Medication Of Ankylosing Spondylitis (Bechterew's Disease)
Ankylosing spondylitis (AS) is the major form of inflammatory diseases of the spine. This disease is also known as Bechterew's disease, idiopathic or primary ankylosing spondylarthritis (spondylitis) - in unlike the secondary spondylarthritis, one of the manifestations entities that are members of the group of seronegative spondylarthritis.
AS is characterized by chronic progressive course and leads to intervertebral joints, calcification spinal ligaments and restrict the mobility of the spine. AS usually begins in young age, and its development over 45 years is very rare. Medium Age debut of the disease accounts for 24 years. AS is more common in men, but often observed in women, although they usually proceeds benign and does not lead to severe spinal deformity. Some authors, by contrast, did not find significant differences in clinical manifestations and during this illness, depending on the gender of patients. If consider all cases of the AU, including its latent within, the ratio of men to women is 2:1 or 3:1. The prevalence of AS is associated with the frequency occurrence of HLA-B27 and varies widely - from 0.15% in Finland to 1,4% in Norway, and even up to 2,5% among the adult population of the Eskimos of Alaska, but in general adult population is 1:200, i-e 0.05%.
Clinical picture and course of AS is characterized by severe heterogeneity. There may be cases with an isolated lesion spine (central form), While lesions spine and the root ( radical form ) Or peripheral joints ( peripheral form ). Inflammatory process in the spine manifested bilateral - cardinal and the earliest sign, ossification of ligaments of the spine and / or external Divisions of the fibrous ring with the formation of single or multiple front corners of the vertebrae and change their shape, destruction of disks and their ossification, nondestructive phone vertebrae, the unevenness of the articular surfaces and intervertebral osteosclerosis and edge-vertebral joints, osteopenia and osteoporosis of the spine. Although most cases there is a progressive failure of the axial skeleton with increasing restriction of mobility of the spine and its deformation, but it is not obligate. A number of patients over a long period, tens of years, there has been joints spine. When AU inflammatory process is not limited to the defeat of the axial skeleton. Typical of these disease arthritis sternocostal, sternoclavicular, and temporo-mandibular joints and, of course, arthritis of peripheral joints, except interphalangeal, metacarpophalangeal and metatarsophalangeal. But the most important involvement in the pathological process of root joints, especially hip, which occurs in one third of patients and is always an indicator unfavorable prognosis and early disability. Occupies an important place and enthesiopathies, determined by a variety of clinical and radiological symptoms (hip joints, erosion, osteosclerosis, osteophytosis, periosteal layers of heel bones, or bones of the pelvis). Sindesmofity also considered as a manifestation of generalized enthesiopathies, inherent in the AU and the whole group of seronegative spondylarthritis .
In addition to the defeat of the locomotor system, in this disease may and a variety of systemic manifestations, which often determine the prognosis disease and its outcomes. This applies primarily to the amyloid nephropathy the development of terminal renal insufficiency, severe violations conduction (atrio-ventricular blockade II and III degree), arachnoiditis of the lower part of the spinal cord, accompanied by sensory and motor disorders and disorders of pelvic organs. Chronic and progressive nature of the defeat of the joints and spine leads to poor quality of life patients with AS. According to Ward M.M., poor quality of life due to severe stiffness is observed in this disease in 90% of patient’s pain (83%), fatigue (62%), poor sleep (54%), anxiety for future (50%) and side effects of ongoing drug therapy (41%). Early in the large percentage of cases occurs and persistent disability.
Predictors of poor prognosis in AU includes large number of clinical, radiological, laboratory and genetic indicators. We belong to the risk factors: male gender, disease progression in age of 19, limiting the mobility of the spine in the first 2 years disease, arthritis of the hip joints in the debut of the AU, the combination of peripheral arthritis with pronounced enthesitis in the first 2 years of illness, high values of ESR and CRP for many months, HLA-B27 +, family aggregation of disease from group seronegative spondylarthritis. Amor B. et al. the study of 328 patients with AS 7 indicators showed the debut of the disease, which correlated with subsequent its heavy flow. Among these indicators are not only arthritis hip joints (relative risk 23), ESR above 30 mm / h (7), beginning disease before age 16 (3), restriction of mobility in the lumbar spine (7), ineffectiveness or inefficiency NSAIDs (8), oligoarthritis (4). Ability to relatively mild or moderate flow in the advanced stages of the AU is possible, if there are none of the above factors in the onset of the disease, while sensitivity represented performance of 92.5% and specificity - 78%. Heavy course of the disease can expect 50% of patients with arthritis of the hip joints at the beginning of the AU or other of any three of the above factors. Such patients should be under close medical supervision, and they show an especially active therapy.
