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| ORIGINAL ARTICLE |
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| Year : 2013 | Volume
: 27
| Issue : 2 | Page : 86-91 |
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Long-term safety and efficacy of intralesional injection of triamcinolone acetonide for sternal keloid pain and pruritis: A double-blind comparison of two concentrations
Babita Ghai1, Dipika Bansal2, Shyam KS Thingnam3
1 Department of Anaesthesia and Intensive Care, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Pharmacy Practice, Clinical Research Unit, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India
3 Department of Cardiothoracic and Vascular Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| Date of Web Publication | 4-Oct-2013 |
Correspondence Address:
Babita Ghai
Department of Anaesthesia, PGIMER, Sector 12, Chandigarh- 160 012
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0970-5333.119342
Background: Intralesional injection of triamcinolone acetonide (TAC) is the most frequently used treatment modality for keloids or hypertrophic scars. However, 20 mg/mL, triamcinolone is reported to have 50% incidence of adverse sequelae. We compared the long-term safety and efficacy of 10 mg/mL with 20 mg/mL intralesional injection of TAC on sternal keloid pain. Methods: Thirty adult patients presenting with pain and/or pruritis at sternal keloid site were randomized into one of the two groups. In group T20 patient received 1 mL of 20 mg/mL TAC, whereas in group T10 patients received 1 mL of 10 mg/mL of TAC intralesional every 2 weeks for a total of 3-4 treatments. Visual analog scale (VAS) scores for pain and pruritis, keloid/scar height, and any adverse sequelae were recorded at 2 weeks interval till 2 months and then at 6, 12, and 15 months. Primary outcome of the study was the percentage of patient developing side effects. Secondary outcome measures were VAS score for pain and itching, keloid height, and recurrence rate of pain or itching. Results: There was a significant decrease in VAS score for pain, pruritis, and keloid height after drug administration in both groups. Side effects was observed in 6 (40%) patients in group T20 and 1 (6.7%) patients in group T10 (P = 0.04). Two patients (13.3%) in group T20 and one in group T10 (6.7%) did not have any improvement in their pain/pruritis scores. Recurrence rate was 13.3% (2 patients) in T20 group compared with 20% (3 patients) in group T10 at 15 months after initial response. Conclusion: Intralesional injection of TAC in concentration of 10 mg/mL is as efficacious as 20 mg/mL for sternal keloid pain but is associated with significantly less side effects. Keywords: Chronic pain, intralesional triamcinolone, sternal keloid
How to cite this article:
Ghai B, Bansal D, Thingnam SK. Long-term safety and efficacy of intralesional injection of triamcinolone acetonide for sternal keloid pain and pruritis: A double-blind comparison of two concentrations. Indian J Pain 2013;27:86-91 |
How to cite this URL:
Ghai B, Bansal D, Thingnam SK. Long-term safety and efficacy of intralesional injection of triamcinolone acetonide for sternal keloid pain and pruritis: A double-blind comparison of two concentrations. Indian J Pain [serial online] 2013 [cited 2023 Apr 2];27:86-91. Available from: https://www.indianjpain.org/text.asp?2013/27/2/86/119342 |
| Introduction | |  |
Keloids and hypertrophic scar are benign fibrous dermal tumors that usually result from excessive and abnormal response to a skin trauma. [1],[2] Keloids and hypertrophic scars occur predominantly in areas of high skin tension and on the chest wall. The specific sites of the body more likely to develop keloid or hypertrophic scar are the presternum, pectoral area of the chest, upper back, lower face, ears, neck, and outer (deltoid) area of the upper arms. [2] The highest incidence of pathological scarring is reported on the ventral side of the trunk (presternal area, 75%). [3] African Americans and Asians are affected more often than Caucasians. [4] Dark-skinned populations have a higher occurrence of keloids than light-skinned populations, but the reported incidence ratio between the two groups ranges from 2:1 to 19:1. [4] In younger age groups and female patients, keloids are found more often in multiple anatomical sites. [5]
Median sternotomy hypertrophy or keloid scarring is prevalent among cardiac surgical patients. The incidence is reported to be approximately 30% in Caucasians and greater than 50% in the Asian population. [6] Scar hypertrophy is most likely in that part of the scar overlying the body of the sternum. Scar stretching occurs most frequently in the lower third of the scar overlying the xiphisternum. [3]
Keloids and hypertrophic scars lead to pruritus, burning, tingling, dysesthesia, or pain, as well as restricted mobility in addition to cosmetic disfigurement. [7] Therefore, these conditions have a direct and indirect effect on the quality of life. [3] The presternal hypertrophic scars are most of the time nonvisible scar, hence frequent presentations of these patients are pain, itching, and allodynia rather than cosmetic disfigurement.
