Comparison of Different Dosages and Volumes of Triamcinolone in the Treatment of Stenosing Tenosynovitis: A Prospective, Blinded, Randomized Trial

Abstract

Background:

Stenosing tenosynovitis is a condition due to a size mismatch between the flexor tendons and the first annular pulley. Corticosteroid injection is the mainstay treatment. The purpose of this study is to compare different dosages and volumes of triamcinolone in the treatment of primary stenosing tenosynovitis.

Methods:

Patients with primary Quinnell grades 1 or 2 stenosing tenosynovitis were recruited in this prospective, blinded, randomized trial. Patients were randomized into 1 of 2 groups. Group A received 0.25 mL of triamcinolone 40 mg/mL, mixed with 0.25 mL of 1% lidocaine with epinephrine (10 mg of triamcinolone, 0.5 mL in total volume). Group B received 0.5 mL of triamcinolone 40 mg/mL, mixed with 0.5 mL of 1% lidocaine with epinephrine (20 mg of triamcinolone, 1 mL in total volume). Patients were assessed by a blinded hand therapist at 2 and 4 weeks, and by a blinded hand surgeon at 6 weeks. The primary outcome was complete symptom resolution at 6 weeks. Both per-protocol and intention-to-treat analyses were performed.

Results:

One hundred ninety-one patients were recruited from 2009 to 2018. Eighty-two and 77 patients had complete data in group A and B, respectively. There was no difference in success rates in complete symptom resolution at 6 weeks between group A (59.8%) and group B (62.3%). The mean visual analogue pain scores on injection were 4.31 ± 2.11 for group A and 4.30 ± 2.09 for group B.

Conclusions:

Triamcinolone 10 mg was as effective as 20 mg in the resolution of symptoms of Quinnell grade 1 or 2 stenosing tenosynovitis at 6 weeks.

Introduction

Stenosing tenosynovitis, also known as “trigger finger,” is a common hand condition due to a size mismatch between the flexor tendons and the first annular pulley. ^1,2 The flexor tendons get mechanically entrapped as they pass through the narrowed first annular pulley, causing pain and dysfunction. Patients may present with volar tenderness in the distal palm, snapping sensation with movement, decreased range of motion, or in more severe cases, a locked digit with fixed flexion contracture.

The Quinnell classification system is a tool, based on physical examination of the patient, used to grade the severity of stenosing tenosynovitis. ³ In grade 0, patient has an asymptomatic digit with normal range of motion. In grade 1, the patient has a history of volar tenderness at the first annular pulley associated with catching, but this is not demonstrable on examination. In grade 2, the patient has catching demonstrable on examination but is able to correct it with active extension. In grade 3, the patient either demonstrates catching that requires passive extension for correction or is unable to flex the digit. Finally, in grade 4, the patient presents with a fixed contracture of the proximal interphalangeal joint.

Local corticosteroid injection is the first-line treatment for stenosing tenosynovitis. The exact mechanism of action is unknown and may be beyond anti-inflammatory effects, as patients typically show degenerative, fibrocartilaginous metaplasia without histological evidence of inflammation at the first annular pulley. ⁴ There is a wide range of reported efficacy for corticosteroid injections, with success rates from as low as 47% ⁵ to as high as 84% to 92%. ^{6 -9} Several prospective studies and systematic reviews more consistently report success rates of around 60%. ^{10 -17} However, corticosteroid injections are less effective in patients with diabetes mellitus. ^{18 -20}

The optimal dosage and choice of a specific type of corticosteroid is unclear, because its clinical application is clouded by the paucity of comparative studies and the inconsistency of study designs in the literature. Specifically, the agent used, the control group, the defined outcomes, and the follow-up periods are not universally consistent. These factors translate into a wide variability in practice patterns regarding corticosteroid use among hand surgeons in North America. ^21,22

The objectives of this study were to determine whether there was a difference in resolution of symptoms at 6 weeks between 2 dosages of triamcinolone, and whether there was a difference in pain on injection between 2 volumes of injection. We hypothesized that lower dosage of triamcinolone (10 mg) was equally as effective as higher dosage (20 mg) and that lower volume of injection resulted in less pain on for the patient.

