Comparing the Efficacy of Intralesional Triamcinolone Acetonide With Verapamil in Treatment of Keloids: A Randomized Controlled Trial

Background Keloid management remains a challenging clinical problem despite numerous therapies reported until now. The efficacy of corticosteroids in the treatment of keloids has been well established. The most commonly used corticosteroid is intralesional triamcinolone. Sporadic reports on the use of intralesional verapamil suggest its efficacy. Aim Since there is not sufficient evidence to support the role of intralesional verapamil as an effective alternative modality, it was decided to undertake a randomized study to determine its efficacy as a treatment for keloids. Methods A randomized, single-blind, single-group comparison with 15 patients (30 scars) was carried out to compare the effects of intralesional triamcinolone with verapamil injections. Injections were scheduled every 3 weeks accompanied by cryotherapy until complete flattening of the scar or maximum 8 sessions, whichever came earlier. Scar evaluation at each stage was done by serial photographic records as well as by Vancouver scar scale. Statistical analysis was done by Wilcoxon and Mann-Whitney U tests using SPSS version 19. Results In both study groups there was a reduction in height and pliability at the end of the study. Better improvement in height and pliability was seen with triamcinolone in comparison with verapamil. However, a desired change in vascularity and pigmentation was not seen with either of the drugs. Conclusion Verapamil is not as effective as triamcinolone in the treatment of keloids.

ake a randomized study to determine its efficacy as a treatment for keloids.Methods:A randomized, single-blind, single-group comparison with 15 patients (30 scars) was carried out to compare the effects of intralesional triamcinolone with verapamil injections.Injections were scheduled every 3 weeks accompanied by cryotherapy until comple e flattening of the scar or maximum 8 sessions, whichever came earlier.Scar evaluation at each stage was done by serial photographic records as well as by Vancouver scar scale.Statistical analysis was done by Wilcoxon and Mann-Whitney U tests using SPSS version 19.Results: In both study groups there was a reduction in height and pliability at the end of the study.Better improvement in height and pliability was seen with triamcinolone in comparison with verapamil.However, a desired change in vascularity and pigmentation was not seen with either of the drugs.Conclusion:Verapamil is not as effective as triamcinolone in the treatment of keloids.

of prior treatment with any intralesional injections were excluded from the study.

The minimum sample size of 15 patients with at least 2 scars (30 scars) was calculated for this trial, where triamcinolone was considered as the standard treatment and verapamil was reg rded as the experimental drug.Fifteen consecutive patients who fulfilled our inclusion criteria entered the study using simple randomization technique.

Two similar keloid scars of each patient w re randomly selected, using simple randomization by random number table.Deciding on putting which lesion into which therapeutic arm was randomly made by flipping a coin.A lidocaine

injecti
n with ring block technique was used to anaesthetize the site of injection before starting the treatment.The injections were made with an insulin syringe, 27-gauge needle.

One of the scars received intralesional TAC (Exir Pharmaceutical Co, Borujerd, Iran), while the other received intralesional verapamil hydrochloride (Verahexal, Knoll AG,

udwigshafen,
ermany) every 3 weeks for a maximum of 8 sessions or until complete flattening of the scar.Each intralesional session was preceded by cryotherapy using cryospray technique for 20 seconds at 1 cm distance from the lesion.The maximum volume of triamcinolone (20 mg/ mL) and verapamil (2.5 mg/mL) at each session was 1.5 cc.


We used multiple intralesional injections


Results


Introduction

Characterized by firm, tender nodules or plaques, keloids occur more frequentl on shoulders, chest, neck, upper arms, and face [1].They are benign overgrowth of fibrous tissue, usually developing after healing of a skin injury due to trauma, inflammation, surgery, or burns and extend beyond the original defect [2].The uncontrolled growth of keloids can lead to cosmetic disfigurement and functional impairment, which might adversely affect the quality of life [3].

