Comparison of Effectiveness of Intralesional Triamcinolone Acetonide with Fractional CO2 Laser Against Intralesional Triamcinolone Acetonide with Intralesional Verapamil in the Treatment of Keloids

Abstract

Background:

Keloids are benign overgrowth of fibrous tissue extending beyond the original wound margin. The management of keloids remains challenging despite the various treatments available. Studies have shown that combination therapies are superior to monotherapy.

Aim and Objective:

To compare the effectiveness of intralesional triamcinolone acetonide with fractional CO2 laser against intralesional triamcinolone acetonide with intralesional verapamil in treating keloids.

Patients and Methods:

This study included 24 patients with single or multiple keloids. After obtaining consent, 12 patients each were allocated to either fractional CO2 with intralesional triamcinolone group (Group 1) or intralesional verapamil with intralesional triamcinolone group (Group 2). Keloid scars were assessed and scored according to the Vancouver scar scale (VSS) during each visit with serial photographs. The procedures were repeated at an interval of four weeks for a total of four sittings and participants were followed up for another six months.

Results:

Both groups showed significant improvement in the clinical appearance of keloids. The overall response was better in Group 2. In VSS assessment, there was a faster and better rate of reduction in height with Group 2. Pliability and vascularity improved significantly and none had recurrences of keloid till the end of the study in both groups.

Limitations:

Limitations of the study are the small sample size and short duration of follow-up.

Conclusion:

Both the combination groups are safe and efficacious methods to treat keloid. Intralesional verapamil with triamcinolone showed better and faster clinical improvement compared to fractional CO2 laser with intralesional triamcinolone.

Introduction

Keloid is a benign dermal fibroproliferative disorder occurring as a result of abnormal fibrous tissue proliferation and excessive collagen production in response to various ranges of cutaneous injury. They can occur anywhere in the body but are more common in areas with increased skin tension, such as the chest, upper back, shoulders, and in earlobes. Keloids usually occur in the younger age group, around 10 to 30 years.[1] It can have a negative psychosocial impact on the patients because of its esthetically disfiguring appearance besides symptoms like pain, pruritus, discomfort, and sometimes decreased range of movement. They are microscopically characterized by excess deposition of thickened collagen and extracellular matrix in the dermis. Keloids are very difficult to treat and a challenge for both patients and treating physicians because of their low response to treatment and frequent recurrences. Currently, there are various modalities of treatment for keloids, but to date, no modality of treatment has been known to fully clear keloids, and most show ranges of side effects with high recurrence rates.

The aim of this study was to compare the effectiveness of intralesional triamcinolone acetonide with fractional CO2 laser against intralesional triamcinolone acetonide with intralesional verapamil in the treatment of keloids.

Patients and Methods

The study was a prospective interventional study conducted over a period of 18 months in the Department of Dermatology, at a Tirunelveli Medical College and Hospital, Tamil Nadu after approval of the protocol by Institutional research ethics committee (vide reference no:1914/DVL/2021 dated April 2021). The study included patients with keloids of age 18 years and above till 60 years, irrespective of gender, with duration of ≤5 years, lesion size up to 5 cm² and height up to 6 mm, who had not received other modalities of treatment in last six months. Patients excluded from the study were keloids with secondary infection, keloids of earlobes and face, and pregnant and lactating mothers. Patients with comorbidities including cardiac, liver and kidney disease, diabetes mellitus, hypertension, malignancies, and those who were immunocompromised were also excluded.

Patients and methods

Patients were recruited in the study after obtaining written informed consent for participation and photography of lesions. A total of 24 patients were recruited in the study. They were allotted into two groups of 12 each, randomized alternatively in a 1:1 ratio to receive either intralesional triamcinolone acetonide with fractional CO2 laser (Group 1) or intralesional triamcinolone acetonide with intralesional verapamil (Group 2). Patients recruited were thoroughly examined with proper history as per predesigned proforma. Patient details included name, age, sex, address, occupation, and contact number. Presenting complaints with associated symptoms, duration, predisposing factors for keloid, past medical history, previous treatment history, and family history were noted and entered in predesigned proforma. Details of keloid were noted which included the number, site, length, width, height, and palpation findings (consistency, tenderness, warmth). Keloid scars were graded according to the Vancouver scar scale (VSS). Clinical photographs were taken. Pre-procedure workup with routine blood investigations was done for all the patients. Electrocardiogram, echocardiogram, and cardiac status were evaluated for patients to be started on verapamil.

