Standardized injection therapy with autologous blood for lateral epicondylitis: a retrospective follow-up study
R. Keijsers1
A.J. de Vries2 K.L.M. Koenraadt3 C.L.E. Gerritsma - Bleeker2 1Department of Orthopaedic Surgery, Amphia Hospital, Breda, The Netherlands 2Department of Orthopaedic Surgery, Martini Hospital, Groningen, The Netherlands
3Foundation for Orthopaedic Research, Care and Education, Amphia Hospital, Breda, The Netherlands
Corresponding author: R. Keijsers, reneekeijsers@gmail.com
Introduction: despite the self-limiting character of lateral epicondylitis (LE), injection therapy with autologous blood (AB) is commonly used when symptoms are persistent. Current studies correlate poorly due to a wide diversity in injection techniques, where injections are usually given manually and blind. In most studies the injection technique is not standardized, which hinders outcome comparisons. This retrospective study describes the effect on pain and function of LE treatment with AB injection using a standardized technique.
Methods: patients diagnosed with LE and with at least four months of complaints received standard treatment with an AB injection using the Instant Tennis Elbow Cure (ITEC) device (ITEC Medical, Enschede). The Visual Analog Scale (VAS) on pain and Oxford Elbow Score (OES) were collected at the baseline and after eight weeks and five months post-treatment. Paired sample T-tests were used to compare postoperative scores with baseline scores. Results: forty patients with LE were treated. Testing scores improved significantly for all patients after eight weeks and after five months. OES on pain, function and socio-psychological improved significantly after eight weeks and after five months. Conclusion: the majority of patients with LE showed an improvement on pain and function after standardized injection therapy with AB. However, the self-limiting nature of the condition must be taken into account.
Introduction Lateral epicondylitis (LE) is the most common cause of lateral elbow pain, with a prevalence of 1% to 3% in the general population.1,2 As LE is associated with employment-age patients, the societal impact is high due to work absenteeism and the substantial burden on the healthcare system.3,4 The extensor carpi radialis brevis (ECRB) tendon is the most commonly affected in LE.2,5
The exact etiology is still not well understood. It is assumed that repetitive overuse of the ECRB tendon leads to a failed repair response, with tenocyte proliferation and production of ground substance. This is thought to result in degeneration of the tendon with macroscopic changes and neovascularization in the end stage.5,6 In general, LE is self-limiting, with 80% of cases resolving within six months and 90% within one year.7,8 Symptoms can nonetheless be persistent and can last for more than two years.9 Despite its self-limiting character, in most cases of LE the burden of disease is high and effective treatment is needed to shorten the duration of symptoms. Injection therapy with autologous blood (AB) is commonly used in the treatment of LE.10,11 AB contains platelets with growth factors that may help in the healing process of chronic injuries. The hypothesis is that these growth factors stimulate angiogenesis and cell proliferation, which increases the recruitment of repair cells and can lead to partial modification of the damaged tissue.11,12 Current studies on the effect of injection therapy in LE correlate poorly due to the great diversity in injection techniques, with its variability in number of injections given and amount of fluid injected. Moreover, injections are often performed manually and blind, without ultrasound guidance or standardization.10 In the current study the injections with AB are given in uniform fashion using a standardized, ultrasound-guided technique with a device especially designed for injecting the insertion of the ECRB tendon. The aim of this study is to describe the outcomes of standardized injection therapy with AB in patients with LE regarding pain and function.
Methods Patients and study design In this retrospective follow-up study, patients diagnosed with LE were recruited between September 2016 and June 2019 in the Martini Hospital, Groningen, The Netherlands. Patients were diagnosed with LE based on a physical examination by one orthopaedic surgeon specialized in the upper limb. Testing of tenderness on palpation of the ERCB insertion at the lateral epicondyle was combined with positive provocation tests of the extensor muscles of the wrist (Maudley’s and Cozen’s tests). Patients with articular complaints of the radiohumeral joint were excluded. This was confirmed by palpation of the radiohumeral joint and a grip and grind test. An X-ray of the affected elbow was taken in all patients to exclude other pathology causing lateral elbow pain, such as radiocapitellar arthrosis. Patients participating in a simultaneously running randomized controlled trial (RCT) comparing different injectables for the treatment of LE were also excluded. The Medical Ethics Committee of Martini Hospital approved the study protocol (MEC no. 2019-134) and concluded that this study does not fall under the scope of the Medical Research Involving Human Subjects Act (WMO), as the intervention and follow-up of this study were considered practice as usual.
