How is juvenile systemic scleroderma treated?

Non-drug treatment of systemic scleroderma

Patients are prescribed physiotherapy, massage and exercise therapy, which help maintain the functional capabilities of the musculoskeletal system, strengthen muscles, expand the range of motion in the joints, and prevent the development of flexion contractures.

Drug treatment of systemic scleroderma

Glucocorticosteroids, cytotoxic agents and antifibrotic drugs are used as basic therapy.

Agents with glucocorticosteroid activity

In the presence of clinical and laboratory signs of inflammatory and immunological activity in the early phase of systemic scleroderma, glucocorticosteroids are indicated - prednisolone or methylprednisolone in average doses of 15-30 mg / day, followed by their reduction upon achieving a therapeutic effect and complete withdrawal. Glucocorticosteroids help stabilize the skin process, relieve manifestations of arthritis, active myositis, serositis, alveolitis. With severe fibrosis, in the late stage of the disease, glucocorticosteroids are not only ineffective, but also intensify sclerotic processes.

There are isolated reports on the effectiveness of pulse therapy with glucocorticosteroids in systemic scleroderma in the treatment of pulmonary hypertension caused by pulmonary vascular disease in the absence of thrombosis and interstitial damage.

Cytotoxic agents

Cyclophosphamide is a cytotoxic drug from the group of alkylating agents, the drug of choice for the treatment of interstitial lung disease, a diffuse form of juvenile systemic scleroderma with a rapidly progressive course.

Various regimens for the use of cyclophosphamide in adults have been proposed, the effectiveness of which has been proven in retrospective studies.

• Pulse therapy (intravenous administration of the drug in megadoses): once a month for 6 months, then with positive dynamics of pulmonary function tests - once every 2 months, if positive dynamics are maintained - once every 3 months.
• The administration of cyclophosphamide is combined with daily oral administration of glucocorticosteroids at a dose of 0.5-0.8 mg/kg for 8 weeks, then the dose is reduced to 0.3 mg/kg for 12-18 months; the duration of pulse therapy with cyclophosphamide is at least 2 years.
• Cyclophosphamide at a dose of 750 mg (IV drip) in combination with methylprednisolone at a dose of 125 mg per infusion, which is administered once every 3 weeks for 6 months.
• Cyclophosphamide orally at 1-2 mg/kg per day in combination with prednisolone orally at 40 mg/day every other day is recognized as a promising method for treating the initial stages of interstitial lung disease in systemic scleroderma.

Both regimens of cyclophosphamide pulse therapy are associated with serious side effects: leukopenia, anemia, hepatotoxicity, hemorrhagic cystitis, hair loss, nausea, vomiting.

Methotrexate is effective in the treatment of early (<3 years from the onset of the disease) diffuse systemic scleroderma with subcutaneous administration and oral administration. Methotrexate is indicated for severe joint and muscle damage, periarticular contractures, and widespread skin lesions. It does not affect visceral lesions. Methotrexate is prescribed at a dose of 10 mg/m2 ^once a week together with folic acid in a standard dose (daily, except for the day of methotrexate intake).

Initially, methotrexate treatment is combined with glucocorticosteroids at a dose of 0.5 mg/kg per day for 6-8 weeks, with a reduction in the dose to a maintenance dose of 0.1-0.25 mg/kg for 12-18 months, followed by complete withdrawal. Methotrexate should be prescribed with caution to children with chronic foci of infection, and the drug should be temporarily discontinued if intercurrent diseases occur. Methotrexate treatment is carried out for at least 2 years. It is necessary to monitor the safety of treatment by monitoring the hemogram and biochemical parameters of liver function quarterly.

There is evidence of greater effectiveness of methotrexate used in children in high doses - 20-25 mg/m2 ^per week intramuscularly or subcutaneously.

Cyclosporine is used in the treatment of systemic scleroderma, but potential nephrotoxicity limits the widespread use of the drug in clinical practice, since it requires careful monitoring of renal function and blood pressure.

Cyclosporine at a dose of 2-3 mg/day has a positive effect on skin changes in systemic scleroderma without affecting the condition of internal organs.

There are isolated reports of the effectiveness of cyclosporine in the treatment of progressive interstitial lung disease in systemic sclerosis when cyclophosphamide is ineffective.

Azathioprine in combination with low doses of glucocorticosteroids can be used in the treatment of interstitial lung disease in systemic sclerosis, which leads to stabilization of lung function and improvement of the condition of patients with systemic sclerosis. This has been shown in pilot studies.

