Ankylosing spondylitis

Definition

Ankylosing spondylitis (AS) is a systemic disorder that refers to inflammation of the joints in the spine. AS is the primary disease in an entire group of conditions known as seronegative spondylarthropathies. It is also known as rheumatoid spondylitis or Marie–Strümpell disease (among other names). AS is an autoimmune disease, as are most forms of arthritis. By definition, other joints, in addition to the spine, can also be affected, including the shoulders, hips, knees, and feet. Tissues in the eye can also be affected.

Description

A form of arthritis, AS is characterized by chronic inflammation, causing pain and stiffness of the back, progressing to the chest and neck. Eventually, the whole back may become curved and inflexible if the bones fuse, which is known as "bamboo spine." Other conditions associated with AS include reactive arthritis, psoriatic arthritis, spondylitis of inflammatory bowel disease , and undifferentiated spondyarthropathy. AS may involve multiple organs, such as the:

• eye (causing an inflammation of the iris, or iritis)
• heart (causing aortic valve disease)
• lungs
• skin (causing a scaly skin condition, or psoriasis)
• gastrointestinal tract (causing inflammation within the small intestine, called ileitis, or inflammation of the large intestine, called colitis).

Less than 1% of the population has AS; however, 20% of AS sufferers have a relative with the disorder.

Causes & symptoms

Genetics, in the form of a gene named HLA–B27, can play an important role in the disease, but the precise cause of AS remains unknown. According to information from the Spondylitis Association of America, HLA–B27 is a perfectly normal gene found in 8% of the general population. Generally speaking, no more than 2% of people born with this gene will eventually get spondylitis. The gene itself does not cause spondylitis, but people with HLA–B27 are more susceptible to getting spondylitis. To date, 15 subtypes of HLA–B27 have been identified. The most common subtypes in the United States being B27.05, and then after that B27.02. The way in which HLA–B27 interacts with some other proteins seems to be very important to the cause of AS, but further research must be conducted to find out exactly how. According to information published in 1997 from The Arthritis Cure, by Dr. Jason Theodosakis, M.D., M.S., M. P. H., and others, research was being conducted regarding the possibility that a certain type of infection could be the trigger for the onset of AS.

Symptoms of AS include:

• low back and hip pain and stiffness
• duration of symptoms longer than three months
• difficulty expanding the chest
• early morning stiffness improved by a warm shower or light exercise
• pain in the neck, shoulders, knees, and ankles
• low-grade fever
• fatigue
• weight loss

AS occurs most often in males between 16 and 35 years of age. Initial symptoms are uncommon after the age of 30, although the diagnosis may not be established until after that age. The incidence of AS in African Americans is about 25% of incidence among Caucasians, but is rarely seen in that population.

Some naturopathic healers link the cause of AS to its autoimmune origins in food allergies and abnormal bowel function, sometimes referred to as "leaky gut" syndrome. According to this theory, food allergies combine with the leaky gut and, according to the Healing-With Nutrition website, from a 1986 article in the Britain Journal of Rheumatology, "..result in the increased circulation of gut-derived antigens into other areas of the body. The body produces antibody-antigen complexes (immune complexes) characteristic of RA (rheumatoid arthritis ) to battle these gut-derived foreign antigens; but these antibody-antigens are thought to also cross-react with antigens in the joint tissues. In other words, the antibodies formed to attack the (leaky gut) microbes also cross-react and attack joint collagen."

Diagnosis

Doctors usually diagnose the disease simply by the patient's report of pain and stiffness. Doctors also review spinal and pelvic x rays since involvement of the hip and pelvic joints is common and may be the first abnormality seen on the x ray. The doctor might also order a blood test to determine the presence of HLA–B27 antigen if the x rays have not clearly determined the diagnosis. If the gene is present, it could facilitate the accuracy of the possible AS diagnosis. When a diagnosis is made, patients may be referred to a rheumatologist, a doctor who specializes in treating arthritis. Patients may also be referred to an orthopedic surgeon, a doctor who can surgically correct joint or bone disorders.

Treatment

To reduce inflammation, various herbal remedies, including white willow (Salix alba ), yarrow (Achillea millefolium ), and lobelia (Lobelia inflata ), may be helpful. Acupuncture , performed by a trained professional, has helped some patients manage their pain. Homeopathic practitioners may prescribe such remedies as Bryonia and Rhus toxicodendron for pain relief.

