Ankylosing Spondylitis

Ankylosing Spondylitis (AS)

Basics

Description

Ankylosing Spondylitis - Inflammatory Back Pain

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
hla b27 test

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 (IBD)

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.).
10 Tips to Cure Your Ankylosing Spondylitis

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.
L-S spine X-ray image, AP view, comparison between normal and ankylosing spondylitis lumbar

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

About Reiter's Syndrome

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.
celebrex for arthritis
  • 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.
OxyContin bottles

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
diazepam

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.
Azathioprine

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
Arthritis and Exercise

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

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