Assistant Professor of Medicine
Albert Einstein College of Medicine
Bronx, NY
Arthur Weinstein, M.D.
Professor of Medicine
Georgetown University Medical Center
Director, Section of Rheumatology
Washington Hospital Center
Washington, DC
Pain and inflammation are common in people with systemic lupus erythematosus (SLE). Sometimes these symptoms indicate serious organ involvement which may require powerful anti-inflammatory and immunosuppressive drugs, such as steroids (cortisone, prednisone). At other times the inflammation is not as severe or does not affect major organs and a less potent drug is indicated. In these cases, other milder anti-inflammatory and analgesic drugs can be used, especially a group of drugs called the non-steroidal anti-inflammatory drugs (NSAIDs). While NSAIDs are not approved specifically for SLE by the Food and Drug Administration, they are approved for use in many musculoskeletal pain conditions such as arthritis and tendinitis, which also afflict people with lupus.
Types of NSAIDs
There are many different types of NSAIDs, available either by prescription or over the counter. Examples are listed in Table 1. Newer ones will be marketed over the next few years. Aspirin is anti-inflammatory when given in high doses; otherwise it is a pain killer like tramedone (Ultram) or acetaminophen (Tylenol).
Mechanism of Action and Use
NSAIDs work primarily by preventing the formation of substances called prostaglandins. Some prostaglandins are produced by the body in response to an inflammatory stimulus, and play a role in causing inflammation and pain. Other prostaglandins are made by the body regularly and play a role in maintaining normal function in several organ systems. Examples include the protective lining of the stomach, normal platelet function, and kidney blood flow. Inflammatory prostaglandins are produced by an enzyme called cox-2; maintenance prostaglandins are produced by an enzyme labeled cox-1 prostaglandins. Traditional NSAIDs inhibit both cox-1 and cox-2 prostaglandins. Newer agents which primarily inhibit cox-2 prostaglandins are now available. These specific NSAIDs are effective for treatment of musculoskeletal pain and are without many of the side effects associated with the non-selective NSAIDs.
As a general rule, NSAIDs are most useful in treating joint pain, muscle pain, and joint swelling experienced by individuals with lupus. Occasionally, NSAIDs can be used to treat the chest pain caused y pleurisy (inflammation of the lung lining). When used for treatment of a mild flare, an NSAID may be the only drug needed. More active disease may require additional medications. Although there is no absolute reason not to use NSAIDs during pregnancy, it is best to avoid using these medications in the first few months after conception and before delivery.
Side Effects
There are two major drawbacks to NSAID therapy in people with lupus: 1) they do not help serious organ inflammation (e.g. kidney or brain involvement), and 2) they may be associated with troublesome, irritating, or even serious side effects. As with all medications, if you experience any adverse reaction when taking one of these medications, you should consult your physician.
Common Side Effects
These include upset stomach, headache, drowsiness, easy bruising, high blood pressure, and/or fluid retention.
NSAIDs commonly cause dyspepsia, a burning, bloated feeling in the pit of the stomach. In some people, stomach inflammation (gastritis) or gastric ulcers may occur. This can cause bleeding, either obvious and painful or hidden and painless. This loss of blood may lead to anemia (low hemoglobin or red blood cells). To help protect the stomach, NSAIDs should always be taken with food or directly after a meal. Some individuals may need additional medications to control their stomach symptoms. These medications include agents which prevent the stomach symptoms. These medications include agents which prevent the stomach from producing acid, such ascimetidine (Tagamet), ranitidine (Zantac), omeprazole (Prilosec), and lansoprazole (Prevacid); and medicines which promote the protective lining of the stomach wall, such as misoprostol (Cytotec).
Some people may tolerate one kind of NSAID, but have gastric irritation with others. A person on long-term NSAID therapy should have a blood count periodically to insure that anemia from gastric bleeding is not occurring. Cox-2 specific inhibitors may also cause dyspepsia. However, there is no increased risk of stomach inflammation or gastric ulcers in people taking these medications. Additional agents which protect the stomach from producing acid are generally not needed. Anyone with a history of gastric (stomach) or duodenal (intestinal) ulcers should tell their physician before starting on NSAIDs. Furthermore, any individual who will not accept blood products for religious or other reasons, should inform their doctor of this prior to starting therapy with NSAIDs. If stomach problems develop while taking an NSAID you should stop the medication and inform you doctor.
