TITLE: 
A randomised control trial to evaluate
the efficacy of autologous blood injection versus local
corticosteroid injection for treatment of lateral epicondylitis



ABSTRACT.OBJECTIVES:
Local corticosteroid infiltration is a common practice of treatment
for lateral epicondylitis. In recent studies no statistically significant
or clinically relevant results in favour of corticosteroid injections
were found. The injection of autologous blood has been reported
to be effective for both intermediate and long-term outcomes. It
is hypothesised that blood contains growth factors, which induce
the healing cascade.

ABSTRACT.METHODS:
A total of 60 patients were included in this prospective randomised
study: 30 patients received 2 ml autologous blood drawn from contralateral
upper limb vein + 1 ml 0.5% bupivacaine, and 30 patients received
2 ml local corticosteroid + 1 ml 0.5% bupivacaine at the lateral
epicondyle. Outcome was measured using a pain score and Nirschl
staging of lateral epicondylitis. Follow-up was continued for total
of six months, with assessment at one week, four weeks, 12 weeks
and six months.

ABSTRACT.RESULTS:
The corticosteroid injection group showed a statistically significant
decrease in pain compared with autologous blood injection group
in both visual analogue scale (VAS) and Nirschl stage at one week
(both p < 0.001) and at four weeks (p = 0.002 and p = 0.018,
respectively). At the 12-week and six-month follow-up, autologous
blood injection group showed statistically significant decrease
in pain compared with corticosteroid injection group (12 weeks:
VAS p = 0.013 and Nirschl stage p = 0.018; six months: VAS p = 0.006
and Nirschl p = 0.006). At the six-month final follow-up, a total
of 14 patients (47%) in the corticosteroid injection group and 27
patients (90%) in autologous blood injection group were completely
relieved of pain.

ABSTRACT.CONCLUSIONS:
Autologous blood injection is efficient compared with corticosteroid
injection, with less side-effects and minimum recurrence rate.

BODY.ARTICLE FOCUS:
The injection of autologous blood is compared with the standard
practice of local corticosteroid injection for the treatment of
lateral epicondylitis
Outcomes are assessed in terms of decrease in pain, rates of
recurrence and complication

BODY.KEY MESSAGES:
This study offers encouraging results of an alternative treatment
that addresses the pathophysiology of lateral epicondylitis that
has been resistant to traditional conservative modalities

BODY.STRENGTHS AND LIMITATIONS:
This is a randomised study where a new modality of treatment
is evaluated by comparing it with a commonly practiced modality
of treatment
There are only a few studies of this kind
Larger studies, with longer periods of -follow-up, and potentially
including -multiple injections over a period of time, are required

BODY.INTRODUCTION:
Lateral epicondylitis, or tennis elbow, is commonly encountered
in orthopaedic practice, being the second most frequently diagnosed
musculo-skeletal disorder in the neck and upper extremity in a primary
care setting.1 It
has an incidence of between four and seven per 1000 cases per year in general practice, with
a peak between the ages of 35 and 54 years, and a mean age of approximately
42 years.2-5 An epidemiological
study reported that 87% of cases involved the dominant arm.6
The characteristic clinical findings are pain and tenderness
over the lateral epicondyle. Lateral epicondylitis has been reported
to be the result of overuse from many activities. Although it is
often referred to as tennis elbow, it is seen to affect non-athletes
rather than athletes.7,8
The pathophysiology of the condition is a matter of controversy,
and there is not enough scientific evidence to favour any particular
type of treatment for acute lateral epicondylitis.9,10 Most current research has proposed degeneration
of the origin of the extensor carpi radialis brevis and repeated
microtrauma and incomplete healing response (tendinosis) as the
cause of lateral epicondy-litis.10-15 The constellation
of findings has been termed angiofibroblastic hyperplasia.16

Most conservative modalities such as local injection of corticosteroid
have focused on suppressing an inflammatory process that does not
actually exist. It is theorised that the beneficial effects of the
steroid injection result from the bleeding caused by forcing fluid
through tissue planes at high pressures.17
Recently an injection of autologous blood has been reported to
be effective for both intermediate and long-term outcomes for the
treatment of lateral epicondylitis, with a significant decrease
in pain.10,15,18 Chemical modifiers of cellular activity
carried in the blood and are known to be mitomorphogenic.16 Injection of autologous
blood might provide the necessary cellular and humeral mediators
to induce a healing cascade.10,19-21
There are very few studies that have evaluated the injection
of autologous blood for lateral epicondylitis as a treatment modality.
The objective of this study was to evaluate the efficacy and role
of autologous blood -injection for the treatment of lateral epicondylitis, -compared
with the commonly used local injection of cortico-steroid.22-25

