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Ankylosing spondylitis

            Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown etiology, characterized by inflammation of sacroiliac joints, vertebrae and adjacent spinal joints and structures, that may lead to progressive and ascending bony fusion of the spine. Peripheral joints are less often affected, but hip and shoulder joints, which are considered as axial manifestation, are affected in one third of cases. Patients have frequent inflammation of enthesis, while extraarticular involvement such as eye, heart valves, lung and kidney occur rarely.


            The prevalence of AS varies between 0.2% to 1.4% in different patient populations.

AS usually starts in the third decade of life.       Men are two to three times more often affected than women, however females often have atypical presentation and are underdiagnosed.


            A strong familial predisposition and an association with major histocompatibility complex class I molecule HLA–B27 is characteristic for AS patients. HLA-B27 antigen is positive in 90-95% of AS patients in most groups.


            The main clinical symptoms in AS are pain and stiffness predominantly in the lower back at disease presentation. Typical for AS is inflammatory back pain, whose characteristics are clinical, but not laboratory and include the following features: 1) starting of back pain at the age < 40 years, 2) insidious onset, 3) improvement with exercise 4) no improvement with rest, 5) pain at night with improvement upon getting up. Inflammatory back pain is characterized also with morning stiffness of the back with duration > 30 minutes and chronic complaints of back pain with duration > 3 months.


            Pain and stiffness in the back usually ascend from lower back to cervical spine during the disease evolution. Cervical spine involvement, classically believed to be a late disease manifestation, may occur earlier in women.


            Enthesitis is a frequent manifestation in AS and is observed in over 50% of AS patients with long standing disease and in 20% at disease presentation. The lower limbs are most frequently affected – especially the insertions of Achilles’ tendon and/or the plantar fascia at the calcaneus. AS patients may have a peripheral arthritis, typically monoarticular or oligoarticular.


            Extraarticular manifestations 

            Acute anterior uveitis may develop in about 25% of AS patients in the disease course. The uveitis is most often unilateral, sudden in onset, limited in duration and often alternating from one eye to the other. Symptoms include ocular pain, redness and photophobia. Prompt diagnosis and treatment is required in order to avoid permanent eye complications.


            Aortic regurgitation and variable degrees of atrioventricular or bundle-branch block occur in approximately 5% of patients with AS, usually after long standing disease although the cardiac symptoms may occasionally precede the articular complaints.


            Lung involvement in AS is rare and includes upper lobe fibrotic changes and chest wall restriction. Despite restricted chest expansion due to costovertebral joint fusion, AS patients rarely have significant reduction in vital and total lung capacities because the function of the diaphragm is preserved. Bilateral apical pulmonary fibrosis is rare and occurs in over 1% of cases, usually in patients with long-standing disease. The most frequent renal involvement in AS is secondary amyloidosis. Other renal manifestations are IgA nephropathy, mesangioprolipherative glomerulonephritis, etc.


            Laboratory and instrumental methods

            The laboratory findings include elevated ERS and CRP, elevated platelet count and anemia in the context of active inflammatory process. HLA-B27 is positive in more than 90% of AS patients, and reaches 100% in those with acute anterior uveitis and with heart involvement.


            X-ray of sacroiliac joints and the spine are an established investigations for diagnosis and staging of patients with AS. Sacroiliitis, usually bilateral, is the most frequent and earliest radiograph manifestation of AS and is a diagnostic criterion for AS. At disease onset, the inflammatory changes of sacroiliac joints can not be detected radiologically, which lead to delay of the diagnosis. Of note, magnetic resonance imaging (MRI) of the sacroiliac joints and the spine is increasingly used to assess disease activity in AS because it is advantageous to have some objective evidence of inflammation and facilitates early diagnosis.


            The lumbar, thoracic and cervical spine are other sides of the pathologic process in AS. The first changes are usually found at the corners of the vertebral bodies at the thoracolumbar junction in the form of small erosions with adjacent bony repair and proliferation. Periostal new bone formation along the anterior aspect of the vertebral body may result in squaring of vertebral body. Ossification of the outer fibres of the annulus fibrosis of the intervertebral disc and the longitudinal ligament lead to sindesmophytes formation. Sindesmophytes are a hallmark of AS and represent vertical bony spurs, which may form a bridge between vertebrae and produce “bamboo-like” appearance of the spine in patients with long-standing disease. These sites are assessed for definition the degree of disease involvement and progression during the follow-up.


            In early disease, with no definite radiograph changes, active inflammation in sacroiliac joints may be visualized on MRI, which in these cases reveals subchondral bone marrow oedema. On the basis of current knowledges and the opportunity to detect sacroiliitis via MRI, new criteria for AS are proposed by ASAS (Assessment in SpondyloArthropathies International Society). According to the new criteria both radiologically proven sacroiliitis (indicating chronic damage) and MRI visualised sacroiliitis (demonstrating active inflammation) are diagnostic for AS.


            Pharmacological treatment includes nonsteroidal anti-inflammatory drugs, disease modifying anti-rheumatic drugs. There is no evidence that sulfasalazine and methotrexate are useful for treatment of axial disease. They may be considered in patients with peripheral arthritis. In cases of persistently high disease activity anti-tumor necrosis factor (TNF) therapy (infliximab, etanercept, adalimumab, golimumab) should be given. Non-pharmacological treatment such as patient education, exercise programmes, swimming is of great importance in AS. The individual therapeutic plan should be chosen according to the form of the disease and disease activity.


                                                                                  Dr Sevdalina Lambova, MD, PhD