The main principles of therapy AU is its individualization, stages and integrated approach to the impact on various parameters pathological process. It should be aimed at relief of pain and suppression of inflammation prevention of progression structural changes or significant slowdown in their development (basic anti-inflammatory therapy), and recovery activities function of the locomotor system that provides a broad range of rehabilitation activities. The volume and content of therapy in each case is determined by the clinical form of the disease, degree of inflammatory process, presence and severity of systemic manifestations, the functional ability of joints and spine.
Symptomatic therapy occupies a leading position in the treatment of AU and aims to control the two main symptoms of the disease -- pain and morning stiffness in the spine and joints. As is known, intensity of pain is one of the criteria of response to treatment or criterion of remission in this disease (ASAS response criteria and ASAS remission criteria). As for the morning stiffness, this symptom most adequately reflects the activity of the inflammatory process in the AU, with a greater degree than laboratory tests. Dynamics of the duration and severity of morning stiffness is of great importance in assessing ongoing treatment.
Symptomatic therapy includes the AU nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, simple analgesics and muscle relaxants. NSAIDs are first-line drugs and necessary component of combination therapy AU, where patients take their continuously for many months and even years. Quick and distinct positive effect of NSAIDs on subjective symptoms of spondylitis, namely, reducing pain and stiffness during the first 48 hours of their admission, used as one of the diagnostic criteria of spondylarthritis. In the study 741 patient with pain in the spine was found that this feature occurred in vast majority of patients with AS and only 15% - at pains spine caused by other pathological conditions. When AU sensitivity of this symptom is 77% and specificity - 85%. Interestingly, if the intensity of back pain is not reduced by taking NSAIDs the first 48 h of admission, the probability of the AU is only 3%. Requires clarification opportunity to actively influence of NSAIDs on the prognosis of the AU. It is believed that these drugs are not affect the rate of progression of structural changes in the spine, including those patients in whom there is a bright clinical (antiinflammatory) effect. However, the decrease in the intensity of pain contributes to reduce or end hypertonus muscles, i-e that factor which, together with the structural revised form characteristic deformity of the spine. Some patients severe pain in the joints or the spine can not be cut short NSAIDs, with their intensity does not correspond to the degree of activity of inflammation. In such cases, appropriate method to combine the NSAID with simple analgesics, and above all paracetamol. Paracetamol is normally appointed for a short period, and after stihaniya intense pain to remove. Appointment of analgesics improves sleep in night and early morning hours in patients with pronounced pain syndrome.
Therapy glucocorticoids (CC) at AU is less important than in rheumatoid arthritis, due to a number of its features .So, when the AU is less effective than in other rheumatic diseases. Besides, Local therapy of GC has a higher therapeutic potential than with the system and the positive effect is more aimed at suppressing inflammatory process in peripheral joints than in the spine. Yet when the AU has to resort to the local as well as to systemic hormonal therapy. A good effect is produced by local application of prolonged GC (eg, betamethasone) in patients with persistent synovitis, or persistent enthesitis. Efforts were successful attempts to introduce local GC in the sacroiliac joints are controlled by magnetic resonance or computed tomography, with possible to obtain remission of up to 7-9 months. Systemic application of the Civil Code is justified by patients with multiple lesions of joints and pronounced exudative phenomena, refractory to other forms of drug therapy, hard coke, long persistence of high concentrations of acute phase proteins, maximum activity of the inflammatory process during the three and more subsequent months, as well as in patients with severe and multiple system manifestations (aortitis with signs and symptoms of angina, formation of defects heart disease Berger's syndrome "horse's tail"). The dose of prednisolone is usually not should not exceed 10-15 mg / day. It remains debatable whether of pulse-therapy super-high doses of methylprednisolone.