BODY.PATIENTS AND METHODS:
This is a randomised control trial as a pilot study.
Our study population has a high proportion of people involved
in manual labour. There is no current published data on the prevalence
of lateral epicondylitis in the region where the study was conducted.
Age > 15 years and a diagnosis of lateral epicondylitis were the
inclusion criteria. The exclusion criteria were: 1) patients receiving steroid
injections in the three months prior to study treatment; 2) history
of substantial trauma; 3) previous surgery for lateral epicondylitis;
4) presence of other causes of elbow pain such as osteochondritis
dessicans of capitellum, epiphyseal plate injuries, lateral compartment arthosis,
varus instability, radial head arthritis, posterior interosseous
nerve syndrome, cervical disc syndrome, synovitis of radiohumeral
joint, cervical radiculopathy, fibromyalgia, osteoarthritis of elbow,
or carpal tunnel syndrome. Each patient was assessed by history
and clinical examination. In some cases radiological and imaging investigations
were carried out to confirm the diagnosis and to identify any exclusion
criteria.
Patients attending outpatient department were included after
a diagnosis of lateral epicondylitis was established. This included
interview and clinical examination comprising testing for tenderness
over the lateral epicondyle or just distal to it, a positive Cozen’s
test and Mill’s maneouvre.26 In
12 cases diagnosis was confirmed with radiography and in two cases
by MRI, after radiographs were inconclusive. Patients were allotted
sequentially into two parallel groups, A and B, of 30 cases each.
Equal randomisation (1:1 allocation ratio) was undertaken according
to a computer-generated randomisation table.
BODY.PROCEDURE:
Group A was designated to receive an injection of autologous
blood. Patients were infiltrated with injection of 2 ml autologous
blood drawn from the contralateral upper limb vein mixed with 1
ml 0.5% bupivacaine, at the lateral epicondyle according to the
technique described below.10 Group
B was designated to receive an injection of local cortiocosteroid.
Patients were infiltrated with 2 ml of local corticosteroid (methyl
prednisolone acetate 80 mg) mixed with 1 ml 0.5% bupivacaine, at
the -lateral epicondyle according to the same technique. 
Briefly, the technique is as follows (Fig. 1).10 With the patient
in supine or sitting posture the elbow is flexed to 90° with the
palm facing down. The anatomical bony landmarks were identified.
Under aseptic precautions the needle is introduced proximal to the
lateral epicondyle along the supracondylar ridge, and gently advanced
in to the undersurface of the extensor carpi radialis brevis while
infiltrating. A small adhesive sterile dressing is applied. Patients
are advised to rest the upper limb for three days, with no restriction of activity after that.
Fig. 1Clinical photograph showing the injection
of autologous blood at the lateral epicondyle.

BODY.OUTCOME EVALUATION:
Outcome in terms of pain relief was assessed using a visual analogue
scale (VAS) and the Nirschl staging system.10,27
The VAS comprised a 10 cm line marked at one end with ‘no pain’
and at other end with ‘worst pain ever’. The participant is asked
to indicate where on the line he or she rates the pain on the day
of presentation.
The Nirschl staging system consists of seven phases in ascending
order of severity of pain (Table I). It ranges from phase 1 (mild
pain with exercise, resolves within 24 hours) to phase 7 (constant
pain at rest, disrupts sleeps).
Table IDetails of the Nirschl staging system
PhaseDescription

1
Mild pain with exercise, resolves within 24 hours
2
Pain after exercise, exceeds 48 hours
3
Pain with exercise, does not alter activity
4
Pain with exercise, alters activity
5
Pain with heavy activities of daily living
6
Pain with light activities of daily living, intermittent pain
at rest
7
Constant pain at rest, disrupts sleeps
Both the VAS and the Nirschl stage were assessed by visit to
the clinic pre-injection, and at one week, four weeks, 12 weeks
and at the six-month final follow-up.

BODY.STATISTICAL ANALYSIS:
The Mann-Whitney U test (non-parametric test) was used to compare
outcome regarding pain between the two groups. The chi-squared test
was used to compare categorical variables between the groups. A
p-value < 0.05 was considered to indicate -statistical significance.


BODY.RESULTS:
Group A comprised 13 males and 17 female patients with a mean
age of 42.9 years (22 to 67), and group B comprised 12 males and
18 females with a mean age of 42.2 years (17 to 62). The characteristics
of both groups are shown in Table II. It was noted that 20 patients
(33%) had diabetes mellitus.
Table IICharacteristics of group A (autologous
blood injection) and group B (corticosteroid injection)
CharacteristicGroup A 
(n = 30)Group B 
(n = 30)p-valueMale:female
13:17
12:18
1
Mean age (yrs) (range)
42.9 (22 to 67)
42.2 (17 to 62)
0.828
Side (right:left)
23:7
23:7
1
Dominant side (n, %)
25 (83)
26 (87)
1
Mean duration of -symptoms (weeks) (range)
  9.5 (2 to 54)
  7.7 (1 to 36)
0.828
Employment (n, %)