Materials and Methods

Study Design

A prospective, blinded, randomized study was conducted following ethics approval by the University of British Columbia Research Ethics Board (H09-00556). This trial was not registered.

Inclusion Criteria

Patients older than age 18, presenting with primary stenosing tenosynovitis of Quinnell grades 1 or 2, were recruited in the outpatient hand clinic at the Gordon and Leslie Diamond Health Care Centre in Vancouver General Hospital, British Columbia, Canada.

Exclusion Criteria

Patients with stenosing tenosynovitis of Quinnell grades 3 or 4, previous corticosteroid injection, previous first annular pulley release, rheumatoid arthritis, or diabetes mellitus were excluded.

Randomization and Treatment Groups

A certified hand therapist or the treating physician performed the initial screening. Following recruitment by informed consent, patients were randomized via coin toss into 1 of the 2 treatment groups. In group A, the low-dose group, patients received 0.25 mL of triamcinolone 40 mg/mL, mixed with 0.25 mL of 1% lidocaine with 1:100 000 epinephrine, which provided 10 mg of triamcinolone and a total injection volume of 0.5 mL. In group B, the high-dose group, patients received 0.5 mL of triamcinolone 40 mg/mL, mixed with 0.5 mL of 1% lidocaine with 1:100 000 epinephrine, which provided 20 mg of triamcinolone and a total injection volume of 1 mL. Both groups received the same concentration of the mixture.

Injection Technique

The non-blinded treating physician administered triamcinolone injections to the blinded patients. The same intra-sheath technique was performed in all patients. Three milliliter syringes and 18-gauge needles were used to withdraw the appropriate amount from the triamcinolone (40 mg/mL; Bristol-Myers Squibb) and lidocaine (1% with 1:100 000 epinephrine; AstraZeneca) vials. The injections were placed into the flexor sheath using a 1-inch 25-gauge needle after cleansing the palmar skin with an alcohol swab. Using the distal palmar crease as a surface landmark, the first annular pulley was identified by palpation. A 25-gauge needle was inserted through skin at a 45° angle, aiming toward the distal longitudinal axis of the digit at the first annular pulley. The needle was advanced through the subcutaneous tissue until it hit bone. The syringe was then aspirated and withdrawn slowly with simultaneous, gentle pressure over the plunger. The medication was delivered into the flexor sheath with loss of resistance over the plunger, avoiding intra-tendinous delivery.

Assessments and Follow-Ups

At the time of recruitment, patients’ demographics including age, gender, affected side, Quinnell grades of the involved digit, and duration of symptoms were recorded. Following triamcinolone injection, patients returned to the hand clinic to be assessed by a blinded certified hand therapist at 2 and 4 weeks and by a blinded attending hand surgeon at 6 weeks for final assessment. Quinnell grades and adverse events were recorded at follow-up visits.

Clinical Outcomes

Quinnell grades can be interpreted as a marker for recovery in stenosing tenosynovitis. Patients with Quinnell grade 0 digits at follow-up visits had complete recovery. Patients with initial Quinnell grade 2 digits, who presented at the final visits with Quinnell grade 1 digits, had partial recovery. Those who had unchanged Quinnell grades at the final visits had no recovery.

The primary clinical outcome of interest was the proportion of patients having complete resolution of symptoms, defined by Quinnell grade 0, at 6 weeks.

The secondary outcomes were pain scores on injection reported immediately after the injection by the patient on a visual analogue scale of 10, and the proportion of patients having partial resolution of symptoms at 6 weeks.

