Spondyloarthritis¶
Chapter 374 | Part 11: Immune-Mediated, Inflammatory, and Rheumatologic Disorders
KEY CLINICAL POINTS¶
- Spondyloarthritis (SpA) is a group of immune-mediated inflammatory disorders characterized by axial and peripheral musculoskeletal involvement, including sacroiliitis, enthesitis, dactylitis, and uveitis.
- Axial SpA (axSpA) includes ankylosing spondylitis (AS) and non-radiographic axial SpA (nr-axSpA), while peripheral SpA (pSpA) encompasses psoriatic arthritis (PsA), reactive arthritis (ReA), and inflammatory bowel disease (IBD)-associated arthritis.
- HLA-B27 is a major genetic risk factor for axSpA, but not for IBD, and its role in pathogenesis involves immune dysregulation, cytokine pathways (TNF- α , IL-17), and microbial interactions.
- Diagnosis relies on clinical patterns (inflammatory back pain, enthesitis, dactylitis), imaging (MRI for early sacroiliitis), and classification criteria (ASAS, CASPAR).
- Treatment includes NSAIDs, csDMARDs, biologics (TNFi, IL-17i, JAKi), and targeted therapies, with emphasis on early intervention to prevent structural damage.
1. DEFINITION & OVERVIEW¶
Spondyloarthritis (SpA) is a family of immune-mediated inflammatory disorders characterized by chronic inflammation of the axial skeleton (sacroiliac joints, spine) and peripheral joints, entheses, and extra-articular manifestations (e.g., uveitis, psoriasis). Axial SpA (axSpA) includes ankylosing spondylitis (AS) and non-radiographic axial SpA (nr-axSpA), while peripheral SpA (pSpA) includes psoriatic arthritis (PsA), reactive arthritis (ReA), and IBD-associated arthritis. SpA is distinguished by asymmetric joint involvement, enthesitis, and dactylitis, with HLA-B27 as a key genetic marker.
Table 374-1 Spectrum of Spondyloarthritis¶
| CONDITION | CLINICAL FEATURES |
|---|---|
| AXIAL SPONDYLOARTHRITIS (axSpA) | Sacroiliitis, spinal inflammation, enthesitis, dactylitis, uveitis, IBD |
| PERIPHERAL SPONDYLOARTHRITIS (pSpA) | Psoriatic arthritis, reactive arthritis, IBD-associated arthritis, undifferentiated SpA |
1.1 Classification¶
SpA is divided into axial (axSpA) and peripheral (pSpA) subtypes. AxSpA includes radiographic (AS) and non-radiographic (nr-axSpA) forms. pSpA encompasses PsA, ReA, IBD-associated arthritis, and undifferentiated SpA. The 2009 ASAS criteria classify SpA based on clinical features (inflammatory back pain, enthesitis, dactylitis) and imaging (sacroiliitis).
1.2 Key Features¶
SpA is characterized by chronic inflammation of the axial skeleton (sacroiliitis, ankylosis), peripheral joints (asymmetric oligoarthritis), enthesitis, dactylitis, and extra-articular manifestations (uveitis, psoriasis, IBD). The disease is associated with HLA-B27 in axSpA but not IBD.
2. EPIDEMIOLOGY¶
The prevalence of SpA is 2–3% globally, with a male-to-female ratio of 2:1 for axial SpA and 1:1 for peripheral SpA. HLA-B27 frequency varies geographically, with higher prevalence in northern Europe (9%) compared to southern regions (7%). The risk of developing AS is 5% in HLA-B27-positive individuals and 20% in first-degree relatives of affected patients. IBD-associated arthritis is more common in patients with SpA, with a prevalence of 5–10%.
2.1 Demographics¶
Axial SpA (AS) is more common in males (2:1 ratio), while peripheral SpA (pSpA) is equally prevalent in both sexes. The median age of onset for axial SpA is 20–30 years, with a male predominance. IBD-associated arthritis is more prevalent in patients with long-standing SpA.
2.2 Risk Factors¶
Genetic predisposition (HLA-B27), environmental triggers (microbial infections), and immune dysregulation contribute to SpA risk. Smoking and obesity exacerbate disease activity and complications (e.g., osteoporosis).
3. ETIOLOGY & PATHOPHYSIOLOGY¶
SpA is driven by genetic (HLA-B27), environmental (microbial infections), and immune factors. HLA-B27 promotes microbial peptide presentation to CD8+ T cells, leading to immune activation. Pathogenesis involves cytokine pathways (TNF- α , IL-17), gut microbiome dysbiosis, and mechanical stress at entheses. The role of HLA-B23 in IBD is less clear, with no direct genetic link.
