If you have lupus, you are likely already using NSAIDs – nonsteroidal anti-inflammatory drugs.  They are the most widely used pharmaceuticals for treating the most common symptoms of lupus – pain and inflammation.  Yet, what do we really know about them, and what should we know?  Read on to find out!

• Introduction
• What are NSAIDs and how do they work?
• Are there things to worry about when using NSAIDs?
• In Conclusion

Introduction

Lupus is a complex condition that affects all parts of the body in ways that are difficult to predict.  However, they all involve an autoimmune response that attacks the body’s tissues and organs, and this leads to either localized or systemic inflammation reactions.  The inflammation associated with lupus can be both acute (short-term) and chronic (long-term).

When this inflammation comes on quickly – as with an injury or sudden lupus flare – it can cause pain, swelling, redness or other color changes, and sometimes the feeling of heat or fever. This inflammation can also dramatically interfere with how your organs function such as the brain (lupus fog), muscles (weakness) and kidneys (nephritis), joints (swelling and pain) and many other secondary symptoms.  Moreover, SLE is a chronic condition and the chronic inflammation of lupus, though often difficult to notice or identify, can lead to extremely serious, and permanent damage to those same organs and their functions.

For an in depth description of the types of inflammation that can occur with lupus, check out our blog-article: Lupus and Inflammation.

Whether acute or chronic, anti-inflammatory drugs are often among the first used to treat these symptoms of lupus.  These symptoms often improve within several days of beginning treatment, and for some living with lupus, an anti-inflammatory drug may be the only medication they normally use to control most symptoms.

By far, the most common forms of anti-inflammatory drugs are the nonsteroidal anti-inflammatory drugs – usually abbreviated as NSAIDs.  As a matter of fact, nearly 80% of patients with systemic lupus erythematosus (SLE) use NSAIDs for general inflammation, fever, arthralgia (joint pain), headaches and milder forms of serositis – the inflammation of internal organs like the lungs, heart and abdomen.  So, understanding what they do and how to use them most safely is the point of this article.

What are NSAIDs, and how do they work?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a diverse group of drugs that fight the body’s inflammatory response and in so doing, reduce pain (like analgesics), swelling, heat, redness, and can even prevents blood clots.  In some ways, NSAIDs work like corticosteroids, but without many of the steroid’s side effects.

You will recognize many of the general NSAIDs, such as:

• Aspirin,
• Ibuprofen (Advil, Motrin), and
• Naproxen sodium (Aleve)

All three are available over-the-counter (OTC) in most countries.

Note: Acetaminophen (paracetamol) is generally not considered an NSAID because it has only minor anti-inflammatory activity.

There are also many NSAIDs that require prescriptions. They include ones you may have heard about or have used as well:

• Celecoxib (Celebrex),
• Diflunisal (Dolobid),
• Diclofenac (Voltaren),
• Fenoprofen (Nalfon),
• Indomethacin (Indocin),
• Ketorolac (Toradol), and many others.

All NSAIDs work in a very similar way, by inhibiting an enzyme called cyclooxygenase, commonly abbreviated as COX.  How does this help?  As it turns out, COX enzymes control the production of another group of molecules called prostaglandins, which actually create the vasodilation (widening of blood vessels), fever and pain associated with inflammation.  When prostaglandins are inhibited, then the inflammatory response can be minimized.

Prostaglandins are important because they can dramatically increase blood flow, regulate blood clotting and smooth muscle contraction as the first steps to fighting infection or injury.  However, as with other aspects of the immune system in those with lupus, they can also produce pain and lead to tissue damage when it is not necessary.