Statistical Analysis

Based on our null hypothesis that triamcinolone 10 mg was not inferior to 20 mg and that the success rate in the literature being around 60%, our sample size estimation required to provide 80% statistical power (α = .05, β = .2) to detect a 20% difference (Δ), if it existed, between the treatment groups was 75 patients per arm. Assuming for 30% loss to follow-up, we planned to enroll 190 patients. Both per-protocol and intention-to-treat analyses were used to eliminate bias.

The Student t test and the Mann-Whitney U test were used to analyze parametric and non-parametric continuous variables. The χ² test and Fisher exact test were used to analyze dichotomous and categorical variables. Statistical significance was set at P < .05.

Results

Between November 2009 and January 2018, a total of 191 patients were recruited. Ninety-five patients were randomized to the low-dose group (group A) and 96 to the high-dose group (group B). Accounting for 16.8% loss to follow-up, 82 and 77 patients had complete data for each group, respectively.

The demographics for both groups were comparable with no statistical differences (Table 1). The distributions between the trigger digits involved were comparable between the 2 groups (P = .06; Figure 1).

Table 1.

Demographics of Patients Recruited at the Outpatient Hand Clinic at the Gordon and Leslie Diamond Health Care Centre From November 2009 to January 2018.

	Group A low dose (N = 95)	Group B high dose (N = 96)	Significance
Age (years)	57.1 (±10.5)	56.4 (±12.9)	t = −0.10; P = .92
Gender (%female)	60 (63.2%)	52 (54.2%)	χ 2 = −1.59; P = .21
Affected side (%right)	56 (58.9%)	55 (57.3%)	χ 2 = −0.05; P = .82
Initial Quinnell Grade 1	28 (29.5%)	30 (31.3%)	χ 2 = −0.07; P = .79
Initial Quinnell Grade 2	67 (70.5%)	66 (68.8%)	χ 2 = −0.07; P = .79
Duration of symptoms (days)	324 (±571)	319 (±526)	t = −0.06; P = .95

Figure 1.

Distribution of trigger digits on presentation (1 = thumb; 2 = index finger; 3 = long finger; 4 = ring finger; 5 = small finger).

As illustrated in Table 2A, there was no difference in the distribution of final Quinnell grades at 6 weeks between the 2 groups with per-protocol analysis (P = .91). As for the primary outcome, there was no difference in success rate in complete resolution of symptoms at 6 weeks between group A (59.8%) and group B (62.3%) with per-protocol analysis (P = .75); similarly for the secondary outcome, there was no difference in the success rate in partial resolution of symptoms at 6 weeks between group A (26.8%) and group B (26.0%) with per-protocol analysis (P = .92; Table 3A). Similarly, intention-to-treat analyses showed no difference in these outcomes between the 2 groups (Tables 2B and 3B).

Table 2A.

Patients’ Quinnell Grades at 6 Weeks (Per-Protocol Analysis).

Final Quinnell Grades	0	1	2
Group A low dose (N = 82)	49 (59.8%)	26 (31.7%)	7 (8.5%)
Group B high dose (N = 77)	48 (62.3%)	22 (28.6%)	7 (9.1%)
			Fisher exact test: P = .91

Table 3A.

Patients’ Response to Triamcinolone Injection at 6 Weeks (Per-Protocol Analysis).

Recovery	Full recovery (Quinnell 0)	Partial recovery (Quinnell 2 to 1)	No recovery (Initial Quinnell 1)	No recovery (Initial Quinnell 2)
Group A low dose (N = 82)	49 (59.8%)	22 (26.8%)	4 (4.8%)	7 (8.5%)
Group B high dose (N = 77)	48 (62.3%)	20 (26.0%)	2 (2.6%)	7 (9.0%)
	Fisher exact test: P = .75	Fisher exact test: P = .92

Table 2B.

Patients’ Quinnell Grades at 6 Weeks (Intention-to-Treat Analysis).