Previously, it was shown that the classical pulse therapy leads to rapid and significant reduce the inflammatory process in peripheral joints and to a lesser extent - In the spine. But the positive effect of holding a short period and uzhespustya 3 months indicators of inflammatory activity reaches its former level. Application of high (1000) and low (375) doses of methylprednisolone in three next day contributes to a significant decrease in pain intensity and increase mobility in the lumbar spine, but treatment super-high doses promotes more lasting remission compared with treatment with low doses.
This disease observed reflex muscle tension, which is more contributes to limit the mobility of the spine, caused primarily structural changes. In these cases the use of muscle relaxants helps increase range of motion in the spine and joints, which makes them Appointment advisable.
Tolperisoneis a central muscle relaxant action. It has a membrane stabilizing effect, inhibits the conductance impulses in primary afferent fibers and motor neurons, influencing on spinal mono-and polysynaptic reflexes. Secondary brake selection of mediators by inhibition of Ca 2 + proceeds in synapses. In the trunk the brain affects the conduction of excitation of reticule-spinal path. It has a selective effect on caudal portion of the reticular formation of the brain, spine blocked mono-and polysynaptic reflexes, has a central H-cholinolytic action, weak spasmolytic and activity. Tolperisone has shown in the presence of severe rigidity, bright spastic syndrome and the presence of muscle contractures. In most cases Tolperisone applied orally at a dose of 450 mg / day. More rapid and distinct effect is observed for intramuscular injection drug. Tolperisone characterized by good tolerability and can be used for several months without the growth toxicity. In combination with NSAIDs can reduce their dose and reduce the risk of side effects of NSAIDs. Thus, Tolperisone as a central muscle relaxant, effectively suppresses pain vertebrogenic origin in the AU, interrupts pathological reflex arc and breaks the vicious circle that occurs in chronic pain. As a result vasodilatation and improved microcirculation in spasm, ischemic muscles Tolperisone reduces the severity of edema, and removes the imbalance increases the threshold of pain sensitivity.
Basic anti-inflammatory therapy(BPVP) at least AU developed than in chronic inflammatory diseases of the joints, for example, with rheumatoid arthritis, and evaluation of its effectiveness is largely hampered by marked heterogeneity of this disease. This therapy is primarily shows the AS patients with moderate and high inflammatory activity, refractory to NSAIDs and GC or with serious adverse reactions to these drugs, as well as patients with risk factors for further adverse the disease. But, basically, it should be conducted in all patients with to prevent the progression of structural changes in the joints and spine or slowing the progression of this. An important aspect of BPVP AU is that it may be an earlier appointment, because known that the formation of intervertebral ankylosis and edge-vertebral joints especially actively occurs in the first years of illness. The spectrum of drugs for BPVP when the AU is limited. So, do not apply derivative, gold salts - because of their ineffectiveness. The same applies equally to low therapeutic activity and high toxicity, which, which was the cause of the interruption of treatment in 68% of patients in a double-blind study
As a reference drug in the AU is widely used sulfasalazine . On chemical structure it is azo compounds sulphidine with salicylic acid. Anti-inflammatory properties due it sulfapiridinom. The reason for its application were the results numerous studies on its undoubted effectiveness in rheumatoid arthritis and, to a greater extent, - primarily with inflammatory bowel disease. The mechanism of action of sulfasalazine is not very clear. It is believed that he has a moderate antiproliferative and immunosuppressant effect. In particular, he is an antagonist of folic acid, inhibits the synthesis of tumor necrosis factor-? by induction apoptosis in macrophages, inhibits the nuclear transcription factor B, which regulates the transcription of genes of many mediators involved in immune response and inflammation. Recently published analysis of numerous Controlled 36-week studies on the effectiveness sulfasalazine in 619 patients with seronegative spondylarthritis, including the 264 - to AU. Among 187 patients with AS have been a central form of the disease and at 432 -- peripheral. The analysis showed high efficiency of sulfasalazine on symptoms of peripheral arthritis and low - on the inflammatory process in spine. From this it follows that sulfasalazine should be used when peripheral form of AU and predominantly in patients with small prescription of the disease.
