Quinolone antibiotics have been implicated as associated with an increased risk of tendon pathology and rupture. Patients to whom we prescribe quinolone antibiotics should receive advice on this potential complication.
In a study in the American Journal of Medicine, Wise and colleagues examined the role of age, sex, glucocorticoid use, obesity, diabetes, renal failure/dialysis in quinolone-associated tendon injury and rupture.1 The authors reviewed a database containing 28,907 cases of Achilles tendinitis and 7,685 cases of tendon rupture. The authors ascertained whether there was prescription of a quinolone antibiotic within 30 days of injury or rupture as well as a prescription within one year of a quinolone antibiotic.
The study demonstrated that the use of a quinolone antibiotic was strongly associated with increased risk of Achilles tendinitis and tendon rupture. There was no association with the use of other antibiotics. The occurrence of tendon injury or rupture was more common in patients older than 60 years, non-obese patients, patients who were utilizing oral glucocorticoids, women, patients with diabetes, and those with end-stage renal disease or on dialysis therapy.1
Based upon the evidence in this study, particularly given the frequency with which the podiatric community treats patients with diabetes who are female and have associated renal disease or are dialysis patients, the use of quinolone antibiotics in treating ulcers, osteomyelitis and infection in these patients should be associated with a warning of possible tendon rupture to the patient. We should also monitor these patients for evidence of tendon rupture.
Alfredson and coworkers evaluated the treatment of bilateral midportion Achilles tendinosis.2 The authors noted that laboratory experiments suggest a potential central neuronal mechanism operative in Achilles tendinosis. This observational study included 13 patients with a history of chronic painful Achilles tendinosis in the midportion of the tendon. The most painful side received ultrasound guided debridement on the ventral portion of the tendon with the patient under local anesthesia. Patients were allowed to ambulate immediately following surgery.
Short-term follow-up demonstrated postoperative improvement on the non-operated side as well as the operated side in 11 of 13 patients, suggesting that indeed a central neuronal mechanism may be operative in Achilles tendinosis.2 The authors concluded that unilateral surgery for Achilles tendinosis may have bilateral benefits and that unilateral surgery in the presence of bilateral Achilles tendinosis symptoms may result in bilateral symptom relief.
The potential role of a central neuronal mechanism in Achilles tendinosis may also be of some potential significance in thinking about the role of Achilles tendon contracture and tendinosis in patients with diabetes and, in particular, Charcot joint disease. Although Alfredson and colleagues did not examine or suggest this, it has long been suggested that contracture or disease in the Achilles tendon may play a role in the evolution of Charcot joint disease.
Radiofrequency Coblation has been suggested for the treatment of Achilles tendinosis and is a commonly used therapy by podiatric physicians. Generally, radiofrequency Coblation occurs when nonoperative management has failed. The procedure is simple and one may perform it by percutaneous technique. It offers a potential alternative to more extensive open surgical debridement and repair.
Shibuya and colleagues focused on the use of percutaneous radiofrequency Coblation in 47 cases of Achilles tendinosis and followed for an average of 8.6 months.3 The incidence of re-operation was 14.9 percent. The authors identified rupture of the Achilles tendon in 6.4 percent of patients following radiofrequency Coblation. The majority of patients in the study had a rather significantly elevated body mass index (BMI). The authors concluded that one should use radiofrequency Coblation cautiously in patients with high body mass index as BMI may be associated with a relatively high rate of failure and some rate of rupture.
Insertional Achilles tendinosis is a frequent finding in the patient who is indeed significantly overweight as opposed to patients with mid-portion Achilles tendinosis who are typically more athletically inclined. Prior to performing radiofrequency Coblation for the treatment of Achilles tendinosis, preoperative musculoskeletal imaging with diagnostic ultrasound or MRI studies seem to be appropriate to rule out the possibility of a preexisting partial tendon rupture. Additionally, prior to performing radiofrequency Coblation, it is prudent to document the absence of tendon rupture by clinical examination via a negative Thompson test and assessing for full palpable continuity of the tendon, and reasonable strength and active range of motion.
Gaida and colleagues reviewed the potential role of tumor necrosis factor (TNFR1) in treating Achilles tendinosis.4 It is known that tumor necrosis factor can induce apoptosis and contribute to Achilles tendon disease. If in fact tumor necrosis factor does play a role in the etiology or progression of Achilles tendinosis, therapies directed at an anti-inflammatory effect, particularly in reducing the presence of TNFR1, would be expected to provide some benefit in the management of Achilles tendinosis.
The authors noted the presence of TNFR1 as well as TNFR1 mRNA tenocytes using immune or histologic and enzyme linked immunosorbent assay (ELISA) techniques.4 They concluded that TNFR1 plays a role in the development of Achilles tendinosis, affecting tenocyte morphology.
Implications of this study would suggest a potential role for anti-inflammatory medications in the treatment of Achilles tendinosis. From a personal standpoint, I have combined topical anti-inflammatories together with topical verapamil to reduce scarring, and have included either bupivacaine or lidocaine for pain relief. The use of anti-inflammatory, anti-fibroblast and analgesic topical therapy is adjunctive together with physical therapy and other necessary interventions.
Platelet rich plasma (PRP) has gained increasing popularity for the treatment of a variety of musculoskeletal disorders including Achilles tendinosis. The therapy is easy to administer as one injects a concentrated bioactive blood component rich in cytokines and growth factors.
