Can you provide a high-yield long-case exam guide for ankylosing spondylitis, including typical history, signs and symptoms, physical examination findings, differential diagnoses, investigations, and management?

High-Yield Long Case Exam Guide for Ankylosing Spondylitis

Typical History

Look for inflammatory back pain (IBP) in patients <45 years old 1, 2. IBP has five key features that distinguish it from mechanical pain:

• Insidious onset (not from trauma)
• Age of onset <40 years (rarely starts after age 45)
• Morning stiffness >30 minutes
• Improvement with exercise but NOT with rest
• Pain in the second half of the night that awakens the patient
• Duration >3 months 2, 3

Additional historical red flags:

• Alternating buttock pain (suggests sacroiliitis) 2
• Family history of SpA (strong genetic component)
• Associated conditions: recurrent uveitis, psoriasis, inflammatory bowel disease 4, 5
• Peripheral arthritis (asymmetric oligoarthritis, lower limb predominance) 1
• Enthesitis (heel pain, Achilles tendon, plantar fasciitis) 1

Common pitfall: The mean delay from symptom onset to diagnosis is 4.9 years 1. Don't dismiss chronic back pain in young patients as "mechanical" without screening for inflammatory features.

Physical Examination Findings

Spinal Assessment

• Schober's test: <5 cm expansion (measures lumbar flexion)
• Chest expansion: <5 cm (age/sex adjusted) indicates thoracic involvement 6
• Occiput-to-wall distance: >0 cm indicates cervical spine involvement
• Lateral spinal flexion: Reduced in both sagittal and frontal planes 6
• Cervical rotation: Reduced
• Thoracolumbar kyphosis: Loss of normal lumbar lordosis, increased thoracic kyphosis in advanced disease

Sacroiliac Joint Assessment

• FABER test (Flexion, ABduction, External Rotation)
• Gaenslen's test
• Sacroiliac compression test
• Tenderness over SI joints

Peripheral Examination

• Enthesitis: Achilles insertion, plantar fascia, patellar tendon, tibial tuberosity 6
• Peripheral arthritis: Asymmetric oligoarthritis, lower limbs
• Dactylitis: "Sausage digits" (less common than in psoriatic arthritis)

Extra-articular Manifestations

• Acute anterior uveitis: Red, painful eye with photophobia (occurs in 25-40% of patients)
• Psoriatic skin lesions
• Signs of inflammatory bowel disease

Differential Diagnoses

Key differentials to exclude:

1. Mechanical low back pain: No morning stiffness, worse with activity, improves with rest, no inflammatory features
2. Diffuse idiopathic skeletal hyperostosis (DISH): Older patients, flowing ossification, preserved disc spaces
3. Psoriatic arthritis: Can have axial involvement but often more peripheral/DIP joints
4. Reactive arthritis: Acute onset, preceding infection, conjunctivitis, urethritis
5. Enteropathic arthritis: Associated with active IBD
6. Spinal infection: Fever, acute onset, elevated WBC
7. Malignancy: Age >50, progressive pain, night pain not relieved by position
8. Compression fracture: Especially in established AS (brittle spine)

Investigations

Laboratory Tests

• HLA-B27: Positive in 74-89% of AS patients 1, but present in 8% of general population (not diagnostic alone)
• CRP and ESR: Elevated in ~50% of active disease 2, 7
• Complete blood count: Rule out infection, anemia of chronic disease
• Rheumatoid factor and anti-CCP: Negative (helps exclude RA)

Important caveat: Normal inflammatory markers do NOT exclude AS 7.

Imaging

First-line imaging 2:

• Plain radiographs of pelvis/SI joints (AP view): Look for bilateral sacroiliitis

  • Grade 2 bilaterally OR Grade 3-4 unilaterally = positive by modified New York criteria 6
  • Findings: erosions, sclerosis, joint space narrowing, ankylosis
  • Limitation: Changes lag 7+ years behind symptoms 2

• Spine radiographs (AP and lateral):

  • Squaring of vertebral bodies
  • Syndesmophytes (vertical ossification)
  • "Bamboo spine" in advanced disease
  • "Dagger sign" (ossification of supraspinous/interspinous ligaments)

Second-line imaging when radiographs are negative 2:

• MRI of sacroiliac joints WITHOUT contrast (rating: 9/9 - usually appropriate) 2

  • STIR or T2 fat-saturated sequences show bone marrow edema
  • Detects "pre-radiographic" inflammation
  • Contrast generally NOT necessary (rating: 5/9 with disagreement) 2

• MRI of spine if spinal symptoms present 2

Usually NOT appropriate 2:

• CT with contrast (rating: 1/9)
• Bone scan with SPECT (rating: 1/9)
• FDG-PET/CT (rating: 1/9)

Diagnostic Criteria

Modified New York Criteria (1984) 6:

• Radiological: Sacroiliitis grade ≥2 bilaterally OR grade 3-4 unilaterally
• PLUS at least 2 of 3 clinical criteria:
  1. Low back pain >3 months, improves with exercise, not relieved by rest
  2. Limitation of lumbar spine motion (sagittal and frontal planes)
  3. Reduced chest expansion (age/sex adjusted)

ASAS Classification Criteria (for axial SpA, includes pre-radiographic):

• Sacroiliitis on imaging (radiographs or MRI) PLUS ≥1 SpA feature
• OR HLA-B27 positive PLUS ≥2 SpA features

