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Irina Alexandrovna Zborovskaya – doctor of medical sciences, professor, head of the department of hospital therapy with the course of clinical rheumatology of the doctors improvement faculty of Volgograd state medical university, deputy director for scientific work of the State institution “Research and development institute of clinical and experimental rheumatology” of the RAMS, head of the regional Osteoporosis Center, presidium member of the Association of rheumatologists of Russia, member of the editorial boards of the magazines “Scientific and practical rheumatology” and “Modern rheumatology” Definition. Bechterew’s disease or ankylosing spondylitis is a member of a group of rheumatic diseases that affects the spinal column known as “seronegative spondylarthritis”. Ankylosing spondylitis is a chronic, inflammatory rheumatic disease that causes inflammation of the spinal joints (vertebrae), perivertebral tissues and sacroiliac joint. The chronic inflammation of vertebrae can eventually cause ankylosis of intervertebral joints and calcification of spinal ligaments. Epidemiology. The incidence of ankylosing spondylitis has been estimated 1:1000 (one case per thousand people). Prevalence of ankylosing spondylitis parallels the prevalence of HLA-B27 gene in the general population and prevalence of ankylosing spondylitis in certain geographic locations. HLA-B27 antigen occurs in 7% of white Americans and in 90% of individuals with ankylosing spondylitis. The gene which codes HLA-B27 antigen is found in chromosome 6. HLA-B27 antigen does not effect the extent of the disease severity. Sex. Ankylosing spondylitis occurs as frequently in men as in women considering sacroileitis as a diagnostic criterion of the disease. However, symptoms of the disease are generally milder among females. Peripheral joints are most commonly involved in females than in males. Genetic predisposition. Families of patients with HLA-B27 antigen have a higher disease incidence which amounts to 20% of all cases. Concordance rate of ankylosing spondylitis among monozygotic twins is about 50%. These findings testify to the fact that not only HLA-B27 antigen but also some other genes and environmental factors play a significant role in pathogenesis of ankylosing spondylitis. Aetiology. The exact cause of ankylosing spondylitis remains unknown. However, it has been demonstrated that ankylosing spondylitis tends to run in families. A specific HLA-B27 histocompatibility antigen occurring in 90-95% of individuals is also of great importance. Infections may be also a factor. There is evidence for a possible role of Klebsiella and some other species in the development of peripheral arthritis in patients with ankylosing spondylitis. Evidence for the development of intestinal inflammation and dysbacteriosis of varying extent of severity in patients with ankylosing spondylitis is supported by research findings. Cold exposure and spine injury may also trigger the disease. Pathogenesis. Pathogenesis of ankylosing spondylitis has not been well studied. Receptor theory considers antigen as a receptor for damaging factor (for example bacterial antigen, virus, etc.) which causes a disease. Another theory is arthritic peptide theory. According to arthritic peptide theory, an increased immune response to bacterial peptide develops due to combination of peptide with HLA-B27 antigen. HLA-B27 antigen molecules act as receptors for microbial (for example, Klebsiella pneumonie) and some other triggering factors. The complex which is formed stimulates the production of cytotoxic T-lymphocytes which are able to damage cells and/or tissues having the molecules of this antigen. In HLA-B27-postitive carriers effector CD8+ response which is necessary for elimination of bacteria is decreased, while CD4+ T-cell immunopathologic response is increased. According to antigen mimicry theory, receptor similarity between HLA-B27 antigen and microbe antigen may contribute to their prolonged persistence in the body of the patient and stimulate the development of an autoimmune process. HLA-B27 peptides do not normally attract T-cells. However, in presence of bacterial peptides which cross-react with them they are typically presented by molecules of the major histocompatibility complex class 2 T-cells and are targeted by T-cell autoimmune attacks. “Leakage of antigen material” theory, especially of lipopolysaccharides, also exists. Antigen material of lipopolysaccharides usually penetrates through the intestinal wall into the bloodstream due to increased intestinal permeability in patients with ankylosing spondylitis and it is transported to the joints, including sacroiliac joint, cartilages and ligaments. Pathomorphology. In ankylosing