   Manual
13 (43)
  9 (30)
0.3
   Non-manual
17 (57)
21 (70)
0.3
 The severity of pain was measured pre-injection and after one,
four and 12 weeks, and at six months by the VAS for pain and Nirschl
staging. Pre-injection, the mean VAS scores for pain were similar between group A and group B (7.7 (sd 1.3) versus 7.5
(sd 1.3), p = 0.5395), as were the mean Nirschl stages
(5.4 (sd 1.1) versus 5.2 (sd 1.0),
p = 0.4918) (Tables III and IV).
Table IIIMean visual analogue scale (VAS)
for pain for group A (autologous blood injection) and group B (corticosteroid
injection)
Mean (sd) VASFollow-upGroup A 
(autologous blood)Group B 
(corticosteroid)p-value



Pre-injection
7.7 (1.3)
7.5 (1.3)
0.5395
1 week
7.2 (1.9)
4.5 (1.9)
< 0.0001
4 weeks
3.2 (2.4)
1.5 (2.3)
0.0022
12 weeks
0.6 (1.9)
1.5 (1.8)
0.0127
6 months
0.5 (1.9)
1.8 (2.0)
0.0058
Table IVMean Nirschl staging for group
A (autologous blood injection) and group B (corticosteroid injection)
Mean (sd) Nirschl stageFollow-upGroup A 
(autologous blood)Group B 
(corticosteroid)p-value



Pre-injection
5.4 (1.1)
5.2 (1.0)
0.4918
1 week
5.1 (1.5)
3.1 (1.4)
< 0.0001
4 weeks
2.2 (1.6)
1.0 (1.6)
0.003
12 weeks
0.43 (1.3)
1.0 (1.3)
0.0184
6 months
0.36 (1.3)
1.2 (1.4)
0.0064
The results of the VAS for pain and Nirschl grades -followed
a remarkably similar course over the period of follow-up, as can
be seen from Figure 2 and Figure 3, respectively. Initially the
patients in group A reported a much smaller effect in terms of pain
resolution, with group B reporting significantly lower VAS and lower Nirschl
scores at one week (both p < 0.0001) and again at four weeks
(p = 0.0022 and p = 0.003, respectively) (Tables III and IV, Figs
2 and 3).
Fig. 2Graph showing the mean visual analogue
scale (VAS) of pain in both groups before treatment and at one week,
four weeks, 12 weeks and six months post-injection.
Fig. 3Graph showing the mean Nirschl stage
in both groups before treatment and at one week, four weeks, 12
weeks and six months post-injection.
However, at 12 weeks, the scores for group B had slowed, and
the VAS and Nirschl scores were significantly lower in group A (p
= 0.0127 and p = 0.0184, respectively). This difference was maintained
at the final six-month follow-up, at which point the pain scores
for group B had begun to rise compared with the four- and 12-week
scores (Tables III and IV, Figs 2 and 3). At six months after injection,
the pain scores were significantly lower in group A compared with
group B (VAS: 0.5 (sd 1.9) versus 1.8
(sd 2.0), p = 0.0058; Nirschl grade: 0.36 (sd 1.3) versus 1.2
(sd 1.4), p = 0.0064).
At the six-month follow-up, a total of 27 patients (90%) in group
A were completely relieved of pain, compared with 14 patients (47%)
in group B (p < 0.001, chi-squared test). However, at the four-week
assessment, 19 patients (63%) in group B had complete relief of
pain, and many of these patientsreported recurrences
at 12 weeks and at six months, resulting in a rate of recurrence
in this group of 36.8%. In comparison, only five patients (17%)
in group A were pain-free at four weeks, but there was a no recurrence
by six months, which reached statistical significance (p < 0.001,
chi-squared test).
In group A, 18 patients (60%) complained of an increase in pain
immediately (and during the following few days) after the injection,
compared with eight (26%) in group B (p = 0.009). Only two patients
(6.6%) had local skin atrophy in group B while no patient in group
A had this problem, but this did not reach statistical significance
(p = 0.150, chi-squared test); demonstrating that the local steroid infiltration
done with proper care minimises this complication. No patients reported
elbow stiffness, infection, reflex sympathetic dystrophy, post-injection
flare, facial flushing, neurovascular damage or tendon rupture or
other untoward complications.

