Spondyloarthropathies
Medicine · Rheumatology · lean revision notes
Spondyloarthropathies
The spondyloarthropathies (SpA) are a family of inter-related, seronegative (rheumatoid factor–negative) inflammatory arthritides that share a strong association with HLA-B27, axial skeleton and sacroiliac joint involvement, enthesitis, dactylitis, and characteristic extra-articular features (uveitis, mucocutaneous lesions, IBD). They are a recurrent NEET PG favourite because the overlapping yet distinguishing features make excellent single-best-answer material.
Definition & classification
A spondyloarthropathy is an inflammatory arthritis predominantly affecting the axial skeleton (spine + sacroiliac joints) and entheses, with a tendency for asymmetric large-joint oligoarthritis of the lower limbs, and characteristically negative rheumatoid factor and anti-CCP ("seronegative").
The classic members:
| Disease | Key clue | HLA-B27 positivity |
|---|---|---|
| Ankylosing spondylitis (AS) | Sacroiliitis, bamboo spine, young man with inflammatory back pain | 90–95% |
| Psoriatic arthritis (PsA) | DIP joints, pencil-in-cup, nail pitting, dactylitis | 40–50% (higher in axial) |
| Reactive arthritis (ReA) | Post-dysenteric/post-urethritic; Reiter triad | 60–80% |
| Enteropathic (IBD-associated) | Crohn/ulcerative colitis + arthritis | 30–70% (axial) |
| Juvenile-onset SpA & undifferentiated SpA | Enthesitis, partial features | Variable |
High-yield: All spondyloarthropathies are HLA-B27 associated and RF/anti-CCP negative. The unifying lesion is enthesitis (inflammation at the insertion of tendon/ligament into bone), which distinguishes SpA from RA where the primary lesion is synovitis.
Modern nomenclature (ASAS classification) divides SpA into:
- Axial SpA — predominant spine/SI joint disease; includes radiographic (= ankylosing spondylitis) and non-radiographic axial SpA (MRI changes without definite x-ray sacroiliitis).
- Peripheral SpA — predominant peripheral arthritis, enthesitis, or dactylitis.
Shared features ("SPINEACHE" approach)
A useful clustering of the SpA family hallmarks:
- Sausage digit (dactylitis)
- Psoriasis
- Inflammatory back pain
- NSAID good response
- Enthesitis (heel — Achilles/plantar fascia)
- Arthritis (asymmetric, lower-limb, oligoarticular)
- Crohn's/colitis
- HLA-B27
- Eye (anterior uveitis)
Inflammatory back pain criteria (Calin / ASAS) — age of onset <40 yrs, insidious onset, morning stiffness >30 min, improvement with exercise but not rest, night pain (second half) with improvement on getting up. This is the opposite of mechanical back pain.
Ankylosing spondylitis (AS)
Epidemiology & pathophysiology
Typically a young man (M:F ≈ 3:1), onset in late teens to 30s, presenting with chronic inflammatory low back pain and buttock pain. There is a striking genetic link — HLA-B27 in 90–95%, though only ~5% of HLA-B27 positive individuals develop AS. Pathology centres on enthesitis at the SI joints and spine, followed by reactive new bone formation (syndesmophytes), leading ultimately to ankylosis (bony fusion).
Clinical features
- Bilateral sacroiliitis — the radiological hallmark and earliest finding.
- Progressive loss of spinal mobility; ascending fusion → fixed kyphosis with "question-mark" posture (loss of lumbar lordosis, fixed thoracic kyphosis, compensatory neck hyperextension).
- Enthesitis — Achilles tendinitis, plantar fasciitis (heel pain).
- Costovertebral involvement → reduced chest expansion (<2.5 cm is abnormal).
- Hip involvement is a poor prognostic marker.
High-yield: Schober's test quantifies lumbar flexion. Mark a point at the lumbosacral junction (level of posterior superior iliac spines / dimples of Venus) and another 10 cm above. On full forward flexion, the distance should increase to ≥15 cm (i.e. >5 cm increase). Increase <5 cm = restricted lumbar flexion → suggests AS.