There are several treatment options with varied rate of success. [1],[8] Most of these have focused on the regression or eradication and cosmetic improvement of these scars. Studies concentrating on the pain and pruritis management are limited.
One of the long-term standards of keloid therapy, and the most commonly used therapeutic modality, is the injection of triamcinolone acetonide (10-40 mg/mL). [2],[9],[10],[11],[12],[13]
When used alone for the treatment of keloid in concentration of 20 mg/mL, triamcinolone is reported to have 50% incidence of adverse sequelae such as telangiectasia, hypopigmentation, and skin atrophy persisting for 32 weeks. [2] The side effects are considered related to the concentration. [9] We hypothesize that lower concentration may reduce these side effects. Hence, we conducted this study to compare long-term efficacy and safety of 10 mg/mL solution with 20 mg/mL intralesional injection of triamcinolone acetonide on the sternal keloid pain. To the best of our knowledge, we found no randomized controlled trial in the literature comparing these two concentrations of triamcinolone for sternal keloid pain treatment.
| Material and Methods | | |
This was a prospective, randomized, and double-blind study. After obtaining ethics committee approval and written informed consent, 30 adult patients (aged 18-60 years) with a clinical diagnosis of sternal/presternal keloid for at least 6 months to 1 year following various open cardiac surgeries presenting with pain and/or pruritis at only one site of keloid were included. A keloid was defined as a well-demarcated area of fibrous tissue overgrowth, which extended over the margins of the original injury. The study was conducted during January 2008 to July 2010.
Patients with a history of any disease associated with neuropathy such as alcoholism, postherpetic neuralgia, HIV infection, hypothyroidism, or diabetes were excluded. Those with any form of eczema within a 5-cm radius of their keloid were also excluded. The study was approved by the institute ethics committee and written informed consent was obtained from patients. All patients had been receiving their routine cardiac medications and did not receive any systemic steroid therapy for at least 7 days before the study, and had not had any treatment for the keloids (eg, intralesional corticosteroids, cryotherapy, topical medicaments, or silica gel sheet application) for 4 weeks before the study session.
Patients were asked to rate, on visual analog scale (VAS) of 0-10 cm, their worst pain, and itch intensity experienced from the keloid during the last 2 weeks (baseline VAS). The severity ranged from no pain or no itch at one end of the line (severity = 0), to maximal pain or itch at the other end (severity = 10). Patients were asked to mark the areas where they felt pain and pruritis.
Patients were randomized into one of the two groups, that is, group T20 or group T10 using a computer-generated randomization list (n=15 for each group). A computer-generated random number was obtained using block of six and kept in opaque sealed envelopes. Envelope was opened by an independent assistant not involved in the study, who prepared the study drugs. The investigators and patients were unaware of study drug concentration.
The study drugs were prepared in two groups as follows:
In group T 20: 0.5 mL of 40 mg/mL of triamcinolone acetonide and 0.5 ml of 2% lignocaine (total of 1 mL). Hence, the final concentration was 20 mg/mL of triamcinolone acetonide in 1% lignocaine.
In group T10 0.5 mL of 20 mg/mL of triamcinolone acetonide and 0.5 mL of 2% lignocaine (total of 1 mL). Hence, the final concentration was 10 mg/mL of triamcinolone acetonide in 1% lignocaine.
In groups T20 the patients received 1 mL of 20 mg/mL (mixed with 1% lignocaine) intralesional triamcinolone acetonide, every 2 weeks for a total of 3-4 treatments.
In group T10 patients received 1 mL of 10 mg/mL (mixed with 1% lignocaine) of intralesional triamcinolone acetonide, every 2 weeks for a total of 3-4 treatments.
No topical anesthesia was used.
The injection technique involved injection into the center of keloid/scar using an insulin syringe with an integral 26G needle. Extreme care was taken not to inject drug subcutaneously.
Scar height was measured for the area under the study. A dial caliper was used to determine the scar height by measuring the maximum vertical elevation above the normal skin. The mean of three measurements was recorded.
