There are a number of treatments available to address the various conditions associated with scleroderma.  None of these is a cure – they are designed to treat symptoms of the disease.  The different classes of drugs listed below are currently approved, either in the US or Europe, to treat each condition. The next section describes how these drugs work. All medications have side effects that vary in severity. If you are a patient taking a drug and experience any of the listed side effects, you should consult with a physician immediately.

Condition:  Raynaud’s Phenomenon
Classes of Drugs:

1. Calcium Channel Blockers
2. Angiotensin II Receptor Antagonists
3. Angiotensin-Converting Enzyme (ACE) Inhibitors
4. Low Dose Enteric-Coated Aspirin

Condition:  Joint Stiffness and Pain
Classes of Drugs:

1. NSAIDS
2. COX-2 Inhibitors
3. Analgesics
4. Low-Dose Corticosteroids
5. Narcotics

Condition: Gastrointestinal Reflux Disease
Classes of Drugs:

1. Antacids
2. H-2 Blockers
3. Proton Pump Inhibitors

Condition:  Intestinal Dysfunction
Classes of Drugs: 

1. Prokinetic Agents
2. Somatostatin Agonist
3. Antibiotics

Condition:  Renal (kidney) Involvement & High Blood Pressure
Class of Drug

1. ACE Inhibitors

Condition:  Pulmonary Arterial Hypertension (PAH)
Classes of Drugs:

1. Prostaglandins
2. Prostacyclin (Prostaglandin Analogs)
3. Endothelin Receptor Antagonists

Condition:  Pulmonary Fibrosis
Classes of Drugs:

1. Immunosuppressants
2. Alkylating agents

Calcium Channel Blockers.  These medications are used to treat Raynaud’s phenomenon and reduce high blood pressure, a condition that increases the workload of the heart and arteries and can lead to malfunction of these organs. Calcium channel blockers affect the movement of calcium into the cells of the heart and blood vessels, increasing the supply of blood and oxygen to the heart while reducing the heart’s workload. The drugs can relax blood vessel muscles and may slow the heart rate. 

Side effects: The most common side effects are swelling of ankles, feet or lower legs. May aggravate esophageal reflux. Less common are chest pain; dizziness, lightheadedness or fainting; and rash.  Rare reactions include swelling of arms, face legs, lips, tongue or throat; shortness of breath; fast heart rate.

Form: Oral

Common brand names: Nifedipine, Procardia, Amlodipine, Norvasc, Dilacor, Tiazac, Adalat, Calan, Verelan, Cardizem, Plendil, Procardia, Vascor, Isoptin, Nimotop, DynaCirc

Angiotensin II Receptor Antagonists.  These drugs relax blood vessels by blocking the action of a natural chemical inside the body that narrows blood vessels, leading to high blood pressure.

Side effects: Headache is most common; less common are cough, fever or sore throat, dizziness, back pain, nasal congestion

Form: Oral

Common brand names: Losatan (Cozaar)

Angiotensin Converting Enzyme (ACE) Inhibitors.  ACE inhibitors block the formation of an enzyme in the body that narrows blood vessels. This causes the blood vessels to relax and lowers blood pressure, increasing the supply of blood and oxygen to the heart. 

Side effects: Swelling of face, mouth, hands or feet; dizziness, lightheadedness or fainting; skin rash, fever or joint pain.  Confusion, irregular heartbeat, nervousness, numbness or tingling in hands, feet or lips, shortness of breath, difficulty breathing, weakness or heaviness of legs can be signs of too much potassium in the body, caused by the medication.

Form: Oral

Common brand names: Captopril (Capoten), benazepril (Lotensin), lisinopril (Prinivil, Zestril), ramipril (Altace), enalapril (Vasotec)

NSAIDS. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to relieve some symptoms caused by arthritis (rheumatism), such as inflammation, swelling, stiffness, and joint pain. For some people with certain medical conditions, NSAIDS can lead to the development of stomach bleeding and kidney disease. The risk is increased for people who take the product daily or regularly, particularly for those 65 and over or who take corticosteroids such as Prednisone.