Intervention

Group 1: Under strict aseptic precaution and topical anesthesia, fractional CO2 laser (power of 10 to 15 Watt, energy of 30 mJ, and density of 100 spots/cm²) was delivered over the keloid, followed by injection of triamcinolone acetonide 40 mg/ml [0.5 ml] intralesional in the keloid (up to 0.2 ml per 1 cm²) using a 30-gauge insulin syringe.

Group 2: Combination of injection triamcinolone 40 mg/ml [0.5 ml] plus injection verapamil 2.5 mg/ml (0.5 ml) was injected into the keloid (up to 0.2 ml per 1 cm²) using a 30-gauge insulin syringe.

Procedures were repeated at an interval of four weeks till complete flattening of the lesion or for a maximum of four sessions, whichever was earlier.

Topical EMLA (eutectic mixture of lidocaine and prilocaine) was applied on the lesion under occlusion 45 minutes before the CO2 laser procedure. Laser parameters were set according to scar character (power of 10 to 15 Watt, energy of 30 mJ, and density of 100 spots/cm²⁾. Laser beams of various shapes were used according to the shape and area of the keloid. Post-procedure cooling was done following laser treatment.

Post-procedure follow-up

Follow-up was done monthly for six months after the last intrevention to note recurrence and delayed side effects. Parameters of the VSS were assessed for clinical response by naked eye examination. For VSS, height was measured with a centimeter scale (0–normal/flat, 1–<2 mm, 2–2 to 5 mm, 3–>5 mm), pliability was assessed by palpation (0–normal, 1—supple, 2—yielding, 3—firm, 4—banding, 5—contracture), pigmentation was graded after blanching and comparing with surrounding skin (0—normal, 1—hypopigmentation, 2—hyperpigmentation), and vascularity was assessed by visual inspection (0—normal, 1—pink, 2—red, 3—purple). A decrease in pruritus and pain was assessed in both groups. Side effects, like discoloration, atrophy, ulceration, necrosis, blistering, and telangiectasia, were noted in both the groups. Photographs were taken at each visit. Responses were recorded as excellent if >75% improvement in VSS parameters, good if 50–75% improvement, fair if 25–49% improvement, and poor if only <25% improvement.

Statistical analysis

Data were entered in Microsoft Excel and analyzed using SPSS version 25.0. Results were expressed in mean, standard deviation, and percentage. The association between variables was tested by the Chi-square test. For all tests, a P value < 0.05 was considered significant.

Results

The age of patients (n=24) ranged from 18 to 37 years. Out of 24 patients, 21 were males and 3 were females [Table 1].

Table 1.

Demographic data and clinical profile

Parameters	Variables	Intralesional triamcinolone with		P
		Fractional CO2 laser (n=12)	Intralesional verapamil (n=12)
Mean age (years)		26.7±5.6	25.6±5.2	0.63
Gender	Male (%)	11 (92%)	10 (83%)	0.53
	Female (%)	1 (8%)	2 (17%)
Duration (years)		2.8±1.6	2.4±1.6	0.58
Symptoms	Pruritus (%)	7 (58%)	4 (33%)	0.09
	Pain (%)	3 (25%)	7 (58%)	0.2
	Burning sensation (%)	1 (8%)	0	0.3
Etiology	Spontaneous (%)	10 (83%)	10 (83%)	0.5
	Acne (%)	1 (8%)	2 (16%)
	Varicella (%)	1 (8%)	0
Site	Chest (%)	10 (83%)	12 (100%)	0.1
	Shoulder (%)	2 (16%)	0

There was a significant reduction in mean VSS in both groups at the end of the study (P value < 0.05 in both groups). The reduction was faster and more remarkable in Group 2 [Table 2].

Table 2.

