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Physicians

ANKYLOSING SPONDYLITIS

EPIDEMIOLOGY:

Ankylosing spondylitis (AS) is the most common of the classic spondyloarthropathies. Prevalence varies with the prevalence of the HLA-B27 gene in a given population, which increases with distance from the equator. In general, AS is more common in whites than in nonwhites. It occurs in 0.1-1% of the general population,(1,2,3) with the highest prevalence in northern European countries and the lowest in sub-Saharan Africa.(4,5)

Its prevalence in Pakistan could be between 0.5 to 1% of the population.(6)

PATHOPHYSIOLOGY:

The spondyloarthropathies are chronic inflammatory diseases that most commonly involve the Sacroiliac (SI) joints and the axial skeleton, with hip and shoulder joints less frequently affected. Peripheral joints and entheses and certain extra-articular organs, including the eyes, skin, and cardiovascular system, may be involved to a lesser degree.

The primary pathology of the spondyloarthropathies is enthesitis with chronic inflammation, including CD4+ and CD8+ T lymphocytes and macrophages. Cytokines, particularly tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), are also important in the inflammatory process by leading to fibrosis and ossification at sites of enthesitis.(7,8,9)

The initial presentation of AS generally occurs in the SI joints; involvement of the SI joints is required to establish the diagnosis. SI joint involvement is followed by involvement of the diskovertebral, apophyseal, costovertebral, and costotransverse joints and the paravertebral ligaments.

Early lesions include subchondral granulation tissue that erodes the joint and is replaced gradually by fibrocartilage and then ossification. This occurs in ligamentous and capsular attachment sites to bone and is called enthesitis.

In the spine, this initial process occurs at the junction of the vertebrae and the anulus fibrosus of the intervertebral discs. The outer fibers of the discs eventually undergo ossification to form syndesmophytes. The condition progresses to the characteristic bamboo spine appearance.

Extra-articular involvement can include acute anterior uveitis and aortitis. Acute anterior uveitis occurs in 25-30% of patients and generally is unilateral. Symptoms include pain, lacrimation, photophobia, and blurred vision. Cardiac involvement including aortic insufficiency and conduction defects is generally a late finding and rare.(10)

Pulmonary involvement is secondary to inflammation of the costovertebral and costotransverse joints, which limits chest-wall range of motion (ROM). Pulmonary fibrosis is generally an asymptomatic incidental radiographic finding. Neurologic deficits are secondary to spinal fracture or cauda equina syndrome resulting from spinal stenosis. Spinal fracture is most common in the cervical spine.

SIGN AND SYMPTOMS:

Symptoms of ankylosing spondylitis (AS) include those related to inflammatory back pain, peripheral enthesitis and arthritis, and constitutional and organ-specific extra-articular manifestations. Because ankylosing spondylitis is a systemic inflammatory disease, systemic features are common.

Symptoms of AS include the following:

  • Those related to inflammatory back pain - Stiffness of the spine and kyphosis resulting in a stooped posture are characteristic of advanced-stage AS.
  • Peripheral enthesitis and arthritis
  • Constitutional and organ-specific extra-articular manifestations

Fatigue is another common complaint, occurring in approximately 65% of patients with AS. Increased levels of fatigue are associated with increased pain and stiffness and decreased functional capacity.(11,12)

Extra-articular manifestations of AS can include the following:

  • Uveitis
  • Cardiovascular disease
  • Pulmonary disease
  • Renal disease
  • Neurologic disease
  • Gastrointestinal (GI) disease
  • Metabolic bone disease

DIAGNOSTIC TESTS:

The diagnosis of AS is generally made by combining the clinical criteria of inflammatory back pain and enthesitis or arthritis with radiologic findings.(13,14,15)

RADIOGRAPHY:

Radiographic evidence of inflammatory changes in the SI joints and spine are useful in the diagnosis and ongoing evaluation of AS.(16)

Early radiographic signs of enthesitis include squaring of the vertebral bodies caused by erosions of the superior and inferior margins of these bodies, resulting in loss of the normal concave contour of the bodies’ anterior surface. The inflammatory lesions at vertebral entheses may result in sclerosis of the superior and inferior margins of the vertebral bodies, called shiny corners (Romanus lesion).

