seronegative spondyloarthritis
Summary
Seronegative spondyloarthritis (SpA) is a group of inflammatory arthritides characterized by axial and/or peripheral joint involvement, enthesitis, and absence of rheumatoid factor (RF) and anti-CCP antibodies. Strongly associated with HLA-B27. Includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, enteropathic arthritis (IBD-associated), and undifferentiated SpA.
Detail
Seronegative spondyloarthropathies are a family of related inflammatory joint diseases unified by: (1) negative RF and anti-CCP ('seronegative'), (2) strong association with HLA-B27, (3) involvement of the axial skeleton (sacroiliac joints, spine) causing inflammatory back pain, (4) enthesitis (inflammation at tendon/ligament insertion sites, e.g., Achilles tendinitis, plantar fasciitis), (5) asymmetric oligoarthritis of large joints, and (6) extra-articular manifestations including anterior uveitis, psoriasiform skin lesions, and IBD-like gut inflammation.
Pathophysiology: HLA-B27 is thought to misfold proteins, trigger ER stress, or present arthritogenic peptides to CD8+ T cells, leading to chronic inflammation at entheses and synovium. There is significant overlap with Th17 pathway activation (IL-17/IL-23 axis), which is a target for biologic therapy (e.g., secukinumab).
Members of the group: - Ankylosing spondylitis: progressive sacroiliitis and spinal fusion ('bamboo spine'), inflammatory back pain improving with exercise, worse with rest, young males, HLA-B27 >90%. - Reactive arthritis (formerly Reiter syndrome): post-infectious (Chlamydia, Shigella, Salmonella, Campylobacter, Yersinia), classic triad of arthritis, conjunctivitis/uveitis, urethritis ('can't see, can't pee, can't climb a tree'). - Psoriatic arthritis: associated with psoriasis, dactylitis ('sausage digits'), nail pitting, 'pencil-in-cup' deformity on X-ray. - Enteropathic arthritis: associated with IBD (Crohn's, UC), peripheral arthritis often correlates with bowel disease activity, axial disease does not. - Undifferentiated SpA: features of SpA without fitting a specific category.
Clinical clues for Step exams: Inflammatory back pain (improves with activity, morning stiffness >30 min, age <40, insidious onset), enthesitis, dactylitis, uveitis, and negative RF/anti-CCP with elevated ESR/CRP but negative ANA. Imaging shows sacroiliitis on X-ray/MRI. Treatment includes NSAIDs first-line, then TNF-inhibitors or IL-17 inhibitors for refractory axial disease.
Sources
- First Aid for the USMLE Step 1
- Robbins Basic Pathology
- UpToDate: Overview of seronegative spondyloarthritis
- Kaplan USMLE Step 1 Lecture Notes - Immunology/Rheumatology
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