A chronic inflammatory arthritis that predominantly affects the spine. It has a strong genetic component, and over 95 percent of AS patients who are of Caucasian extraction have a gene called HLA-B27. The disease affects mainly young men and has a male to female ratio of 5:1.

The frequency of AS in women may be underestimated because they develop milder disease. Symptoms almost always start before the age of 40 years, usually in the 20- to 30-year age range. AS affects approximately 0.5–1 percent of people in the U.S.

Cause - The association of AS with the HLA-B27 gene was first described in the early 1970s and stimulated considerable research into the causes of AS and associated SPONDYLOARTHROPATHIES. The HLA-B antigens are molecules that human cells express on their surface.

In Caucasian populations, approximately 10 percent of people have the HLA-B27 gene. The frequency of this gene varies widely in other populations. It almost never occurs in the black African population living south of the Sahara Desert but is found in as many as 50 percent of Haida Indians in Canada.

Generally AS is common where the gene HLA-B27 is common and rare where HLA-B27 is rare. Experimental evidence also suggests that the HLA-B27 molecule carries a particular predisposition for AS. Experiments transferring the human HLA-B27 gene to rodents resulted in their developing an AS-like illness.

One role of the HLA molecules is to carry small peptide antigens processed in the cell to the surface where they can be recognized by a subgroup of lymphocytes called CD8+ T cells. Less than 2 percent of all people with HLA-B27 have AS. However, in families of patients with AS, nearly 20 percent of people who carry HLA-B27 will develop AS.

These findings suggest that other genetic factors in addition to HLA-B27 are important. Environmental factors may be needed to activate the disease in people who carry the gene. HLA-B antigens are expressed on all cells in the body, so it is not clear why the spine is particularly affected by AS.

One popular theory is that of molecular mimicry. Simply put, this theory suggests that an immune response is started against an infecting bacterium and that the response continues because antigenic determinants (small parts of an organism or other structure recognized by the immune system) are shared between the bacterium and the HLA-B27 molecule.

Some bacteria and the HLAB27 molecule do have identical antigenic determinants. That is, they look alike to the immune system. The related diseases REACTIVE ARTHRITIS and REITER’S SYNDROME are known to occur after infection with such organisms. This lends support to the theory that AS has a similar trigger. However, we still do not understand exactly why AS develops.

Symptoms - Inflammation typically affects the large sacroiliac (SI) joints at the base of the spine and the small joints between vertebral bodies and between ribs and vertebral bodies (spondylitis). This leads to pain and stiffness, which is most severe in the mornings and tends to improve with exercise.

The lower back and neck are affected more than other parts of the spine. In many people this stiffness can progress to complete loss of movement as ligaments and joints are gradually replaced by bone and fuse (ankylosis). This process takes many years, and the rate at which it occurs varies in different people.

Ankylosing spondylitis can also affect the peripheral joints, usually large joints such as the hips, knees, and shoulders. The hips are more likely to be involved if the disease starts before the age of 20. If hip arthritis does not occur in the first 10 years after diagnosis, it is unlikely to do so.

Enthesitis, or inflammation where tendons or ligaments join onto bone, is a hallmark of this disease. This occurs particularly at the heel where the ACHILLES TENDON joins the calcaneus (heel bone), in the lower pelvis where the inner thigh muscles attach, and along the spine and the breastbone where the ribs join.

Involvement of the joints where the ribs meet the breastbone and spine can cause severe chest pain and difficulty in breathing. Many patients have had tests performed to exclude a myocardial infarction (heart attack) or lung disease as a cause of unexplained chest pain before the diagnosis of AS was made.

In teenagers a variant of AS occurs. In this condition, enthesitis is the most common manifestation. The clinical presentation of enthesitis and arthritis in a teenager is sometimes called the SEA (seronegative enthesitis and arthropathy) syndrome. Not all teenagers with the SEA syndrome develop the adult form of AS.

In many with SEA, the arthritis lasts for a few months or years and then disappears. In many patients, fusion of the joints in the spinal column causes increasing stiffness and eventually a stooped posture that is typical of AS. Restricted movement in the neck makes it difficult for patients with AS to turn their heads.

As a consequence, activities such as reversing a car become difficult. Stiffness and restricted movement in the hips and knees can cause these joints to become permanently flexed, making walking difficult. Fusion of the rib joints reduces the ability of the chest to expand when a deep breath is taken.

Reduced lung expansion can cause recurrent chest infections and shortness of breath when the patient exercises. Scarring of the upper lobes of the lungs may develop late in the disease and can become infected with organisms that do not usually affect healthy lungs (opportunistic infection).

Patients with AS can also develop several medical problems that are unrelated to their joints. Eye inflammation is common, and anterior uveitis or iritis occurs in 25 percent of patients (see EYE PROBLEMS). Usually this presents with pain in one eye, blurred vision, discomfort in bright light (photophobia), and increased redness and watering of the eye.

Attacks of iritis or uveitis usually subside within a few months but may recur later in either eye. The eye inflammation in AS seldom causes permanent loss of vision, but if treatment is delayed it can. A number of cardiovascular complications may occur and are thought to be caused by chronic inflammation. Why the heart is a specific target in AS is not known.

Cardiovascular complications include the following conditions:

• Inflammation of the first part of the aorta that originates from the left ventricle (aortitis)
• Leaking of the aortic valve (aortic regurgitation), causing blood to flow back into the left ventricle after it has been pumped out
• Heart block, in which electrical impulses fail to pass normally from specialized conducting tissue in the upper chambers of the heart, the atria, to the lower chambers, the ventricles that pump blood
• Enlargement of the heart
• Pericarditis (inflammation of the lining layers around the heart)

Aortic regurgitation and heart block are the most common cardiovascular complications. These are more likely to occur in patients who have had AS for many years with involvement of peripheral joints such as the wrists, shoulders, or knees. Spinal fracture can occur after relatively minor trauma because the spine is rigid and less flexible.