POWER DOPPLER ULTRASONOGRAPHY:

Power Doppler ultrasonography can be used to document active enthesitis. In addition, this technology may be useful in the assessment of changes in inflammatory activity at entheses during the institution of new therapies.(17)

MRI AND CT SCANNING:

Magnetic resonance imaging (MRI) or computed tomography (CT) scanning of the SI joints, spine, and peripheral joints may reveal evidence of early sacroiliitis, erosions, and enthesitis that are not apparent on standard radiographs.(18,19)

TREATMENT OPTIONS:

Life style

Patient education, exercise, and medications are all very important in the management of ankylosing spondylitis (AS).(20)

Smoking cessation is recommended for everyone who smokes. It is a modifiable risk factor for poor functional outcome in AS.(21)

Home exercises are effective, but supervised exercise programs or formal physical therapy can be of greater benefit.(22) Optimally, an initial evaluation and training by a physical therapist should be part of the therapeutic regimen. Exercises include postural training, range of motion stretching, recreational activities, and perhaps hydrotherapy.

In addition, pain relief measures such as local heat or cold can be given a trial. At a minimum, patients with AS should participate in an unsupervised home exercise program.(23) Inpatient rehabilitation is rarely needed.(24)

PHARMACOLOGICAL OPTIONS:

Agents used in the treatment of AS include the following:

Nonsteroidal anti-inflammatory drugs (NSAIDs): Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful for reducing pain secondary to inflammation and systemic symptoms in AS patients. These agents reduce inflammatory symptoms of spinal and peripheral joint pain and morning stiffness and appear to have a modest disease-modifying effect on spinal disease. Cyclooxygenase-2 (COX-2) inhibitors appear to be as effective as traditional NSAIDs.

INDOMETHACIN: Indomethacin is thought to be the most effective NSAID for the treatment of AS, although no scientific evidence supports this claim. It is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of COX, which results in a decrease of prostaglandin synthesis.

IBUPROFEN: Ibuprofen is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of COX, which results in a decrease of prostaglandin synthesis.

NAPROXEN: Naproxen is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of COX, which results in a decrease of prostaglandin synthesis.

DICLOFENAC: Diclofenac inhibits prostaglandin synthesis by decreasing COX activity, which, in turn, decreases formation of prostaglandin precursors.

5-AMINOSALICYLIC ACID DERIVATIVES: 5-Aminosalicylic acid derivatives inhibit prostaglandin synthesis and reduce the inflammatory response to tissue injury.

Sulfasalazine has been shown to reduce the inflammatory symptoms of AS in controlled studies; it’s most common toxicities include nausea, diarrhea, and hypersensitivity reactions (rash).

TUMOR NECROSIS FACTOR-Α (TNF-Α) ANTAGONISTS: Tumor necrosis factor alpha (TNF-α) antagonists are biologic agents and include etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol. These agents inhibit TNF-α and have been shown to improve symptoms and function in AS patients in clinical trials. All have been approved for the treatment of AS.

ETANERCEPT: Etanercept consists of a fusion protein of the extracellular portion of the p75 TNF-α receptor and the Fc portion of immunoglobulin G (IgG). It inhibits TNF-α, reducing inflammation and symptoms of ankylosing spondylitis. It is given as a subcutaneous (SC) injection and is available in a prefilled syringe, an autoinjector, or lyophilized powder. It is also approved for rheumatoid arthritis, PsA, psoriasis, and juvenile idiopathic arthritis.