Assessment of Response and Follow Up
Patients were asked to keep a diary for pain and pruritis. VAS score for pain and pruritis, keloid/scar height, and any adverse sequelae, including hypopigmentation, telangiectasia, or skin atrophy were recorded at 2 weeks interval till 2 months and then at 6, 12, and 15 months. No improvement in VAS score of pain after four injections was considered failure of treatment.
Primary outcome of the study was the percentage of patient developing side effects. Secondary outcome measures were VAS score for pain and itching, keloid height, and recurrence rate of pain or itching.
Statistical Analysis
The incidence of side effects of 20 mg/mL triamcinolone intralesional injection is reported to be 50%. [9] We hypothesized that reducing the concentration to 10 mg/mL may reduce the incidence of side effects. In the absence of available published data comparing these two concentrations of triamcinolone, the statistician of our institution suggested initially to recruit 16 patients (eight in each group), with an intermediate step of calculation and randomization. The results of pilot study suggested that four (50%) patients developed side effects in T20 group compared with one (12.5%) patient in group T10. A reduction in the incidence of side effects from 50% to 10% was considered as clinically meaningful reduction justifying concentration of TAC reduction. Assuming one-tailed 5% significance level (α = 0.05) and power of 80% (β = 0.20) to detect a reduction from 50% to 10% in side effects, a sample size of 14 patients in each group was required after applying Yates continuity correction. We recruited 30 (15 in each group) patients for the study for possible dropout.
Statistical analysis was performed using the SPSS version 10.0 for windows (SPSS Inc., Chicago, IL, USA). Data were inspected for distribution. Demographic data were analyzed using Student's t test (continuous data) and Fischer's exact test (categorical variable). Serial changes in VAS scores of pain, pruritis, and keloid height were analyzed using two-way repeated measures analysis of variance (ANOVA). In this analysis, the independent (qualitative) variable was defined as patient group, and the dependent variable (quantitative) was defined as VAS scores for pain, pruritis, and keloid height recorded repeatedly over times for each subject. Data were tested for normality using Kolmogorov - Smirnov test, for homogeneity of between-groups variance using the Levene's test, and for sphericity using the Mauchly test. If the Mauchly test was significant indicating violation of the assumption of sphericity, we used the Greenhouse - Geisser test with adjustment. We used the univariate approach to analyze within subject effects. Paired Student's t test was used to compare baseline VAS for pain, pruritis, and keloid height to these values at different time intervals. Bonferroni adjustments were carried out to take into account type 1 error for multiple comparisons. Where treatment failure occurred, data were analyzed as if treatment has been delivered (intention-to-treat analysis).
The results are presented as mean (standard deviation), median (range), or number of patients as appropriate. A P value of <0.05 was considered significant.
| Results | | |
Patient's demographic and baseline data were comparable with respect to age, gender, weight, duration of sternal keloid, duration of pain, and baseline VAS scores for pain and pruritis [Table 1].
The mean follow-up period of patients was 14.33 ± 1.40 months in group T20 and 15.13 ± 2.07 months in group T10 (P > 0.05, Student's t test).
Baseline VAS scores for pain and pruritis were comparable between the two groups [Table 1]. Two patients (13.3%) in group T20 and one in group T10 (6.7%) did not have any improvement in their pain/pruritis scores and were considered failure of treatment. They were advised alternative treatments after 3 months of follow up.
Side effects were observed in 6 (40%) patients in group T20 and one (6.7%) patient in group T10 (P = 0.04, Fischer's exact test). The side effects were hypopigmentation in two patients in T20 group and one patient in T10 group, hypopigmentation with skin atrophy in one patient in group T20 and telangiectasia in 3 patients in group T20, which appeared between 2 and 4 months and lasted for 6-12 months.
Serial changes of pain, pruritis, and keloid height over time are shown in [Figure 1], [Figure 2] and [Figure 3]. Results of two-way repeated ANOVA analysis showed no major violation of assumptions of normality and homogeneity of between-group variance. However, for each, that is, pain, pruritis, and keloid height, Mauchly test of sphericity was significant, and therefore, the Greenhouse - Geisser adjustment was applied. Analysis results showed a drug - time interaction for pain, pruritis, and keloid height in both the groups; however, there was no difference between the groups. There was a significant decrease in VAS score for pain, pruritis, and keloid height after drug administration in both the groups. A significant decrease in VAS for pain started at 2 weeks, continued till 6 weeks, and remained static till the end of study thereafter. Significant decrease in VAS for pruritis started at 4 weeks, continued till 8 weeks, and remained static till the end of study thereafter. A significant decrease in keloid height was noted at 6 weeks, continued to decrease till the end of the study thereafter. | Figure 1: Mean visual analog scale (VAS) scores for pain at various time intervals. Baseline indicates pretreatment VAS for pain. Other time intervals indicate posttreatment time. Error bar indicates standard deviation (SD).*Indicate P < 0.05 from the baseline (paired t test), within group comparisons.
