How is juvenile ankylosing spondylitis treated?

Non-pharmacological methods of juvenile ankylosing spondylitis

In the treatment of juvenile ankylosing spondylitis, special emphasis should be placed on teaching the patient a rational regimen, developing the correct functional stereotype, and a carefully developed set of therapeutic exercises (LFK) aimed at limiting static loads, maintaining correct posture, and maintaining sufficient range of motion in the joints and spine. It is important to encourage the patient to perform daily physical exercises to prevent progressive kyphosis. Intensive ERT and especially balneological procedures, which often provoke exacerbations, should be used with caution in patients with JIA who have active (or subacute) manifestations of peripheral arthritis and/or enthesitis. Magnetic laser therapy can be used quite widely, especially in the treatment of coxitis, as well as electrophoresis with 5% lithium chloride, hyaluronidase (lidase), and other antifibrotic agents.

Drug treatment of juvenile ankylosing spondylitis

Treatment goals for juvenile ankylosing spondylitis:

• suppression of inflammatory and immunological activity of the process;
• relief of systemic manifestations and articular syndrome;
• maintaining the functional capacity of joints;
• prevention or slowing down of joint destruction and patient disability;
• achieving remission;
• improving the quality of life of patients;
• minimizing side effects of treatment.

Therapeutic tactics for juvenile ankylosing spondylitis are basically not much different from those for ankylosing spondylitis in adults. It depends mainly on the spectrum of clinical manifestations of the disease at one stage or another.

Nonsteroidal anti-inflammatory drugs

NSAIDs are indispensable in the treatment of juvenile ankylosing spondylitis as symptomatic agents that can reduce and even completely relieve the manifestations of pain and inflammation in the joints.

The list of NSAIDs approved for use in pediatric practice is very limited, especially for preschool-aged children, for whom the vast majority of NSAIDs are "off-label" drugs.

Given the wide range of side effects induced by NSAIDs, preference should be given to a new class of non-steroidal compounds, the so-called selective COX-2 inhibitors. Among the drugs of this class, only nimesulide can be used with virtually no age restrictions; it is prescribed to children at a dose of 5 mg/kg per day. Meloxicam is approved for use only in children over 12 years of age at a dose of 0.15-0.25 mg/kg per day.

These agents are less toxic to the gastrointestinal tract and kidneys with good anti-inflammatory activity.

Nimesulide, in addition, having antihistamine and antibradykinin action, serves as a drug of choice for patients with concomitant allergic diseases and bronchial asthma, and it is also considered the most pathogenetically substantiated drug, since it is a derivative of sulfonanilide related to sulfasalazine. In patients with high disease activity, a gradual accumulation of the anti-inflammatory potential of selective COX-2 inhibitors over 2-3 weeks is possible, i.e. a pronounced anti-inflammatory effect of drugs may not occur as quickly as with the use of indomethacin or high doses of diclofenac. However, after achieving a therapeutic effect, the anti-inflammatory effect of this drug is almost identical to the effectiveness of diclofenac. It should be emphasized that in some patients with highly active juvenile ankylosing spondylitis, as well as in adults with ankylosing spondylitis, selective efficacy of indomethacin occurs with insufficient response to any other NSAIDs. These few patients are forced to take indomethacin, despite the highest frequency of adverse reactions caused by it among all NSAIDs.

Indomethacin is prescribed to children at a rate of 2.5 mg/kg of body weight per day. Diclofenac is also used in a similar dosage (2.5-3 mg/kg). Naproxen at a dose of 10-15 mg/kg (for a short period to suppress activity - 20 mg/kg) or piroxicam (0.3-0.6 mg/kg in children over 12 years old) can be successfully used, without forgetting, however, about the high gastrointestinal toxicity of the latter. Other NSAIDs for JIA, as a rule, are ineffective.

General recommendations for the duration of NSAID use in JIA are focused on maintaining signs of disease activity, primarily articular syndrome. After the signs of activity have been relieved, NSAID treatment should be continued for 1.5-2 months.

Basic anti-inflammatory treatment of juvenile ankylosing spondylitis

Indications for the use of disease-modifying (basic) drugs are persistent disease activity with peripheral arthritis, enthesitis, and uveitis. It is advisable and pathogenetically justified to use sulfasalazine as a basic drug at a rate of 30-50 mg/kg per day (in total no more than 2 g per day).

In order to prevent serious adverse reactions that may occur in a small proportion of patients with individual metabolic characteristics (slow acetylation type), the full daily therapeutic dose is achieved gradually, over 1.5-3 weeks, starting with 0.25 g/day under the control of general well-being and peripheral blood analysis. Sulfasalazine should be avoided in patients with IgA nephropathy, as it may worsen the severity of urinary syndrome.

