Glucocorticoids

Glucocorticoid injections have a long history in the treatment of lateral epicondylitis, with descriptions of their use as early as the 1950s. Originally, when lateral epicondylitis was believed to be an inflammatory process, steroid injections were thought to act as a local anti-inflammatory modality. However, as the understanding of the pathology of lateral epicondylitis has evolved, so have the explanations for the beneficial effects of steroid injections. Although there are few inflammatory cells present in the affected tissue, studies have shown an increase in the levels of substance P, or neurokinin-1, receptors in patients suffering from lateral epicondylitis. This demonstrates a possible neurogenic cause for pain in lateral epicondylitis. Corticosteroids have been shown to reduce substance P levels in other parts of the body, suggesting that steroid injections may provide relief for pain of a neurogenic origin in lateral epicondylitis.

Many different steroids have been utilized as injection therapies for lateral epicondylitis. Price and colleagues compared hydrocortisone with 2 different doses of triamcinolone and found both 10 mg and 20 mg doses of triamcinolone to be superior to hydrocortisone in the first 8 weeks, with no differences beyond this time point.

There have been numerous randomized trials comparing steroid injections with local anesthetic or saline injections, as well as with NSAIDs, physiotherapy, and a wait-and-see protocol. Overall, most studies have shown that in the acute follow-up time period, patients receiving steroid injections have improved Visual Analog Scale (VAS) pain scores and functional scores during the first 2 to 6 weeks after injection. Other studies, however, found no significant difference even in the short term between steroid injections and placebo injections. Lindenhovius and colleagues performed a double-blind RCT of 64 patients treated with steroid or lidocaine and found no significant difference in disabilities of the arm, shoulder, and hand (DASH) or pain scores at 1 or 6 months follow-up. In another double-blind RCT comparing steroid with bupivacaine in 39 subjects, Newcomer and colleagues found no significant differences in outcomes from 8 weeks to 6 months.

In the longer term, steroid injections may even be harmful in the treatment of lateral epicondylitis. Smidt and colleagues performed an RCT with long-term follow-up at 1 year of 185 patients, comparing corticosteroid injections with physiotherapy (PT) and a wait-and-see strategy. They defined success as patients rating themselves as completely recovered or much improved. Although corticosteroids performed better than PT and the wait-and-see groups at 6 weeks (92% vs 47% and 32% success, respectively), these patients were worse at 52 weeks (69% vs 91% and 83% success, respectively). The authors hypothesize that steroid injections worsen long-term results by either weakening the tendon or by allowing patients to further aggravate their tendinosis initially by relieving pain in the short term.

Steroid injections are not without risks. In Gaujoux-Viala’s meta-analysis of 744 patients receiving injections for shoulder or elbow tendonitis, 10.7% of patients had transient pain after injection, and 4.0% of patients had skin atrophy or depigmentation. No tendon ruptures or infections were reported in this large study group, indicating that although these have been reported in the literature after Achilles tendon injections, their occurrence is exceedingly rare.

Overall, steroid injections have a long track record in the treatment of lateral epicondylitis and have been shown to have a beneficial effect on pain in the short term, averaging 6 weeks for many patients. However, there is no evidence that patients do any better with corticosteroid injections than with no treatment beyond 6 to 8 weeks, and in some studies, patients receiving steroid injections have inferior long-term outcomes compared with controls.

Botulinum Toxin

Botulinum toxin A is a presynaptic acetylcholine blocker that has the ability to cause a palsy of skeletal muscle. Botulinum toxin is theorized to help healing in lateral epicondylitis by causing a reversible partial paralysis of the wrist extensors that can last 2 to 4 months. This in turn avoids microtrauma to the tendon and allows the pathologic tissue to heal. Botulinum toxin A was first described in the treatment of lateral epicondylitis in 1997 by Morre and colleagues. Since then, several RCTs have shown promising results for botulinum toxin for tennis elbow.

