High-yield overview
The HLA-B27 Family of Inflammatory Arthritides
HLA-B27Shared genetic association
EnthesitisThe hallmark lesion
SeronegativeRF & anti-CCP negative
Bamboo spineFractures dangerously
The seronegative spondyloarthritis family
Ankylosing spondylitis / axial SpA
PatternPrototype: inflammatory back pain, sacroiliitis, ascending spinal ankylosis (bamboo spine). Strongest HLA-B27 link.
Treatment
Psoriatic arthritis
PatternWith psoriasis; dactylitis, nail changes, DIP involvement, asymmetric oligoarthritis or axial disease.
Treatment
Reactive arthritis (Reiter's)
PatternPost-infective (GU/GI); classic triad arthritis + urethritis + conjunctivitis ('can't see, can't pee, can't climb a tree').
Treatment
Enteropathic (IBD-associated)
PatternArthritis complicating Crohn's/ulcerative colitis; gut-joint axis.
Treatment
Juvenile-onset & undifferentiated
PatternChildhood onset; or features of SpA not meeting a specific subtype.
Treatment
Critical Must-Knows
- The seronegative spondyloarthropathies (SpA) are a FAMILY of inflammatory arthritides that are RHEUMATOID-FACTOR (and anti-CCP) NEGATIVE, share an association with HLA-B27, and present with a characteristic pattern of AXIAL and asymmetric PERIPHERAL (large-joint) arthritis, ENTHESITIS, DACTYLITIS and extra-articular manifestations.
- The family comprises ANKYLOSING SPONDYLITIS / axial SpA, PSORIATIC arthritis, REACTIVE arthritis (Reiter's), ENTEROPATHIC (IBD-associated) arthritis, JUVENILE-onset SpA and undifferentiated SpA - they overlap clinically and share genetic and immunopathogenic mechanisms.
- The unifying clinical features are: INFLAMMATORY BACK PAIN (insidious, onset under 45, morning stiffness over 30 minutes, improves with exercise not rest, night pain, alternating buttock pain) with SACROILIITIS; ENTHESITIS (inflammation at tendon/ligament-bone insertions - the primary lesion of SpA); DACTYLITIS ('sausage digit'); and EXTRA-ARTICULAR manifestations - acute anterior UVEITIS, PSORIASIS, and INFLAMMATORY BOWEL DISEASE (the 'gut-joint axis').
- Unlike rheumatoid arthritis (symmetrical small-joint, RF/anti-CCP positive, erosive), SpA is RF-negative, axial/asymmetric/large-joint, enthesis-centred, and characteristically forms NEW BONE (syndesmophytes, ankylosis) - radiographically sacroiliitis, syndesmophytes and the fused 'BAMBOO SPINE'; MRI sacroiliac BONE-MARROW OEDEMA detects early (non-radiographic) disease.
- Pathogenesis centres on the IL-23/IL-17 axis and HLA-B27 with a strong gut-joint link; treatment is a ladder: NSAIDs and EXERCISE/physiotherapy first-line for AXIAL disease, conventional DMARDs (sulfasalazine/methotrexate) for PERIPHERAL (not axial) disease, and BIOLOGICS - anti-TNF, anti-IL-17 (secukinumab), and JAK inhibitors - for active/refractory disease.
- ORTHOPAEDIC HAZARD: the ANKYLOSED ('bamboo') spine behaves like a long bone and fractures with MINOR trauma - typically UNSTABLE, often EXTENSION-type, three-column injuries that are EASILY MISSED and carry a HIGH risk of spinal-cord injury; image the WHOLE spine (CT, often MRI) and treat as unstable.
Clinical Pearls
- “Seronegative = RF/anti-CCP negative; the family is unified by HLA-B27, enthesitis, dactylitis, inflammatory back pain and the extra-articular triad (uveitis/psoriasis/IBD).
- “SpA makes NEW bone (syndesmophytes/ankylosis, bamboo spine); RA makes erosions - and SpA is axial/asymmetric/large-joint vs RA's symmetric small joints.
- “A fracture in an ankylosed AS spine is unstable until proven otherwise - low-energy, often extension-type, high cord-injury risk; CT the whole spine.