^{In recent years, methotrexate at a dose of 10 mg/ m2} per week has been used as a basic drug for juvenile ankylosing spondylitis, and in some patients, the use of a combination of sulfasalazine and methotrexate is justified. Methotrexate is prescribed orally or intramuscularly (subcutaneously) on a fixed day of the week, with the parenteral route of administration characterized by better tolerability and higher efficiency due to better bioavailability compared to the oral route of administration. Methotrexate is prescribed in cases of persistent clinical and laboratory activity resistant to the treatment, especially in combination with erosive arthritis of the small joints of the feet, recurrent uveitis, and in patients with IgA nephropathy. Folic acid is also used to improve the tolerability of methotrexate. On the day of its administration, it is advisable to cancel NSAIDs (especially diclofenac) or reduce the dose.

In a significant proportion of patients with juvenile ankylosing spondylitis, basic treatment is not used either because of poor tolerance of sulfasalazine and the impossibility of taking methotrexate (for example, with concomitant foci of infection, frequent viral diseases, erosive gastroduodenitis), or due to the lack of clinical indications for prescribing basic agents. Our experience, consistent with the opinion of most other researchers, shows that basic drugs are ineffective in isolated spinal lesions (the so-called central form of juvenile ankylosing spondylitis).

Glucocorticoid treatment of juvenile ankylosing spondylitis

Sometimes it is necessary to prescribe corticosteroids at a dose of 0.2-0.5 mg/kg per day as an equivalent of high doses of NSAIDs. The use of corticosteroids is justified in patients with long-term persistent high disease activity with pronounced stable shifts in humoral immunity parameters, as well as in the development of such systemic manifestations as IgA-associated nephropathy or uveitis, provided that the use of NSAIDs in adequate doses is ineffective. In patients with predominant symptoms of axial skeletal damage, especially with severe inflammatory pain and stiffness in the spine, a decrease in respiratory excursion, a three-day pulse therapy with methylprednisolone 15 mg/kg (both as a single course and programmatically, for example, quarterly) is effective.

Of great importance is the performance of intra-articular injections, as well as the introduction of corticosteroids into the sites of the most pronounced enthesitis and tenosynovitis. For intra-articular injections, prolonged-release corticosteroids are used: betamethasone preparations, triamcinolone, and less often, methylprednisolone. In European countries and North America, in pediatric practice, almost exclusively triamcinolone hexacetonide is used for intra-articular injections, which has repeatedly proven its advantage over other drugs in the course of controlled studies.

Anti-cytokine drug treatment of juvenile ankylosing spondylitis

The ongoing search for effective means of pathogenetic treatment of rheumatic diseases has led to the introduction of anti-cytokine drugs into clinical practice in recent years, primarily tumor necrosis factor (TNF-a) blockers. Infliximab, which is a monoclonal antibody to TNF-a, and etanercept (soluble TNF-a receptor). They have been successfully used in the most severe cases of seronegative spondyloarthritis in adults; the drugs are very effective in highly active spondyloarthritis in children. The possibility of active use of these drugs is limited by age limits, since they are not registered for use in children and can only be prescribed in special clinical situations to overcome drug refractoriness in the absence of contraindications (foci of chronic infection, tuberculosis infection, risk of neoplasms, etc.). Many years of experience in using infliximab in spondyloarthritis in adults has shown the possibility of a stable decrease in disease activity and an improved prognosis. Infliximab is administered at an average dose of 5 mg/kg intravenously by drip at intervals of 2 weeks, 4 weeks (between the second and third infusions) and then every 8 weeks. Contraindications to the use of infliximab are untreated infectious foci, especially tuberculosis infection.

The use of rational treatment regimens for patients with juvenile ankylosing spondylitis, its timely correction in case of ineffectiveness or the appearance of new symptoms allows achieving control over the activity of the pathological process in the vast majority of patients and significantly improving the prognosis.

Evaluation of the effectiveness of treatment of juvenile ankylosing spondylitis

In clinical practice, the criteria for treatment effectiveness are a decrease in the frequency and severity of relapses of peripheral arthritis and enthesitis, a decrease in laboratory activity, and an improvement in functional capacity achieved as a result of using medications. The effect of using NSAIDs, corticosteroids (oral and intra-articular), and biological agents occurs in a short time - usually within the first few days. In contrast, the disease-modifying effect of basic drugs can be expected no earlier than after 2-3 months of use, with a gradual increase in effectiveness as the drug accumulates during long-term use.