A key alternative treatment for AS is massage therapy . Reported benefits include a decrease in pain, increase in circulation, lymph flow improvement, and increase in range of motion. The major benefit of this therapy could be that it provides further motivation for a regular excerise program, considered the most beneficial of all treatments for AS.

Diets of various regimens have been offered that include supplements of fatty acids and antioxidants , as with other arthritis diets. Naturopaths and some medical doctors have theorized that certain foods should be eliminated from the diet in order to alleviate symptoms. Possible problem foods include wheat, corn, milk and other dairy products, beef, tomatoes, potatoes, and peppers. Tobacco has also been thought to aggravate the condition. Various reports have surfaced in many books and articles that indicate a diet high in fiber and fresh fruits and vegetables—minus those listed above—and low in sugar, meat, refined carbohydrates, and animal fats might help in the treatment of the symptoms, particularly with pain or swelling.

Allopathic treatment

Nonsteroidal anti-inflammatory drugs (NSAIDs), like naproxen (Naprosyn) or indomethacin (Indocin) are used to relieve pain and stiffness. In severe cases, sulfasalazine (Azulfidine), another drug to reduce inflammation, or methotrexate (Rheumatrex), an immune-suppressing drug, are recommended. In cases where chronic therapy is needed, potential drug side effects must be taken into consideration. Corticosteroid drugs are effective in relieving symptoms, but are usually reserved for severe cases that do not improve when NSAIDs are used. To avoid potential side effects, treatment with corticosteroids is usually limited to a short amount of time with a gradual weaning from the drug.

In April 2002, a study published revealed that a drug already approved for patients with rheumatoid arthritis was successful in helping most AS patients as well. Infliximab helped alleviate pain and improved functioning in more than 80 % of patients in a clinical trial. The drug worked rapidly and reduced disease activity by more than half in about 50% of patients. Some serious side effects did occur, so researchers continued to test the drug and seek Food and Drug Administration (FDA) approval for Infliximab for AS patients. In the same year, scientists were testing another drug called Etanercept that also showed promising results in preliminary trials.

Physical therapists prescribe exercises to prevent a stooped posture and breathing problems when the spine starts to fuse and ribs are affected. Back braces may be used to prevent continued deformity of the spine and ribs. Only in severe cases of deformity is surgery performed to straighten and realign the spine, or to replace knee, shoulder, or hip joints. Because it is a major and complicated procedure, with a potential for complications, this surgery is recommended cautiously even in severe cases.

Expected results

There is no cure for AS, and the course of the disease is unpredictable. Generally, AS progresses for about 10 years, then levels off. Most patients can lead normal lives with treatment to control symptoms. Claims that homeopathic remedies have cured them have not been verified.

Prevention

There is no known way to prevent AS. With twenty-first century advances in gene therapy, the possibility exists for further determination of the factor that HLA–B27 gene plays in its manifestation, and what role it could play in preventing it for future generations.

Resources

BOOKS

Brewer Jr., Earl J., and Kathy Cochran Angel. The Arthritis Sourcebook. Los Angeles: Lowell House, 1993.

Swezey, Robert L. Straight Talk on Spondylitis. Spondylitis Association of America, 1994.

Taurog, Joel D., and Peter E. Lipsky. "Ankylosing Spondylitis, Reactive Arthritis, and Undifferentiated Spondyloarthropathy." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw–Hill, 1998.

PERIODICALS

Babayev, Marietta and Leonard Bleicher. "Low Back Pain in an Elderly Man." The Journal of Musculoskeletal Medicine (April 2000).

Breban, M., B. Gombert, et al. "Thalidomide: A New Use in Ankylosing Spondylitis?" Rheumatoid Arthritis Research News (April 1999).

"Etanercept for 'Rapid Improvement' in Joint Disease." Chemist & Druggist (May 18, 2002): 24.

Feldtkeller, et al. "Impact of Sex on Inheritance of Ankylosing Spondylitis." The Lancet (March 25, 2000).

"Infliximab Highly Effective Therapy." Immunotherapy Weekly (May 8, 2002): 3.

Nuki, George. "Ankylosing Spondylitis, HLA B27, and Beyond." The Lancet (14 March 1998). Available from http://web2.infotrac.galegroup.com.

Sussman, Sharon. "Now He's Blind." Discover (June 1999).

