Treatment of systemic scleroderma

The basis of treatment of systemic scleroderma is the prescription of drugs with the antifibrotic effect of penicillamine (cuprenil) in combination with arterial vasodilators and antiplatelet agents. In the treatment of SSc with heart damage, the effectiveness of oxygen therapy, slow calcium channel blockers and ACE inhibitors has been proven.

Treatment of pulmonary arterial hypertension associated with systemic sclerosis is a very difficult task, since it is characterized by a small choice of drugs. Treatment consists of general measures, medication and, in some cases, surgical treatment.

General recommendations are aimed at minimizing harmful external influences in patients with PAH. Patients are advised to avoid potentially dangerous symptoms such as severe dyspnea, syncope, and chest pain. Only at the asymptomatic level is it possible to exert an adequate physical fitness. It is necessary to avoid physical activity after taking lishi and at elevated air temperatures. Since hypoxia can worsen vasoconstriction, it is advisable for patients with PAH to avoid hypobaric hypoxia, which occurs at an altitude of between 1500 and 2000 m, which is equivalent to flying, so patients are advised to either avoid flying or to undergo oxygen therapy in flight,

The basic principles of using oral anticoagulants in patients with PAH are based on the presence of both traditional risk factors for venous thromboembolism, such as heart failure, sedentary lifestyle, the presence of hematogenous thrombophilia predisposing to thrombosis, and thrombotic changes in the microcirculatory bed and pulmonary artery,

Treatment with diuretics can improve the patient's condition, but there are no specific randomized clinical trials on their use. According to recent data, 49-70% of patients take diuretics. In pulmonary arterial hypertension, the preferred class of diuretics is not defined, so the physician can choose the diuretic and its dose in a specific clinical situation. Patients receiving diuretic treatment should have their electrolytes, which reflect renal function, monitored.

Oxygen therapy in patients with PAH should be used to continuously maintain oxygen saturation above 90%. However, there is currently no evidence of beneficial effects of long-term oxygen inhalation.

The use of such traditional vasodilators as calcium channel blockers is based on the reduction of pulmonary vascular resistance, which leads to a decrease in pulmonary artery pressure. However, favorable clinical and prognostic effects of high doses of calcium channel blockers have been shown in patients with a positive response to an acute test with vasodilators, which is observed in only 10-15% of patients with pulmonary hypertension. In recent studies, nifedipine and diltiazem were used predominantly. Their choice depends on the heart rate: with relative bradycardia, nifedipine should be prescribed, with initial tachycardia - diltiazem. The greatest effectiveness of these drugs is observed when prescribing high doses of the drugs: the daily dose for nifedipine should be 120-240 mg, for diltiazem - 240-720 mg. Factors limiting the use of calcium channel blockers include systemic hypotension, edema of the shins and feet. Addition of digoxin and/or diuretics in some cases helps reduce the side effects of calcium channel blockers.

Prostacyclin, produced primarily by endothelial cells, is a potent endogenous vasodilator. Prostacyclin has been shown to cause selective pulmonary vasodilation (reduction in pulmonary vascular resistance and pulmonary artery pressure) in patients with secondary pulmonary hypertension due to pulmonary fibrosis. Long-term intravenous use of prostacyclinar increases two-year survival to 80% compared to 33% with traditional treatment, improves patients' quality of life, increases exercise tolerance, and reduces manifestations of pulmonary hypertension.

The clinical use of prostacyclin is associated with the synthesis of its stable analogues, which have different pharmacokinetic but similar pharmacodynamic properties. The greatest experience has been accumulated in the use of epoprostenol. Beraprost is the first stable analogue of prostacyclin for oral administration. In our country, only prostaglandin E1 - alprostadil (vasaprostan) is used from the group of prostanoids for the treatment of patients with pulmonary arterial hypertension.

Endothelin-1 is a peptide produced primarily by endothelial cells that has potent vasoconstrictor and mitogenic properties on smooth muscle cells. Endothelin-1 causes pulmonary and systemic vasoconstriction by acting on smooth muscle cells, causing their spasm and wall hypertrophy, and has a negative inotropic effect. Bosentan is the first drug from the class of endothelin receptor antagonists that has been shown in randomized trials in patients with pulmonary hypertension to improve exercise tolerance, functional class, hemodynamic, and echocardiographic parameters. Bosentan is the drug of choice for patients with pulmonary hypertension and prostanoid intolerance. The drug is recommended for the treatment of patients with FC III and IV PAH in the USA and Canada. In Europe, it is only recommended for patients with FC III and PAH associated with SSc without significant pulmonary fibrosis.

Sildenafil is a potent, selective orally administered cGMP phosphodiesterase-5 inhibitor. Its effect is due to the accumulation of intracellular pGMP, which leads to relaxation and suppression of smooth muscle cell proliferation. Beneficial effects of sildenafil have been demonstrated in patients with pulmonary arterial hypertension associated with SSc. Treatment of systemic sclerosis with sildenafil should be considered in patients with pulmonary hypertension in whom other drug treatments are ineffective.