Case Report: Efficacy of dobesilate in insertional Achilles tendinopathy

Case description

A 37-year-old healthy Caucasian male runner presented with a 3 month history of chronic pain and swelling on top of his left heel. There was no history of direct trauma to his left heel. He experienced a constant dull pain when walking. He had to discontinue sport because of the severity of his pain. At the beginning of symptomatology, the patient initiated sporadic treatments with over-the-counter analgesic and anti-inflammatory drugs. One week before presentation, following recommendations of his physician, the patient initiated, unsuccessfully, a treatment with paracetamol (1g twice a day) and ibuprofen (400mg three times per day). At presentation heel pain was rated as 6 out of 10 on the visual analogue scale (VAS). Colour doppler ultrasound examination at the insertional site of the left Achilles tendon revealed significant neovascularity, mainly at intratendinous mass (Figure 1). After discussing the various treatment options, the patient opted to try a dobesilate injection to the Achilles tendon and gave informed consent. Lidocaine was infiltrated into the skin overlying the Achilles tendon insertional junction. Dobesilate (2 ml of diethylammonium salt formulation; etamsylate, Dicynone^®, Sanofi, France) was peritendinously injected under ultrasound guidance into the Achilles tendon. The procedure was uneventful. The patient was advised to perform some gentile range of motion exercises the following day. He was back to his regular life the day after injection. At the 1 month follow-up visit, the patient reported a marked reduction of his pain, and the VAS was rated as 1. Colour doppler ultrasound scans revealed a significant reduction of tendon hypervascularity at the time (Figure 1). The patient was able to return to running and his previous level of sport without any restrictions. No adverse events were observed during treatment and the 2 month follow-up period.

Figure 1. Effect of dobesilate injection in insertional Achilles tendinopathy.

Long-axis colour doppler ultrasound scans taken at three different planes before and after one month of treatment. Note the reduction of hypervascularity after treatment. The large vessels were persistently observed in real time ultrasonography examination. Achilles tendon mass was delimited by discontinuous line.

Discussion

Tendinopathy is a common health problem affecting nearly 8% of middle and long distance runners under the age of 45. The consequences of this medical condition include pain, disability, early retirement from sport and work, mental distress and health care cost¹. The treatment of tendinopathies is a significant challenge for sport medicine physicians wishing to avoid surgery, since there is no obvious non-surgical options as efficacious therapeutic treatments².

Inflammation and angiogenesis are two cardinal biological processes which cause tendinopathies³. Consequently, control of inflammation and neovascularization seem two obvious targets to develop new treatments for management of tendinopathies.

The anti-inflammatory treatments, by themselves, do not seem to achieve a significant success in the case of Achilles tendinopathies, in addition they seem less effective in patients with Achilles insertional tendinopathies than in those with mid-portion tendinopathies⁴.

Hypervascularity has been reported in human and animal Achilles tendinopathies, as well as in patellar disease, long head biceps tendons and in the rotator cuff^5,6. Furthermore, the tendon area of hypervascularization coincides with the most common localisation for tears^5,6. Healthy tendons are not painful, and have no detectable blood vessels, as assessed by ultrasonography⁹. However, pain is a common symptom which accompanies neovascularization in chronic Achilles tendinopathies. Furthermore, tendon neovascularization is accompanied with nerve in-growth facilitating pain transmission in Achilles tendinopathy¹⁰. Consequently, strategies to destroy neovessels (i.e local application of sclerosing agents as polidocanol) cause pain amelioration^11,12, despite the associated side effects^13,14. Inhibiting angiogenesis in addition to inflammation seems, thus, a reasonable strategy for development of new therapies against Achilles tendinopathies^4,7,8,15.

Fibroblast growth factor (FGF) is nowadays considered a pro-inflammatory and pro-angiogenic protein^16–18. FGF can be inhibited with dobesilate¹⁹. This old drug, with a high safety profile²⁰ but with considerably vague pharmacological and therapeutic targets until its anti-FGF activities were described, has been shown, since this precise point in time, to relieve inflammation and prevents undesirable neovessel formation in many different pathological scenarios^21–25. The data presented in this case report show that local administration of dobesilate seems also effective in reducing neovessel formation and inflammation in the case of insertional Achilles tendinopathies. Recently, it has been reported that FGF is a nociceptive modulator²⁶. Since target inhibition of FGF in tissues undergoing pathological angiogenesis is safe without significant off-target effects on non-diseased tissues²⁷, dobesilate seems an attractive drug for treating tendinopathies.

Large-scale therapeutic trials are obviously needed for more solidly establishing the efficacy of dobesilate in the treatment of Achilles tendinopathy. The results presented in this report seem a reasonable support for undertaking these trials.

Consent

Written informed consent for publication of the clinical details and images was obtained from the patient.