Extra-articular manifestations — the "A" mnemonic
Apical pulmonary fibrosis, Anterior uveitis (most common extra-articular feature, ~25–40%, acute, unilateral, recurrent), Aortic regurgitation / Aortitis & conduction defects, Achilles enthesitis, Amyloidosis (AA type → renal failure), Atlanto-axial subluxation, Autoimmune bowel (subclinical IBD), and restrictive lung disease (Ankylosis of thoracic cage). IgA nephropathy is also associated.
Investigations
| Test | Finding |
|---|---|
| Pelvic X-ray (SI joints) | Bilateral, symmetric sacroiliitis — earliest = juxta-articular sclerosis & erosions ("pseudo-widening"), late = fusion |
| Spine X-ray | Squaring of vertebrae (Romanus lesion / "shiny corners"), syndesmophytes, "bamboo spine", "dagger sign" (ossified interspinous ligaments) |
| MRI SI joints (STIR) | Bone marrow oedema — detects early/non-radiographic disease before x-ray changes |
| HLA-B27 | Positive in 90–95% (supportive, not diagnostic) |
| ESR/CRP | Often raised; CRP correlates with activity |
High-yield: Investigation of choice for early/non-radiographic axial SpA = MRI of sacroiliac joints (STIR sequence showing bone marrow oedema). Plain x-ray sacroiliitis takes years to appear. Bamboo spine = late finding due to flowing syndesmophytes + facet fusion.
Romanus lesion = inflammation at vertebral corner → "shiny corner sign" → later squaring. Andersson lesion = inflammatory destructive discovertebral lesion.
Management
Approach: Patient education + regular spinal/postural exercise & physiotherapy (most important for function) → NSAIDs (first-line drug; continuous use slows radiographic progression) → TNF-α inhibitors (etanercept, adalimumab, infliximab) or IL-17 inhibitors (secukinumab, ixekizumab) for NSAID failure → JAK inhibitors (tofacitinib, upadacitinib) as alternatives.
High-yield: DMARDs like methotrexate & sulfasalazine do NOT work for axial (spinal) disease — they are reserved for peripheral arthritis. Biologics (anti-TNF / anti-IL-17) are the agents that control axial disease. Sulfasalazine helps peripheral joints and is preferred if there is associated IBD.
Disease activity is scored using BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and ASDAS. BASMI measures metrology/mobility.
Complications
- Spinal fusion → rigid spine prone to fracture with minor trauma (often at C5–C7), risk of spinal cord injury — even trivial trauma in a fused spine is a surgical emergency.
- Cauda equina syndrome (arachnoid diverticula).
- Restrictive lung disease, aortic regurgitation, AA amyloidosis.
Psoriatic arthritis (PsA)
Inflammatory arthritis in a patient with psoriasis (skin usually precedes joints, but ~15% the arthritis comes first). Occurs in ~10–30% of psoriasis patients. Equal sex distribution.
Moll & Wright five patterns
- Asymmetric oligoarthritis (commonest classically).
- Symmetric polyarthritis (RA-like, but RF negative).
- DIP-predominant arthritis (with adjacent nail disease) — classic and highly characteristic.
- Arthritis mutilans — severe destructive osteolysis → "telescoping"/opera-glass fingers.
- Spondylitis / sacroiliitis (often asymmetric, unlike AS).
High-yield: PsA characteristically involves the DIP joints (unlike RA which spares DIP). The radiographic hallmark is the "pencil-in-cup" deformity (whittled proximal bone end inserts into the cupped expanded distal bone). Dactylitis ("sausage digit") and enthesitis are typical. Sacroiliitis in PsA is often asymmetric, in contrast to the symmetric sacroiliitis of AS.
Key associations & findings
- Nail changes correlate with DIP arthritis: pitting, onycholysis, oil-drop sign.