Spondyloarthritis vs Rheumatoid Arthritis
Seronegative spondyloarthritis
RF/anti-CCP negative, HLA-B27 associated. Axial (sacroiliitis/spine) and asymmetric large-joint peripheral arthritis, ENTHESITIS and dactylitis; new-bone formation (syndesmophytes/ankylosis). Extra-articular: uveitis, psoriasis, IBD.
Rheumatoid arthritis
RF/anti-CCP positive, HLA-DR4. Symmetric small-joint (MCP/PIP/wrist) polyarthritis; EROSIVE with joint destruction; subcutaneous nodules. Spares the DIPs and (mostly) the axial skeleton except the cervical spine.
The Family & What Unites It
One Family, Shared Features
The seronegative spondyloarthropathies usually start in the third decade, are rheumatoid-factor negative, carry the HLA-B27 genetic marker, and share clinical features of spinal (axial) and peripheral arthritis, dactylitis, enthesitis and extra-articular manifestations. They are classified as ankylosing spondylitis (now within the axial spondyloarthritis concept), psoriatic arthritis, reactive arthritis, enteropathic (IBD-associated) arthritis, or juvenile-onset / undifferentiated spondyloarthritis. Joint and gut inflammation are intimately linked (the gut-joint axis), with shared genetic and immunopathogenic mechanisms (notably the IL-23/IL-17 pathway).
| 0 | 1 |
|---|---|
| Ankylosing spondylitis / axial SpA | Inflammatory back pain, sacroiliitis, ascending ankylosis; strongest HLA-B27 link |
| Psoriatic arthritis | Psoriasis, nail pitting/onycholysis, DIP involvement, dactylitis; axial or peripheral patterns |
| Reactive arthritis (Reiter's) | 1-4 weeks after GU (Chlamydia) or GI infection; arthritis + urethritis + conjunctivitis |
| Enteropathic (IBD) | Arthritis with Crohn's/ulcerative colitis; peripheral often mirrors gut activity, axial does not |
| Juvenile / undifferentiated | Childhood onset; or SpA features not meeting a single subtype |
Investigations
Seronegative, HLA-B27, and New Bone
- Bloods: RF and anti-CCP NEGATIVE (hence 'seronegative'); HLA-B27 is positive in most (strongest in AS) but is neither necessary nor sufficient; raised CRP/ESR in active disease.
- Radiographs: sacroiliitis (erosion/sclerosis/fusion), syndesmophytes, vertebral 'squaring', and the fused 'BAMBOO SPINE' in advanced AS.
- MRI: detects early disease - bone-marrow oedema at the sacroiliac joints/spine - defining non-radiographic axial SpA before radiographic changes appear. Classification (e.g. the ASAS criteria for axial and peripheral SpA) integrates clinical features, HLA-B27, CRP and imaging.
Management
The Treatment Ladder
- First line (axial disease): NSAIDs and a structured exercise/physiotherapy program - the cornerstone for axial SpA.
- Conventional DMARDs (sulfasalazine, methotrexate): useful for PERIPHERAL arthritis but NOT effective for axial disease.
- Biologics/targeted therapy: anti-TNF agents, anti-IL-17 (secukinumab) and JAK inhibitors for active/refractory axial or peripheral disease; choice is tailored to the EAMs (e.g. an anti-TNF monoclonal for coexisting IBD/uveitis).
- Treat-to-target, early diagnosis and managing comorbidities (osteoporosis, cardiovascular risk) are emphasised. Management is multidisciplinary (rheumatology, and gastroenterology/dermatology/ophthalmology for the EAMs).
The Ankylosed Spine - a Surgical Emergency Waiting to Happen
The fused 'bamboo' spine behaves biomechanically like a long bone: even low-energy trauma can cause a highly unstable, often EXTENSION-type, three-column fracture (frequently through the disc/bone of the rigid segment). These fractures are easily missed on plain films, are prone to displacement and epidural haematoma, and carry a high risk of spinal-cord injury. In any AS patient with new spinal pain after even trivial trauma, assume an unstable fracture, CT (and often MRI) the WHOLE spine, and manage with great care (avoid lying the patient flat if they have a fixed kyphosis - support in their habitual posture).