Final Quinnell Grades	0	1	2
Group A low dose (N = 95)	49 (51.6%)	30 (31.6%)	16 (16.8%)
Group B high dose (N = 96)	48 (50.0%)	29 (30.2%)	19 (19.8%)
			Fisher exact test: P = .87

Table 3B.

Patients’ Response to Triamcinolone Injection at 6 Weeks (Intention-to-Treat Analysis).

Recovery	Full recovery (Quinnell 0)	Partial recovery (Quinnell 2 to 1)	No recovery (Initial Quinnell 1)	No recovery (Initial Quinnell 2)
Group A low dose (N = 95)	49 (51.6%)	22 (23.2%)	4 (4.2%)	7 (7.4%)
Group B high dose (N = 96)	48 (50.0%)	20 (20.8%)	2 (2.1%)	7 (7.3%)
	Fisher exact test: P = .89	Fisher exact test: P = .73

The data were fitted into a logistic regression model to determine whether there was a significant treatment effect between the 2 groups. The odds for each group were calculated as ratio of having full recovery versus not having full recovery. These were 1.48 (49/33) in group A and 1.66 (48/29) in group B. The odds ratio was 0.9, which meant the odds of having full recovery versus not having full recovery were 10% higher in the high-dose group but was not statistically significant (95% CI = 0.47-1.70, P = .74). The odds ratio was similar at 0.89 when adjusted for initial Quinnell grades (95% CI = 0.45-1.76, P = .75).

Figure 2 shows that there was no difference in the distribution of visual analogue pain scores between lower and higher volumes of injection (P = .90). The mean visual analogue pain scores on injection were 4.31 ± 2.11 for group A and 4.30 ± 2.09 for group B.

Figure 2.

Distribution of visual analogue pain scores on injection.

There were 13 (6.8%) total adverse events reported in the study: 8 (4.2%) were corticosteroid flare reactions and 4 (2.1%) were skin or fat atrophy. Two patients in group A and 6 patients in group B reported having corticosteroid flare reactions that were self-limiting. One patient in group A and 3 patients in group B had skin or fat atrophy; these were identified at the final 6-week follow-up assessment.

Discussion

In an American Society for Surgery of the Hand member survey, triamcinolone was the most used corticosteroid. ²¹ This is also the senior author’s preference, because of its longest lasting effect from its low solubility. ²³ The variability of dosage used by North American surgeons is vast. The rationales of adding a local anesthetic are to relieve patient’s symptoms and to distribute the corticosteroid along the flexor sheath. Some also suggest that it serves diagnostic value of differentiating local pain from referred pain of other pathologies. ²⁴

Our study showed that triamcinolone had an 85% success rate in improving symptoms and 60% in resolving symptoms of stenosing tenosynovitis at 6 weeks; these were comparable to reported success rates by several level I evidence, placebo controlled studies. Lambert et al compared methylprednisolone plus lidocaine versus lidocaine alone in 41 patients and found that 60% had complete resolution of symptoms at a month in the corticosteroid group compared with 16% in the placebo group. ²⁵ Murphy et al compared betamethasone plus lidocaine versus lidocaine alone in 24 patients and found that 64% had complete resolution of symptoms at 4 months compared with 20% in the placebo group. ¹⁰ Peters-Veluthamaningal et al compared triamcinolone versus saline injection in 50 patients and found that 64% had complete resolution of symptoms at 3 weeks compared with 20% in the placebo group. ¹³ As illustrated, the reported duration of follow-up can be varied and should be interpreted with caution.

In this study, we arbitrarily chose 6 weeks as the final assessment period, because we were interested in the primary effect of a single triamcinolone injection in treating stenosing tenosynovitis. It generally takes several weeks to observe the optimal onset of corticosteroid injections. It is less likely that triamcinolone exerts additional benefits beyond this time frame. ¹² In fact, Sheikh et al showed that giving a staged, additional triamcinolone injection at 6 weeks regardless of symptoms did not improve success rates. ²⁶ It is beyond the scope of this study to comment on recurrence rates, because a study with much longer follow-up periods would be necessary.