Yacyshyn, Elaine A. and Marc D. Cohen. "Ankylosing Spondylitis: Early Detection and Management." The Journal of Musculoskeletal Medicine (December 1999).

ORGANIZATION

Arthritis Foundation. 1330 West Peachtree St., Atlanta, GA 30309. (404) 872–7100. http://www.arthritis.org.

National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse. 1 AMS Circle, Bethesda, MD 29892–3675. (301) 495–4484.

Spondylitis Association of America. PO Box 5872, Sherman Oaks, CA 91413. (800) 777–8189.

OTHER

Harris, Brian. The Ankylosing Spondylitis Site. http://www.asweb.com/ (2000).

HealingWithNutrition. http://www.HealingWithNutrition.com/ (2000).

Matsen III, Frederick, ed. "Ankylosing Spondylitis." http://www.orthop.washington.edu/bonejoint/azzzzzzz1_1.html/ (December 2000).

Penn State University, Department of Orthopaedics and Rehabilitation, M. S. Hershey Medical Center. Adult Spin Surgery Service. http://www.psu.edu/ortho/ (December 2000).

The Spondylitis Association of America. http://www.spondylitis.org/(December 2000).

Jane Spear

Teresa G. Odle

Ankylosing spondylitis

Definition

Ankylosing spondylitis (AS) is a relatively common disease that causes inflammation of the area where ligaments and tendons insert into the bone. The inflammatory process eventually leads to reduced mobility or immobility of affected joints. Specific joints are characteristically involved, notably in the spine and pelvis.

Description

Ankylosing spondylitis belongs to a group of disorders called the seronegative spondyloarthropathies. Each disease in this group is characterized by arthritis affecting the spine, as well as the absence of rheumatoid factor, a diagnostic marker that is present in rheumatoid arthritis and helps distinguish it from the group of diseases that includes AS. AS affects primarily the spine and the sacroiliac joint where the spine meets the hips. Progressive symptoms eventually result in fusion of these joints, pain, and markedly decreased joint mobility. AS is considered an autoimmune disease, meaning that symptoms are the result of the action of the immune system of the body against its own tissues. Although the exact mode of action is unknown, there is a strong association of AS with a specific type of human leukocyte antigen, HLA-B27. HLA are genetically-determined proteins that play an important role in the functioning of the immune response of the body, in that they enable the immune system to distinguish between its own cells and foreign cells. Therefore, HLA type is important in immunity, as well as organ and tissue transplantation.

Genetic profile

AS is considered a multifactorial disorder, or one that is the result of both genetic and environmental factors interacting. Two genes have been identified that confer susceptibility to AS, both of which are forms of an HLA gene on chromosome 6. Some HLA types have been implicated in various autoimmune diseases, meaning diseases in which the immune system attacks the body's own cells and tissues.

The association of HLA B-27 and AS has been clearly established. Ninety-five percent of individuals with AS are B-27 positive, and since AS appears to be a dominant trait, the presence of at least one B-27 allele (a form of the gene) confers a greatly increased chance of developing symptoms. While this population risk may seem relatively high, it is important to realize that only about 9% of the population carries the B-27 allele. Of these individuals who are B-27 positive, only 2-8% will develop AS.

Other environmental and genetic factors most certainly contribute to development of the disease. This becomes more evident when considering that B-27 positive individuals with an affected first-degree relative have a significantly higher chance of developing AS than a B-27 positive individual with no family history. In families with multiple affected members, studies estimate that no more than half of AS recurrence is explained by HLA type. Additionally, there are several B-27 subtypes that have been studied; some confer susceptibility and some do not. Importantly, about 5% of people with AS are B-27 negative. Other environmental and/or genetic factors must certainly be associated with disease in these individuals. Another HLA type—B-60—has also been shown to confer susceptibility, although the association appears to be much weaker and is not seen in all studies. Certain infections are suspected as being necessary for triggering AS in some individuals. In the future, additional susceptibility genes and environmental factors can be expected to be identified.

Demographics

Approximately 0.25% to 1.5% of the population is affected with AS. Prevalence of the disease is comparable to the frequency of the HLA B-27 allele in the population, which varies among ethnic groups. Native North Americans, Alaskan Eskimos, and Norwegian Lapps all have relatively high levels of B-27 and AS. Low levels of B-27 and AS occur among individuals of most types of African ancestry, Australian aborigines, and Native South Americans. Generally, for every affected female, there are two to three affected males.