Wong and colleagues (2005) evaluated 60 patients who received a blinded injection of botulinum toxin or placebo. Patients in the botulinum toxin group had significantly lower VAS pain scores at 4 and 12 weeks ( P = .006). Espandar and colleagues in 2010 saw similar reductions in pain from 4 to 16 weeks, with 100% follow-up. This study used anatomic measurement to guide injection placement. In the largest RCT evaluating botulinum toxin, Placzek and colleagues (2007) compared botulinum toxin and placebo in 130 patients in a multicenter double-blind RCT. Patients in the treatment group showed significantly improved VAS and clinical pain scores at 6, 12, and 18 weeks after injection compared with controls ( P = .001). There were no significant differences in grip strength.

However, not all trials have shown positive results for botulinum toxin. In 2005, Hayton and colleagues stratified 40 patients into botulinum toxin and placebo groups. They found no difference between the groups at 3 months with regard to pain, grip strength, or quality of life. Lin and colleagues (2010) compared botulinum toxin with corticosteroid injection at 4, 8, and 12 weeks in a small double-blinded RCT of 19 elbows. They found significantly decreased pain scores in the steroid group at 4 weeks compared with botulinum toxin, but no difference in VAS pain scores at 8 and 12 weeks. Grip strength was consistently higher in the corticosteroid-treated group.

The major adverse effect seen with botulinum toxin injection is finger and wrist extensor weakness. Wong and colleagues found a 13% incidence of mild paresis in the fingers at 4 weeks after injection. Placzek and colleagues showed no difference in grip strength, but significantly decreased strength in third finger extension, lasting from 2 to 14 weeks ( P = .001–.007). Espandar and colleagues observed similar weakness of third and fourth finger extension in almost all patients. Wong and Hayton reported that this weakness was not tolerated by a small percentage of patients whose work required intricate hand movements.

Randomized trials of botulinum toxin injection for tennis elbow have shown promising results in relieving pain, at the expense of weakness in the finger extensors. However, these results have not been shared by all studies, and no RCTs have evaluated patients beyond 4 months, so longer-term follow-up is needed.

Autologous Blood

Autologous blood injection for the treatment of lateral epicondylitis was first described by Edwards and Calandruccio. The authors noted that techniques such as forceful closed manipulation, traumatic injection, and percutaneous release resulted in improved outcomes for patients, and theorized that this was due to bleeding at the extensor origin following the trauma. This bleeding would then stimulate an inflammatory cascade to begin a healing response for the tendinopathy. They proposed that autologous blood injection, specifically composed of 2 to 3 mL of autologous blood combined with lidocaine, would deliver the cellular and humoral mediators to the elbow for a similar healing process.

In their case series of 28 patients with lateral epicondylitis symptoms present for 6 or more months who had failed conservative therapy, Edwards and Calandruccio found that after receiving 1 to 3 autologous blood injections, pain scores and Nirschl stages decreased at an average follow-up of 9.5 months. Overall, they found 79% relief of pain following autologous blood injections.

There have been several RCTs evaluating autologous blood injections for lateral epicondylitis, although only 1 study with comparison to a placebo injection. Wolf and colleagues performed an RCT of 28 patients comparing autologous blood, corticosteroid, and a saline injection. The study was double-blinded, and patients were evaluated at 2 weeks, 2 months, and 6 months after injection with VAS, DASH, and the patient-related forearm evaluation. Although all of these outcomes demonstrated improvement from baseline in each group, there were no significant differences in any of the groups.

In 2010, Ozturan compared autologous blood injection to both corticosteroid injection and extracorporeal shock wave therapy in a 3-armed randomized trial of 60 patients. Although corticosteroid treatment showed the best outcomes at 4 weeks, success rates at 1 year were greatest for the autologous blood (83%) and extracorporeal shock wave therapy (90%) groups, compared with only 50% for the corticosteroid group. Kazemi directly compared autologous blood with corticosteroid injections in a short-term RCT of 60 patients. At 8 weeks, autologous blood was significantly more effective at decreasing pain scores and increasing quick DASH scores.