Evidence & Key Studies
Evidence
Seronegative spondyloarthropathy-associated inflammatory bowel disease
Wang C-R, Tsai H-W • World Journal of Gastroenterology (2023)
Key Findings:
- Seronegative spondyloarthropathy starts in the third decade with negative rheumatoid factor and the HLA-B27 marker, and features spinal and peripheral arthritis, dactylitis, enthesitis and extra-articular manifestations.
- It is classified as ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis or juvenile-onset spondyloarthritis, with joint and gut inflammation intricately linked (shared genetic/immunopathogenic mechanisms).
- Treatment: NSAIDs first-line for peripheral and axial SpA; conventional DMARDs help peripheral but not axial disease or IBD; anti-TNF agents are effective across SpA and IBD; JAK inhibitors are emerging.
Evidence
Clinical management of psoriatic arthritis
Van den Bosch F, Coates L • The Lancet (2018)
Key Findings:
- Psoriatic disease is an inflammatory disorder affecting skin and joints with extra-articular manifestations and comorbidities and a substantial clinical burden.
- Early diagnosis and treatment are crucial to prevent long-term structural damage and disability.
- Biological and targeted synthetic DMARDs have transformed treatment, with strategies including treat-to-target, early remission-induction and tapering.
Evidence Attribution
According to PubMed, the seronegative-SpA definition, the family classification, the shared features and the treatment ladder come from the cited Wang & Tsai review, and the treat-to-target/biologic principles (exemplified in psoriatic arthritis) from the cited Lancet review. The ASAS classification, the inflammatory- back-pain features and the ankylosed-spine fracture hazard are standard, well-established teaching. (See also our Ankylosing Spondylitis, Psoriatic Arthritis, Reactive Arthritis and Rheumatoid Arthritis topics.)
Clinical Decision Scenarios
Practise clinical reasoning and management decisions out loud
Viva scenarioStandard
Clinical prompt
“What unifies the seronegative spondyloarthropathies, what conditions are in the family, and how do they differ from rheumatoid arthritis?”
Practical approach
The seronegative spondyloarthropathies are a family of inflammatory arthritides unified by being rheumatoid-factor and anti-CCP negative, by their association with HLA-B27, and by a characteristic pattern: axial disease with sacroiliitis and inflammatory back pain, asymmetric large-joint peripheral arthritis, enthesitis - which is the defining lesion at tendon and ligament insertions - dactylitis or sausage digits, and extra-articular manifestations, classically acute anterior uveitis, psoriasis and inflammatory bowel disease through the gut-joint axis. The family comprises ankylosing spondylitis, now within axial spondyloarthritis, psoriatic arthritis, reactive arthritis or Reiter's, enteropathic arthritis associated with inflammatory bowel disease, and juvenile-onset or undifferentiated spondyloarthritis. They differ from rheumatoid arthritis in several ways: rheumatoid arthritis is seropositive for rheumatoid factor and anti-CCP, is a symmetrical small-joint polyarthritis of the hands and wrists, and is erosive and destructive, whereas spondyloarthritis is seronegative, axial and asymmetric large-joint, centred on the enthesis rather than the synovium, and characteristically forms new bone - syndesmophytes and ankylosis, the bamboo spine - rather than eroding it.
Key clinical points
Unified by: RF/anti-CCP negative, HLA-B27, axial+asymmetric peripheral, enthesitis, dactylitis, EAMs (uveitis/psoriasis/IBD)
Family: AS/axial SpA, psoriatic, reactive (Reiter's), enteropathic, juvenile/undifferentiated
vs RA: SpA is seronegative, axial/asymmetric/large-joint, enthesis-centred, NEW bone
RA: seropositive, symmetric small-joint, erosive
Common pitfalls
Calling SpA seropositive (it is seronegative)
Forgetting enthesitis as the defining lesion / new-bone (vs RA erosion)
Omitting the extra-articular triad (uveitis/psoriasis/IBD)
Further questions
“Which is the commonest extra-articular manifestation? - Acute anterior uveitis”
“What is the reactive arthritis triad? - Arthritis + urethritis + conjunctivitis”
Viva scenarioStandard
Clinical prompt
“An ankylosing spondylitis patient with a fused spine presents with new neck pain after a minor fall. Why does this worry you, and how do you investigate and manage it?”