Treatment All recruited patients were treated with an AB injection by the Instant Tennis Elbow Cure (ITEC) device (CE 621544, ITEC Medical B.V. Enschede, The Netherlands) This device consists of a table with an injection arm attached and is developed to administer accurate injections with a disposable set of 12 (3x4) small needles at the ECRB tendon (Figure 1).13 Before treatment, autologous blood was obtained by venipuncture of the patient’s preferred arm. The ECRB tendon was injected with 0.4 cc AB, at a patient-specific premeasured depth. Physiotherapy was allowed after treatment.
The standardized procedure of the AB injection with the ITEC device is as follows: 1. Positioning of the arm on the table, 90° abduction of the shoulder and 90° flexion of the elbow. 2. Local anaesthesia by applying topical Xylocaine spray 100 mg/ml. 3. Depth measurement of the ECRB tendon with ultrasound (distance from the skin to the middle of the ECRB tendon). 4. Sets the measured depth of injection on the device. 5. Positioning of a sterile ITEC-injection disposable in the injection arm, immediately above the ECRB tendon on the skin, based on the anatomic landmarks. 6. Perforation of the ECRB by a single movement of the arm of the device, once down the infiltration is conducted by emptying the attached syringe with 0.4 cc AB.
Measurements Baseline patient characteristics were collected, including age, gender, BMI, and duration of symptoms. Questionnaires on the following outcome measures were scored at the baseline and after eight weeks and after five months follow-up: pain, health status, function, and psychological status. The changes in pain were scored by the Visual Analog Scale on pain (VAS, 0-100, with a higher score representing more pain) during rest and during activity and by the Oxford Elbow Score (OES, 0-100 with a higher score representing fewer symptoms).14,15 The overall health status was measured by the EuroQol Visual Analog Scale (EQ VAS, 0-100, with 100 indicating the best health status).16 Elbow function and patients’ psychological status were measured using the OES in the domains, function and socio-psychological.15 Patients were also categorized into three groups based on the effect of the treatment after eight weeks and after five months follow-up compared to the baseline: patients who benefited from the treatment, patients who had no effect from the treatment, and patients who had deteriorated after the treatment. A difference of more than 10 points was determined as clinically relevant for both the VAS score and OES.17,18 No effect is therefore stated for a > -10 to < 10-point difference from the baseline.
Statistical analyses Statistical analysis was performed using IBM SPSS statistics for Windows (Version 26.0., IBM Corp., Armonk, NY). A p-value < 0.05 was considered statistically significant. Data was checked for normal distribution. Paired students T-tests were used to compare the eight weeks and five months follow-up scores with the baseline, so that missing data at a specific follow-up moment is not included in the analysis. Bonferroni correction was applied for multiple comparisons, resulting in a p-value < 0.025 to be considered as statistically significant.
Results Patients During the study period 59 elbows were injected with the ITEC device for LE: 16 patients were excluded because of participation in another trial, 1 patient was excluded because of a simultaneous second injection in the same elbow. A total of 42 elbows in 40 patients were treated for this study. Patient characteristics are shown in Table 1. Duration of symptoms at the baseline was at least 4 months (range 4 to 180 months). Eight weeks post-treatment four patients were lost to follow-up and after five months eleven patients were also lost.
Outcome measures Table 2 displays the scores on the VAS and OES domains. Both VAS scores and OES improved after eight weeks and after five months follow-up compared to the baseline. As can be seen in Figure 2, VAS at rest had improved significantly by 19 points (SD:25) after 8 weeks and by 26 points (SD: 26) after 5 months. For VAS during activity the improvement was higher: 24 points (SD:28) after 8 weeks and 37 points (SD:31) after 5 months. For the OES the improvements on all domains were at least 15 points (SD:18-24) after 8 weeks and at least 24 points (SD:19-29) after 5 months (Table 2, Figure 3).
Figure 2. Changes in VAS pain score (0-100) during rest and activity after eight weeks and after five months follow-up compared to the baseline. *= p<0.001
Figure 3. Changes in OES score (0-100) on pain, function and socio-psychological (SP) after eight weeks and after five months follow-up compared to the baseline. *= p<0.001
Table 3 shows the number of patients for whom symptoms remained the same (a difference < 10 points compared to the baseline), increased or decreased. For all outcome measures an improvement was measured in the majority of patients (range 61.5-71.1%) after eight weeks. After eight weeks no difference was observed in 18.4-29.7% of patients and scores decreased in 5.4-15.4%. After five months the percentage of patients who had an improvement increased for all outcome measures (range 72.4-79.3%). No adverse events were reported.