- Skin: psoriatic plaques (look in scalp, umbilicus, natal cleft, behind ears).
- CASPAR criteria are used for classification (psoriasis, nail dystrophy, negative RF, dactylitis, juxta-articular new bone on x-ray).
- Radiology: erosions + new bone formation together, "fluffy" periostitis, pencil-in-cup, acro-osteolysis.
Management
NSAIDs for mild disease → conventional DMARDs (methotrexate, leflunomide, sulfasalazine) for peripheral disease (methotrexate also helps skin) → biologics: TNF inhibitors, IL-17 (secukinumab), IL-12/23 (ustekinumab), IL-23 (guselkumab), and PDE-4 inhibitor apremilast; JAK inhibitors as options. Axial PsA, like AS, does not respond to methotrexate → use biologics.
Reactive arthritis (ReA) — formerly Reiter syndrome
A sterile, immune-mediated synovitis arising 1–4 weeks after a distant infection — either genitourinary (Chlamydia trachomatis) or gastrointestinal/dysenteric (Shigella, Salmonella, Yersinia, Campylobacter). Most common in young men; HLA-B27 positive in 60–80% (also predicts more severe/chronic disease).
High-yield: Reiter's triad = "Can't see, can't pee, can't climb a tree" → conjunctivitis (uveitis) + urethritis + arthritis. The classic mnemonic; the arthritis is an asymmetric lower-limb oligoarthritis.
Clinical features
- Asymmetric oligoarthritis, lower limbs (knee, ankle), within a month of infection.
- Enthesitis / dactylitis, heel pain.
- Mucocutaneous: keratoderma blennorrhagicum (pustular hyperkeratotic lesions on soles/palms — mimics pustular psoriasis), circinate balanitis (painless penile lesions), painless oral ulcers, nail changes.
- Ocular: conjunctivitis (early) and anterior uveitis.
- The causative organism is not in the joint — synovial fluid culture is sterile (distinguishes from septic and Lyme arthritis).
Investigations & management
Raised ESR/CRP; HLA-B27; sterile inflammatory synovial fluid; stool/urethral cultures or NAAT for Chlamydia. Sacroiliitis (often unilateral/asymmetric) on imaging in chronic cases.
Management: NSAIDs are first-line. Treat the triggering infection if Chlamydia identified (doxycycline/azithromycin — and treat partner); antibiotics do NOT help post-dysenteric ReA once arthritis has started. Persistent disease → intra-articular steroids, then sulfasalazine / methotrexate; refractory → TNF inhibitors. Most cases self-limit within 3–12 months.
Enteropathic (IBD-associated) arthropathy
Arthritis associated with Crohn's disease and ulcerative colitis. Two patterns:
| Type | Joints | Relation to gut activity |
|---|---|---|
| Type 1 (pauciarticular) | ≤4 large joints, asymmetric, lower limb | Parallels bowel disease activity; self-limiting |
| Type 2 (polyarticular) | >5 joints, small joints, symmetric | Independent of bowel activity; chronic |
| Axial (sacroiliitis/AS-like) | Spine, SI joints | Independent of bowel activity |
High-yield: Peripheral type 1 enteropathic arthritis improves when the bowel disease is controlled (e.g. after colectomy in UC). Axial disease and type 2 run an independent course. NSAIDs can flare IBD, so use them cautiously; sulfasalazine is useful (treats gut + joints). Anti-TNF (infliximab/adalimumab) treats both bowel and joint disease — preferred in active IBD; etanercept does NOT treat the bowel disease of Crohn's.
