About the author: David Borenstein, MD,is the author or co-author of more than 100 journal articles and books including Heal Your Back (2011) and Back in Control (2003); and three medical textbooks: Low Back and Neck Pain: Comprehensive Diagnosis and Management 3rd Edition, Low Back Pain: Medical Diagnosis and Comprehensive Management 2nd Edition*, and* Neck Pain: Medical Diagnosis and Comprehensive Management. The low back pain text has been recognized by the American Association of Medical Libraries as one of the 200 essential books for a medical library.
My patient, Sarah Wise, a 26-year-old woman, came to my office with a typical story. In her late teens, she noticed some low back and neck pain. Sarah was active in school sports, and her discomfort was initially ascribed to her physical activities. The problem was that her pain continued even during the off-season when she was “resting.” In fact, her spine pain was worse when she was inactive. She had some stiffness when getting out of bed in the morning, which would last for an hour or so. During the day she could do all of her activities, but she would ache again in the evening. She noticed when she took a non-steroidal medicine for her menstrual cramps that her spine pain was improved.
Sarah was seen by an orthopedist and was told that her spine looked fine; she had no scoliosis and was able to bend forward and back. X-rays showed what looked normal for a teenage girl. She was told to do some exercises and that everything would be fine.
Sarah went to college and tried to take her mind off her spine. Some days were better than others, but her spine pain remained. She participated in intramural sports but could not play field hockey as she had in the past, and she felt more fatigued than her friends. She was also worried about her relationship with her boyfriend; she did not want back pain to interfere with times she would be intimate with him, but her pelvis bothered her, too. At times her discomfort was noticeable.
Sarah moved to Washington, DC, and was referred to me for an evaluation of her back pain. Her story was remarkable for a number of characteristic findings: her back pain was inflammatory; X-rays of her pelvis and lower spine had findings associated with inflammatory arthritis of the sacroiliac joints and the lumbar spine; and lab tests showed that she was inflamed with an elevated erythrocyte sedimentation rate.
Sarah was diagnosed with ankylosing spondylitis. She had gone seven years without a correct diagnosis.
What Is Ankylosing Spondylitis?
Ankylosing spondylitis (AS) is a form of spondyloarthritis, an immune-mediated inflammatory disease that causes chronic inflammation of the structures of the spine. Immune-mediated inflammatory diseases are those in which the cells in the immune system, instead of fighting off infections and killing abnormal cells that can grow into cancers, become activated in different areas of the spine and start damaging the body’s own tissues. These inflamed tissues produce chemical signals, which are released into the bloodstream and recruit additional immune cells. The end result is chronic inflammation that can, in the most advanced cases, lead to the calcification of spinal structures, causing the spine to become fused.
What Are the Symptoms of AS?
The most common initial symptom of AS is persistent, localized low back pain. The muscles on the side of the spine can contribute to this pain because of spasms. The characteristics of inflammatory back pain include the following:
- Prolonged morning stiffness of the spine lasting hours
- Spine stiffness associated with sitting for variable lengths of time
- Back pain improvement with exercise
- Onset before age 40
- Improvement with non-steroidal anti-inflammatory drugs
Sarah had these complaints as she was growing up, and she also experienced typical fatigue associated with inflammatory back pain.
With progression of AS, the chest and neck develop pain associated with decreased motion. Compared with men, women may notice more difficulties with neck stiffness initially. The lower back or other parts of the spine become more difficult to move. AS patients may also suffer from fever, weight loss, and disordered sleep. Breathing becomes painful when moving ribs that are inflamed at the connection with the thoracic spine. In a majority of patients, the initial symptoms are in the sacroiliac or other spinal joints. Pain in the hips or shoulders is the initial complaint in a minority of patients.
Women and Ankylosing Spondylitis
Aspects of Sarah’s story are common among women with AS: her initial symptoms were related to her athletic activities; her symptoms of inflammatory back pain were confused with those of mechanical low back pain; and she received minimal instruction on how to use exercises to maximize her spinal range of motion to improve her condition.
In the past AS was thought to affect men more often than women. In the 1950s the ratio was originally reported to be 10 men for every woman, but these reports were flawed. The frequency of men to women is actually 3 to 1, but this too may be an overestimation.