A variety of treatment modalities such as silicone gel s eeting, intralesional injections, surgical manipulation, laser, and radiotherapy have been used, but no particular treatment has been shown to be effective for all cases [4].Drugs like bleomycin and 5-fluorouracil have better efficacy, but they are costly and cause severe drug reactions.Surgery and laser therapy have their own limitations, while radiotherapy can cause malignancy [5].

Corticosteroids seem to be effective in the treatment of keloids as they diminish collagen and glycosaminoglycan synthesis, inhibit fibroblast growth, e hance collagen and fibroblast degeneration, and have a powerful anti-inflammatory effect.Triamcinolone acetonide (TAC) is the most commonly used intralesional corticosteroid for keloid treatment.TAC is cost-effective and practical and has become first-line treatment for keloids, in spite of some local adverse effects such as dermal atrophy, telangiectas a, and hypopigmentation [2].

It has been demonstrated that calcium channel blockers decrease extracellular matrix production in scars.Furthermore, they depolymerize actin fila

nts to m
dify fibroblast morphology by a consequent increased secretion of pro-collagenase [6].Intralesional verapamil hydrochloride has already been successfully applied for the treatment of keloids [7].

This study was hence conducted to assess the efficacy of intralesional ve apamil in the treatment of keloids by its comparison with the effects of intralesional triamcinolone.


Methods

The


Discussion

Despite numerous developed therapies, keloid treatment has remained a challenging clinical problem.This might be due to the fact that the mechanisms of development of keloids have not been completely understood [9].Laser therapy, surgical removal, radiation therapy, silicone gel, cryosu gery, intralesional injection of various agents, and occlusive dressing have all been used either alone or in various combinations [10].

However, evolution of different therapies has not significantly improved their success rates.In addition, each method has its own limitations such as high cost, poor efficacy, recurrence, and adverse effects (such as malignancy).

The VSS parameters for both treatment groups are presented in Table 1.At the beginning of the s udy, there was no significant difference in parameters of the 2 groups (P > 0.05).In both study groups, there was a reduction in height and pliability at the end of the study as determined by Wilcoxon test (Table 2).Using Mann-Whitney U test, statistically better improvement in height and pliability was observed in the triamcinolone-receiving group compared with the verapamil-receiving group (P < 0.001).However, a desired change in vascularity and pigmentation was not seen with either of the drugs (Table 2).Scar vascularity became worse in  3).No significant difference was detected in vascularity and pigmentation in the 2 groups (P > 0.05).

The changes in VSS score parameters within 24 weeks of follow-up in both groups are shown in Figure 1.

production.They suggested that calcium antagonists depolymerize acti filaments and alter the shape of fibroblast cells from bipolar to spherical, which may result in increased procollagenase production [12].

Shan hi et al showed a reduction in vascularity, pliability, and height of the scars with both triamcinolone and verapamil injections [5].It has also been found that this reduction is faster by triamcinolone injection.However, a desired change in pigmentation was not observed with either of the drugs.They found that similar to triamcinolone, verapamil significantly improved the clinical parameters of the scars;

Keloids are overgrowth of dense fibrous tissue developing after trauma to the skin [11].Although the basis of keloid formation has not been fully understood, an imbalance of matrix degradat

n and collag
n biosynthesis, which could result in excess accumulation of collagen in wound, has been considered the primary biochemical feature of these skin lesions [10].Furthermore, inflammation or alteration of growth factors may contribute to keloid formation [11].

As cellular secretion of macromolecules is known to be a calcium-dependent process, Lee and Ping in 19

examined the ef
ects of calcium antagonists on extracellular matrix compare with those treated with verapamil.In contrast to studies of Shanthi et al [5] and Ah ja and Chatterjee [6], the scars of both groups in our study did not reach complete flattening and normal pliability at the end of the study.The possible reason could be the higher initial mean scores of height and pliability in both groups relative to the mentioned studies.However, no significant difference was found in the pigmentation of the scars before and fter treatment in both groups.It could be due to the fact that most of the scars had normal pigmentation at the beginning of our study.This finding is compatible with previous tudies.

However, in contrast to previous works, scar vascularity did not show significant difference with both treatments at the end of our study [5,6].

The results of the present study suggest that verapamil can be considered a saf