Monto evaluated the long-term efficacy in treating chronic Achilles tendinosis with PRP, focusing on 30 patients with chronic Achilles tendinosis who were non-responsive to six months of conservative care treated by a single ultrasound guided injection of PRP.5 The author completed the American Orthopaedic Foot and Ankle Society (AOFAS) scoring systems on all patients at pre-treatment and up to 24 months following injection.
Monto found that the average score increased from 34 to 92 for three months following PRP injection. He noted that the effects of the injection remained up to 24 months following treatment. In addition, Monto noted that pre-treatment abnormalities present on MRI or diagnostic ultrasound resolved in 27 of 29 patients at six months post-treatment. It was the author’s opinion that PRP was a clinical success in 28 of 30 patients.
Obaid and colleagues assessed the safety and efficacy of autologous skin-derived collagen producing cells (fibroblasts) for the treatment of chronic Achilles tendinosis.6 The study was a randomized double-blind study of 32 patients. Authors injected patients under ultrasound guidance with laboratory expanded, skin-derived fibroblasts suspended in autologous plasma. A control group received ultrasound guided injections of a local anesthetic and physiotherapy. The study noted significant differences in outcome and the authors concluded that short-term results indicated injection of skin-derived fibroblasts for the treatment of Achilles tendinosis was safe and appeared to be beneficial in reduction of pain and more rapid recovery.
Increasingly, we have seen recommendations for the utilization of various orthobiologic substances to assist in the surgical treatment of Achilles tendinosis. However, the overwhelming majority of such recommendations involve materials that do not include living cell therapy. Given the abnormalities in tenocytes present in patients with Achilles tendinosis, the injection of living cells for the repair of the damaged and necrotic tissue is certainly a reasonable potential alternative therapy to consider.
Wegrzyn and coworkers evaluated 11 patients who had treatment for chronic Achilles tendinosis by flexor hallucis longus (FHL) transfer.7 Seven of the patients presented with a necrotic Achilles tendon rupture, one patient had an chronic Achilles tendon rupture with associated tendinosis and three patients had Achilles tendon re-rupture and associated symptoms. The defect following debridement and surgery averaged 7.4 cm.
At long-term follow-up, all patients demonstrated some degree of strength deficit on testing of the gastrocnemius-soleus muscle with functional improvement following transfer of the FHL.7 The authors noted excellent outcomes for patients with Achilles tendon rupture and a gap of at least 5 cm utilizing the modified FHL transfer.
Utilization of prolotherapy is generally considered controversial. Ryan and colleagues were able to demonstrate successful reduction of pain by the injection of hyperosmolar dextrose for the treatment of Achilles tendinosis.8 No significant adverse sequelae occurred and the authors recommended consideration for this therapy.
This study reported on short-term sonographic appearance and a two-year follow-up of pain relief for patients with chronic Achilles tendinosis who received sonographically-guided dextrose injections.8 Researchers included mid-portion and insertional Achilles tendinosis patients with pain greater than six months in the study. They utilized a 27-gauge needle to inject 25% dextrose/lidocaine solution within the tendon at the site of pathology. An average of five injections with a range of one to 13 occurred in this study. The authors noted a significant reduction in the Visual Analogue Scale (VAS) for both mid-portion and insertional Achilles tendinosis treated in this manner.
In addition, ultrasound demonstrated a reduction in the size and severity of changes within the tendon following injection therapy. The authors concluded that dextrose injections mixed with lidocaine presented a safe and inexpensive alternative for the reduction of pain and reversal of pathology for the treatment of Achilles tendinosis.
1. Wise BL, Peloquin C, Choi H, Lane NE, Zhang H. Impact of age, obesity, and steroid use on quinolone-associated tendon disorders. Am J Med. 2012; 125(12):1228.
2. Alfredson H, Sprang C, Forsgren S. Unilateral surgical treatment for patients with midportion Achilles tendinopathy with a result in bilateral recovery. Br J Sports Med. 2012; Epub Nov. 28.
3. Shibuya N, Thorud JC, Humphers JM, et al. Is percutaneous radiofrequency Coblation for treatment of Achilles tendinosis safe and effective? J Foot Ankle Surg. 2012; 51(6):767-71.
4. Gaida JE, Bagge J, Purdam C, et al. Evidence for TNF-alpha system in the human achilles tendon: expression of TNF-alpha and TNF-receptor at both prorein and mRNA levels in the tenocytes. Cells Tissues Organs. 2012; 196(4):339-52.
5. Monto RR. Platelet rich plasma for chronic Achilles tendinosis. Foot Ankle Int. 2012; 33(5):379-85.
6. Obaid H, Clarke A, Rosenfeld P, et al. Skin derived fibroblasts for the treatment of refractory Achilles tendinosis: Preliminary short term results. J Bone Joint Surg. 2012; 94(3):193-200.
7. Wegrzyn J, Luciani JF, Philippot R, et al. Chronic Achilles tendon rupture reconstruction using a modified flexor hallucis longus transfer. Int Orthop. 2010; 34(8):1187-92.
8. Ryan M, Wong A, Taunton J. Favorable outcomes after sonographically guided intratendinous injection of hyperosmolar dextrose for chronic insertional and midportion Achilles tendinosis. AJR Am J Roentgenol. 2010; 194(4):1047-53.