How is juvenile dermatomyositis treated?

Indications for hospitalization

Primary examination and treatment of patients with juvenile dermatomyositis is always carried out in a specialized rheumatology hospital.

Non-drug treatment of juvenile dermatomyositis

Patients with juvenile dermatomyositis are recommended early activation to prevent the development of severe muscular dystrophy, contractures and osteoporosis. As the disease activity subsides, dosed physical exercise (LFK) is prescribed. Massage is not performed until the inflammatory activity in the muscles has completely subsided. During the remission period, rehabilitation therapy is possible in special sanatoriums (sulfur, radon, brine baths) to reduce the severity of contractures.

Drug treatment of juvenile dermatomyositis

Pathogenetic (basic) immunosuppressive and anti-inflammatory therapy is indicated.

The main treatment for juvenile dermatomyositis is aimed at suppressing autoimmune inflammation in the skin, muscles and other organs. The basis of pathogenetic therapy for juvenile dermatomyositis is glucocorticosteroids; cytostatics are prescribed as indicated.

Symptomatic therapy is aimed at eliminating microcirculation and metabolic disorders, maintaining the functions of internal organs, preventing complications of the disease and therapy.

Principles of pathogenetic therapy:

• early appointment;
• an individual approach to choosing the most rational treatment regimen, taking into account the clinical manifestations, degree of activity and nature of the course of the disease;
• continuity (timely alternation of suppressive and maintenance doses of drugs, taking into account the phase of the disease);
• continuous monitoring of the effectiveness and safety of the therapy;
• duration and continuity of treatment;
• gradual slow reduction of the dose;
• cancellation only against the background of persistent clinical and laboratory remission.

The basis of treatment of juvenile dermatomyositis, as well as many other rheumatic diseases, is systemic glucocorticosteroids. Glucocorticosteroids are prescribed orally, in case of dysphagia, they can be administered through a tube, and in case of severe dysphagia, parenterally. Treatment of juvenile dermatomyositis is carried out with short-acting glucocorticosteroids (prednisolone, methylprednisolone).

Treatment of juvenile dermatomyositis begins immediately after diagnosis, as early onset leads to a better outcome, up to complete regression of the disease. The maximum suppressive dose of prednisolone for juvenile dermatomyositis is 1 mg/kg. In case of high disease activity, crisis conditions, a higher dose may be prescribed, but not more than 1.5 mg/kg. Preferably, a combination of prednisolone at a dose of 1 mg/kg orally with other treatment methods is used. The daily dose of the drug is divided, and the dose is prescribed in the first half of the day, with an emphasis on the early morning hours. Alternating administration (every other day) is ineffective for juvenile dermatomyositis.

The maximum dose is prescribed for the 6th-8th week (depending on the activity of the disease), after which a gradual slow reduction of the dose to the maintenance dose is started (prednisolone should be replaced with methylprednisolone due to its lesser mineralocorticoid activity; 5 mg of prednisolone is equivalent to 4 mg of methylprednisolone). The lower the dose of prednisolone, the slower it is reduced, and this is done by taking it later. With a good response to glucocorticosteroids, the dose of prednisolone is reduced so that after 6 months of treatment it is at least 0.5 mg/kg, and by the end of the first year of treatment - at least 0.25-0.3 mg/kg from the initial (1 mg/kg). If there are signs of torpidity of the process, the rate of reduction of the dose of glucocorticosteroids is slowed down, and additional methods of treatment are used to overcome steroid resistance.

The duration of glucocorticosteroids is calculated individually in each case depending on the effectiveness of this type of treatment in a given patient, determined by the timing of relief of clinical manifestations and achievement of remission, the presence of relapses, and the timeliness of the start of adequate therapy. But even with early administration of glucocorticosteroids, a good response to treatment and the absence of relapses, the total duration of treatment is at least 3 years (on average - 3-5 years), with a torpid and / or recurrent course - 3 years or more. Glucocorticosteroids are discontinued only against the background of persistent, long-term (> 1 year) clinical and laboratory remission.

In case of high disease activity (II-III degree of activity, crisis), life-threatening disorders, special indications, therapy is enhanced with additional treatment methods. These include pulse therapy with glucocorticosteroids, including in combination with plasmapheresis, cytostatic drugs, intravenous immunoglobulins.