OSTEOPOROSIS is common and may occur early in the disease, suggesting that it results from the inflammatory process rather than immobility. AMYLOIDOSIS, glomerulonephritis caused by deposition of immunoglobulin IgA, and cauda equina syndrome are rare complications.

In the cauda equina syndrome, the fluid-filled membranes at the lower end of the spinal cord enlarge. This causes pressure and damage to the lower spinal nerves, particularly those supplying function to the bladder and bowels.

Diagnosis - AS is often not diagnosed for several years after the onset of symptoms, especially in women. This is because the onset of back pain and stiffness is gradual and in a young person is often ascribed to back strain. Women develop AS less often than men and therefore the diagnosis may not be considered in women.

A history of back pain with unusual morning stiffness and signs of enthesitis or arthritis that affects large joints in a young adult should suggest the diagnosis of AS. X-ray evidence of inflammation of the sacroiliac joints is required to make a definite diagnosis of AS.

However, it is important to recognize that X-ray changes can take up to 10 years to develop. Therefore, in early disease, the X rays can be normal. X rays of the SI joints are difficult to interpret in teenagers and young adults. Radioisotope bone scans can show increased uptake in the SI joints in the early stages of disease before X-ray changes are visible.

CT scans are both sensitive and specific but have the disadvantage that they expose the reproductive organs to significant radiation. MRI of the SI joints is sensitive very early on, but its place in investigation is not yet clear. Inflammatory markers in the blood such as ESR may be raised but are not reliable, particularly in patients who have disease that is limited to the spine.

Tests for RHEUMATOID FACTOR and ANTINUCLEAR ANTIBODIES are negative. The presence of HLA-B27 increases the likelihood of the diagnosis of AS in patients of Caucasian extraction. However, because approximately 10 percent of healthy people have the HLA-B27 gene, this test is of limited value both in patients with features typical of AS and in those with poorly characterized back pain.

Treatment and Outcome - The aims of treatment are relief of symptoms (pain and stiffness), improvement in flexibility, and maintenance of posture thus enabling the individual to continue his or her occupation and partake in leisure activities. Crucial to achieving these aims is early diagnosis and patient education.

Self-care through stretches, exercises, and appropriate knowledge and use of medications is essential for a good outcome. Learning a routine of stretches and exercises under the supervision of a physical therapist is very useful. Swimming is an excellent exercise for patients with AS because it exercises the heart and lungs and puts many joints through a wide range of motion.

For most people with AS physical therapy, NSAIDs and occasional analgesics are sufficient. A small number of patients with severe disease require more aggressive treatment with drugs that attempt to control inflammation or slow down the progression of disease.

Most patients with established disease and fused joints or deformity will benefit from occupational therapy, including assessment for work environment alteration or use of ASSISTIVE DEVICES. Many NSAIDs are used to treat AS. PHENYLBUTAZONE is an NSAID that has a reputation among older rheumatologists for being particularly effective in controlling the symptoms of AS.

Because it occasionally causes serious bone marrow damage, phenylbutazone is no longer available in many countries. In surveys of patients with AS, INDOMETHACIN was the preferred NSAID but it has a relatively high frequency of side effects, including central nervous system effects such as dizziness.

NAPROXEN was the next preferred NSAID. However, it is likely that most of these drugs can improve symptoms, although individual patients may have preferences for a particular NSAID. Some evidence indicates that treatment with phenylbutazone and indomethacin may slow or prevent fusion of joints, but NSAIDs are used primarily to control symptoms rather than to slow progression of disease.

Among the drugs that are prescribed to control inflammation if NSAIDs alone are insufficient, SULFASALAZINE is safe and effective in some patients, particularly those with involvement of peripheral joints. AZATHIOPRINE and METHOTREXATE have some effect on both spinal and peripheral disease, but clinical trials are inadequate to assess the efficacy of these drugs.

The newer anti-TNF drugs have been highly effective in patients with resistant disease. Future trials will establish their role in treatment. Early reports suggest that a BISPHOSPHONATE drug, pamidronate, may have useful effects. This group of drugs is more often used to treat osteoporosis but is under investigation for the treatment of AS.

Radiotherapy was used in the 1930s for spinal disease with good responses. A report in 1950 that AS patients who had received radiotherapy had a higher than expected incidence of leukemia resulted in a marked decline in this form of therapy. Although modern radiotherapy is probably much safer, it is still seldom used.

However, it still has a role in intractable disease and has been used in small doses to control local problems such as enthesitis of the Achilles tendon refractory to other treatments. Local CORTICOSTEROID injections are useful in treating swollen peripheral joints and enthesitis, but there is little role for long-term oral corticosteroids in AS.

If the hip joint is severely damaged, total joint replacement can dramatically improve a patient’s quality of life. This is a common operation in AS. However, many patients are young at the time of surgery and are likely to need a second operation years later to replace the artificial hip when it wears out.

Patients with AS who undergo hip replacement surgery have a greater chance of developing heterotopic ossification, a condition where new bone grows around and into the new joint, thus restricting its motion. To prevent heterotopic ossification, many orthopedic surgeons treat the hip with a low dose of radiotherapy before surgery.

Surgery is also occasionally used to correct a severe spinal deformity when the patient is bent so far forward that forward vision is impossible. The majority of patients with AS can lead an active life and continue to work.

Indeed, some patients with mild disease who have had back pain but never sought medical advice for it are diagnosed only when a routine X ray late in life shows the typical findings of AS. A poorer prognosis is more likely if there is peripheral joint disease, a young age of onset, a raised ESR, and a poor response to NSAIDs.