Signs and symptoms

The signs of AS vary, but a typical case involves progressive lower back pain and morning stiffness. The immune response at the point where the ligaments or tendons insert into the bones initially causes bone inflammation and fragility, followed by fibrosis, meaning the formation of fiber tissue. The area reacts by forming new bone, which eventually fuses, limiting motion. AS can also affect peripheral joints in a manner similar to other types of arthritis. The vertebral joints of everyone with AS are affected, and 50% of people will also have significant hip arthritis. Osteoporosis in advanced AS commonly results in fractures of the spine.

AS also affects areas other than the bones and joints. An eye complication called anterior uveitis, which is easily treated and generally does not affect vision, develops in 5-35% of people with AS. Rarely, the disease may affect the heart or aorta. Kidney failure is a rare complication. Lung function can be affected due to bone changes that affect the mechanics of breathing. Therefore, individuals with AS should refrain from smoking to avoid early respiratory failure. Ninety percent of affected individuals experience the first symptoms before age 45. Males are more commonly affected than females, who tend to be diagnosed later partly due to milder symptoms.

Diagnosis

Diagnostic criteria were established by the European Spondyloarthropathy Study Group in the early 1990s. A clinical diagnosis of AS requires the presence of spinal pain caused by inflammation or inflammation of the membrane surrounding the joints, which can be either asymmetric or involving primarily the lower limbs. One or more of the following conditions must also be present:

• family history of AS
• sacroilitis (inflammation of the sacroiliac joint) demonstrated by x ray
• acute diarrhea within one month before the appearance of symptoms
• inflammatory bowel disease
• psoriasis (a scaly skin disease)
• urethritis (inflammation of the urethra)
• cervicitis (inflammation of the cervix)
• alternating buttock pain
• enthesopathy (disorder of the ligament attachment to the bone)

This diagnostic description has close to an 87% sensitivity, meaning that 87% of those with AS are picked up using this description. Conversely, 13% of those with AS will not be identified as having the disease based on this description. The description has a specificity that is also approximately 87%, meaning that 87% of the time a person classified as having AS actually has AS, as opposed to another disease or no disease. Conversely, about 13% of the time this description will incorrectly classify someone who actually has a different disease as having AS.

This is a challenging diagnosis to make correctly. Testing for HLA B-27 can improve diagnosis by confirming specificity. In other words, when it looks like someone has AS based on the above description of conditions, a positive B-27 test will make the physician more certain that person is a true positive for AS. As imaging of the sacroiliac joint improves through the use of a technology called magnetic resonance imaging (MRI), diagnosis of AS may also improve. Although, diagnosing a person with AS prior to the development of signs seen on x ray or MRI will continue to be very difficult.

Treatment and management

Phyical therapy plays a major role in maintaining flexibility, range-of motion, posture, and ultimately mobility. Surgery can improve joint function, as well as minimize associated pain, which may be treated with nonsteroidal anti-inflammatory medications. Other medications—sulfasalazine and methotrexate—can provide some relief for peripheral arthritis. Cycloplegics (medications that paralyze the ciliary muscle of the eye) and local steroids are effective at treating anterior uveitis. Rare complications are treated depending on their symptoms. Avoidance of smoking is encouraged to maintain lung function.

Prognosis

For most affected individuals, treatment and management is successful at maintaining quality of life. Quality can be significantly impacted, however, for the occasional individual with a severe, progressive course of the disease. Vision can be affected in some individuals with anterior uveitis that is not responsive to treatment, but this is rare. The rare complication of kidney failure can limit life-expectancy, as can respiratory failure that may result from smoking.

Resources

BOOKS

Wordsworth, P., and M. Brown. "Rheumatoid arthritis and allied inflammatory arthropathies." In Emery and Rimoin's Principles and Practice of Medical Genetics. 3rd ed. D. L. Rimoin, J. M. Connor, and R. E. Pyeritz, editors. New York: Churchill Livingston, 1997, pp. 2751–2771.

PERIODICALS

Benjamin, R., and P. Parham. "Guilt by association: HLA-B27 and ankylosing spondylitis." Immunology Today 11 (1990): 137–43.

Thomson, G. "HLA disease associations: models for the study of complex human genetic disorders." Critical Reviews in Clinical Laboratory Sciences 32 (1995): 183–219.

