Spondyloarthropathies: Ankylosing Spondylitis, Psoriatic Arthritis, and Reactive Arthritis

Spondyloarthropathies (SpA) are a family of chronic inflammatory rheumatic diseases characterized by inflammation of the spine, sacroiliac joints, and entheses (sites where tendons and ligaments attach to bone). The three major subtypes are ankylosing spondylitis (AS), psoriatic arthritis (PsA), and reactive arthritis (ReA).

[KEY_CONCEPT] All spondyloarthropathies share common features: axial involvement, asymmetric oligoarthritis, enthesitis, and strong association with HLA-B27.

Pathophysiology:

• Genetic predisposition: HLA-B27 positive in 90-95% of AS patients, 60-70% of ReA, and 60% of PsA with axial involvement
• Molecular mimicry: Environmental triggers (bacterial infections in ReA) may cross-react with HLA-B27
• IL-23/IL-17 pathway: Central inflammatory cascade driving chronic inflammation
• Enthesitis: Primary pathologic process affecting fibrocartilaginous insertions

Epidemiology:

• AS: Prevalence 0.2-0.5%; male predominance 3:1; onset typically 20-30 years
• PsA: Affects 30% of psoriasis patients; equal gender distribution; onset 30-50 years
• ReA: Incidence 0.6-28/100,000; male predominance 9:1; onset weeks to months after triggering infection

[CLINICAL_PEARL] The "PAIR" mnemonic helps remember shared features: Psoriasis, Arthritis, Iritis (uveitis), Rash (keratoderma blennorrhagicum in ReA).

Ankylosing Spondylitis:

• Inflammatory back pain: Insidious onset, morning stiffness >30 minutes, improves with exercise
• Reduced spinal mobility: Loss of lumbar lordosis, thoracic kyphosis, "question mark" posture
• Sacroiliitis: Bilateral, symmetric involvement causing buttock pain
• Extra-articular: Acute anterior uveitis (25-30%), aortic regurgitation, apical pulmonary fibrosis

Psoriatic Arthritis:

• Five clinical patterns: Symmetric polyarthritis (40%), asymmetric oligoarthritis (35%), DIP involvement (10%), arthritis mutilans (5%), spondylitis (10%)
• Dactylitis: "Sausage digits" from tenosynovitis and joint inflammation
• Enthesitis: Achilles tendon, plantar fascia insertion pain
• Nail changes: Pitting, onycholysis, oil spots in 80% of patients
• Skin psoriasis: May precede, follow, or occur simultaneously with arthritis

Reactive Arthritis:

• Classic triad (20% of patients): Arthritis, urethritis, conjunctivitis
• Triggering infections:
  • Genitourinary: Chlamydia trachomatis
  • Gastrointestinal: Salmonella, Shigella, Campylobacter, Yersinia
• Mucocutaneous features: Keratoderma blennorrhagicum (palms/soles), circinate balanitis, oral ulcers

[HIGH_YIELD] Inflammatory vs. Mechanical Back Pain Comparison:

Modified New York Criteria for Ankylosing Spondylitis:

Clinical Criteria:

• Low back pain ≥3 months duration, improved by exercise, not relieved by rest
• Limitation of lumbar spine motion in sagittal and frontal planes
• Chest expansion decreased relative to age/sex norms

Radiological Criterion:

• Sacroiliitis grade 2 bilaterally OR grade 3-4 unilaterally

Diagnosis: Definite AS requires radiological criterion PLUS ≥1 clinical criterion

[KEY_CONCEPT] ASAS Classification Criteria (newer, includes non-radiographic axial SpA):

• Sacroiliitis on imaging PLUS ≥1 SpA feature, OR
• HLA-B27 positive PLUS ≥2 SpA features

Classification of Psoriatic Arthritis (CASPAR) Criteria:

Established inflammatory arthritis (joint, spine, or entheseal) PLUS ≥3 points:

• Current psoriasis (2 points)
• History of psoriasis (1 point)
• Family history of psoriasis (1 point)
• Typical psoriatic nail dystrophy (1 point)
• Negative rheumatoid factor (1 point)
• Current or history of dactylitis (1 point)
• Radiographic evidence of juxta-articular new bone formation (1 point)

Laboratory Studies:

• HLA-B27: Supportive but not diagnostic (present in 8% of general population)
• Inflammatory markers: ESR, CRP elevated during active disease
• RF and anti-CCP: Negative (helps exclude RA)
• Synovial fluid: Inflammatory (WBC 2,000-50,000, low glucose, low complement)

Imaging:

Diagnostic Imaging Algorithm:

1. Plain radiographs (initial) ├── Sacroiliac joints (AP pelvis) ├── Lumbar/thoracic spine (lateral) └── Symptomatic peripheral joints

2. If radiographs normal but high suspicion └── MRI sacroiliac joints ├── Bone marrow edema (active inflammation) └── Structural changes (chronic damage)

3. Advanced imaging for complications ├── CT chest (pulmonary fibrosis) └── Echocardiogram (aortic regurgitation)

[CLINICAL_PEARL] MRI is superior to plain radiographs for detecting early sacroiliitis and is included in ASAS criteria for non-radiographic axial SpA.

