Ankylosing Spondylitis (AS)

Basics

Description

A chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures; sacroiliac joint (SIJ) involvement is the hallmark of ankylosing spondylitis (AS).

Epidemiology

Incidence

• Age of onset: Third decade of life
• Worldwide prevalence: 0.9%
  • Common in white males
  • Less common in women and blacks
• Male: Female ratio is 3:1.

Risk Factors

• Presence of HLA B27
• Family history of AS
• Male sex
• Frequent GI infections

Pathophysiology

• Pathogenic antigen from fibrocartilage/cartilage is presented by HLA B27 to CD8+ T cells.
• Immune reaction directed against gut bacteria may explain the association of AS with inflammatory bowel disease.
• Pattern of cytokine secretion:
  • Relative deficiency of T-helper (Th) 1 cytokines such as TNF-α and IFN-γ coupled with increase IL-10 levels might lead to longer persistence of bacterial antigens at the beginning of immune response.
  • Such prolonged antibacterial immune response could trigger an autoimmune response.

Etiology

Unknown

Associated Conditions

• Inflammatory bowel disease (60% of patients)
• Acute anterior uveitis (20% to 30%)
• Psoriasis
• Aortic root dilatation (20%)
• Pleuritic pain (usually early)

Diagnosis

Signs and Symptoms

History

• Dull, deep, insidious, unilateral pain, present initially in buttock and/or lower lumbar area.
• Morning stiffness in the same area lasts for a few hours, improves with activity, and returns with inactivity.
• Pain progresses to become bilateral; persistent in several months and present more at night.
• Bone tenderness can be the initial sign.
• Neck pain and stiffness are present in advanced disease.
• Associated conditions can be present for extra-articular manifestations of the disease (uveitis, aortic insufficiency, etc.).

Physical Exam

• Loss of spine mobility with restrictions in flexion, extension of lumbar spine
• Limitation of chest expansion with restrictive lung disease pattern
• Pain over the SIJ with direct pressure or movement
• In advanced disease, lumbar lordosis is destroyed, buttock atrophy is present, thoracic kyphosis is exaggerated, and neck stoops forward.
• Hip, shoulder, or knee complaints

Interventional Diagnosis

• Synovial fluid: Mild leukocytosis, decreased viscosity
• Cerebrospinal fluid: Increased protein
• EKG: conduction defects
• Pulmonary function tests: Restrictive pattern
• Measurement of respiratory excursions of chest wall—less than 5 cm maximal respiratory excursions of chest wall measured at fourth intercostal space; less than 2.5 cm is diagnostic for AS.

Tests

Lab

• HLA B27 is present in 90% to 95% of white patients with AS.
• C-reactive protein and ESR is elevated in 50% to 70% patients with AS.
• Rheumatoid factor is absent.
• Normochromic, normocytic anemia is present.
• Increased alkaline phosphatase is present in severe cases. Increased IgA levels are present.

Imaging

• X-ray: New York grading system for sacroiliac joint:
  • Grade I: suspicious
  • Grade II: evidence of erosions and sclerosis
  • Grade III: erosions, sclerosis, and early ankylosis
  • Grade IV: total ankylosis
• MRI
  • Contrast enhancement of periarticular bone showing acute inflammation
  • Useful in early stages

Diagnostic Procedures/Surgery

• Radiologic criteria:
  • Sacroiliitis grade >II bilateral or grade III or IV unilateral
• Clinical criteria:
  • Low-back pain and stiffness for more than 3 months that improves with exercise but is not improved with rest
  • Limitation of motion of lumbar spine in both the sagittal and frontal planes
  • Limitation of chest expansion relative to normal values correlated for age and sex

Pathological Findings

Enthesopathy:

• New bone formation at the attachment of tendons/ligaments to bone
• Can affect the intervertebral disc with whole involvement of annulus fibrosus
• Erosive changes coupled with new bone formation, with ossification of periarticular soft tissues

Differential Diagnosis

• Reiter’s syndrome
• Psoriatic arthritis
• Diffuse idiopathic skeletal hypertrophy
• Spondylitis associated with inflammatory bowel disease
• Rheumatoid arthritis

Medication (Drugs)

First Line

• NSAIDs:
  • Selection is empiric; first drug used was phenylbutazone, with high effects in controlling pain but serious side effects (aplastic anemia, hepatic injury, etc.).
  • Indomethacin 50 mg t.i.d. or b.i.d. commonly is used.
  • Can choose from many others (sulindac, etodolac, meloxicam [Mobic], diclofenac sodium-misoprostol [Arthrotec], etc.).
  • Do not alter the course of disease and are the mainstay of treatment, together with physical therapy (PT).
• Cox-2 inhibitors:
  • Celecoxib use showed efficacy similar to ketoprofen.