Some Interesting and Important NSAID Facts:

• NSAIDs are among the most commonly used drugs for pain and inflammation with lupus, yet no NSAID has ever been approved for use for SLE by the FDA.
• There are two kinds of COX enzymes: COX-1 and COX-2.
  • COX-1 is always present in the body and tends to protect the stomach lining and kidneys.
  • COX-2, is only produced in case of injury or acute inflammation.
  • Aspirin and most other NSAIDs can inhibit both kinds.  This reduces overall inflammation, but can also prevents protection of the stomach lining.
  • A few NSAIDs, like Celebrex, only target COX-2.  For that reason COX-2 inhibitors are better targeted to specific areas of inflammation and also have fewer gastrointestinal side effect.
• People often do better with one particular NSAID than another. So, it is common to try several different NSAIDs to determine the best one for you.
• NSAIDs, like all anti-inflammatories, attack the symptoms of lupus, and can help prevent organ damage, but they do not address the underlying autoimmune response that causes these symptoms.

Are there things to worry about when using NSAIDs?

Side effects depend on the specific drug but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.

Some specifics to keep in mind:

• Some NSAIDs, like aspirin, can irritate the stomach, because the prostaglandins that they inhibit tend to be protective of the stomach lining. This can lead to serious gastrointestinal problems, such as a bleeding ulcer. To reduce the chance of these problems, NSAIDs are often taken with food, milk, antacids or other prescription medications to prevent gastric damage.  The use of prednisone may also increase the risk of ulcers.
• NSAIDs can damage the kidneys and so are often not recommended for those with lupus nephritis. They can also cause abnormal urine tests results, and that may be mistaken for signs of active lupus.
• NSAIDs can damage the liver, causing elevated creatinine or liver function test results in patients with active systemic lupus erythematosus.
• NSAIDs can increase high blood pressure and reduce the effects of hypertension medications and diuretics – resulting in fluid retention and swelling.
• Some NSAIDs can cause rashes and other allergic reactions.
• Aseptic meningitis has been reported more frequently in NSAID-treated SLE patients.
• Finally, it is very important not to mix over-the-counter NSAIDs, like aspirin, with prescription NSAIDs. That can lead to serious gastrointestinal bleeding and other  toxic drug interactions.

Despite these possible side effects, NSAIDs can safely be prescribed to most lupus patients as long as the patient and their healthcare team carefully monitor their use.

 

In Conclusion

NSAIDs are some of the most commonly used and prescribed drugs for lupus and many other inflammatory conditions.  Yet, so many of us take them without appreciating how so much about them is still not understood.  There are many to choose from, and they can be the key to living successfully with pain other inflammatory symptoms.  However, they can also have serious side effects, and don’t be surprised if you and your healthcare provider have to try many different NSAIDs before you find the ones that work best for you.

 

References

Cleveland Clinic. (2020, January 25). Non-steroid anti-inflammatory drugs (NSAIDs). https://my.clevelandclinic.org/health/drugs/11086-non-steroidal-anti-inflammatory-medicines-nsaids

Horizon, A. A., & Wallace, D. J. (2004). Risk:benefit ratio of nonsteroidal anti-inflammatory drugs in systemic lupus erythematosus. Expert Opinion on Drug Safety, 3(4), 273-278. DOI: 10.1517/14740338.3.4.273.

Johns Hopkins Lupus Center. (2021). Treating lupus with NSAIDs. https://www.hopkinslupus.org/lupus-treatment/lupus-medications/nsaids/

Lander, S. A., Wallace, D. J., & Weisman, M., H. (2002) Celecoxib for systemic lupus erythematosus: case series and literature review of the use of NSAIDs in SLE. Lupus, 11(6) 340-347.  https://doi.org/10.1191/0961203302lu204oa

Ostensen, M., & Villiger, P. M. (2001). Nonsteroidal anti-inflammatory drugs in systemic lupus erythematosus. Lupus 10(3) 135-139.  https://doi.org/10.1191/096120301668183556

Wallace, D. J. (2019). The lupus book: A guide for patients and their families. Oxford University Press.

 

Author: Greg Dardis, MS

Professor Dardis is the Chair of the Science Department at Marylhurst University and currently an Assistant Professor at Portland State University.  His focus has been human biology and physiology with an interest in autoimmunity.

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