Treatment Algorithm for Spondyloarthropathies:

Step 1: First-line therapy ├── NSAIDs (continuous, not PRN) │ ├── Indomethacin 25-50mg TID │ ├── Naproxen 500mg BID │ └── Celecoxib 200mg BID ├── Physical therapy/exercise └── Patient education

Step 2: Inadequate response after 4-12 weeks ├── Switch to different NSAID class ├── Local corticosteroid injections │ ├── Sacroiliac joints │ └── Peripheral joints └── Sulfasalazine (peripheral arthritis only)

Step 3: Conventional DMARDs (limited efficacy) ├── Methotrexate (PsA peripheral arthritis) ├── Sulfasalazine (peripheral > axial) └── Leflunomide (PsA)

Step 4: Biologic therapy ├── TNF inhibitors (first-line biologic) │ ├── Adalimumab, Etanercept │ ├── Infliximab, Golimumab │ └── Certolizumab pegol ├── IL-17 inhibitors │ ├── Secukinumab (AS, PsA) │ └── Ixekizumab (PsA) └── IL-23 inhibitors └── Ustekinumab (PsA)

Step 5: Refractory disease ├── JAK inhibitors (Tofacitinib for PsA) ├── Combination therapy └── Clinical trial enrollment

Specific Management Considerations:

Ankylosing Spondylitis:

• NSAIDs: Cornerstone therapy; continuous dosing preferred over PRN
• Exercise: Daily spinal mobility exercises, swimming, physiotherapy
• Biologics: TNF inhibitors first-line; IL-17 inhibitors if TNF failure
• [HIGH_YIELD] Sulfasalazine ineffective for axial disease but may help peripheral arthritis

Psoriatic Arthritis:

• Methotrexate: First-line DMARD for peripheral disease
• Skin-joint considerations: Coordinate with dermatology for psoriasis management
• Nail involvement: Often requires systemic therapy

Reactive Arthritis:

• Antibiotics: Treat underlying infection if identified
• NSAIDs: Mainstay for symptomatic relief
• Sulfasalazine: May be beneficial for chronic cases
• Prognosis: Often self-limited (6-12 months), but 20% develop chronic arthritis

[CLINICAL_PEARL] TICORA and BeSt studies demonstrated that early aggressive therapy with DMARDs improves long-term outcomes in inflammatory arthritis.

Monitoring Parameters:

• Disease activity: BASDAI (AS), DAS28 (PsA), clinical assessment
• Laboratory: CBC, liver function, tuberculosis screening before biologics
• Imaging: Annual radiographs to assess structural progression
• Extra-articular: Ophthalmologic screening for uveitis

Acute Complications:

• Acute anterior uveitis: Medical emergency requiring immediate ophthalmologic evaluation
  • Symptoms: Unilateral eye pain, photophobia, blurred vision, red eye
  • Treatment: Topical corticosteroids, cycloplegics
• Atlantoaxial subluxation: Cervical spine instability from longstanding inflammation
• Cauda equina syndrome: Rare complication of advanced AS

Chronic Complications:

Ankylosing Spondylitis:

• Spinal ankylosis: Progressive fusion leading to kyphotic deformity
• Vertebral fractures: Increased risk due to osteoporosis and rigid spine
• Cardiovascular: Aortic regurgitation (2-10%), conduction abnormalities
• Pulmonary: Apical pulmonary fibrosis (1-2%), restrictive lung disease
• Renal: Secondary amyloidosis (rare)

Psoriatic Arthritis:

• Arthritis mutilans: Severe destructive arthritis with "pencil-in-cup" deformity
• Cardiovascular disease: Increased risk of MI, stroke
• Metabolic syndrome: Higher prevalence of diabetes, dyslipidemia
• Osteoporosis: Increased fracture risk

Disease Activity Monitoring Tools:

Prognostic Factors:

Poor Prognosis:

• Young age at onset (<16 years)
• HLA-B27 positive with family history
• Elevated acute phase reactants
• Hip involvement
• Poor response to NSAIDs
• Smoking
• Male gender

Functional Outcomes:

• AS: 70-90% maintain good functional capacity with treatment
• PsA: Variable course; 47% develop erosive disease within 2 years
• ReA: 80% resolve within 6 months; 20% develop chronic arthritis

[HIGH_YIELD] Pregnancy Considerations:

• Most patients experience disease improvement during pregnancy
• Safe medications: Sulfasalazine, corticosteroids, certolizumab pegol
• Contraindicated: Methotrexate, leflunomide (teratogenic)
• TNF inhibitors: Most should be discontinued in second/third trimester

[CLINICAL_PEARL] Early recognition and treatment within 2 years of symptom onset significantly improves long-term functional outcomes and reduces radiographic progression.