WEBSITES

"Arthritis associated with spondylitis." The Merck Manual<http://www.merck.com/pubs/mmanual/section5/chapter51/51a.htm>.

Spondylitis Association of America. (800) 777-8189. <http://www.spondylitis.org>.

Jennifer Denise Bojanowski, MS, CGC

Ankylosing Spondylitis

Definition

Ankylosing spondylitis (AS) refers to inflammation of the joints in the spine. AS is also known as rheumatoid spondylitis or Marie-Strümpell disease (among other names).

Description

A form of arthritis, AS is characterized by chronic inflammation, causing pain and stiffness of the back, progressing to the chest and neck. Eventually, the whole back may become curved and inflexible if the bones fuse (this is known as "bamboo spine"). AS is a systemic disorder that may involve multiple organs, such as the:

• eye (causing an inflammation of the iris, or iritis)
• heart (causing aortic valve disease)
• lungs
• skin (causing a scaly skin condition, or psoriasis)
• gastrointestinal tract (causing inflammation within the small intestine, called ileitis, or inflammation of the large intestine, called colitis)

Less than 1% of the population has AS; however, 20% of AS sufferers have a relative with the disorder.

Causes and symptoms

Genetics play an important role in the disease, but the cause of AS is still unknown. More than 90% of patients have a gene called HLA-B27, but only 10-15% of those who inherit the gene develop the disease. Symptoms of AS include:

• low back and hip pain and stiffness
• difficulty expanding the chest
• pain in the neck, shoulders, knees, and ankles
• low-grade fever
• fatigue
• weight loss

AS is seen most commonly in males 30 years old and older. Initial symptoms are uncommon after the age of 30, although the diagnosis may not be established until after that age. The incidence of AS in Afro-Americans is about 25% of the incidence in Caucasians.

Diagnosis

Doctors usually diagnose the disease simply by the patient's report of pain and stiffness. Doctors also review spinal and pelvic x rays since involvement of the hip and pelvic joints is common and may be the first abnormality seen on the x ray. The doctor may also order a blood test to determine the presence of HLA-B27 antigen. When a diagnosis is made, patients may be referred to a rheumatologist, a doctor who specializes in treating arthritis. Patients may also be referred to an orthopedic surgeon, a doctor who can surgically correct joint or bone disorders.

Treatment

Physical therapists prescribe exercises to prevent a stooped posture and breathing problems when the spine starts to fuse and ribs are affected. Back braces may be used to prevent continued deformity of the spine and ribs. Only in severe cases of deformity is surgery performed to straighten and realign the spine, or to replace knee, shoulder, or hip joints.

Alternative treatment

To reduce inflammation various herbal remedies, including white willow (Salix alba ), yarrow (Achillea millefolium ), and lobelia (Lobelia inflata ), may be helpful. Acupuncture, performed by a trained professional, has helped some patients manage their pain. Homeopathic practitioners may prescribe such remedies as Bryonia and Rhus toxicodendron for pain relief.

Prognosis

There is no cure for AS, and the course of the disease is unpredictable. Generally, AS progresses for about 10 years and then its progression levels off. Most patients can lead normal lives with treatment to control symptoms.

Prevention

There is no known way to prevent AS.

KEY TERMS

Ankylosing— When bones of a joint are fused, stiff, or rigid.

HLA-B27— An antigen or protein marker on cells that may indicate ankylosing spondylitis.

Immune suppressing— Anything that reduces the activity of the immune system.

Inflammation— A reaction of tissues to disease or injury, often associated with pain and swelling.

Spondylitis— An inflammation of the spine.

Resources

ORGANIZATIONS

Arthritis Foundation.1300 W. Peachtree St., Atlanta, GA 30309. (800) 283-7800. 〈http://www.arthritis.org〉.

National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse. 1 AMS Circle, Bethesda, MD 29892-3675. (301) 495-4484.

Spondylitis Association of America. P.O. Box 5872, Sherman Oaks, CA 91413. (800) 777-8189.

OTHER

Matsen III, Frederick, ed. "Ankylosing Spondylitis." University of Washington Orthopaedics and Sports Medicine. 〈http://www.orthop.washington.edu/arthritis/types/ankylosingspondylitis〉.

ankylosing spondylitis (anki-loh-zing) n. see spondylitis.