Ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic, painful, progressive inflammatory arthritis primarily affecting spine and sacroiliac joints, causing eventual fusion of the spine; it is a member of the group of the autoimmune spondyloarthropathies with a probable genetic predisposition. Complete fusion results in a complete rigidity of the spine, a condition known as bamboo spine.

Signs and symptoms

The typical patient is a young man of 15-30 years old with chronic pain and stiffness in the lower part of the spine. Males are affected by ankylosing spondylitis three times more than women. Younger patients may experience knee pain even at very young ages (3 years old), commonly misinterpreted as simple rheumatisms. Recurring aphtae may also be experienced and are part of typical AS symptoms. Fatigue is also a widely spread symptom.

In 40% of cases, ankylosing spondylitis it is associated with iridocyclitis (anterior uveitis) causing eye pain and photophobia (increased sensitivity to light). Other less common complications are ulcerative colitis, psoriasis and Reiter's disease.

Osteopenia or osteoporosis of AP spine, causing eventual compression fractures and a back "hump" if untreated.

Organs affected by AS, other than the axial spine, are the hips, heart, lungs, heels, and other areas (peripheral).

Diagnosis

The diagnosis of AS is done by X-ray studies of the spine, which show characteristic spinal changes and sacroiliitis. Other options for effective diagnosis are tomography and magnetic resonance of the sacroiliac joints.

During acute inflammation periods, AS patients will usually show an increased values of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

Variations of the HLA-B gene increase the risk of developing ankylosing spondylitis. Those with the HLA-B27 variant are at highest risk of developing the disorder. HLA-B27, demonstrated in a blood test, is occasionally used as a diagnostic, but does not distinguish AS from other diseases and is therefore not of real diagnostic value. Over 95% of people with AS are HLA-B27 positive, although this ratio varies from population to population (only 50% of African American patients with AS possess HLA-B27, and it is close to 80% among AS patients from Mediterranean countries).

Unattended cases normally lead to knee pain, resulting in a fair assumption of normal rheumatism.

Pathophysiology

AS is a systemic rheumatic disease, and about 90% of the patients are HLA-B27 positive. HLA-DR and IL1ra are also implicated in ankylosing spondylitis. Although specific autoantibodies cannot be detected, its response to immunosuppresive medication has prompted its classification as an autoimmune disease.

Hypotheses on its pathogenesis include a cross-reaction with antigens of the Klebsiella bacterial strain (Tiwana et al. 2001). Particular authorities argue that elimination of the prime nutrients of Klebsiella (starches) would decrease antigenemia and improve the musculoskeletal symptoms. On the other hand, Khan (2002) argues that the evidence for a correlation between Klebsiella and AS is circumstantial so far, and that the efficacy of low-starch diets has not yet been scientifically evaluated. Similarly, Toivanen (1999) found no support for the role of klebsiella in the etiology of primary AS.

The Radical Induction Theory of Ulcerative Colitis proposes that ulcerative colitis is initiated by a metabolic aberration that results in accumulation of hydrogen peroxide and related free radicals between the cells of intestinal wall and the epithilial membrane that protects the cells from bacteria in the gut. The immune system then attacks the bacteria in the gut, producing the inflammatory symptoms of that disease. It is plausible that AS could also be initiated by loss of the epithelial membrane and activation of the immune system against bacteria in the gut, but without obvious inflammation in the colon. This could explain why sulfasalazine is effective against AS even though it is poorly absorbed and is believed to mainly act within the intestine.

Epidemiology

The sex ratio is 3:1 for men:women. In the USA, the prevalence is 0.25%, but as it is a chronic condition, the number of new cases (incidence) is fairly low.

Therapy

No cure is known for AS, although treatments and medications are available to reduce symptoms and pain.

