpondyloArthritis International Society (ASAS), in which structural damage is visible on plain radiographs of the SI joints.
2. Aetiology
AS has a multifactorial aetiology involving genetic and environmental components:
- Genetic: The strongest association is with HLA-B27 - approximately 90% of AS patients are HLA-B27 positive. More than 30 subtypes of B27 exist; HLA-B2705 is the primordial subtype. Subtypes B2706 and B2709 do NOT confer susceptibility. Non-MHC genes also contribute - aminopeptidase genes (ERAP1, ERAP2), IL-23 receptor gene, IL-1 receptor, and others.
- Molecular mimicry: Sequence homology between HLA-B27 and gram-negative enteric bacteria (e.g., Klebsiella pneumoniae, Salmonella, Shigella) may trigger autoimmunity.
- Gut inflammation: Subclinical gut inflammation is common in AS; microbial translocation from the gut is thought to drive systemic inflammation.
- Cytokines: TNF-alpha and IL-17/IL-23 axis play central roles in driving inflammation and new bone formation.
3. Types / Classification
AS falls under the broader umbrella of Spondyloarthritis (SpA):
| Group | Subtype |
|---|---|
| Axial SpA | Radiographic (AS) / Non-radiographic axial SpA |
| Peripheral SpA | Psoriatic arthritis, Reactive arthritis, Enteropathic arthritis |
Within AS specifically:
- Primary AS - idiopathic, HLA-B27-related
- Juvenile AS - onset before age 16 (up to 15% of juvenile idiopathic arthritis cases)
- Late-onset AS - small subset; presents with sacroiliitis and oligoarthritis in older adults
4. Predisposing Factors
| Factor | Detail |
|---|---|
| HLA-B27 positivity | Most critical genetic risk; ~90% of patients carry it |
| Sex | Male:female ratio is 3:1; males have more severe spinal disease |
| Age | Young adults, typically 2nd-3rd decade; onset rarely after 45 |
| Family history | Strong familial clustering; first-degree relatives have significantly elevated risk |
| Race/Ethnicity | HLA-B27 rare in Australian Aboriginals; prevalent in 50% of western Canadian native tribes |
| Gut dysbiosis | Subclinical ileocolitis and altered microbiome implicated |
| Recurrent genitourinary/enteric infections | May trigger disease in genetically susceptible individuals |
5. Pathogenesis
- HLA-B27 and antigen presentation: HLA-B27 presents arthrogenic peptides (possibly derived from self or bacterial proteins) to CD8+ cytotoxic T cells, initiating an autoimmune response.
- Misfolding hypothesis: HLA-B27 heavy chains can misfold and form homodimers, activating unfolded protein response (UPR) and promoting IL-23 production.
- Enthesitis: Primary site of pathology is the enthesis (bone-tendon/ligament junction), especially at the annulus fibrosus attachment to vertebral bodies.
- Inflammatory cascade: TNF-alpha, IL-17, IL-23 drive synovitis, osteitis, and enthesitis.
- Bony erosion then new bone formation: Initial inflammation causes erosion at corners of vertebral bodies ("Romanus lesion" or "shiny corners"). This is followed by reactive new bone formation - syndesmophytes form at the annulus fibrosus.
- Ankylosis: Progressive syndesmophyte bridging of adjacent vertebrae leads to the classic "bamboo spine."
- Sacroiliitis: Begins in the lower iliac portion of the SI joint (richest in hyaline cartilage), progressing to total joint obliteration.