Side effects: The most common side effects are abdominal or stomach cramps, pain, or discomfort (mild to moderate);  diarrhea (if taking mefenamic acid, stop taking it and check with your doctor immediately);  dizziness, drowsiness, or lightheadedness;  headache (mild to moderate);  heartburn, indigestion, nausea, or vomiting  

Form: Oral

Common brand names: aspirin (Bayer, St. Joseph’s); ibuprofen (Advil, Motrin); naproxen (Aleve), nabumeton (Relafen)

COX-2 Inhibitors. These drugs work by blocking the COX-2 enzyme which is involved in the inflammation pathway. COX-2 inhibitors are used to relieve symptoms such as inflammation, swelling, stiffness, and joint pain.

Caution: If you are using a non-steroidal anti-inflammatory drug (NSAID) such as celecoxib (Celebrex®), with an ACE inhibitor, some studies suggest that NSAIDs may reduce the effectiveness of the ACE inhibitor.  Consult your physician.

Side effects: The most common side effects are back pain;  dizziness;  gas;  headache;  heartburn;  inability to sleep;  nausea;  pain or burning in throat;  stomach pain;  stuffy or runny nose 

Form: Oral

Common brand names: Celebrex (celecoxib)

Analgesics.Acetaminophen is an analgesic, which is used to relieve pain (headaches, muscle aches) and reduce fever. Unlike aspirin, it does not relieve redness, stiffness, or swelling, though it may relieve the pain caused by mild forms of arthritis. This medicine is available without a prescription; check with your physician, however, if you are taking other medications.

Using too much acetaminophen can lead to serious liver damage (this risk is increased in people who use alcohol regularly). Avoid taking multiple medications that contain acetaminophen.

Side effects: Though rare, check with your doctor as soon as possible if any of the following side effects occur: bloody or black, tarry stools;  bloody or cloudy urine;  fever with or without chills (not present before treatment and not caused by the condition being treated);  pain in lower back and/or side (severe and/or sharp);  pinpoint red spots on skin;  skin rash, hives, or itching;  sores, ulcers, or white spots on lips or in mouth;  sore throat (not present before treatment and not caused by the condition being treated);  sudden decrease in amount of urine;  unusual bleeding or bruising;  unusual tiredness or weakness 

Form: Oral

Common brand names: Tylenol, Datril, Aceta

Low-Dose Corticosteroids. These cortisone-like medicines are used to provide relief for inflamed areas of the body, by lessening swelling, redness, itching, and allergic reactions. They are often used as part of the treatment for a number of different diseases, such as severe allergies or skin problems, asthma, or arthritis.

NOTE: Corticosteroids are very strong medicines. In addition to their potential helpful effects, they have side effects that can be very serious. Glucocorticosteroids, also sometimes used to treat pulmonary fibrosis, have been found to increase risk of scleroderma renal crisis and should be used with caution and only in select cases under close observation such as frequent blood pressure checks. Be sure that you discuss the risks and benefits of this medicine with your doctor.

Corticosteroids may lower your resistance to infections, and any infection you get may be harder to treat. Always check with your doctor as soon as possible if you notice any signs of a possible infection, such as sore throat, fever, sneezing, or coughing.

Side effects: The most common side effects are increased appetite; indigestion; nervousness or restlessness. Less common or rare are darkening or lightening of skin color;  dizziness or lightheadedness;  flushing of face or cheeks;  increased joint pain (after injection into a joint);  increased sweating;  sensation of spinning.

Form: Oral; injected

Common brand name: Prednisone

Narcotics. Narcotic analgesics act in the central nervous system to relieve pain. Many of their side effects are also caused by actions in the Central Nervous System. When narcotics are used for a long time, your body may get used to them so that larger amounts are needed to relieve pain. They may also become habit-forming, causing mental or physical dependence. Physical dependence may lead to withdrawal symptoms when you stop taking the medicine.