Physical therapy and exercise, along with medication, are at the heart of therapy for ankylosing spondylitis. Physiotherapy and physical exercises are clearly preceded by medical treatment in order to reduce the inflammation and pain, and commonly followed by a physician. This way the movements will help in diminish pain and stiffness, while exercises in an active inflammatory state will just make the pain worse.

Medication

There are three major types of medications used to treat ankylosing spondylitis.

NSAIDs such as aspirin, ibuprofen, indometacin, naproxen and COX-2 inhibitors, which reduce inflammation and pain. These drugs tend to have a personal response to the pain and inflammation, although commonly used anti-inflammatory drugs like nimesulide are less effective than others;
DMARDs such as methotrexate, sulfasalazine, and corticosteroids, used to reduce the immune system response through immunosuppression;
TNFα receptors such as etanercept, infliximab and adalimumab (also known as biologics), are effective immunosuppressant on AS as on other autoimmune diseases;

TNFα blockers have been shown to be the best promising treatment, slowing the progress of AS in the majority of clinical cases. They have also been shown to be highly effective in treating not only the arthritis of the joints but the spinal arthritis associated with AS. A drawback is the fact that these drugs increase the risk of infections. For this reason, the protocol for any of the TNF-α blockers include a test for tubercolosis (like Mantoux or Heaf) before starting taking any drug. In case of recurrent infections, like even recurrent sore throats, the therapy may be suspended due to the involved immunosuppression.

Surgery

In severe cases of AS, surgery can be an option in the form of joint replacements, particularly in the knees and hips. Surgical correction is also possible for those with severe flexion deformities (severe downward curvature) of the spine, particularly in the neck, although this procedure is considered risky.

Physical therapy

Physiotherapy has shown to be of great benefit to AS patients;
Swimming is one of the preferred exercises since it involves all muscles and joints in a low gravity environment;
Slow movements exercises like stretching, yoga, tai chi;
Any physical movement like, jogging, Pilates method, etc.

Alternative medicine

Although the effectiveness of alternative medicines has not been proved by any clinical trial, some patients find some relief in adding these alternative treatements to the medicaments and physical exercises:

Diet: Starch free diet (Ebringer et al, 1996), london diet, paleolithic diet;
Acupuncture.

Prognosis

AS can range from mild to progressively debilitating, and from medically controlled to refractive.

Famous patients

Well known sufferers of AS include:

Ramses II
Mötley Crüe guitarist Mick Mars
former England cricket captain Mike Atherton
former Australian cricketer Michael Slater
British comedian Lee Hurst
Canadian radio personality Mike Stafford
Norwegian Prime Minister Jens Stoltenberg
chess player Vladimir Kramnik
Former author and "Saturday Review" editor Norman Cousins
Scottish former snooker player Chris Small
former American Major League baseball player Rico Brogna.

References

Ebringer A, Wilson C. The use of a low starch diet in the treatment of patients suffering from ankylosing spondylitis. Clinical Rheumatology 1996 Jan;15 Suppl 1:62-66. PMID 8835506.
Khan MA. 2002. Ankylosing spondylitis: The facts. Oxford University Press. ISBN 0192632825.
Tiwana H, Natt RS, Benitez-Brito R, Shah S, Wilson C, Bridger S, Harbord M, Sarner M, Ebringer A. Correlation between the immune responses to collagens type I, III, IV and V and Klebsiella pneumoniae in patients with Crohn's disease and ankylosing spondylitis. Rheumatology (Oxford) 2001;40:15-23. PMID 11157137.
Toivanen, Paavo, et al. "Somatic Serogroups, Capsular Types, and Species of Fecal Klebsiella in Patients with Ankylosing Spondylitis" Journal of Clinical Microbiology, September 1999, p. 2808-2812, Vol. 37, No. 9.

External links

National organizations

Spondylitis Association of America (USA)
National Ankylosing Spondylitis Society (UK)
The Ankylosing Spondylitis group of Queensland (Australia)

Support groups

KickAS.org (online community; support and information)

Arthritis Autoimmune diseases

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