In order to eliminate bias, it is recommended that both per-protocol and intention-to-treat analyses to be included in a non-inferiority trial, and that non-inferiority should be confirmed only if both analyses show no differences. ²⁷ Our analyses confirmed our hypothesis that triamcinolone 10 mg was not inferior to the 20 mg in treating Quinnell grades 1 or 2 digits. Nevertheless, intention-to-treat analysis could potentially under-estimate the success rates of triamcinolone, because patients lost to follow-up likely had positive clinical outcomes without requiring further interventions.

Multiple dosages of triamcinolone have been studied in the literature: 5, 10, 20, or even as high as 40 mg; ^6,12,15,28 however, to date, there is only one head-to-head study that compared different dosages of triamcinolone in the treatment of stenosing tenosynovitis. In their randomized controlled trial of 120 patients, Kosiyatrakul et al compared the use of 5, 10, and 20 mg triamcinolone and found no difference at 6 weeks; however, they observed that there was a dose–response characteristic with the 20 mg group having significantly higher success rates at 3 and 6 months. ²⁹ This study was limited by the lack of power analysis. The difference in dose–response may be contributed by the inclusion of patients with Quinnell grade 3 digits. The success of corticosteroid injection decreases with increasing severity, ³⁰ and Quinnell grades 3 or 4 digits may indeed require higher dosages or even surgery as the initial treatment.

A good treatment principle is to achieve satisfactory clinical outcomes using the minimally effective dose with tolerable safety profiles. The adverse events in this study were low. Previous studies have reported that corticosteroid flare, a reaction due to inflammatory reaction to ester crystals, can be up to 25% to 33% ^23,31 ; our study population had a much lower, 4.2% incidence of corticosteroid flare reactions. The duration of this study was, however, not long enough to reasonably generate conclusions on the incidence of skin or fat atrophy. The literature suggests that there is no difference in success rates between extra-sheath and intra-sheath injection techniques. ^{32 -34} Since the depth of injection is inversely related to subcutaneous atrophy, ^2,35 we prefer using the intra-sheath technique to minimize this risk. There were no reported serious adverse events such as tendon ruptures or deep tissue infection in this study. Case reports of tendon ruptures had occurred in patients who received triamcinolone 40 mg and in a patient who received 7 corticosteroid injections ^36,37 ; this adverse event had also occurred atypically in a patient receiving triamcinolone 20 mg. ³⁸ To optimize safety margins, it may be prudent to consider using triamcinolone 10 mg as the initial treatment for Quinnell grade 1 or 2 digits, as our study showed that it is just as effective.

Our hypothesis that higher total volumes with associated sheath distension causing more pain on injection was disproved. We observed no difference in pain on injection between the 2 injection volumes. Our mean visual analogue pain scores on injection of 4.3 were equivalent to a previous study that investigated on the predictors on pain on injection in stenosing tenosynovitis. ³⁹ Julka et al found that there are multiple factors, including expected pain, heightened illness concern, catastrophic thinking, depression, physician, and female gender, which correlated with immediate pain on injection. Interestingly, in our subgroup analysis, we found that females reported higher mean pain scores than males in the high-dose group only (5.0 vs 3.5; P < .01). The significance of this is unclear.

In our study, the concentrations of the mixtures were controlled in both groups. Potential ideas for future research are to examine whether lowering volumes of the same dosage, or lowering dosages while maintaining the same volume would improve adverse event profile.

There are several limitations of this study. Using coin toss as a randomization method may produce unbalanced allocation; a better approach to ensure equal numbers in each treatment arm may be to use computer generated blocked randomization. Moreover, there are other important clinical information that are beyond the scope of this study, which include the clinical trajectory of those with partial improvement beyond 6 weeks, the difference in recurrence rates between the groups beyond 6 weeks, and the effect of multiple injections in symptom resolution.