Side effects: Dizziness, light-headedness, or feeling faint;  drowsiness;  nausea or vomiting.  Less common or rare side effects are blurred or double vision or other changes in vision;  constipation (more common with long-term use and with codeine) ;  decrease in amount of urine;  difficult or painful urination;  dry mouth;  false sense of well-being;  frequent urge to urinate;  general feeling of discomfort or illness;  headache;  loss of appetite;  nervousness or restlessness;  nightmares or unusual dreams;  redness, swelling, pain, or burning at place of injection;  stomach cramps or pain;  trouble in sleeping;  unusual tiredness or weakness

Form: Oral; patch; injection; suppository

Common brand names: Percoset, Vicodin, Darvacet, Oxycontin

Antacids.  Antacids work by neutralizing excess stomach acid to relieve heartburn, sour stomach, or acid indigestion. These medicines are available without a prescription. However, your doctor may have special instructions on the proper use and dose of these medicines.

Side Effects: Chalky taste; less common side effects are mild constipation; diarrhea; increased thirst

Form: Oral

Common brand names: Maalox, Mylanta, Phillips, Gaviscon, Rolaids, Tums

H-2 Blockers. Histamine H 2-receptor antagonists, also known as H 2-blockers, work by decreasing the amount of acid produced by the stomach. In over-the-counter strengths, these medicines are used to relieve and/or prevent heartburn, acid indigestion, and sour stomach.

Side Effects: Though uncommon, side effects may include constipation;  diarrhea;  difficult urination;  dizziness;  drowsiness;  dryness of mouth or skin;  headache

Form: Oral

Common Brand Names: Axid, Pepcid, Tagamet, Zantac

Proton Pump Inhibitors. These medications decrease stomach acid production, minimizing gastrointestinal reflux disease, and help prevent esophageal ulcers

Side Effects: Though uncommon, side effects may include headache; diarrhea; constipation

Form: Oral

Generic (brand) names: omeprazole (Prilosec; Prilosec OTC is available over-the-counter; "Zegerid" is an immediate-release form of omeprazole), lansoprazole (Prevacid), esomeprazole (Nexium), rabeprazole (Aciphex) , pantoprazole (Protonix)

Prokinetic Agents. Metoclopramide is a medicine that increases the movements or contractions of the stomach and intestines. When given by injection, it is used to help diagnose certain problems of the stomach and/or intestines. Metoclopramide is also used, for a short time, to treat symptoms such as heartburn in patients who suffer esophageal injury from a backward flow of gastric acid into the esophagus.

Side effects: Diarrhea—with high doses; drowsiness;  restlessness.  Less common are breast tenderness and swelling; changes in menstruation;  constipation;  increased flow of breast milk; mental depression;  nausea;  skin rash;  trouble in sleeping;  unusual dryness of mouth;  unusual irritability

Form: Oral; injection

Common brand names: Metoclopramide (Reglan)

Somatostatin Agonist.  This medication, octreotide, is used for severe impairment of intestinal movement. Octreotide will be either injected subcutaneously (beneath the skin) or added to an intravenous fluid that will drip through a needle or catheter placed in the vein for 15-30 minutes, one to four times a day. Your physician may measure the effectiveness and side effects of your treatment using laboratory tests and physical examinations.

Side effects: Side effects from octreotide are not common, though pain or burning at the injection site may last for up to 15 minutes. Tell your physician if any of these symptoms are severe or do not go away: upset stomach; vomiting; diarrhea; stomach pain; bloating; flatulence; loss of appetite or increased hunger

Form: Injection

Common brand name: Ocreotide (Sandostatin)

Antibiotics. Reduced movement of the intestines can lead to bacterial overgrowth which in turn can lead to diarrhea and impaired absorption. The bacteria can be treated by antibiotics, which are best prescribed on a rotational basis to help prevent development of resistant strains.

