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).
- Age of onset: Third decade of life
- Common in white males
- Less common in women and blacks
- Male: Female ratio is 3:1.
- Presence of HLA B27
- Family history of AS
- Male sex
- Frequent GI infections
- 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
- 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.
- Inflammatory bowel disease (60% of patients)
- Acute anterior uveitis (20% to 30%)
- Aortic root dilatation (20%)
- Pleuritic pain (usually early)
Signs and Symptoms
- 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.).
- 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
- 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.
- 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.
- 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
- Contrast enhancement of periarticular bone showing acute inflammation
- Useful in early stages
- Sacroiliitis grade >II bilateral or grade III or IV unilateral
- 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
- 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
- Reiter’s syndrome
- Psoriatic arthritis
- Diffuse idiopathic skeletal hypertrophy
- Spondylitis associated with inflammatory bowel disease
- Rheumatoid arthritis
- 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.
- 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
Sedating muscle relaxants, in combination with other sedating analgesics (e.g., opioids), may cause dangerous sedation and respiratory depression.
- 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.
- Conventional agents having little or no effect:
- 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.
- Local corticosteroid injections of joints and entheses provide symptomatic relief.
- Fluoroscopic or CT-guided SIJ injections proved to be beneficial.
- 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
- Stop smoking, if smoker
- Avoid trauma
Patients have sleeping disorders, fatigue, and pain. They can become depressed and disabled, therefore cognitive/behavioral techniques, group supports are useful.
- 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
- 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
- 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
- Spine fractures, especially in the cervical area
- C1–C2 subluxation carries a high mortality rate
- Aortic insufficiency and cardiac conduction disturbances
- Restrictive lung disease, diaphragmatic breathing, upper lobe
- Fibrosis (rare)
- Amyloid deposition
- Cauda equina syndrome