INFLIXIMAB: Infliximab is a chimeric IgG1κ monoclonal antibody (mAb) directed against TNF-α. The variable regions of heavy and light chains are murine in origin, and the constant regions are human. Infliximab inhibits TNF-α, reducing inflammation and symptoms of AS. It is given as an intravenous (IV) infusion. It is also approved for rheumatoid arthritis, PsA, psoriasis, and Crohn disease.

ADALIMUMAB: Adalimumab is a human IgG1κ mAb directed against TNF-α. It inhibits TNF-α, reducing inflammation and symptoms of AS. It is given as an SC injection and is available in a prefilled syringe or an autoinjector. It is also approved for rheumatoid arthritis, PsA, psoriasis, juvenile idiopathic arthritis, and Crohn disease.

GOLIMUMAB: Golimumab is a human IgG1κ mAb directed against TNF-α. It inhibits TNF-α, reducing inflammation and symptoms of AS. It is given as an SC injection and is available in a prefilled syringe or an autoinjector. It is also approved for rheumatoid arthritis and PsA.

CERTOLIZUMAB PEGOL: Certolizumab pegol is a recombinant humanized anti-human TNF-α neutralizing antibody. It inhibits TNF-α, reducing inflammation and symptoms of ankylosing spondylitis. It is given as a subcutaneous injection and is available as a powder for injection. It is FDA-approved for active ankylosing spondylitis, and is also indicated for Crohn Disease, rheumatoid arthritis, and psoriatic arthritis.

METHOTREXATE: Methotrexate has an unknown mechanism of action in AS; it may affect immune function. Effects are observed in the 3-6 weeks following administration. Methotrexate ameliorates symptoms (e.g. pain, swelling, stiffness), but there is no evidence that it induces remission. Adjust the dose gradually to obtain a satisfactory response.

SURGICAL THERAPY:

The following procedures can be used in the surgical management of AS:

  • Vertebral osteotomy - Patients with fusion of the cervical or upper thoracic spine may benefit from extension osteotomy of the cervical spine
  • Fracture stabilization
  • Joint replacement - Patients with significant involvement of the hips may benefit from total hip arthroplasty.

GOALS OF THERAPY:

The primary goal of management for patients with ankylosing spondylitis (AS) is to maximize long-term health-related quality of life through the following:

  • Relief of symptoms – To eliminate symptoms such as pain, stiffness, and fatigue or to reduce them to the minimal possible level
  • Maintenance of function – To maintain the best possible functional capacity
  • Prevention of complications of spinal disease – To prevent flexion contractures, especially dorsal kyphosis
  • Minimization of extraspinal and extraarticular manifestations and comorbidities – To reduce the impact of AS-associated disorders such as uveitis and aortic valve insufficiency

GUIDELINES:

Treatment for Ankylosing spondylitis is based on guidelines from the prestigious societies such as American College of Rheumatology (ACR) and European league Against Rheumatism (EULAR).

To review the guidelines of ACR for the management of Ankylosing Spondylitis, click on the below link:

http://www.rheumatology.org/Portals/0/Files/Recommendations%20for%20the%20Treatment%20of%20Ankylosing%20Spondylitis.pdf

To review 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis, click on the below link:

http://ard.bmj.com/content/70/6/896.abstract?etoc

PRECAUTIONS:

  • If patient smoke and have ankylosing spondylitis, he / she will be more likely to have breathing problems. Quitting smoking can help with this.
  • Exercise can help prevent some of the stiffness caused by ankylosing spondylitis.
  • Recommend calcium and vitamin D – This can help to keep patient’s bones from getting weak.
  • Suggest to use a thin pillow – Sleeping on a thick pillow can cause neck problems in people with ankylosing spondylitis.

REFERENCES:

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  • De Angelis R, Salaffi F, Grassi W. Prevalence of spondyloarthropathies in an Italian population sample: a regional community-based study.Scand J Rheumatol. 2007 Jan-Feb. 36(1):14-21.
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