Side effects: Nausea, vomiting, diarrhea, skin rash

Form: Oral; injection; intravenous

Common brand names: Amoxicillin (Augmentin), metronidazole (Flagyl), tetracycline, vancomycin

Scleroderma patients generally have low blood pressure, so even modest increases in blood pressure could be a signal of an impending renal crisis and should be addressed immediately. The best way to treat renal crisis in scleroderma is to control the patient’s blood pressure, often with a short-acting ACE inhibitor such as captopril.

Angiotensin Converting Enzyme (ACE) Inhibitors.  ACE inhibitors block the formation of an enzyme in the body that narrows blood vessels. This causes the blood vessels to relax and lowers blood pressure, increasing the supply of blood and oxygen to the heart. 

Caution: Do not use ACE inhibitors if you are pregnant, intend to become pregnant or think you are pregnant. In pregnant women, ACE inhibitors can lower blood pressure to dangerously low levels and/or malformation of fetuses.  For more information, see the package insert for the drug or contact the drugmaker. If you are using a non-steroidal anti-inflammatory drug like celecoxib (Celebrex®) while you are taking an ACE inhibitor, be aware that the NSAID may reduce the effectiveness of the ACE inhibitor to control hypertension.  Consult your physician.

Side effects: Swelling of face, mouth, hands or feet; dizziness, lightheadedness or fainting; skin rash; fever or joint pain.  Confusion, irregular heartbeat, nervousness, numbness or tingling in hands, feet or lips, shortness of breath, difficulty breathing, weakness or heaviness of legs can be signs of too much potassium in the body, caused by the medication.

Form: Oral

Common brand names: Captopril (Capoten), benazepril (Lotensin), lisinopril (Prinivil, Zestril) ramipril (Altace), enalapril (Vasotec)

Pulmonary hypertension results from high blood pressure that occurs in the main artery that carries blood from the right side of the heart to the lungs. When the smaller blood vessels in the lungs become more resistant to blood flow, the right ventricle must work harder to pump blood through the lungs. 

Prostaglandins.

Epoprostenol belongs to the group of agents called prostaglandins, which occur naturally in the body and are involved in many biological functions. Epoprostenol works by relaxing blood vessels and increasing blood to the lungs.

Side effects: With initial dosage adjustments and/or dosage excess: diarrhea;  fast heartbeat;  headache;  light-headedness or fainting;  nausea;  redness of face or neck (flushing);  vomiting. More common side effects are anxiety and/or nervousness;  diarrhea;  dizziness;  flu or infection-like symptoms, such as chills, confusion, delirium, light-headedness or fainting, fast heartbeat, fever, and/or rapid, shallow breathing;  headache;  jaw pain (when chewing);  local infection at the catheter site;  pain at injection site;  pain in muscles or bones;  redness of face (flushing);  unusual bleeding such as nosebleeds or bleeding gums or bruising

Form: Epoprostenol must be administered continuously by a portable pump that is operated by a small computer. The medicine will be delivered directly to the heart through a catheter that will be inserted into a vein in the chest.

Common brand name: Flolan

Treprostinil also belongs to the prostaglandin group. It is used to treat symptoms of  primary pulmonary hypertension by relaxing blood vessels and increasing the supply of blood to the lungs, thus reducing stress on the heart.

Side effects: The most common include edema, such as swelling; accumulation of blood, and/or dry, red, hot or irritated skin, and/or hardening of skin at infusion site; flushing, faintness, dizziness or lightheadedness. Less common are blurred vision, confusion, dizziness; sudden sweating; unusual tiredness or weakness

Form: Treprostinil must be administered by continuous intravenous infusion

Common brand name: Remodulin

Prostacyclin.

Iloprost is a stable, inhalable form of prostacyclin, an imitator of prostaglandin. Its relaxing effect on the blood vessels is similar to a prostaglandin. The advantage of inhaled iloprost is that it is introduced directly to the lungs, thus avoiding potential side effects to the rest of the body.

