Immunology · Year 2 · from Immunology
Case 2: Ankylosing Spondylitis (HLA-B27 Association)
Patient Demographics
- Age: 28 years old
- Sex: Male
- Ethnicity: Caucasian
Chief Complaint
Chronic low back pain and morning stiffness
History of Present Illness
A 28-year-old man presents with a 2-year history of low back pain that began insidiously without any trauma. The pain is worst in the morning, accompanied by 2 hours of stiffness, and improves with exercise but not with rest. He has noticed decreased flexibility in his lower back. NSAIDs provide moderate relief. He also reports an episode of painful red eye 6 months ago diagnosed as acute anterior uveitis.
Past Medical History
- Acute anterior uveitis (iritis) 6 months ago - treated with topical steroids
- No history of psoriasis, inflammatory bowel disease, or reactive arthritis
Family History
- Father has "bad back" and required hip replacement at age 55
- Paternal uncle diagnosed with ankylosing spondylitis
Physical Examination
- General: Well-appearing young man
- Vital Signs: Normal
- Spine:
- Loss of normal lumbar lordosis
- Reduced chest expansion (3 cm; normal >5 cm)
- Positive modified Schober test (4 cm expansion; normal >5 cm)
- Limited lateral flexion
- Tenderness over sacroiliac joints bilaterally
- Eyes: Currently normal; history of previous iritis
- MSK: No peripheral joint swelling
Laboratory Workup
| Test | Result | Reference Range |
|---|---|---|
| ESR | 45 mm/hr | 0-15 mm/hr |
| CRP | 28 mg/L | <3 mg/L |
| HLA-B27 | Positive | Present in 8% of Caucasians |
| RF | Negative | -- |
| Anti-CCP | Negative | -- |
| ANA | Negative | -- |
| CBC | Normal | -- |
| Sacroiliac joint XR | Bilateral sacroiliitis (grade 2-3) | Normal |
| MRI sacroiliac joints | Bilateral bone marrow edema, erosions | Normal |
Clinical Image
Image showing bilateral sacroiliitis with joint space narrowing and sclerosis, characteristic of ankylosing spondylitis. Image source: Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Bilateral_sacroiliitis.jpg). Licensed under CC BY-SA 3.0.
Diagnosis
Ankylosing Spondylitis - an HLA-B27-associated spondyloarthropathy.
Discussion
Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the axial skeleton, with the strongest known HLA-disease association:
HLA-B27 and Disease:
- ~90% of AS patients are HLA-B27 positive
- HLA-B27 is present in only ~8% of the general Caucasian population
- Relative risk: HLA-B27+ individuals have ~100x increased risk of AS
- However, most HLA-B27+ individuals never develop AS (~5% lifetime risk)
Proposed mechanisms for HLA-B27 association:
- Arthritogenic peptide hypothesis: HLA-B27 presents specific self-peptides that trigger autoreactive CD8+ T cells
- HLA-B27 misfolding: Misfolded HLA-B27 in the ER triggers the unfolded protein response, causing IL-23 production and Th17 activation
- HLA-B27 homodimers: Cell surface HLA-B27 homodimers activate NK cells and Th17 cells
Clinical features of AS:
- Inflammatory back pain (morning stiffness >30 min, improves with exercise)
- Sacroiliitis (hallmark finding on imaging)
- Progressive spinal fusion ("bamboo spine")
- Extra-articular manifestations:
- Acute anterior uveitis (25-30%)
- Inflammatory bowel disease
- Aortitis, conduction abnormalities
- Apical pulmonary fibrosis
Other HLA-B27-associated spondyloarthropathies:
- Reactive arthritis
- Psoriatic arthritis (axial)
- IBD-associated arthritis
- Juvenile spondyloarthropathy
Treatment
- NSAIDs: First-line; continuous use may slow radiographic progression
- Physical therapy: Essential for maintaining mobility
- TNF inhibitors: For inadequate response to NSAIDs (adalimumab, etanercept, infliximab)
- IL-17 inhibitors: Secukinumab, ixekizumab - effective for AS
- Treatment of uveitis: Topical steroids; biologics reduce recurrence
- Smoking cessation: Smoking worsens outcomes