Pulse therapy is an intravenous administration of ultra-high, shock doses of the drug. Its use allows for the fastest possible relief of high inflammatory activity of the disease, thus avoiding the use of very high doses of oral glucocorticosteroids. Methylprednisolone is used in a single dose of 10-15 mg/kg, on average 2-5 procedures daily or every other day. The drug is diluted in 100-250 ml of physiological sodium chloride solution or 5% glucose solution and administered over 35-45 minutes. Open studies have shown the effectiveness of pulse therapy in patients with acute, active disease; with early administration, it reduces the degree of functional insufficiency and the prevalence of calcification in the future. Pulse therapy with methylprednisolone has proven itself well in mild exacerbations of juvenile dermatomyositis, allowing for the relief of increasing disease activity without increasing the dose of prednisolone. Severe exacerbations of juvenile dermatomyositis, however, always require increasing the dose of oral glucocorticosteroids to the maximum.

Domestic controlled studies have proven the effectiveness of discrete plasmapheresis (DPP) in juvenile dermatomyositis, especially in combination with pulse therapy, the so-called synchronous therapy. Depending on the activity of the disease, 3-5 DPP procedures are used every other day, 6 hours after each session, pulse therapy is administered at a rate of 10-12 mg / kg. The use of DPP without adequate immunosuppression leads to deterioration of the condition due to the development of the "rebound" syndrome. Indication for synchronizing DPP with pulse therapy with glucocorticosteroids is high activity of juvenile dermatomyositis (grade III, myopathic crisis), including severe exacerbations (against the background of an increase in the dose of prednisolone - up to 1 mg / kg). Other indications for synchronous therapy in juvenile dermatomyositis: pronounced widespread skin syndrome, long-term untreated or inadequately treated process, torpidity of clinical symptoms against the background of oral glucocorticosteroid therapy.

Modern tactics of management of patients with juvenile dermatomyositis involve early administration of cytostatic drugs at moderate and high disease activity, allowing to achieve stable clinical and laboratory remission faster, reducing the period of taking high doses of glucocorticosteroids. It is necessary to remember that cytostatics are ineffective as monotherapy, they are prescribed for juvenile dermatomyositis only in combination with glucocorticosteroids.

Traditionally, methotrexate is used for juvenile dermatomyositis; in many guidelines for the treatment of inflammatory myopathies, it is designated as the drug of choice from the “second-line agents” due to the optimal “efficacy/toxicity” ratio. Methotrexate is classified as an antiproliferative agent, but when used in low doses, it has a predominantly anti-inflammatory effect.

Methotrexate is prescribed once a week, since more frequent use of the drug is associated with the development of acute and chronic toxic reactions. In children, methotrexate is taken orally at a dose of 10-15 mg / m ² of body surface once a week. The dose is increased gradually under the control of a complete blood count and transaminase levels. To reduce the toxicity of the drug, folic acid is additionally prescribed at a dose of 1 mg / day daily, except for the day of methotrexate intake. The effect develops after 1-2 months of treatment, the duration of administration is 2-3 years until stable clinical and laboratory remission is achieved, provided there are no complications.

Alternative cytostatics for juvenile dermatomyositis (for example, when methotrexate is ineffective) are azathioprine, cyclophosphamide and cyclosporine A. Azathioprine is less effective than methotrexate.

Cyclophosphamide is administered orally at a dose of 1-2 mg/kg or as intermittent pulse therapy (10-15 mg/kg per month) for life-threatening changes. The drug has proven itself in interstitial lung lesions in juvenile dermatomyositis.

In the steroid-resistant variant of the disease, cyclosporine A is effective, used at a dose of 3-5 mg/kg per day with a subsequent transition to a maintenance dose of 2-2.5 mg/kg per day for several months or years until a clinical effect is achieved. Currently, the drug is successfully used for interstitial lung disease, including rapidly progressing.

Aminoquinoline (antimalarial) drugs have no independent value in the treatment of juvenile dermatomyositis, their effectiveness in this disease is controversial. In foreign literature, there is an opinion that these drugs can be used to relieve exacerbations of the skin syndrome in dermatomyositis without increasing the dose of glucocorticosteroids, and in "dermatomyositis without myositis" they are effective as monotherapy. In some cases, they are used to maintain remission of the disease against the background of a low maintenance dose of glucocorticosteroids.

Data on the efficacy of new drugs such as mycophenolate mofetil, tacrolimus, fludarabine, and biological agents (infliximab, rituximab) in adult and juvenile dermatomyositis are contradictory.