Side effects: Headache; cough; flushing; jaw pain; influenza-like syndrome

Form: Inhaled

Common brand names: Ventavis

Endothelin Receptor Antagonists.  These drugs work by preventing a small protein, endothelin-1, from binding to its receptors. By blocking the endothelin receptors, the blood supply to the lungs increases and workload of the heard decreases.

Side effects: Possible yet serious side effects include liver toxicity and birth defects. Other side effects include blurred vision; confusion; dizziness; dark urine; faintness or lightheadedness; fever; chills; light colored stools; loss of appetite; nausea and vomiting; stomach pain; sudden sweating; unusual tiredness or weakness; yellow eyes or skin.  Swelling is less common.

Form: Oral 

Common brand names: Bosentan (Tracleer)

Phosphosdiesterase (PDE) type 5 inhibitors.  PDE type 5 inhibitors prevent the metabolism of a signaling molecule called cGMP.  Treatment with a PDE type 5 inhibitor builds up cGMP.  cGMP relaxes smooth muscles, so arterial blood flow increases in the lungs and pulmonary arterial hypertension decreases.  In men who are sexually aroused and are taking a PDE-type 5 inhibitor, they usually have easier erections than usual.

Caution:  Do not take PDE type 5 inhibitors with nitroglycerin or other nitrates as the combination of drugs may lower blood pressure to dangerous levels.

Side effects:  Headache, facial flushing, and upset stomach. Less common side effects are bluish or blurred vision, or sensitivity to light.

Form:   Oral

Brand name:  Sildenafil citrate (Revatio®)

Immunosuppressants. This class of drugs works by weakening the body's immune system so it will not attack a transplanted organ or the body’s own tissue in the case of autoimmune diseases.

Caution: Cyclophosphamide (Cytoxan®, Neosar®), mycophenalate mofetil (CellCept®), azathioprine (Imuran®) should not be given to pregnant women or if a woman thinks she is pregnant or would like to be.  These drugs have caused malformations in fetal development of rodents and rabbits. For more information, see the product insert, consult your physician or contact the drug manufacturer.

Side effects: These are very strong drugs with severe side effects.  High blood pressure, kidney and liver problems may result.  Some immunosuppressants may contribute to the development of new cancers. The body may be less able to fight infections.  Common effects are bleeding, tender or enlarged gums.  Less common are seizures, fever or chills, vomiting, frequent urination.  Rare side effects are confusion, irregular heartbeat, numbness or tingling in hands, feet, or lips, shortness of breath, difficult breathing, severe stomach pain, nervousness, unusual tiredness or weakness, weight loss.

Form: Oral; injected

Common brand names: cyclosporine (Neoral, Sandimmune), mycophenalate (CellCept), azathioprine (Imuran)

Alkylating agents. Cyclophosphamide is in a class of drugs known as alkylating agents, which slow or stop the growth of cancer cells in your body. Cyclophosphamide is used to treat leukemias, lymphoma, bronchogenic carcinoma, small cell lung carcinoma, and other types of cancer. It has been shown to be effective in scleroderma lung disease. Talk to your doctor about the possible risks of using this drug. Cyclophosphamide may contribute to the development of new cancers.

Side effects: Thinned or brittle hair; darkened and thickened skin; blistering skin or acne; loss of appetite or weight; mouth blistering; fatigue

Forms: Oral; injected

Common brand names: Cytoxan, Neosar 

A note about Minocycline:

A recent controlled trial of the antibiotic minocycline has led to the conclusion that the drug is not an effective therapy for scleroderma. Results of the study, published in the February 2004 issue of “Arthritis & Rheumatism,” showed a degree of change in the modified Rodnan skin thickness score (the measurement used to determine effectiveness of the drug) that is similar to what can be expected in the natural course of the disease.