• Opioid analgesics:
  • Can be used as an alternative to NSAIDs when those are contraindicated (GI bleed, renal insufficiency), initially in short-acting formulations.
  • Due to the chronic course of the disease, the careful use of long-acting opioid analgesics (fentanyl patch [Duragesic], sustained-release morphine or oxycodone, methadone) is appropriate.

Second Line

• Muscle relaxants:
  • Can be used in combination with analgesics.
  • Several classes are available:
    • GABA agonists: baclofen, diazepam
    • CNS depressants: carisoprodol, chlorzoxazone, metaxalone (least sedating), methocarbamol
    • Antihistamines: orphenadrine
    • Central α2-adrenergic agonists: clonidine, tizanidine TCA-like drugs: cyclobenzaprine

Alert

Sedating muscle relaxants, in combination with other sedating analgesics (e.g., opioids), may cause dangerous sedation and respiratory depression.

• TCA:
  • Low-dose amitriptyline (30 mg q.h.s.) improves sleep and decreases the disease activity index.
  • Exercise caution when using TCAs with muscle relaxants due to additive CNS effects.
• Disease-modifying antirheumatic drugs:
  • Conventional agents having little or no effect:
    • Corticosteroids: Low-dose therapy decreases symptoms; contraindicated as prolonged treatment; can aggravate the osteoporosis associated with AS; pulsed intravenous methylprednisolone therapy, 375 to 1,000 mg/day for 3 days, has been reported to decrease morning stiffness, but results are controversial.
    • Pamidronate: Shown to produce improvement in functional, global, and metrology indexes; side effects are arthralgias, myalgias, transient lymphopenia.
    • Sulfasalazine: Recommended at 30 to 40 mg/kg/day; beneficial in the treatment of arthritis associated with AS.
    • Methotrexate: Small studies have shown improvement of physical function and decreases in ESR and CRP levels at doses of 7.5 to 10 mg/week.
    • Azathioprine: Isolated case reports show response using 40 mg/kg loading dose followed by oral therapy of 2 mg/kg in refractory cases of AS.
• Biological agents: These TNF-α inhibitors were developed due to lack of response of AS to conventional drugs:
  • Infliximab: 5 mg/kg at weeks 0, 2, and 6. Shows onset of benefit within 24 hours after first infusion; benefit lasted for 6 weeks after the last infusion and showed improvement on MRI images.
  • Etanercept: Patients showed improvement in morning stiffness, nocturnal pain, and decreased ESR and CRP, as well as improved MRI results.

Interventional

• Local corticosteroid injections of joints and entheses provide symptomatic relief.
• Fluoroscopic or CT-guided SIJ injections proved to be beneficial.

Rehabilitation

• Physical therapy/aquatherapy: Regular exercises to maintain function and posture, range-of-motion (ROM), and strengthening exercises
• Firm bed
• Sleep in prone position or supine without a pillow
• Breathing exercises two to three times per day
• Swimming
• Stop smoking, if smoker
• Avoid trauma

Mental Health/Behavioral

Patients have sleeping disorders, fatigue, and pain. They can become depressed and disabled, therefore cognitive/behavioral techniques, group supports are useful.

Follow-Up

Prognosis

• AS is a chronic condition with an unpredictable pattern of progression.
• Prognosis good if mobility and upright posture are maintained; usually results in progressive disability.
• Factors of poor prognosis:
  • Hip involvement
  • Plus 3 of the following in the first 2 years of disease:
    • ESR >30 mm/h
    • Unresponsive to NSAIDs
    • Limitation of lumbar spine Sausage-like fingers or toes
    • Oligoarthritis
    • Onset <16 years old

Issues for Referral

• When suspected by clinical, laboratory, and imaging, refer to rheumatologist
• Referral to pain clinic for fluoroscopic or CT-guided intra-articular injections

Complications

• Spine fractures, especially in the cervical area
• C1–C2 subluxation carries a high mortality rate
• Prostatitis
• Cardiac:
  • Aortic insufficiency and cardiac conduction disturbances
• Pulmonary:
  • Restrictive lung disease, diaphragmatic breathing, upper lobe
  • Fibrosis (rare)
  • Amyloid deposition
  • Cauda equina syndrome
  • Uveitis