Comparison with rheumatoid arthritis (the classic exam contrast)
| Feature | Spondyloarthropathy | Rheumatoid arthritis |
|---|---|---|
| RF / anti-CCP | Negative | Positive |
| HLA association | HLA-B27 | HLA-DR4 / DR1 |
| Primary lesion | Enthesitis | Synovitis |
| Joint distribution | Asymmetric, large, lower limb, axial | Symmetric, small, upper limb (MCP/PIP), spares DIP |
| Spine | SI joints + whole spine | C-spine only (atlanto-axial) |
| New bone | Yes (syndesmophytes, periostitis) | No (only erosions/osteopenia) |
| Sex | Male predominance (AS, ReA) | Female predominance |
| Eye | Anterior uveitis | Scleritis / keratoconjunctivitis sicca |
High-yield: Syndesmophytes (vertical, marginal, AS) vs osteophytes (horizontal, degenerative) vs non-marginal bulky syndesmophytes / "parrot-beak" (psoriatic & reactive). RA does not produce new bone — this single fact answers many questions.
Key differentials
- DISH (Diffuse Idiopathic Skeletal Hyperostosis / Forestier disease): older man, flowing "candle-wax" ossification along ≥4 contiguous vertebrae on the right side of thoracic spine, but SI joints and disc spaces are PRESERVED and it is not inflammatory → distinguishes from AS.
- Mechanical low back pain: worse with activity, relieved by rest, no morning stiffness, normal inflammatory markers.
- Septic arthritis / disseminated gonococcal infection: acute, organism in joint fluid.
- Rheumatoid arthritis: as above.
- Gout / pseudogout and Behçet disease (also HLA-B*51, oral/genital ulcers, uveitis) in relevant scenarios.
Recently asked / exam angle
- "Young man, low back pain worse in the morning, improves with exercise, reduced chest expansion, bilateral sacroiliitis" → ankylosing spondylitis. Next best/early investigation when x-ray normal → MRI SI joints.
- "Most common extra-articular manifestation of AS" → acute anterior uveitis.
- Schober's test description and the >5 cm normal increase cut-off is directly asked.
- "Pencil-in-cup deformity / DIP joint arthritis with nail pitting" → psoriatic arthritis.
- "Arthritis + urethritis + conjunctivitis after dysentery" → reactive arthritis; remember keratoderma blennorrhagicum and circinate balanitis, and that the joint fluid is sterile.
- "Which DMARD is ineffective in axial AS?" → methotrexate / sulfasalazine (axial disease needs biologics).
- "Skin lesion in reactive arthritis resembling pustular psoriasis on soles" → keratoderma blennorrhagicum.
- DISH vs AS differentiation (SI joint sparing + disc space preserved) is a recurring image-based item.
- "Cardiac lesion in AS" → aortic regurgitation and conduction block.
- HLA-B27 highest positivity → ankylosing spondylitis (>90%).
Rapid revision
- SpA = seronegative (RF/anti-CCP negative), HLA-B27 associated, axial + enthesitis, lower-limb asymmetric oligoarthritis.
- Enthesitis is the unifying lesion (vs synovitis in RA).
- AS: young man, bilateral symmetric sacroiliitis, inflammatory back pain improving with exercise.
- Schober's test increase <5 cm = restricted lumbar flexion; chest expansion <2.5 cm abnormal.
- MRI SI joint (STIR, marrow oedema) = earliest/non-radiographic detection; bamboo spine = late.
- Anterior uveitis = most common extra-articular feature of AS; AR is the classic cardiac lesion.
- Axial disease needs NSAIDs → anti-TNF / anti-IL-17; methotrexate/sulfasalazine work only on peripheral joints.
- PsA → DIP joints, pencil-in-cup, nail pitting, dactylitis; sacroiliitis is asymmetric.
- Reactive arthritis → Reiter triad (urethritis + conjunctivitis + arthritis), sterile joint, keratoderma blennorrhagicum, circinate balanitis.
- Enteropathic: type 1 peripheral follows gut activity; axial/type 2 independent; anti-TNF treats both bowel & joint.
- Syndesmophytes (vertical, marginal) in AS; osteophytes (horizontal) in OA; DISH = flowing ossification with preserved SI joints.
- Fused (bamboo) spine fractures with minor trauma → high risk of cord injury — treat as emergency.