Can toxic exposure cause rotator cuff tendinosis?

Can Toxic Exposure Cause Rotator Cuff Tendinosis?

Yes, toxic exposure—specifically to fluoroquinolone antibiotics—can directly cause rotator cuff tendinosis and tendinopathy through multiple cellular mechanisms including oxidative stress, matrix metalloproteinase upregulation, and direct tenocyte toxicity. 1

Fluoroquinolone-Induced Rotator Cuff Pathology

Documented Clinical Evidence

• Fluoroquinolones cause tendinopathy in multiple rotator cuff tendons, including the supraspinatus, subscapularis, and biceps brachii, with symptoms occurring as early as 2 hours after initial exposure and as late as 6 months after discontinuation. 1
• The FDA mandates a black box warning on all fluoroquinolones citing increased risk of tendinitis and tendon rupture, which explicitly includes rotator cuff tendons. 2
• Levofloxacin labeling specifically warns that "tendinitis and tendon rupture in the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendon sites have also been reported." 2

Pathophysiological Mechanisms

The toxic effects occur through several well-established pathways:

• Reactive oxygen species (ROS) production: All tested fluoroquinolones (pefloxacin, ofloxacin, levofloxacin, ciprofloxacin) stimulate ROS production in tenocytes, causing moderate cytotoxicity at 24 hours and severe toxicity at 72 hours. 1
• Matrix metalloproteinase (MMP) upregulation: Fluoroquinolones increase MMP-1 and MMP-13 in human tenocytes, leading to excessive collagen breakdown and impaired tendon repair. 1
• Mitochondrial damage: Fluoroquinolone-induced oxidative damage specifically targets mitochondria in tenocytes, disrupting cellular energy metabolism and repair mechanisms. 1
• Magnesium chelation: Fluoroquinolones chelate divalent cations (particularly Mg2+), altering cell signaling proteins and disrupting normal cell regulation and repair processes. 1

Risk Factors for Fluoroquinolone Tendinopathy

When evaluating toxic exposure as a cause, identify these high-risk factors:

• Age >60 years: Dramatically increases risk, with adjusted relative risk of 3.2 (95% CI 1.7-6.1) for Achilles tendinitis in older patients. 1
• Concurrent corticosteroid use: In patients >60 years, concomitant corticosteroid use increases risk to 6.2 (95% CI 3.0-12.8). 1
• Organ transplant recipients: Kidney, heart, or lung transplant patients have substantially elevated risk. 2
• Previous tendon disorders: History of rheumatoid arthritis or prior tendinopathy increases susceptibility. 2
• Strenuous physical activity: Athletes and laborers performing repetitive overhead activities face compounded risk. 2

Other Toxic Exposures

Corticosteroid Toxicity

While not typically considered an "exposure," corticosteroids represent another toxic mechanism:

• Direct biomechanical weakening: A single subacromial corticosteroid injection significantly decreases maximum load (37.9 N to 27.5 N), maximum stress (18.1 MPa to 13.6 MPa), and stiffness (26.3 N/mm to 17.8 N/mm) in rat rotator cuff tendons at one week. 3
• This effect is transient, with biomechanical properties returning to baseline by three weeks, but the acute weakening period creates vulnerability to rupture. 3
• Histological changes include fat cell infiltration and collagen attenuation. 3

Clinical Recognition and Management

When to Suspect Toxic Etiology

Consider fluoroquinolone-induced tendinopathy when:

• Patient reports recent or remote (up to 6 months) fluoroquinolone use (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin). 1
• Shoulder pain develops acutely without clear mechanical precipitant in the context of antibiotic therapy. 1
• Patient has multiple risk factors (age >60, corticosteroid use, transplant recipient). 1, 2
• Bilateral or multifocal tendon involvement suggests systemic toxic rather than mechanical etiology. 1

Immediate Management Steps

• Discontinue the fluoroquinolone immediately upon first sign of tendon pain, swelling, or inflammation. 2
• Advise complete rest of the affected shoulder and avoid loading activities. 2
• Switch to a non-quinolone antimicrobial agent for ongoing infection treatment. 2
• Consider antioxidant supplementation (vitamin E or coenzyme Q10) based on preliminary protective evidence, though further research is needed. 1

Common Pitfalls

• Do not assume mechanical overuse is the sole cause in patients with recent fluoroquinolone exposure—the drug may be the primary etiology. 1
• Avoid intratendinous corticosteroid injections in fluoroquinolone-exposed patients, as this compounds toxic effects and further weakens tendon structure. 3
• Do not overlook remote exposure: Symptoms can manifest up to 6 months after fluoroquinolone discontinuation. 1

Distinguishing Toxic from Mechanical Tendinosis

While mechanical factors (repetitive overhead activity, impingement, scapular dyskinesis) remain the most common causes of rotator cuff tendinosis 1, 4, 5, toxic exposure should be considered when:

• Temporal relationship exists between drug exposure and symptom onset. 1
• Symptoms are disproportionate to mechanical loading history. 1
• Multiple tendons are affected simultaneously. 1
• Patient has documented risk factors for drug-induced tendinopathy. 1, 2

The diagnosis remains clinical, as imaging cannot distinguish toxic from mechanical tendinosis—both show similar degenerative changes on MRI and ultrasound. 6, 4