Intravenous immunoglobulins (IVIG) occupy a special place in the therapy of juvenile dermatomyositis. In juvenile dermatomyositis, the effectiveness of IVIG has been demonstrated in several open studies, a multicenter analysis of which was conducted by Rider L. and Miller F. in 1997. It showed that the use of IVIG at a dose of 2 g / kg per month for 3-9 months (against the background of taking GC) made it possible to stop the manifestations of skin syndrome in 29% and myopathic - 30% of 27 patients with juvenile dermatomyositis resistant to glucocorticosteroid therapy. In 8 patients, a decrease or disappearance of calcifications was noted. The mechanisms of the immunosuppressive action of IVIG are considered to be the inhibition of proinflammatory cytokines, blocking the deposition of components of the complement system, competitive binding to Fc receptors of macrophages, B lymphocytes and target antigens, competition for recognition of antigens by sensitized T cells. In dermatomyositis, the most important is the ability of IVIG to block the deposition of complement protein complexes (MAC) in the endomysial capillaries due to the binding of C3b, which prevents the inclusion of activated protein C3 in C5 convertase.

A clear scheme for the use of IVIG in juvenile dermatomyositis has not been developed. To achieve an immunosuppressive effect, IVIG is prescribed at a dose of 2 mg / kg per month, splitting this dose into 2 doses for 2 consecutive days (an alternative option is 0.4 mg / kg per day for 5 consecutive days). Treatment is carried out for 6-9 months until significant clinical improvement is achieved, the level of "muscle breakdown" enzymes is normalized and the dose of glucocorticosteroids can be reduced. IVIG is ineffective as a starting and monotherapy for dermatomyositis, they are used as an additional agent for steroid-resistant variants of the disease.

IVIG is also used as a replacement drug in the development of intercurrent infections. In this case, the course dose is 200-400 mg/kg, the greatest effectiveness is noted when combining IVIG with antibacterial drugs.

Of great importance in the treatment of juvenile dermatomyositis is symptomatic therapy aimed at correcting disorders caused by the disease itself, and preventing and treating complications of therapy.

In the acute period of juvenile dermatomyositis, it is necessary to prescribe infusion, detoxification therapy (glucose-salt solutions), drugs that improve microcirculation (pentoxifylline, nicotinic acid drugs), antiplatelet agents and anticoagulants. In severe vasculitis, concomitant antiphospholipid syndrome, after completing a course of direct anticoagulants (sodium heparin), the patient is transferred to oral anticoagulants (warfarin) with dose adjustment according to INR values. Long-term use of acetylsalicylic acid is possible.

To improve microcirculation when the activity of the process subsides, during the period of incomplete remission, while taking glucocorticoids, the patient with juvenile dermatomyositis constantly receives vascular drugs (pentoxifylline, nicergoline, etc.) and antiplatelet agents.

The most effective prevention of calcinosis is adequate therapy, which allows for rapid relief of the inflammatory-necrotic process in the muscles. However, etidronic acid, which also has a moderate anti-osteoporotic effect, is additionally used for the prevention and treatment of calcinosis. Etidronic acid is used internally, in the form of applications with DMSO and electrophoresis on areas of calcinosis. Unfortunately, long-standing widespread calcinosis is practically not amenable to correction, but relatively fresh calcifications are reduced or even completely resorbed.

It is necessary to timely connect drugs that prevent the development of severe side effects of glucocorticosteroids. First of all, steroid osteoporosis is prevented: throughout the entire period of treatment with glucocorticosteroids, the patient receives calcium preparations (but not more than 500 mg / day) in combination with cholecalciferol and calcitonin. Against the background of taking prednisolone or methylprednisolone, especially in large doses, almost constant prevention of damage to the upper gastrointestinal tract is necessary - alternation of antacid and enveloping agents. Given the property of glucocorticosteroids to increase the excretion of potassium and magnesium, the patient should constantly receive the appropriate drugs.

Surgical treatment of juvenile dermatomyositis

Recently, data have appeared in the literature on the possible surgical correction of severe disabling consequences of juvenile dermatomyositis (calcifications, contractures).

Indications for consultation with other specialists

Patients with juvenile dermatomyositis, like all patients taking glucocorticosteroids, are advised to consult an ophthalmologist once every 6 months due to the fact that one of the rare side effects is cataracts.

Forecast

In recent years, due to improved diagnostics and an expanded range of drugs, the prognosis for juvenile dermatomyositis has improved significantly. With timely initiation and adequate treatment, most patients can achieve stable clinical and laboratory remission. According to L.A. Isaeva and M.A. Zhvania (1978), who observed 118 patients, fatal outcomes were noted in 11% of cases, and profound disability in 16.9% of children. In recent decades, severe functional insufficiency has developed in juvenile dermatomyositis in no more than 5% of cases, and the proportion of fatal outcomes does not exceed 1.5%.

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