Women tend to have milder symptoms to start and may have more neck symptoms. During the course of the illness, however, women have a higher burden of disease and less improvement than men. This pattern of disease results in an under diagnosis of AS in women.
What Causes Ankylosing Spondylitis?
Exactly what causes AS is not known. Approximately 80 to 90 percent of patients who develop the disease carry a genetic marker, HLA-B27, but not everyone with this genetic marker will develop the disease; approximately 8 percent of the US population is B27-positive but does not develop AS, and you can develop AS even if you are not B27-positive.
In a recent study, women were less frequently B27-positive (76 percent of women versus 85 percent men), suggesting that about a quarter of women will have AS without the characteristic genetic marker, another factor that can potentially delay diagnosis.
Some additional environmental factors beyond the genetic marker are necessary for the illness to progress. Preliminary studies suggest that specific bacteria that populate our gastrointestinal tract may increase the risk of developing AS. Modifying this bacterial microbiome is an area of active research.
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How Is AS Diagnosed?
The diagnosis of AS is based on a range of characteristic findings noted in a patient’s medical history and from a physical examination, including inflammatory back pain for longer than three months, an age of onset before 40 years, no improvement in pain and stiffness with rest, marked improvement with exercise, gradual onset, and increased pain at night. Plain X-rays of the lower spine will show definite signs of arthritis in the sacroiliac joints. Laboratory findings of HLA-B27 positivity and blood test signs of inflammation (elevated C-reactive protein or erythrocyte sedimentation rate) are compatible but not specific for AS.
Inflammation of AS starts before X-ray findings are identified. This is described as a preradiographic form of AS. In these individuals with early AS, a magnetic resonance imaging scan of the spine can identify inflammation in areas of the spine compatible with the diagnosis.
How Is AS Treated?
The goals of therapy for AS are to control inflammation, decrease pain, maintain function, and prevent deformity with the least toxicity. A therapeutic program will include both nondrug and drug components.
What Are non drug Therapies for AS?
It is important for anyone diagnosed with AS to consistently work to maintain maximum motion of the skeleton, particularly of the entire spine. This is a main focus of non-drug therapy for AS. Physical therapy that includes range-of-motion exercises to maintain function is essential, and supervised exercises are better than unsupervised exercises to improve pain, stiffness, and spinal mobility and to help maintain overall well-being in AS patients. In addition, aerobic conditioning activities, such as walking or riding a stationary bicycle, are helpful in maintaining respiratory function and cardiovascular health.
In Sarah’s case, she received a prescription to see a physical therapist to learn exercises that involved all portions of her spine. Pelvic-strengthening exercises helped decrease her low back pain, and range-of-motion exercises improved her neck motion. Deep-breathing exercises also helped maximize her lung capacity.
Patient education from health professionals and reliable online sources is essential because it can reinforce important messages involving posture, proper lifting techniques, avoidance of thick sleeping pillows, and the importance of consistent exercise. Accurate information about exercise and rest is important and should be emphasized because rigorous exercise can exacerbate symptoms, and patients should learn to find a healthy balance between rest and exercise. Education about proper nutrition to reach and maintain an ideal weight to minimize stress on weight-bearing joints is also important for an ideal outcome.
Psychological support may be needed for patients to help them process what it means to live with a chronic illness and to manage the psychological impact of the pain, fatigue, and joint stiffness associated with the disease. Coping with AS can challenge interpersonal relationships and professional obligations, so learning coping skills is essential to maintaining well-being.
What Are Drug Therapies for AS?
A wide variety of drug therapies are available for the treatment of AS. The key to success is matching the degree of illness with the corresponding drug. Each drug category has associated side effects, so keeping exposures to a minimum is key. Essentially, patients should take the appropriate number of medicines and not any additional.
- Nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs, which include ibuprofen (Advil®, Motrin®, Nuprin®), naproxen (Aleve®, Naprosyn®), and COX-2 inhibitors (Celebrex®), can decrease pain, fever, and inflammation. They are anti-inflammatory and pain relieving when given in larger doses over the long term. In the treatment of AS, NSAIDs decrease spine stiffness and pain. In a significant number of patients, NSAIDs alone are adequate to control symptoms and improve function. There is also clinical evidence that NSAIDs may slow the calcification of spine structures when taken on a long-term basis.
