Which Drugs Are Linked to Arthritis Development? Part 2

Which Drugs Are Linked to Arthritis Development? Part 2 Posted By:
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As mentioned in my previous posting, there are a number of drugs that may be associated with rheumatologic symptoms and disease. Here I will continue discussion of drugs/classes that were not mentioned in part 1.

Aromatase inhibitors (ie, letrozole, anastrozole, exemestane) are adjuvant therapies given for hormone receptor-positive breast cancer. Up to 50% of patients using these therapies experience significant joint or muscle pain—the cause of which is unknown but is speculated to be due to drug metabolism, acute changes in estrogen levels, reduced vitamin D levels, or proinflammatory cytokines. I have seen consults in patients who experience osteoarthritis flares, or in some who have developed peripheral synovitis while taking aromatase inhibitors. Switching between aromatase inhibitors can solve the problem in about 10% to 20% of cases; some patients also have reduction in symptoms by switching to tamoxifen. In addition, there are negative bone effects that can worsen bone density and lead to fracture. With these drugs, bone mineral density dual-energy x-ray absorptiometry (DXA) scans are recommended; and if appropriate, anti-resorptive therapy should be initiated.

Quinolone and fluoroquinolone antibiotics (ie, ciprofloxacin, levofloxacin, ofloxacin) can lead to tendinitis and tendon ruptures (ie, Achilles tendon rupture). The FDA has added boxed warnings to these agents, and recommends use of alternative antibiotics when possible.

Checkpoint inhibitors used in cancer therapy (ie, nivolumab, ipilimumab, pembrolizumab) have improved survival in many cancers. However, they can stimulate immune-related adverse events. These immune-related adverse events can present in many organ systems and vary from patient to patient; rheumatologically, they can present as polymyalgia rheumatica, rheumatoid arthritis, psoriatic arthritis, Sjogren's syndrome, or myositis, among others.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors (ie, canagliflozin, empagliflozin, dapagliflozin), often used in diabetes management, can increase the risk of osteoporosis and fracture, but can also have a gout reduction effect. Also used in diabetes management, dipeptidyl peptidase-4 (DPP-4) inhibitors (ie, sitagliptin, linagliptin) may cause arthritis and arthralgias; these symptoms may increase with continued use.

Serum sickness, an immunologic reaction after exposure to a drug, can be caused by injectables, IV therapies, and oral medications. Serum sickness typically manifests as fever, rash, polyarthralgia, and polyarthritis. It has been associated with various vaccines, anti-toxin/anti-venom therapies, and rituximab and infliximab infusions. Serum sickness can also occur with commonly prescribed antibiotics such as cefaclor, amoxicillin, sulfonamides, tetracyclines, and ciprofloxacin.

Interferon infusions, interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), or filgrastim can cause musculoskeletal side effects such as joint pain or myositis. These adverse events are thought to be due to stimulation of the immune system.

Drugs that are used for ADHD are associated with indirect causes of non-inflammatory rheumatic disease—think fibromyalgia with attendant fatigue, sleep disturbances, or muscle aches and pains. Personally, I have had several consults for Raynaud's phenomenon symptoms in young persons who are on drugs such as amphetamine/dextroamphetamine, lisdexamfetamine, or methylphenidate—all of which can exacerbate or cause Raynaud's phenomenon.

Hopefully the information provided in blogs 1 and 2 will help you be better equipped to differentially identify when these symptom onsets and flares are drug related and enhance your ability to discontinue/adjust the drug and improve patient outcomes.

References
  • Bidell MR, Lodise TP. Fluoroquinolone-associated tendinopathy: Does levofloxacin pose the greatest risk? Pharmacotherapy. 2016;36:679.
  • Breast Cancer Answers YouTube Channel. Side effects of aromatase inhibitors, from a medical oncologist's view. www.youtube.com/watch?v=b1qy0EYppHA. Accessed Jan 28, 2022.
  • Cush J. Best of 2021: 11 drugs that cause arthritis. rheumnow.com/news/best-2021-11-drugs-cause-arthritis. Accessed Jan 28, 2022.
  • Umair HM, et al. Association between central nervous system stimulants used to treat attention deficit hyperactivity disorder (ADHD) and Raynaud's phenomenon: a scoping review. Sem Arthritis and Rheum. 2021;51:1200.

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Filed under: Orthopedics , Rheumatology

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