There have been few adverse effects demonstrated from autologous blood injections. Most commonly, authors have cited the pain after injection as the most difficult for patients. Ozturan described 89% of patients having no more pain after 2 days, and the remaining 11% of patients had pain from 4 to 6 days. Additionally, 21% of patients had elbow erythema; 16% had swelling, and 21% had nausea. Wolf and colleagues and Kazemi and colleagues described no adverse effects.

Autologous blood injections offer numerous factors to stimulate a healing cascade in the degenerative tendinous origin, and studies have shown beneficial effects for patients receiving these injections in the short and long term, especially compared with steroid injections. Although the literature has not definitively shown any benefit compared with placebo in small studies, this may warrant further investigation.

Platelet-rich Plasma

Autologous platelet-rich plasma (PRP) is a concentrated source of platelets and platelet-derived growth factors that has been used in numerous medical fields. PRP is theorized to enhance the healing of wounds, bone, and tendons through release of specific growth factors upon platelet activation. For lateral epicondylitis, the reasoning for use is similar to that of autologous blood injections, but proponents of PRP laud the increased concentration of platelets and therefore platelet-derived growth factors. PRP has been used for various musculoskeletal diagnoses, and Mishra and Pavelko were the first to study its efficacy in lateral epicondylitis treatment.

PRP is prepared by drawing up 30 to 60 cc of blood from the patient and using a US Food and Drug Administration (FDA)-approved blood separation device to centrifuge the blood for 15 minutes to isolate PRP. This produces 3 to 6 mL of PRP, which can be combined with 1 to 2 mL of local anesthetic for injection.

Mishra and Pavelko treated 20 patients with chronic lateral epicondylitis with PRP in an unblinded prospective study. They found that patients who received PRP injections had significantly better VAS scores at 8 weeks than placebo. At final follow-up of 1 to 3 years, 93% of patients had reduction in VAS pain scores.

There have been few RCTs evaluating PRP in the treatment of tennis elbow. Peerbooms and colleagues evaluated 100 patients in a double-blind randomized trial comparing PRP with corticosteroid injection. The authors defined successful treatment as greater than 25% reduction in VAS score with no reintervention. They found that although the corticosteroid group showed slightly more improvement at 4 weeks, VAS and DASH scores were significantly better for the PRP group at 26 and 52 weeks ( P <.001 and P = .005). Overall, 73% of the PRP group versus 49% the corticosteroid group had successful outcomes. In a 2-year follow-up study, the authors found that 81% of PRP patients met their definition of success as opposed to 40% of the corticosteroid group.

Krogh and colleagues compared PRP with corticosteroid and placebo injections in 60 patients in a randomized, double-blind trial. Corticosteroids showed improved pain relief at 1 month compared with PRP and placebo. However, at 3 months follow-up, there were no significant differences between the groups.

Creaney and colleagues and Thanasas and colleagues both compared PRP with autologous blood injections in RCTs of 28 and 150 patients, respectively, who had failed first-line therapy for lateral epicondylitis. Creaney and colleagues defined success as a 25-point reduction in the patient-related tennis elbow evaluation. They found 66% success for the PRP group and 72% success for the autologous blood group, which was not significantly different. They found that twice as many patients in the autologous blood group (20% vs 10%) sought eventual surgery. Thanasas and colleagues found their PRP group to have significantly better pain improvement than autologous blood at 6 weeks ( P <.05), but that the differences were not significant beyond this time point.

Regarding the safety of PRP, similar to autologous blood, there are no concerns for immunogenic reactions. Several patients have reported postinjection pain that can last up to 3 to 4 weeks. Thanasas and colleagues found that patients who received PRP had more postinjection pain as compared to autologous blood injections.

PRP has certainly shown benefits in a difficult cohort of patients with chronic lateral epicondylitis who have failed other therapies. Although it has not shown superiority compared with corticosteroids or placebo at 3 months, its superiority to corticosteroids in long-term follow-up was demonstrated in 1 large double-blinded RCT with 2 years follow-up. On the other hand, PRP has not been shown to have a clinical advantage to autologous blood injection thus far in the literature. Therefore, with the current body of evidence, it is difficult to justify the additional expense of preparing PRP compared with autologous blood injections for lateral epicondylitis.