January 25, 2022

Which Drugs Are Linked to Arthritis Development? Part 1

Posted By: Richard S. Pope, PA-C, MPAS

Since the art and science of diagnosing arthritis is not often straightforward, it is always helpful to get additional insights in this area. Here, I'd like to expand our knowledge on some of the most common drugs linked to arthritis development and flare-ups. If patients are complaining of new-onset arthritis or musculoskeletal symptoms, it may behoove us to consider whether they are taking certain medications. The impetus for this blog came from a recent posting on RheumNow.com, where you can find more in-depth information. Because the list of linked drugs is lengthy, this will be a 2-part series.

Thiazides and loop diuretics—similar but different subclasses—may cause an increase in serum uric acid, thereby creating ripe conditions for gout onset or attack. Thiazide diuretics may also cause drug-induced subacute cutaneous lupus.

Corticosteroids (CS) are a major contributor to osteoporosis, osteonecrosis, and myopathy. Lower doses of CS (≤10 mg/d) can have effects on both osteoclasts and osteoblasts, leading to negative bone balance. The spine is at particular risk, as the trabecular matrix is rich in osteoclasts and osteoblasts in comparison to cortical bone, leading to increased risk for compression fractures. CS in higher doses (30-60 mg/d) can cause muscle weakness and, more uncommonly, pain (steroid myopathy). Osteonecrosis of joints is also associated with CS use—most commonly affecting the knee, hip, and shoulder areas.

Alcohol, which is a categorized as a central nervous system depressant, can lead to a host of musculoskeletal conditions; beer is a main culprit. Alcohol use can cause initial onset or flare-up of gout. Chronic alcohol use or high-dose exposure also have toxic effects on muscle and can lead to weakness, pain, and myopathy.

Several drugs/classes can induce a lupus-like syndrome, referred to as drug-induced lupus (DIL), and antinuclear antibody positivity. Drugs such as hydralazine, procainamide, sulfasalazine, quinidine, propylthiouracil, and lithium carbonate are all recognized as potential triggers for DIL. More recently, tumor necrosis factor-alpha inhibitors and minocycline (and other tetracycline-related drugs) have been identified as agents that more frequently cause DIL. Other drugs that are commonly associated with DIL are fexofenadine, levothyroxine, metronidazole, and terbinafine.

In 2017, a study published in the European Journal of Dermatology suggested that drug-induced subacute cutaneous lupus may be more common than previously thought. In this article, drug-induced lupus-like reactions were more specific to skin, in contrast with DIL which has more multiorgan involvement including serositis, fever, and weight loss. In the presentation of drug-induced subacute cutaneous lupus, be alert to a widespread rash with lesions that look like erythema multiforme and, on rare occasions, a more severe reaction akin to bullous epidermolysis. The drug classes that are most frequently associated with these rashes are proton pump inhibitors, antihypertensives (especially thiazide diuretics, as mentioned above) and antifungals.

Allopurinol also can cause severe hypersensitivity skin syndromes although I have never witnessed this in clinical practice. Recognizing these more severe skin rashes as drug-induced is critical, as the rash often disappears with discontinuation.

In my next posting, I will provide more information on arthritic syndromes associated with widely varying categories of drugs that are commonly used in practice.

References

Cush J. Best of 2021: 11 drugs that cause arthritis. heumnow.com/news/best-2021-11-drugs-cause-arthritis. Accessed Jan 25, 2022.
Laurinaviciene R, et al. Drug-induced cutaneous lupus erythematosus: 88 new cases. Eur J Dermatol. 2017;27:28.
Stamp L, Barclay M. How to prevent allopurinol hypersensitivity reactions? Rheumatology. 2018;57(suppl 1):i35.

Filed under: Orthopedics , Rheumatology