spondylitis “cartilage” joints rather than “synovial” ones are typically involved. They include sacroiliac joints, small intervertebral joints, sternoclavicular and sternocostal joints, symphysis. Sacroiliitis is a typical early manifestation of ankylosing spondylitis. At the initial stage of the disease granulations which contain lymphocytes, mast cells, macrophages and chondrocytes occur in the subchondral part of the bone. Destruction of cartilage occurs slowly. First articular surfaces are sclerosed. Then fibrous and bone ankylosis of sacroiliac joint typically develops. The articular space usually becomes narrow and ultimately disappears. Enthesitis, that is inflammation of tendons generally where they attach to bone, ligaments, fibrous part of intervertebral discs and articular capsules, is also typical of ankylosing spondylitis. Inflammation and erosions are typically seen in the foci. In the course of the disease tendons and ligaments are often ossified. Cartilage and fibrous tissue of ligaments and intervertebral discs are most commonly involved. Fibrous tissue of articular capsules of intervertebral joints are less commonly affected. Spine inflammation and granulation typically occur at the junction of the fibrous ring of the intervertebral disc and vertebral body. External fibers of the fibrous ring are destroyed and replaced by bone tissue which causes formation of bone bridges between vertebrae known as syndesmophytes. Formation of syndesmophytes stops as soon as the intervertebral disc is ossified. The process typically spreads upwards, and radiographic abnormalities of the spine usually resemble a bamboo stick. Along with these changes, diffuse osteoporosis, inflammation and destruction of vertebral bodies at the junction of the intervertebral disc and square-shaped vertebral bodies are often seen in ankylosing spondylitis. Proliferation of the synovial membrane of intervertebral joints causes destruction of the cartilage of articular processes which sometimes results in bone ankylosis of these joints. Proliferation of the synovial membrane infiltrated by lymphocytes typically results in peripheral joint involvement. Subchondral granulations and erosions of the cartilage are usually found in the centre of the articular surface. Proliferative synovitis which is less common, may result in pronounced fibrosis of the synovial membrane of the articular capsule. Proliferative synovitis may also predispose to ossification and ankylosis, destruction of the articular cartilage and bone erosions. Classification. According to the course of the disease, ankylosing spondylitis may be: 1 Slowly progressive 2 Slowly progressive with exacerbations of the disease 3 Highly progressive (within a short period of time it may lead to complete ankylosis) 4 “Septic” type (it is characterised by an acute onset of the disease, excessive sweating, chills, fever, visceritis, erythrocyte sedimentation rate (ESR) is typically 50 – 60 mm per hour and even more). The following stages of ankylosing spondylitis are singled out: The 1st stage is initial or early. It is characterised by moderate limitation of the range of motion of the spine or affected joints; X-ray abnormalities may be absent or may indicate irregular surface of sacroiliac joints, foci of subchondral osteosclerosis, widening of articular spaces. The 2nd stage is characterised by moderate limitation of the range of motion of the spine or peripheral joints; narrowing or ankylosing of spaces of sacroiliac joints, narrowing of intervertebral articular spaces or signs of ankylosis in spine joints. The 3rd stage is late. It is characterised by marked limitation of the range of motion of the spine or large joints due to ankylosis; bone ankylosis of sacroiliac joints, intervertebral and costovertebral joints associated with ossification of the ligamentous apparatus. The following degrees of disease activity are singled out:
- Minimum (It is characterised by slight stiffness and pain in the spine and joints of extremities in the morning; ESR is usually 20 mm per hour, C-reactive protein (CRP) +).
- Moderate (It is characterised by persistent pain in the spine and joints, morning stiffness usually lasts for some hours, erythrocyte sedimentation rate is 40 mm per hour, C-reactive protein ++).
- Severe (It is characterised by severe persistent pain in the spine and joints; joint stiffness typically lasts all day long; exudative changes in joints, subfebrile body temperature, visceral manifestations are often seen; ESR is more than 40 mm per hour, C-reactive protein +++).
- Low back pain with inflammatory characteristics
- Limitation of lumbar spine motion in sagittal and frontal planes
- Osteochondrosis of the spine
- Rheumatoid arthritis (especially in peripheral joint involvement)