Scleroderma

Description

Alternative Names

Medications

Drugs that relax and open blood vessels (called vasodilators) have been a mainstay for treating and preventing complications in scleroderma. As more is known about the disease, however, additional novel agents are used to treat this difficult disease. Some of these drugs affect smooth muscles in the blood vessels and blood clotting.

Vasodilators. Vasodilators have been key agents in the treatment of scleroderma. They relax and dilate blood vessels and are important for treating most of the symptoms and complications of scleroderma. [These agents are also discussed under many of the sections covering complication of treatments.]

• Calcium-Channel Blockers. Calcium-channel blockers are the standard vasodilating agents. Short- or sustained release nifedipine (Adalat, Procardia) is the gold standard. Others used include diltiazem (Cardizem, Dilacor). Side effects vary among different preparations, and may include fluid accumulation in the feet, constipation, fatigue, impotence, gingivitis, flushing, and allergic symptoms. Grapefruit juice appears to boost the effects of these drugs.
• Nitrates. Nitrates relax smooth muscles and so dilate arteries. These drugs release nitric oxide, thereby relaxing the smooth muscles in blood vessels. They are available as topical or oral agents. Side effects of nitrates include headaches, dizziness, nausea, blurred vision, fast heartbeat, and sweating. Lying down with the legs elevated can relieve low blood pressure and dizziness. Alcohol, beta blockers, calcium-channel blockers, and certain antidepressants can significantly worsen these effects. Withdrawal from nitrates should be gradual; some severe reactions have occurred when people have stopped abruptly.

Prostacyclins (also called Prostaglandins). Prostacyclins open blood vessels and also have anti-blood clotting properties. Specific agents, such as iloprost, appear to reduce levels of connective tissue growth factor, a molecule important in the abnormal proliferation of cells that cause collagen buildup. A number of prostacylins are being used for scleroderma, although none have been approved specifically for the condition. Iloprost has been studied the longest. Other promising prostacylins or similar agents include alprostadil (prostaglandin E1), epoprostenol (Flolan,), and treprostinil (Remodulin).

Endothelin Receptor Antagonists. Bosentan (Tracleer) is an oral agent called an endothelin receptor antagonist. It controls endothelin, a powerful molecule that causes blood vessels to narrow. It improves blood flow and is becoming important for treating patients with scleroderma, especially in those with pulmonary hypertension.

ACE Inhibitor and Similar Agents for Hypertension and Renal Crises

The most effective approach at this time for preventing renal crises is to institute aggressive anti-hypertension therapy before blood tests indicate serum creatinine levels over 3 mg/dl. (Creatinine is a nitrogen compound that is measured as an indication of kidney function.)

Angiotensin Converting Enzyme (ACE) Inhibitors. Many medications are available for controlling blood pressure, but angiotensin converting enzyme (ACE) inhibitors appear to be the most effective for scleroderma patients because of their protective actions in the kidney. ACE inhibitors include captopril (Capoten), enalapril (Vasotec), quinapril (Accupril), benazepril, and lisinopril (Prinivil, Zestril). Side effects are uncommon but may include an irritating cough, excessive drops in blood pressure, and allergic reactions. (The drug picotamide can help reduce the frequency of coughs.) One rare but severe side effect, granulocytopenia, has been observed, which is an extreme reduction in white blood cells; this can be minimized with lower dosages. There has been some concern that they may impair lung function, but studies to date have been reassuring.

Angiotensin II Receptor Antagonists. Angiotensin II receptor antagonists (losartan, candesartan cilexetil, and valsartan) have benefits similar to ACE inhibitors and may have fewer or less severe side effects, including coughing. They may also have positive effects on blood vessels. Small studies showing improvement in Raynauds phenomenon warrant further research.

Immunosuppressive Agents

One major approach to scleroderma is to use agents and other therapies to suppress the immune system and therefore reduce the activity of the harmful processes leading to scleroderma. Such treatments are being used effectively in other autoimmune diseases. Their use in scleroderma varies depending on the location and severity of the disease process.

An important 2002 study employed an approach called high-dose immunosuppressive therapy, which uses radiation, powerful immunosuppressant drugs, and other therapies to severely suppress the immune system. This is a very toxic treatment, but improvements in skin and other indicators of scleroderma were more significant than those reported with other therapies. More research is warranted.

Cyclophosphamide (Cytoxan) is the most important immunosuppressant currently used for scleroderma. Results of a large trial comparing oral cyclophosphamide to placebo (sugar pill) for the treatment of scleroderma with pulmonary fibrosis are expected in late 2004.

Other drugs used to suppress the immune system may be useful in specific cases. They include D-penicillamine (which may useful for skin symptoms), methotrexate (Rheumatrex), corticosteroids, cyclosporine (Sandimmune, Neoral), and chlorambucil (Leukeran). All of these agents have potentially severe side effects.