In the literature of a small number of studies on the effectiveness of methotrexatewith the AU, while open trials were held only on small clinical material. The study Samhaio-Barros R.D. et al. results of methotrexate treatment of 34 patients with AS .Drug appointed by intramuscular injection of 12.5 mg / week. Throughout the year. All patients were refractory to NSAIDs. By the end of observation in 53% of patients registered a decline ESR 25% or more, as well as reducing the daily requirement of NSAID by 50% compared to baseline. The drug is actively influencing the expression peripheral arthritis, but not spondylitis. In another study, obtained good effect of treatment with MTX in his appointment to 7,5 mg / week. within 3 years . This therapy led to the restoration of functional insufficiency musculoskeletal system, significant reduction in ESR and CRP. Some authors believe that if patients observed torpid to NSAIDs and sulfasalazine, then they will not respond to therapy and methotrexate. It is advisable to conduct multicenter controlled studies on the effectiveness of methotrexate in the AU as a monotherapy and combined it with sulfasalazine, and the study whether treatment with high doses of methotrexate, as part of intensive therapy of severe AS.
An interesting trend is the use of BMT AS bisphosphonates. They are inhibitors of osteoclast-mediated bone resorption and then same time, possess anti-inflammatory potential, as shown in the model rheumatoid arthritis. Their use in the AU is of interest in the sense that this disease is observed osteitis in the attachment to the bone tendons, ligaments, articular capsule. Effectiveness patients with AS is proved as in the open and in a randomized double-blind studies. Treatment with this drug at 60 mg / month. Intravenously for 4 months leads to a significant reduction of inflammatory activity and improve function of joints and spine (in terms of index BASDAI and BASFI), reduce the number of inflamed and painful joints at 93,8% and 98,2% respectively, as well as significant reduction in ESR . After discontinuation of the drug its positive effect lasts for 4 more months. It is unclear how Pamidronate affect the structural changes the AU and whether he disease-modifying or only symptomatic effect. The presence of systemic expressions introduced in the therapy AU its peculiarities. Secondary reactive amyloidosis requires the appointment of colchicine. With good tolerance should be applied to 1.0 mg 2 times a day. Treatment of acute anterior uveitis should be with the optical, while the drug of choice is dexamethasone. Cardiopathy, accompanied by severe impairments conductivity type closures 2 and 3 degrees, dictate the appointment? -Stimulants oral steroids, and in some cases, implantation pacemaker. At restrictive or (rarely) obstructive respiratory insufficiency requires a detailed analysis of the causes of its development, including the possibility of adverse reactions conducted drug therapy, the prohibition smoking, for symptomatic treatment. Difficult dilemma arises from patients with neurological disorders. When syndrome "horse's tail" should be an immediate and super-high-dose therapy metolprednizolona - the only effective means.
New trend in therapy is the AU use of biological Agents(« biologics ") - Anti-inflammatory drugs XXI century. Although the etiopathogenesis of the majority of chronic inflammatory diseases joints and the spine is not decrypted, no doubt about the crucial role immune system disorders in their development. Recent studies have expanded existing understanding of the pathogenesis of AS and other seronegative spondylarthritis from the position of the imbalance of pro-and anti-inflammatory cytokines, in which TNF-? Occupies a central position. Vraun J. et al. with AU showed expression of TNF - ? And its mRNA in sacroiliac joints. Elevated levels of cytokine detected in the plasma of patients, and its values correlate with AC activity index (BASDAI). These data provided the basis for the anticytokine therapy in idiopathic AU, the more so that this disease occur inflammatory changes in the intestine, similar changes in Crohn's disease, i-e that disease in which the high therapeutic potential inhibitors of TNF-? Demonstrated most clearly.
It is extremely important place belongs to physical treatment and a wide range rehabilitation activities , aimed at the prevention and correction of spinal deformity and limitation mobility of joints. Therapy, physical therapy should be actively engaged in all patients regardless of clinical forms and inflammatory activity disease. It is aimed at restoring muscle strength and decrease amyotrophy and should be conducted on individual programs with a combination of static and dynamic exercises. Physiotheraty provides phonophoresis of hydrocortisone on peripheral inflamed and sacroiliac joints, the laser-magnetic therapy to the hip joints, iontophoresis of lithium chloride in increasing concentrations (from 5% to 10%) on the spine, diadynamic and sinusoidally-dynamic currents. Such patients show repeated courses of massage and treatment radon or hydrosulphuric baths. High efficiency has radiotherapy But Currently; it takes place only a few medical centers because of induced tumors. Surgical treatments are shown above only in severe lesions of the hip joints. Timely delivery Prosthetics one or both hip joints can restore disabled patients. Is also important as surgical correction of severe deformities spine, joint, flexion contracture large joints.
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