Physician's Perspective

Ankylosing Spondylitis

Dr. Gambert is professor of medicine and associate chair for clinical program development, co-director, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Maryland School of Medicine; director, Geriatric Medicine, University of Maryland Medical Center and R Adams Cowley Shock Trauma Center; and professor of medicine, Division of Gerontology and Geriatric Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

I first heard of ankylosing spondylitis (AS) as a child. I had been told that Ed Sullivan, the well-known television personality, had this disease, and I watched him every week as he introduced America to such performers as the Beatles and the Supremes. I was particularly drawn to his obvious straight back and apparent inability to move fluidly across the stage. For some reason, I have seen several elderly patients with this disease in recent days and thought it would be a good time to review AS with you, our readers. While AS was not the reason I saw these patients, in each case, it limited their functional capacity and made it considerably more difficult for them to be rehabilitated back to their baseline capacity.

AS is derived from the Greek words ankylos, meaning “still,” and spondylos, meaning “vertebrae.” In the literature, the condition has been referred to as Marie-Strümpell disease, Bekhterev syndrome, and Bekhterev’s disease, although these are now considered largely outdated terms. AS is a chronic, inflammatory disease of the axial skeleton, with variable involvement of nonarticular structures and peripheral joints. It mainly affects joints in the spine and the sacroiliac joint in the pelvis, and it may eventually lead to a fusion of the spine. When the spine is completely fused, there is a resultant rigidity often referred to as “bamboo spine.” AS is thought to be due to some immunological abnormality and to have a strong genetic predisposition. Because there is no known cure, treatment is focused on controlling pain and improving physical function. While it has been observed in skeletal remains of 5000-year-old Egyptian mummies, it was not until the late nineteenth century when Vladimir Bekhterev of Russia, Adolph Strümpell of Germany, and Pierre Marie of France provided sufficient descriptions to permit an accurate diagnosis before the development of severe spinal deformity.

AS is three times more common in men than in women, with an overall prevalence of 0.25% in the general US population.1 The majority of patients with AS have the HLA-B27 antigen and high levels of immunoglobulinA in the blood.1 Interestingly, the HLA-B27 antigen is expressed by Klebsiella bacteria, which are found in high levels in the feces of patients with AS. It has been proposed that the Klebsiella bacteria may trigger the disease. Based on this finding, it has been suggested that reduced consumption of dietary starch may benefit AS patients,2 although this has not been proven in rigorously controlled studies. Although possibly linked, only 5% of persons with the HLA-B27 genotype contract AS. Tumor necrosis factor-alpha (TNF alpha) and interleukin-1 have also been implicated in the pathogenesis of AS.

AS typically develops between the ages of 20 and 40 years, with the first symptoms typically being chronic pain and stiffness in the middle part of the spine; sometimes the entire spine may be affected with pain felt in the buttock or even the back of the thigh. Men are usually more significantly affected. Pain is often severe at rest, but reportedly improves with certain physical activities. After more than 20 years of living with the disease, more than 80% of patients report daily pain and stiffness and more than 60% require daily use of medications to control these symptoms.

There is no single test to help diagnose AS. Clinical evaluation coupled with radiography studies of the spine show characteristic spinal changes and sacroiliitis. By the time a diagnosis has been made on a radiograph, however, the disease has usually been present for as long as 10 years. Computed tomography and magnetic resonance imaging can help clinicians make an earlier diagnosis, although the reliability of these studies remains unclear.

The hallmark of treatment is physical therapy and exercise along with analgesics and anti-inflammatory medications. Pain is commonly worse when walking and standing, and many persons with AS find it difficult to sit or stand for prolonged periods of time, sometimes for as little as 20 minutes. Nonsteroidal anti-inflammatory drugs (NSAIDs) are given to reduce pain and inflammation; studies have shown that patients with elevated acute phase reactants benefit most from continuous use of NSAIDs. Opioid analgesics may alleviate pain and are the last resort for many persons suffering from this disease.

In recent years, disease-modifying antirheumatic drugs, such as cyclosporine, methotrexate, sulfasalazine, and corticosteroids, have been used to reduce the immune system response, though data are varied as to their effectiveness. Tumor necrosis factor-alpha blockers, such as etanercept, infliximab, golimumab, and adalimumab, are also being used to reduce symptoms, but do not totally eliminate inflammation and pain. While they may help reduce symptoms and improve function, they increase the risk of infections; thus, testing for tuberculosis before starting treatment is suggested and persons taking tumor necrosis modifiers are advised to limit their exposure to others who may be ill with any bacterial, viral, or fungal infection. Anti-interleukin-6 inhibitors are currently being tested. In severe cases of AS, surgery may be an option to improve function for problems such as severe flexion deformities of the spine or neck.

Physical therapy has been shown to benefit patients with AS. Moderate to high impact exercises (eg, jogging) are not recommended due to the jarring effect of involved vertebrae, which may worsen pain and increase joint stiffness.

While some individuals with AS have long periods of remission, others are chronically affected, with approximately one-third of patients with AS having a severe course of the disease and a reduced life expectancy. For others, it is a life-long process with pain and limited ability to function. Osteopenia and osteoporosis of the spine are more commonly found in persons with AS. Compression fractures and kyphosis are major risks. Osteophytes also are frequently noted, leading to localized and referred pain. Organs commonly affected by AS other than the axial spine and joints include the heart, lungs, eyes, colon, and kidneys. Aortic regurgitation, Achilles tendinitis, atrioventricular node block, amyloidosis, pulmonary fibrosis, and even cauda equina syndrome all occur in higher frequency in persons with AS.3 Clearly, AS is a major cause for reduced quality of life, and when coupled with other diseases affecting the older individual, a major cause of disability and pain that may not only present as a problem in itself, but also negatively impact one’s ability to recover from an illness. In addition, involvement of the cervical spine may impair the ability to provide general anesthesia, further complicating issues of disease management.

Both of my patients with AS had fallen and suffered broken bones that needed to be surgically repaired. Fortunately, they were intubated without difficulty, but their ability to actively participate in a follow-up full rehabilitation program was not possible, which resulted in their placement in a subacute facility.

References

1.          Braun J, Bollow M, Remlinger G, et al. Prevalence of spondylarthropathies in HLA B-27 positive and negative blood donors. Arthritis Rheum. 1998;41(1):
58-67.

2.          Carette S, Graham D, Little H, Rubenstein J, Rosen P. The natural disease course of ankylosing spondylitis. Arthistis Rheum. 1983;26(2):186-190.

3.          Brophy S, Mackay K, Al-Saidi A, Taylor G, Calin A. The natural history of ankylosing spondylitis as defined by radiological progression. J Rheumatol. 2002;29(6):1236-1243.