Management

Treatment Algorithm

Step 1: Non-pharmacological (ALL patients) 4, 6:

• Patient education (disease course, prognosis, treatment options)
• Regular exercise program (daily stretching, strengthening)
• Physical therapy (individual or group sessions) 4, 6
• Smoking cessation (associated with worse outcomes)
• Posture training

Step 2: First-line pharmacological 4, 6, 5:

• NSAIDs at full anti-inflammatory doses (rating: strongly recommended) 4, 6
• Continuous NSAID therapy preferred over on-demand for persistently active disease 4, 5
• Consider cardiovascular, GI, and renal risks when prescribing 4
• COX-2 selective NSAIDs may be preferred for long-term use (lower GI toxicity) 3

Step 3: Local corticosteroid injections 4, 6:

• SI joint injections for persistent sacroiliitis
• Intra-articular injections for peripheral arthritis
• Periarticular injections for enthesitis
• Systemic corticosteroids NOT recommended for axial disease 4, 6

Step 4: Conventional DMARDs 4, 6:

• NO evidence for efficacy in axial disease (methotrexate, sulfasalazine) 4, 6
• Sulfasalazine may be considered ONLY for peripheral arthritis 4, 6
• Do NOT delay biologics by trying DMARDs first for axial disease 4

Step 5: Biologic/Targeted Synthetic DMARDs 5, 7:

Indications for starting biologics 4, 6:

• BASDAI ≥4 (0-10 scale) OR ASDAS ≥2.1
• Persistently high disease activity despite NSAIDs (adequate trial of ≥2 NSAIDs)
• PLUS at least one of: elevated CRP, MRI inflammation, or radiographic sacroiliitis 5

Choice of biologic 5, 7:

1. First-line: TNF inhibitors (infliximab, adalimumab, etanercept, golimumab, certolizumab)

   • All TNFi have similar efficacy for axial disease 4
   • TNF monoclonal antibodies preferred if:
     • Recurrent uveitis 5, 7
     • Active inflammatory bowel disease 4, 5

2. Second-line: IL-17 inhibitors (secukinumab, ixekizumab)

   • Preferred over TNFi if:
     • Significant psoriasis 5, 7
   • Consider as first biologic if primary non-response to first TNFi 5

3. Third-line: JAK inhibitors (tofacitinib)

   • TNFi and IL-17i favored over JAK inhibitors 5

Important: NO evidence to support mandatory DMARD use before or with biologics for axial disease 4, 6, 5.

Step 6: Treatment failure 5, 7:

• Re-evaluate diagnosis and consider comorbidities 5
• If confirmed active axSpA: Switch to another biologic
• Switching to second TNFi may be beneficial, especially with loss of response 4
• Consider switching class (TNFi → IL-17i or vice versa) 5

Step 7: Stable disease 5, 7:

• Tapering biologics may be considered in sustained remission 4, 5
• Do NOT discontinue abruptly 5
• Do NOT use strict treat-to-target strategy (conditionally recommended against) 7

Surgical Management

Total hip arthroplasty 4, 6:

• Strongly indicated for refractory hip pain or disability with radiographic damage
• Independent of age 4, 6

Spinal corrective osteotomy 4:

• Consider for severe disabling deformity (severe kyphosis)

Acute vertebral fracture 4:

• Consult spinal surgeon immediately
• AS patients have brittle, ankylosed spines prone to unstable fractures 8

Disease Monitoring 4, 6, 7

Regular monitoring should include:

• Patient-reported outcomes: BASDAI, BASFI questionnaires 7
• Clinical examination: Spinal mobility measures (Schober's, chest expansion, occiput-to-wall)
• Inflammatory markers: CRP/ESR 7
• Imaging:
  • Spinal radiographs: NOT more frequently than every 2 years unless clinically indicated 4
  • MRI: Only if disease activity unclear while on treatment 7

Screening for complications:

• DXA scan for osteoporosis: Recommended, especially with syndesmophytes/fusion 7
• Cardiovascular risk assessment: AS increases CV risk
• Ophthalmology referral: For any eye symptoms (acute uveitis requires urgent treatment) 7
• Do NOT routinely screen with ECG or echocardiogram 7

Extra-articular Manifestations Management

Acute anterior uveitis 7:

• Immediate ophthalmology referral (strongly recommended)
• Topical corticosteroids for acute episodes
• TNF monoclonal antibodies for recurrent episodes 7

Inflammatory bowel disease 7:

• TNF monoclonal antibodies preferred (not etanercept)
• No specific NSAID preferred to avoid IBD flares 7

Psoriasis 5, 7:

• IL-17 inhibitors preferred if significant skin involvement

High-Yield Discussion Points

Genetic associations:

• HLA-B27 accounts for ~20% of genetic risk 9
• Over 100 genes associated with AS susceptibility 9
• IL-23/IL-17 axis crucial in pathogenesis 9

Prognosis factors:

• Hip involvement = poor prognostic indicator
• Elevated CRP = more active disease
• Early diagnosis and treatment improves outcomes 3

Common pitfalls:

1. Waiting for radiographic changes (7+ year delay) 2
2. Dismissing normal CRP/ESR as excluding AS
3. Using DMARDs before biologics for axial disease (no evidence) 4, 6
4. Missing acute vertebral fractures in ankylosed spine 4
5. Not screening for extra-articular manifestations

Prevalence: 0.2-1.4% in adults; up to 5% of chronic back pain is due to axSpA 1, 2.