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 | Figure 2: Mean visual analog scale (VAS) scores for pruritis at various time intervals. Baseline indicates pretreatment VAS for pruritis. Other time intervals indicate posttreatment time. Error bar indicates standard deviation (SD).*Indicate P < 0.05 from the baseline (paired t test), within group comparisons.
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 | Figure 3: Keloid height at different time intervals. Baseline indicates pretreatment keloid height. Other time intervals indicate posttreatment time. Error bar indicates standard deviation (SD). *Indicate P < 0.05 from the baseline (paired t test), within group comparisons.
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At 12-month follow-up, one (6.7%) patient in group T20 and two (13.3%) patients in group T10 had recurrence of pain after initial response. At 15 months recurrence rate was 13.3% (two patients) in T20 group compared with 20% (3 patients) in group T10.
With regard to patient satisfaction and complaints, 73.3% (11/15) in both groups have currently no pain and irritation at the keloid site. Sixty percent (nine patients) in each group reported to have improvement in their choice of clothing and could wear tight clothes on chest without experiencing pain or pruritis.
| Discussion | | |
Patients suffering from keloids and hypertrophic scars demonstrate a severe impairment of quality of life. Pain, pruritis, and restriction of mobility associated with keloid correlate with the impairment of quality of life. [3] In the last few years, many different treatments have been described, both medical and surgical, but no modality has been completely successful. [1] The simple surgical excision results in recurrence rate varying from 50% to 80%. [8] Medical options including physical modalities, such as pressure after surgery, laser therapy, silicone gel sheeting, or the intralesional use of interferon, retinol acid, or 5-flurouracil and also the use of medical agents, including immune response modifiers, [1] are reported with varying degree of success. Most of these therapeutic modalities are focused on the cosmetic improvement. The sternal keloid lesions are usually quite painful and the patient is often seeking pain relief more than cosmetic repair. [14]
One of the long-term standards of keloid therapy, and the most commonly used therapeutic modality, is the injection of triamcinolone acetonide (10-40 mg/mL). [2],[9],[10],[11],[12],[13] The concentration of 20 mg/mL triamcinolone injection is reported to have 50% incidence of adverse sequelae such as telangiectasia, hypopigmentation, and skin atrophy persisting for 32 weeks. [2]
In this study, we compared the efficacy and side effects of intralesional injection of triamcinolone 10 mg/mL with 20 mg/mL concentration for sternal keloid pain and pruritis.
The results of the current study suggest that intralesional triamcinolone injection of 10 mg/mL is as effective as 20 mg/mL for the treatment of sternal keloid pain and pruritis but is associated with significantly less side effects.
In our study, 20 mg/mL intralesional injection of TAC was associated with 40% incidence of side effects, which is comparable with previously reported incidence of 50%. [2] We followed our patients till approximately 15 months and noted a recurrence rate of 6.7% in group T20 and 13.3% in group T10 at 12 months with 13.3% and 20% recurrence rate in group T20 and T10, respectively, at 15 months after initial response. Intralesional injection of corticosteroids previously has been reported to have a 5-year response rate around 50%. [15]
We found 73% and 86% female patients in our study with a mean age of 36 and 37 years in group T20 and T10, respectively. This is in contrast to previous studies where a higher incidence has been reported in males (68%) with higher mean age (61 years) of sternal keloids. [16] This could be because of high prevalence of rheumatic heart disease in India affecting young females. The majority of open heart operations performed in our hospital is valve replacement for rheumatic heart disease. Most of the patients in our study were postoperative cases of valvular heart disease. However, the mean age of our study correlates with the mean age mentioned by Bock et al., for keloids (36.1 years). [3]
Sixty percent (nine patients) in each group reported to have improvement in their choice of clothing and could wear tight clothes on chest without experiencing pain or pruritis; and led to major change in the clothing being chosen by these patients.
In conclusion, intralesional injection of triamcinolone acetonide in concentration of 10 mg/mL is as efficacious as 20 mg/mL for sternal keloid pain, pruritis, and keloid height reduction but is associated with significantly less side effects.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1]
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