Table 374-2 Modified New York Classification Criteria for Ankylosing Spondylitis (AS)¶
| CLINICAL CRITERIA | RADIOGRAPHIC CRITERIA |
|---|---|
| Low back pain >3 months, improvement with exercise, morning stiffness >30 min | Bilateral sacroiliitis grade 2 or unilateral grade 3/4 on x-ray |
| Limited lumbar motion, reduced chest expansion | Sacroiliitis grade 2 or higher |
3.1 Genetic Factors¶
HLA-B27 is a major genetic risk factor for axial SpA but not IBD. Other genes (e.g., IL-23R, IL-12p40) are implicated in both SpA and IBD. HLA-B27 variants (e.g., B2704, B2705) confer higher risk, while B2706 and B2709 are not associated with SpA.
3.2 Immune Mechanisms¶
SpA involves dysregulated T-cell responses, cytokine storms (TNF- α , IL-17), and innate immune activation. Microbial antigens (e.g., Chlamydia, Salmonella) and mechanical stress at entheses drive inflammation. IL-23/IL-17 pathways are central to pathogenesis.
4. CLINICAL FEATURES¶
SpA presents with axial (sacroiliitis, spinal inflammation) and peripheral (asymmetric oligoarthritis, enthesitis, dactylitis) involvement. Extra-articular manifestations include uveitis, psoriasis, IBD, and skin lesions (e.g., keratoderma blennorrhagica). Inflammatory back pain (IBP) is characterized by morning stiffness, nocturnal pain, and improvement with activity.
Table 374-3 Grading of Sacroiliitis¶
| GRADE | DESCRIPTION |
|---|---|
| Grade 0 | Normal |
| Grade 1 | Suspicious change |
| Grade 2 | Minimum abnormality (erosions, sclerosis) |
| Grade 3 | Unequivocal abnormality (moderate sacroiliitis) |
| Grade 4 | Severe abnormality (total ankylosis) |
4.1 Axial Involvement¶
Axial SpA (AS) presents with chronic low back pain, sacroiliitis, and spinal ankylosis (bamboo spine). Inflammatory back pain (IBP) is insidious, improves with exercise, and worsens at night. Radiographic features include marginal sclerosis, erosions, and syndesmophyte formation.
4.2 Peripheral Involvement¶
Peripheral SpA (pSpA) includes asymmetric oligoarthritis, enthesitis, dactylitis, and skin manifestations (psoriasis, acne). Psoriatic arthritis (PsA) is associated with nail changes, dactylitis, and joint destruction. IBD-associated arthritis co-occurs with Crohn’s or ulcerative colitis.
5. DIFFERENTIAL DIAGNOSIS¶
SpA must be differentiated from mechanical back pain, rheumatoid arthritis (RA), and other inflammatory conditions. Key differentiators include asymmetric joint involvement, enthesitis, dactylitis, and HLA-B27 positivity. IBD-associated arthritis overlaps with SpA but lacks HLA-B27 association.
5.1 Mechanical Back Pain¶
Mechanical back pain is non-inflammatory, improves with rest, and lacks axial involvement. It is common in the general population and lacks the inflammatory markers (ESR, CRP) seen in SpA.
5.2 Rheumatoid Arthritis¶
RA is symmetric, involves small joints, and lacks enthesitis or dactylitis. SpA is asymmetric with peripheral arthritis and axial involvement. HLA-B27 is not a feature of RA.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis of SpA relies on clinical patterns (inflammatory back pain, enthesitis), imaging (MRI for early sacroiliitis), and classification criteria (ASAS, CASPAR). Laboratory tests (ESR, CRP) reflect disease activity, while HLA-B27 is a supportive marker.
Table 374-4 Clinical Features of Inflammatory vs Mechanical Back Pain¶
| FEATURE | INFLAMMATORY BACK PAIN | MECHANICAL BACK PAIN |
|---|---|---|
| Age at onset | Before 40–45 years | 20–65 years |
| Morning stiffness | Prolonged (>30 min) | Less than 30 min |
| Improvement with exercise | Improves pain and stiffness | Worsens pain |
| FEATURE | INFLAMMATORY BACK PAIN | MECHANICAL BACK PAIN |
|---|---|---|
| Night pain | Yes, after midnight | No, late in the day |
| Duration | Chronic | Acute or chronic |
6.1 Imaging¶
MRI is the gold standard for early sacroiliitis detection, showing bone marrow edema and fatty metaplasia. X-rays are used for late-stage assessment (sclerosis, syndesmophytes). Ultrasound detects enthesitis and synovitis.