6. Clinical Features and Signs
Spinal / Axial Features
- Inflammatory low back pain: Onset insidious, persists >3 months, worse at rest and at night, improved by exercise - a key distinguishing feature from mechanical back pain
- Early-morning stiffness lasting >30 minutes
- Pain in SI joint region, with or without radiation to the buttock
- Midthoracic and cervical pain (suggests inflammatory pathology)
- Fatigue - often a major complaint in young male patients
Signs on Examination
- Schober's test: <5 cm increase in lumbar flexion (tests lumbar spine mobility)
- Chest expansion reduced (<5 cm at 4th intercostal space) - due to costovertebral joint involvement
- Occiput-to-wall distance increased - due to cervical rigidity
- Tragus-to-wall distance increased
- Loss of normal lumbar lordosis - early finding
- Kyphotic posture - late finding ("question mark" posture)
- Sacroiliac tenderness on direct compression
- FABER (Patrick's) test positive - pain on Flexion, ABduction, External Rotation of hip
Extra-Articular Features
- Anterior uveitis (25-30%) - acute, unilateral, painful red eye; recurrent
- Cardiovascular: Aortitis, aortic regurgitation, conduction defects (AV block)
- Pulmonary: Upper lobe bilateral reticulonodular infiltrates with cyst formation (apical fibrobullous disease)
- Skin: Psoriasis (in some overlap patients)
- Bowel: Subclinical ileocolitis (~60% at colonoscopy)
- Peripheral arthritis: Asymmetric, predominantly lower extremity large-joint oligoarthritis (hip, knee, ankle)
- Enthesitis: Heel pain (Achilles/plantar fascia), chest wall tenderness
7. Diagnosis / Investigations
Classification Criteria - Modified New York Criteria (1984)
Clinical Criteria:
- Low back pain and stiffness >3 months, improved by exercise but NOT by rest
- Limitation of lumbar spine motion in sagittal AND frontal planes
- Limitation of chest expansion
Radiological Criterion:
- Sacroiliitis grade ≥2 bilateral, OR grade 3-4 unilateral
Grading:
- Definite AS: Radiological criterion + at least 1 clinical criterion
- Probable AS: 3 clinical criteria alone, OR radiological criterion alone
Investigations
| Investigation | Finding |
|---|---|
| HLA-B27 | Positive in ~90% of cases |
| X-ray pelvis/SI joints | Sacroiliitis (bilateral, symmetrical); "bamboo spine" (late) |
| MRI SI joints | Gold standard for EARLY disease; shows bone marrow oedema (active inflammation) before X-ray changes |
| ESR / CRP | Elevated in active disease (not always raised) |
| FBC | Mild normocytic anaemia in active disease |
| Rheumatoid factor | Negative (seronegative) |
| ANA | Negative |
| X-ray spine | Syndesmophytes, "squaring" of vertebrae, "bamboo spine" (advanced) |
| BASMI | Bath AS Metrology Index - measures spinal mobility |
| BASDAI | Bath AS Disease Activity Index - patient-reported disease activity score |
| Schober's test | Objective lumbar spine mobility measurement |
| Slit-lamp eye exam | For anterior uveitis |
| Echo/ECG | If aortic regurgitation or AV block suspected |
8. Complications
| Complication | Detail |
|---|---|
| Bamboo spine | Complete spinal fusion; loss of all mobility |
| Spinal fracture | Even minor trauma can cause fracture through ankylosed spine (often at C5-C6); high risk of spinal cord injury |
| Cauda equina syndrome | Late rare complication due to dural ectasia and arachnoid adhesions |
| Osteoporosis | From local chronic inflammation and abnormal biomechanical loading; leads to compression fractures |
| Aortic regurgitation | Aortitis causes root dilatation; may need valve replacement |
| Heart block / AV conduction defects | From inflammation of the conduction system |
| Anterior uveitis | Recurrent; may lead to synechiae, glaucoma, cataract, vision loss |
| Restrictive lung disease | Chest wall rigidity from costovertebral fusion reduces thoracic excursion |
| Apical fibrobullous disease | Upper lobe bilateral fibrocystic change; may be colonised by Aspergillus |
| Amyloidosis | Secondary (AA) amyloidosis from chronic inflammation (rare, late) |
| Work disability | Significant impact on quality of life and functional capacity |
| Spondylodiscitis | Destructive discovertebral lesion (Andersson lesion) |
Sources: Goldman-Cecil Medicine (International Edition) - Spondyloarthritis chapter; Firestein & Kelley's Textbook of Rheumatology; Murray & Nadel's Respiratory Medicine
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