BODY.DISCUSSION:
The mean age of the patients included in our study was 42.6 years
(17 to 67), with a peak incidence in the fourth decade. A study
by Hamilton2 included
a population with age ranging between 14 and 78 years with a mean
age of 45 years. Other studies have reported mean ages of approximately
42 years.3-5
There has been much controversy over the pathophysiology of this
disorder.28,29 The most widely
held theory proposes macro- or microscopic tears in the common tendon,
coupled with an incomplete healing response.30-32
Theorigin of the extensor carpi radialis brevis is
the primarysite of this injury, and pathological changes
have been consistentlydocumented at this location.12,31,33-35 Histopathologicalstudies
have demonstrated that tennis elbow is not an inflammatorycondition;
rather, it is a fibroblastic and vascular responsecalled
angiofibroblastic degeneration, now more commonly knownas
tendinosis.27,36 Thus, the terms
epicondylitis and tendinitis are misnomers.7,14,28,33
Assendelft et al,37 in
their 1996 systematic review, compared the validity and outcome
of randomised controlled trials of corticosteroid injections for
lateral epicondylitis. Pooled analysis indicated short-term effectiveness
only (two to six weeks). At
follow-up > six weeks, no difference was found between corticosteroid
injection and other treatments, including placebo. No conclusions
could be made about the most suitable corticosteroid, dose, injection
interval or volume.37
Bisset et al38 concluded
that physiotherapy combining elbow manipulation and exercise has
a superior benefit to ‘wait-and-see’ in the first six weeks and
to corticosteroid injections after six weeks. The significant short-term
benefits of corticosteroid injection are paradoxically reversed after
six weeks, with high recurrence rates, implying that this treatment
should be used with caution in the management of tennis elbow.38 These are comparable
to our results, which by 12 weeks were showing a slight reversal of
the early pain relief in the corticosteroid group, with high rates
of recurrence. 
Studies on animal models have shown that intra-tendinous corticosteroid
adversely affect the biomechanical properties of tendons.39-42 Corticosteroid injection has also
been associated with side-effects such as sepsis, tendon rupture,
post-injection pain, local skin atrophy, facial flushing, post-injection
flare, hyperglycaemia and hypersensitivity reactions.8,24,30,42-44
Resuscitation facilities should be available in case patients
have a rare severe reaction.
Edwards and Calandruccio,10 investigating
autologous blood injections in 28 patients in whom conservative therapy
had failed to resolve symptoms of lateral epicondylitis, found that
22 patients (79%) had a reduction in pain over 9.5 months post-injection.
All patients maintained their maximal benefit throughout the course
of their follow-up evaluation, with no recurrence.10
There are very few studies in the literature comparing the efficacy
of injection of autologous blood with injection of local corticosteroid
for lateral epicondylitis.45,46 This is a pilot
study to evaluate the efficacy and role of single auto-logous blood
injection with single local corticosteroid injection for treatment
of lateral epicondylitis.
There are studies with more than one injection of auto-logous
blood and local corticosteroid in patients who had suboptimal relief
of symptoms after the initial injection.10,18,22,37,38 The
optimal interval between autologous blood injections is unknown,
but postulated to be six weeks, with up to three injections. The
time required to reach maximal benefit after the repeat injection
was on average shorter (one to two weeks) than after the initial injection
– possibly because the healing cascade was already underway.10,18 However, in this study the role
of only one injection of autologous blood or corticosteroid was
used, as the follow-up was limited to six months.
In our study group B showed a statistically significant decrease
in VAS score and Nirschl stage at one and four weeks compared with
group A. Hay et al30 found
similar results when local corticosteroid injection was compared with
oral naproxen.
At six months, we found that significantly more of group A had
complete relief of pain compared with group B (90% versus 47%,
p < 0.001). Edwards and Calandruccio10 found that 22 of 28 patients (79%)
were relieved completely of pain with autologous blood injections,
with the mean Nirschl stage decreasing from 6.5 to 2.0 at a mean
of 9.5 months.
38 described 72%
recurrence after three to six weeks on longer follow-up.
In conclusion, autologous blood injection demonstrated statistically
significant lower pain compared with corticosteroid injection group
at long-term follow-up (six months), with 90% of patients in this
group having complete relief of pain. Corticosteroid injection group showed
early decrease in pain compared to autologous blood injection group
but the short-term benefits of -corticosteroid injection were followed
by high rates of recurrence (Figs 2 and 3).
This study offers encouraging results of an alternative treatment
that addresses the pathophysiology of lateral epicondylitis, which
has failed to resolve with traditional nonsurgical modalities. We
feel with larger control trials with one or more than one injection
and with a longer -follow-up period, a fair conclusion can be drawn
with regard to the efficacy and otherwise of this treatment modality.

Question: Compared to 2 ml local corticosteroid + 1 ml 0.5% bupivacaine what was the result of 2 ml autologous blood drawn from contralateral upper limb vein + 1 ml 0.5% bupivacaine on pain at the 12-week and six-month follow-up?
Evidence: At the 12-week and six-month follow-up, autologous
blood injection group showed statistically significant decrease
in pain compared with corticosteroid injection group (12 weeks:
VAS p = 0.013 and Nirschl stage p = 0.018; six months: VAS p = 0.006
and Nirschl p = 0.006).
Answer: significantly decreased