6.2 Classification Criteria¶
ASAS criteria for axial SpA require inflammatory back pain, sacroiliitis on imaging, and ≥ 4 of 6 features (psoriasis, IBD, family history, HLA-B27, uveitis, enthesitis). CASPAR criteria for PsA include inflammatory arthritis, psoriasis, and ≥ 3 of 5 features (dactylitis, nail changes, family history, HLA-B27, radiographic evidence).
7. MANAGEMENT & TREATMENT¶
Treatment of SpA includes NSAIDs, csDMARDs (sulfasalazine, methotrexate), biologics (TNFi, IL-17i, JAKi), and targeted therapies. Early intervention is critical to prevent structural damage. Biologics are preferred for axial SpA, while IL-17i and JAKi are effective for PsA.
Table 374-5 Pharmacologic Management of Axial Spondyloarthritis (axSpA)¶
| DRUG CLASS | EXAMPLES | USES |
|---|---|---|
| NSAIDs | Ibuprofen, naproxen | Mild axial/pain, short-term use |
| csDMARDs | Sulfasalazine, methotrexate | Peripheral arthritis, enthesitis |
| TNFi | Etanercept, adalimumab | Axial SpA, IBD-associated arthritis |
| IL-17i | Secukinumab, ixekizumab | PsA, axial SpA |
| JAKi | Upadacitinib | Axial SpA after TNFi failure |
7.1 Pharmacologic Interventions¶
NSAIDs (e.g., ibuprofen) are first-line for mild disease. Biologics (TNFi, IL-17i, JAKi) are used for active disease. IL-17i (secukinumab, ixekizumab) and JAKi (upadacitinib) are preferred for PsA. TNFi (etanercept, adalimumab) are effective for axial SpA.
7.2 Surgical Interventions¶
Total hip arthroplasty is indicated for refractory hip pain in axSpA. Spinal surgery is reserved for severe kyphotic deformities. Biologics are contraindicated in active infections.
8. PROGNOSIS & COMPLICATIONS¶
SpA has a variable prognosis, with chronic inflammation leading to structural damage (ankylosis, joint destruction). Complications include osteoporosis, cardiovascular disease, and uveitis. Early treatment reduces disability, but long-term risks (e.g., cardiovascular events) persist.
8.1 Long-Term Outcomes¶
Axial SpA (AS) may progress to ankylosis, while peripheral SpA (pSpA) is more likely to involve joint destruction. Early treatment with biologics improves outcomes but does not eliminate long-term risks.
8.2 Complications¶
Complications include osteoporosis (25% after 10 years), cardiovascular disease (linked to chronic inflammation), and uveitis (10% of patients). IBD-associated arthritis increases risk of Crohn’s disease progression.
9. SPECIAL CONSIDERATIONS¶
SpA management must address pregnancy, pediatric cases, and elderly patients. HLA-B27 is not a contraindication for pregnancy, but biologics (e.g., TNFi) are used cautiously. Pediatric SpA (juvenile SpA) requires early intervention to prevent joint damage. Elderly patients face higher risks of osteoporosis and cardiovascular complications.
9.1 Pregnancy¶
NSAIDs are avoided in late pregnancy. TNFi (e.g., infliximab) are used cautiously, while IL-17i and JAKi are contraindicated. Methotrexate is avoided due to teratogenic risks.
9.2 Pediatrics¶
Juvenile SpA (JSpA) presents with axial or peripheral involvement, enthesitis, and dactylitis. Early diagnosis and biologic therapy (TNFi) are critical to prevent structural damage.
10. KEY POINTS & CLINICAL PEARLS¶
- SpA is a heterogeneous group of disorders with axial and peripheral involvement, requiring tailored management.
- HLA-B27 is a key genetic marker for axial SpA but not IBD.
- Early diagnosis with MRI and ASAS criteria improves outcomes.
- Biologics (TNFi, IL-17i, JAKi) are effective for active disease, with careful monitoring for infections.
- Multidisciplinary care (rheumatology, dermatology, gastroenterology) is essential for comorbidities like IBD and psoriasis.