Symptoms of headache or drowsiness are usually mild, but if severe, the medicine may have to be stopped.
NSAIDs affect the function of platelets, a type of blood cell important in normal blood clotting. Although aspirin has the greatest effect, all NSAIDs have some effect on platelet function. If the function of these cells is impaired, it will take longer for blood to clot and bruising can occur more readily. Some people are very susceptible and experience easy bruising. If severe bruising occurs, the medication should be discontinued. Since platelet function is dependent on cox-1 prostaglandins, the newer cox-2 inhibitors do not affect the platelets.
In older people or in people with lupus who already have kidney or blood pressure problems, common side effects include fluid retention, high blood pressure, and reduced kidney function. These side effects may occur with either selective or non-selective NSAIDs, because both cox-1 and cox-2 prostaglancins are important for normal kidney function. In young, otherwise healthy people, these side effects are not common. People with lupus nephritis often have some reduction in kidney function. Therefore, NSAID use in this type of SLE may cause further deterioration in kidney function and should be closely supervised.
Uncommon Side Effects
Other important side effects that are more rare include abnormal liver tests, asthma, severe headache with neck stiffness, and skin rasher.
Aspirin and other NSAIDs occasionally cause elevations in liver enzyme blood tests, suggesting mild liver inflammation (hepatitis). People with active lupus appear to be especially susceptible to this side effect. This usually does not mean that the NSAID should be stopped, but the liver tests may have to be monitored on a regular basis.
People with asthma may notice a worsening of their asthmatic symptoms when they use aspirin or other NSAIDs. If this occurs, theses drugs should not be used.
Severe headache with neck stiffness is a rare side effect seen almost exclusively in people with lupus. It is important to be aware of this symptom as it mimics meningitis.
Hives and other skin rashes, although uncommon, occur with these medications and may require the discontinuation of the NSAID. Photosensitive skin rashes, which could mimic a flare of SLE, also rarely occur with some NSAIDs.
While NSAIDs are widely used with good results and without problems, individuals with lupus and their prescribing doctors need to payspecial attention to the potential side effects. Since drug side effects and symptoms of increased lupus activity may be identical, it is important to alert a physician if any of these symptoms occur. For example: fluid retention, headache, or rash may be side effects, but they also may occur when the disease activity increases. Notify your doctor when any side effect occurs so therapy can be adjusted. The majority of NSAID-related side effects are reversible once the drug is stopped. Some side effects are seen initially or only in the blood. Therefore, with continued NSAID use, regular blood counts (including test of liver and kidney function) should be monitored every three-four months.
Summary
NSAIDs are often used to treat the musculoskeletal pain and inflammation which may accompany active lupus. If well tolerated, they can be effective as the only treatment for people with mild lupus flares. They can also be used in combination with stronger medications to treat greater disease activity. These medications are not immunosuppressive; therefore it is inappropriate to use them alone for the treatment of severe lupus. NSAIDs may have either irritating or serious side effects. People with SLE taking NSAIDs require clinical and laboratory monitoring by their physicians.
Table 1
Traditional NSAIDs
diclofenac (Voltaren, Cataflam)
diflunsial (Dolobid)
etodolac (Lodine)
flurbiprofen (Ansaid)
ibuprofen (Motrin, Advil)
indomethacin (Indocin)
ketoprofen (Orudis, Oruvail)
ketorolac (Toradol)
nabumetone (Relafen)
naproxen (Naprosyn, Alleve)
oxaprozin (Daypro)
piroxicam (Feldene)
sulindac (Clinoril)
tolmetin (Tolectin)
Cox-2 selective NSAIDs
celecoxib (Celebrex)
rofecoxib (Vioxx)