In scientific research and clinical trials, special methods are used to evaluate the effectiveness of treatment. In adults with AS, the combined BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) is used, which evaluates five clinical indicators based on a patient questionnaire using the 100-mm visual analogue scale BASDAI: pain in the spine, pain in the joints, duration and severity of pain in the spine, fatigue, and the degree of discomfort that occurs during palpation of any areas. The BASDAI index is not used to evaluate the effectiveness of treatment in children due to the lack of validation, as well as special versions of questionnaires. In pediatric practice, a method developed in recent years for JIA can be used for this purpose in JIA. According to this method, six indicators are evaluated:

• number of “active” joints (75 joints are taken into account);
• number of joints with limited function ( 75 joints are taken into account);
• ESR and/or C-reactive protein;
• overall assessment of disease activity according to the physician (VAS);
• assessment of general well-being according to the patient or his parents (VAS);
• assessment of functional capacity using the Childhood Health Assessment Questionnaire (CHAQ).

The dynamics of the listed indicators during the treatment process gives grounds to judge the degree of effectiveness: 30% improvement in indicators allows us to consider the effect moderately positive, 50% - good; 70% - very good.

Complications and side effects of treatment for juvenile ankylosing spondylitis

The range of side effects of drug treatment varies and depends on the pharmacological group, as well as the specific drug used.

The spectrum of side effects of NSAIDs includes the following, listed in order of priority:

• gastropathy in the form of dyspepsia and/or the development of NSAID-induced damage to the mucous membrane of the upper gastrointestinal tract, most characteristic of indomethacin, acetylsalicylic acid, piroxicam, diclofenac;
• hepatotoxicity, which is possible with the use of any NSAIDs, most often diclofenac;
• nephrotoxicity, which occurs with the use of any NSAIDs, including selective COX-2 inhibitors;
• myelotoxicity characteristic of phenylbutazone, indomethacin;
• adverse reactions from the central nervous system observed when using ascetylsalicylic acid, indomethacin, and sometimes ibuprofen;
• increased chondrodestruction, characteristic of indomethacin.

The most important side effects of sulfasalazine and methotrexate are potential hepatotoxicity, as well as idiosyncratic side effects characteristic of the entire group of antimetabolites, which depend on the individual characteristics of a particular patient. When using methotrexate, dyspeptic reactions occur, the frequency of which increases with increasing duration of drug administration.

The use of biological agents, especially modern TNF-a blockers, is associated with a high risk of developing opportunistic infections, as well as a hypothetical risk of increasing the incidence of neoplasms.

Strict adherence to recommendations for indications and dosages of medications, as well as monitoring side effects, helps prevent the development of complications and a significant portion of adverse reactions.

Errors and unjustified appointments

The most common errors in the treatment of juvenile ankylosing spondylitis concern the unjustified prescription of glucocorticosteroids with the development of exogenous hypercorticism (most often in situations where the diagnosis is mistakenly interpreted as juvenile rheumatoid arthritis). Sometimes basic drugs are unjustifiably used in case of overdiagnosis of spondyloarthritis in patients with peripheral arthritis and non-rheumatic spinal pathology. Isolated damage to the axial skeleton in reliable juvenile ankylosing spondylitis is also not a sufficient basis for basic treatment, since the main point of application of the pathogenetic action of these drugs is peripheral arthritis and enthesitis. Serious consequences can be caused by the use of active physiotherapy and balneotherapy in patients with "active" peripheral joint syndrome and enthesitis. Underestimation of co-morbid infections prior to initiation of immunosuppressive treatment with methotrexate and biologic agents may result in potentially dangerous complications.

Surgical methods of treatment of juvenile ankylosing spondylitis

According to the generally accepted opinion, the juvenile onset of spondyloarthritis determines an unfavorable prognosis regarding destructive joint damage, especially hip joints. In this regard, 20-25% of patients with juvenile ankylosing spondylitis in adulthood require endoprosthetics of large joints.

In pediatric patients with fixed contractures of the hip joints, low-trauma surgical treatment methods can be successfully applied - myoadductofasciotomy, use of a distraction system, which improves function and postpones the time of endoprosthetics.

Forecast

The prognosis for life and long-term preservation of functional capacity is generally favorable. In the case of long-standing juvenile ankylosing spondylitis, as a rule, already in adulthood the cause of disability may be destruction of the hip joints, requiring endoprosthetics, or ankylosis of the intervertebral joints of the cervical spine. Eye damage rarely has an unfavorable course; aortitis worsens the prognosis and can be the cause of death, which occurs extremely rarely. Mortality in juvenile ankylosing spondylitis is affected by amyloidosis, in this regard, timely and adequate treatment of the active inflammatory process is of particular importance.

Possible paths of evolution of juvenile ankylosing spondylitis and its prognosis should be taken into account by a pediatric rheumatologist in professional orientation and social rehabilitation of adolescents. It is advisable to discuss the problem of the genetic basis of the disease with older patients and their parents as a risk factor for future offspring. According to literature, the risk that an HLA-B27-heterozygous father will pass the disease on to his son is no more than 5%, and even less to his daughter. Systematic long-term medical observation with control of laboratory parameters and timely correction of treatment can significantly reduce the risk of complications of juvenile ankylosing spondylitis and improve the prognosis.

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