Antifibrotic therapy for systemic scleroderma

Penicillamine is the most widely used drug of this group in the treatment of systemic scleroderma. It disrupts collagen synthesis, breaks down cross-links between newly formed tropocollagen molecules, promotes its elimination from the body, and inhibits fibroblast function. The drug is initially prescribed in small doses of an average of 3 mg/kg per day, and if well tolerated, the dose is gradually increased to 8-10 mg/kg per day (250-375 mg/day), which the patient takes for 3-5 years. The antifibrotic effect of penicillamine is realized slowly, with a pronounced clinical effect observed 6 months after the start of treatment. In rapidly progressing scleroderma, diffuse skin induration, and fibrosis of internal organs, penicillamine is combined with glucocorticosteroids at a dose of 0.5 g/kg for 8 weeks. Then the dose of glucocorticosteroids is gradually reduced until completely discontinued after 12-18 months.

The benefits of high-dose penicillamine treatment have not been confirmed. The drug in medium doses is usually well tolerated by patients, but if side effects develop (dyspeptic disorders, aphthous stomatitis, skin rashes, nephropathy, eosinophilia, cytopenia, etc.), it is necessary to reduce the dose or stop taking it.

Other medicines

The effectiveness of colchicine, as well as a- and g-interferons, which were previously used as antifibrotic drugs, has not been confirmed in open studies, which does not allow them to be recommended for use.

Correction of microcirculation disorders

Drugs of various groups are used - vasodilators, disaggregants, if necessary - anticoagulants. Indications for use - Raynaud's syndrome and its complications (ischemia, necrosis), pulmonary, renal hypertension.

• Calcium channel blockers lead to a moderate but reliable decrease in the frequency and severity of vasospasm attacks. The dose of calcium channel blockers in children is selected taking into account individual tolerance, age and weight of the child. Short-acting drugs - nifedipine, prolonged-action drugs - nifedipine (corinfar retard), amlodipine (norvasc), the appointment of which is preferable.
• Angiotensin-converting enzyme (ACE) inhibitors - captopril, enalapril - are prescribed to patients with true scleroderma kidney, accompanied by severe vasoconstriction and arterial hypertension. In adults, captopril is used at 12.5-50 mg 3 times a day, enalapril - at 10-40 mg per day.
• The selective serotonin reuptake inhibitor ketanserin at a dose of 60-120 mg/day has shown efficacy in the treatment of Raynaud's syndrome in placebo-controlled studies in adults.
• Angiotensin II receptor antagonists - losartan 25-100 mg per day. A pilot study compared the efficacy of losartan (50 mg/day) and nifedipine (40 mg/day) for 12 weeks for the treatment of secondary Raynaud's syndrome in systemic scleroderma. A decrease in the severity of vasospasm attacks was noted, moreover, with losartan treatment than with nifedipine treatment, and a decrease in the frequency of attacks was noted only with losartan treatment. It is used for long-term treatment.
• Sympatholytics, particularly prazosin, provide a temporary effect that disappears after a few weeks.
• In clinical practice, pentoxifylline (Trental) is widely used in high doses (in adults - up to 400 mg 3 times a day), but there are no controlled studies assessing the results of its use.

Low molecular weight heparins are used to treat severe Raynaud's syndrome. The effect occurs after 4 weeks of treatment.

In recent years, the synthetic analogue of prostaglandin E1 alprostadil (IV 0.1-0.4 mcg/kg per min) and iloprost (IV 0.5-2 ng/kg per min) have been used to treat severe ischemic complications in patients with systemic scleroderma, which allows for rapid improvement of the patients' condition. The course of treatment consists of an average of 7-10 infusions.

Local treatment of systemic scleroderma

Externally, apply 20-30% dimethyl sulfoxide solution with the addition of vasodilators and anti-inflammatory agents to the affected areas of the skin. Phonophoresis is used to administer the drugs. Apply ointments containing corticosteroids - methylprednisolone aceponate (advantan), mometasone (elocom); vasotropic drugs - heparin ointment, troxerutin (troxevasin); agents for improving tissue trophism - chondroitin sulfate (chondroxide), actovegin, solcoseryl, contractubex, etc.

Surgical treatment of systemic scleroderma

Surgical treatment is practically not used in children.

Indications for specialist consultation

If scleroderma lesions are localized on the head and face, patients need to consult an ophthalmologist (slit lamp examination) and a neurologist.

Indications for hospitalization

• Newly diagnosed juvenile systemic scleroderma for a complete examination and selection of treatment.
• The need to monitor the child's condition and control the treatment, assess its effectiveness and tolerability.
• The appearance of signs of disease progression and the need to adjust treatment.

Forecast

The prognosis for life in children with systemic scleroderma is significantly more favorable than in adults. The mortality rate in children with systemic scleroderma under the age of 14 is only 0.04 per 1,000,000 population per year. The five-year survival rate of children with systemic scleroderma is 95%. The causes of death are progressive cardiopulmonary insufficiency, scleroderma renal crisis. The formation of pronounced cosmetic defects, disability of patients due to dysfunction of the musculoskeletal system and the development of visceral lesions are possible.

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