Practical approach
This worries me greatly because the ankylosed bamboo spine behaves biomechanically like a long bone, so even low-energy trauma such as a minor fall can cause a highly unstable, typically extension-type, three-column fracture, often through the rigid disc-bone segment, frequently in the cervical spine. These fractures are easily missed on plain radiographs, are prone to displacement and to epidural haematoma, and carry a high risk of spinal-cord injury - so new spinal pain after even trivial trauma in an AS patient is an unstable fracture until proven otherwise. I would immobilise carefully, crucially supporting the patient in their habitual posture and not forcing them flat if they have a fixed kyphosis, which could displace the fracture or compress the cord. I would image the whole spine with CT, because the fracture may be remote from the symptomatic level and plain films are unreliable in the fused osteoporotic spine, and add MRI to assess the cord, ligaments and any epidural haematoma. Management is to treat it as an unstable injury - typically surgical stabilisation, often long-segment fixation given the long lever arms of the fused spine - with meticulous attention to positioning and to the high complication rate in these patients.
Key clinical points
Ankylosed spine = long-bone behaviour -> unstable, often extension-type 3-column fracture from minor trauma
Easily missed; high risk of displacement, epidural haematoma, cord injury
Immobilise in habitual posture (don't force flat); CT the WHOLE spine + MRI
Treat as unstable - usually surgical (long-segment) stabilisation
Common pitfalls
Being reassured by normal plain films / a minor mechanism
Forcing the kyphotic patient supine (can displace fracture/cord)
Imaging only the painful level (fracture may be remote)
Further questions
“Why CT the whole spine? - Fractures are easily missed and may be at a different level in a fused spine”
“Typical fracture type? - Unstable extension-type three-column injury”
Mnemonics & Memory Aids
Mnemonic
PAIR
P
Psoriatic arthritis
A
Ankylosing spondylitis (axial SpA) - the prototype
I
Inflammatory bowel disease-associated (enteropathic)
R
Reactive arthritis (Reiter's) - post-infective
Hook:The seronegative SpA family is a PAIR: Psoriatic, Ankylosing, IBD-associated, Reactive (+ juvenile/undifferentiated).
Mnemonic
SPINEACHE
S
Sausage digit (dactylitis)
P
Psoriasis
I
Inflammatory back pain
N
NSAID response (good)
E
Enthesitis
A
Arthritis (asymmetric, large-joint) + Anterior uveitis
C
Crohn's/Colitis (IBD)
HE
HLA-B27 + Elevated CRP
Hook:SPINEACHE captures the spondyloarthritis features - the classic SpA screening checklist.
Exam day cheat sheet
Seronegative Spondyloarthropathy - Exam Day Cheat Sheet
The family & what unites it
- RF/anti-CCP negative; HLA-B27 associated
- AS/axial SpA, psoriatic, reactive (Reiter's), enteropathic (IBD), juvenile/undifferentiated
- Shared: inflammatory back pain/sacroiliitis, enthesitis, dactylitis, EAMs (uveitis/psoriasis/IBD)
vs RA
- SpA: seronegative, axial/asymmetric large-joint, enthesis-centred, NEW bone (syndesmophytes/ankylosis)
- RA: seropositive, symmetric small-joint, erosive
- SpA spares synovium-first pattern; enthesitis is the defining lesion
Investigations
- RF/anti-CCP negative; HLA-B27 (not necessary/sufficient); CRP/ESR up
- X-ray: sacroiliitis, syndesmophytes, bamboo spine
- MRI: sacroiliac bone-marrow oedema (non-radiographic axial SpA); ASAS criteria
Management & ortho hazard
- NSAIDs + exercise first-line (axial); DMARDs for peripheral only; biologics (anti-TNF/IL-17, JAK)
- Treat-to-target; manage EAMs and comorbidities (osteoporosis, CV risk)
- Ankylosed (bamboo) spine: unstable extension fractures from minor trauma - CT whole spine, treat as unstable