Discussion In this study, most patients with LE improved on pain and function after standardized injection therapy with AB. Most patients in this group had long-term complaints before treatment. By contrast, a small number of patients have more complaints after treatment than before. The average improvement in VAS pain score during activity of at least 24 (8-week follow-up) and 37 points (5-month follow-up) seems to be clinically relevant. This also holds for the OES, where the score had improved by at least 15 and 24 points after 8 weeks and after 5 months follow-up, respectively. The improvements in pain scores in this study (in 68.4–79.3% of patients) are comparable to other studies on the effect of AB in the treatment of LE.19,20 After 8 weeks and after 6 months follow-up, a study by Raeissadat et al. reported an improvement in 73.3% and 76.7% of patients as well as in VAS pain scores, dropping from 6.8 (10-point scale at baseline) to 3.75 and 3.41, respectively.19 An RCT by Linnanäki et al. reported a change in VAS pain scores from 5.7 (10-point scale at baseline) to 4.1 after 8 weeks and 3.9 12 weeks after treatment with AB.21 These scores are comparable to the results of the current study, with VAS scores at rest improving from 53.3 (100-point scale at baseline) to 34.3 after 8 weeks and 27.4 5 months post-treatment. That study did not report data on the percentage of patients who did not improve, or whose symptoms worsened, after treatment.21 In this study the ITEC device was used to infiltrate the ECRB tendon. The accuracy of the device is reported in a still-unpublished study in which an experienced upper limb surgeon and an orthopaedic resident infiltrated cadaveric arms with dye using the ITEC device. They showed that, regardless of the user’s experience, the device is able to perform an accurate perforation of the ECRB tendon.13 This is in contrast to another cadaveric study on the accuracy of manual perforation of the ECRB tendon in which the majority of the injections miss the intended ECRB tendon.22 The first clinical pilot study on the ITEC device showed no side effects in patients with LE.13 This is consistent with our study findings. To our knowledge, no studies on the clinical outcomes of the ITEC device have yet been published. The current study did not use strict inclusion or exclusion criteria and therefore gives a good representation of patients with LE in daily practice. Since patients were excluded when eligible and were willing to participate in another study on the treatment of LE, this study population is more heterogeneous than that of most studies and reflects patients with the most persistent symptoms. Most patients had long-term complaints before treatment, with the majority receiving previous treatment for LE. Most patients seem to benefit from treatment with AB injections and results are comparable to other studies. This study comes with some limitations. Due to the lack of a control group, no firm conclusions can be drawn on the overall treatment effect of the injections with AB. Also, a convenient sample was included, where no a priori sample size calculation was performed. Several patients were lost to follow-up, with eleven patients missing at the five-month measurement (reasons unknown). Despite the small group size, a clinically relevant difference in VAS and OES scores was observed (> 10 points).17,18 Another limitation of this study is the lack of standardization of the aftercare: it has not been reported whether patients received additional treatment (e.g., physiotherapy) in addition to their injection treatment. The positive treatment effect of AB injections for LE must be viewed from the perspective that, in most cases, LE is a self-limiting, one-year condition, although symptoms can persist for more than two years in recalcitrant cases.7,8 Treatment can be beneficial in shortening the duration of symptoms and to counteract healthcare costs and work absenteeism. A study by Sanders et al. reported that the majority of direct medical costs were incurred in the first six months. The indirect costs of LE (e.g., due to work absenteeism or loss of productivity) are high and can add significantly to the financial burden on society, with 16% of LE patients reporting work restrictions and 4% taking sick leave for at least one week.20 It might therefore be interesting to initiate treatment for LE at an earlier stage of complaints, not only to reduce healthcare costs but also to shorten the time of returning to work. Current literature states that when treating LE, regardless of the type of treatment, 74% of patients no longer seek care three months after the initial diagnosis.23 Although that study reported on all types of treatment and did not mention the reason for not seeking care, this percentage does not differ much from the percentage of improvement after AB injection therapy in our study. Besides AB, different types of injection therapy are commonly used in the treatment of LE, such as platelet-rich plasma or dextrose (prolotherapy).10 To our knowledge, none of these injectables are superior in the treatment of LE. Current studies on the treatment effect of injection therapy are not comparable due to heterogeneity of study designs and lack of standardization of the injection.10 To accurately compare these injections, an RCT must be conducted in which the different injectables are compared in a standardized fashion. In order to distinguish effective treatment for LE from the self-limiting effect, it is important to compare the different treatment options with a cohort following a wait-and-see policy. It is also important to properly educate patients about possible negative treatment effects. Conclusion The majority of patients with LE improve on pain and function after standardized injection therapy with AB. Disclosure statement No disclosures.
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