- Muscle relaxants. Spasms in spinal muscles in AS patients cause pain and limit motion. The addition of a muscle relaxant to an NSAID helps decrease muscle pain and tightness. The most common side effect of muscle relaxants is sleepiness.
- Disease-modifying agents. (DMARDs). DMARDs are drugs that work more slowly than NSAIDs but have the capability to modify the progression of disease. These drugs have greater benefit in rheumatoid arthritis. DMARDs do not have a beneficial effect on spinal disease. Some benefit may exist for arthritis of peripheral joints like the shoulders and hips. Examples of DMARDs include Azulfidine® (sulfasalazine), Trexall® (methotrexate), and Arava® (leflunomide).
- Anti–tumor necrosis factor (TNF) inhibitors. Cell messengers, or cytokines, are released by cells to initiate a variety of functions. An inflammatory cytokine, tumor necrosis factor (TNF) is associated with the clinical manifestations of AS: fatigue, joint swelling, stiffness, and pain. A decrease in the production of TNF, or its removal from the bloodstream, can decrease disease-associated complaints, but the total removal of TNF can be associated with an increased risk of infection. The goal of therapy is to obtain a physiologic level of TNF. Anti-TNF therapies available for the treatment of AS include Enbrel® (etanercept), Humira® (adalimumab), Simponi® (golimumab), Cimzia® (certolizumab), and Remicade® (infliximab). The efficacy of the TNF therapies shows no benefit of one agent compared with another. The use of specific agents in individuals is based on personal preferences related to injections versus infusion and frequency of dosing.
Toxicities associated with the use of TNF inhibitors include the activation of latent tuberculosis and an increased risk of viral and bacterial infections. If infections occur, the infection is treated and the TNF therapy is suspended until the infection is resolved. Although an increased risk of malignancy has been reported, the degree of this increase, which is reported to be small, is undergoing active evaluation.
Sarah’s therapy included the use of a daily NSAID and a small dose of a muscle relaxant to decrease muscle tension during the evening to allow her to obtain a more restful sleep, but her fatigue persisted and her inflammatory markers remained elevated. A TNF inhibitor was added, with resolution of her remaining complaints. Her drug therapy is effective, but she is not fully comfortable unless she does her spinal exercises on a daily basis.
What Are Surgical Therapies for AS?
Surgical therapies for AS are more commonly used for the peripheral joints than for the spine. At times the spine can become so brittle that it will fracture. The neck is the most common location for this fracture. Stabilization of the spine is necessary to prevent damage to the spinal cord.
Peripheral joints can be damaged to the degree of requiring a replacement. The hips and shoulders are the most commonly affected peripheral joints. The decision about joint replacement must be done in the setting of spine involvement and how the replacement will result in improved function.
Ankylosing spondylitis is an illness that affects both women and men. The findings of the disease are not identical in both sexes. A bias exists suggesting that spinal inflammation does not occur in women. This factor results in a delay in diagnosis and needless suffering. Women younger than 40 who have a family history of spinal arthritis are prime targets for AS.
If you suspect that you have symptoms of AS, ask your doctor about this diagnosis. Have the tests to discover if inflammation is affecting your spine. Getting the correct diagnosis is important so that effective therapy can be started. Current therapies can stop the progression of this disease.
- Van der Horst-Bruinsma IE, Zack DJ, Szumski A, Koenig AS. Female patients with ankylosing spondylitis: Analysis of the impact of gender across treatment studies. Annals of the Rheumatic Diseases. 2013;72(7):1221-24. doi: 10.1136/annrheumdis-2012-202431.
- Borenstein D. Heal Your Back: Your Complete Prescription for Preventing, Treating, and Eliminating Back Pain. Lanham, MD: M. Evans; 2011: 85-90.
- Lee W, Reveille JD, Weisman MH. Women with ankylosing spondylitis: A review. Arthritis and Rheumatism. 2008;59(3):449-54. doi: 10.1002/art.23321.