Mean Vancouver Scar Scale (VSS) at baseline and end of study in both the study groups

VSS Score	Intralesional triamcinolone with
	Fractional CO2 laser [Group 1, n=12]	Intralesional verapamil [Group 2, n=12]
Baseline	9	9.83
Week 12	5.75	4.75
Post- treatment follow-up at third month	5.33	4
Post-treatment follow-up at sixth month	5.25	3.83
P	0.047	0.031

In VSS parameters, there was a visible reduction in height, pliability, and vascularity from the first follow-up assessment at 4 weeks after first intervention in both the study groups. Considering the individual parameters, the reduction in keloid height was better and faster with intralesional triamcinolone % verapamil compared to fractional CO2% intralesional triamcinolone at each visit and this difference in reduction was statistically significant with P value = 0.04 at the end of 12- week study period. There was a noteworthy reduction in pliability and vascularity in both groups with a mean reduction greater in Group 2 compared to Group 1, but this difference was not statistically significant. There was no improvement in scar pigmentation in either group even after two sittings [Table 3]. Out of three patients in Group 1 who had pain (subjective grading visual analog scale (VAS) 3 / 10), two patients had complete disappearance of pain by week 8 and one patient by week 12. In Group 2, out of seven patients (subjective grading 2–4 in VAS), four patients had complete disappearance of pain by week 12 and for three patients, mild pain on pressure persisted till the end of the study. Out of seven patients who had pruritus in Group 1, three patients had complete disappearance of itching by week 8 and 2 by week 12. Itching persisted in two patients. One patient with burning sensation had complete resolution by week 4 in Group 1. Among four patients who had pruritus in Group 2, one patient had complete disappearance by week 4, and three patients by week 12. Figures 1 and 2 show the reduction in the size of keloid after 4 sittings at an interval of 4 weeks of intralesional triamcinolone acetonide with fractional CO2 laser and intralesional triamcinolone acetonide with intralesional verapamil, respectively.

Table 3.

Comparison of reduction in mean Vancouver scar scale (VSS) parameters in four sittings

VSS parameters (Mean)		Week 0	Week 4	Week 8	Week 12	P
Height	Group 1	2.25	2	1.75	1.5	0.04
	Group 2	2.42	1.83	1.67	1
Pigmentation	Group 1	2	2	1.92	1.67	0.44
	Group 2	2	2	1.83	1.42
Pliability	Group 1	3.08	2.92	2.42	1.58	0.5
	Group 2	3.25	2.75	2.17	1.33
Vascularity	Group 1	1.67	1.67	1.67	1	N/A
	Group 2	2.27	2.17	1.5	1

N/A: Not applicable

Figure 1.

Group 1—Photographs at baseline and after four sittings of fractional CO2 laser with intralesional triamcinolone acetonide

Figure 2.

Group 2—Photographs at baseline and after four sittings of intralesional verapamil with triamcinolone acetonide

The side effect profile was similar in both groups with depigmentation at the injection site observed in two patients in Group 1, while one had depigmentation with atrophy in Group 2.

The mean overall improvement in scar was 61.03% in the intralesional triamcinolone + verapamil group and 41.66% in the fractional CO2 laser + intralesional triamcinolone group at the end of the study. The difference was statistically significant (P = 0.024).

At the end of the study, in the group 2, 33.3% of patients had an excellent response (>75% improvement) in keloid scar and none had a poor response (<25% improvement.). In group 1, 17% of patients had excellent response and 25% had poor response [Figure 3]. In both groups, none of the patients had a recurrence of keloid till the sixth month of post-treatment follow-up.

Figure 3.

Comparison of improvement in grading at the end of the study

Discussion

Keloids have many modalities of treatment with variable success rates but no universally accepted method of treatment exists that shows complete resolution. Recent advances in laser technology have provided newer options to improve the appearance of scars.

Carbon dioxide lasers have been shown to stimulate basic fibroblast growth factor and inhibit transforming growth factor-1, resulting in dermal collagen remodeling.[1] Fractionated CO2 laser creates discrete columns of ablated tissue surrounded by intact skin, known as microthermal zones, which assist with tissue regeneration and also generate multiple holes in a scar which helps in greater drug penetration and enhances their effect.[2] Carbon dioxide lasers are effective with minimal side effects.[2]

A study by Al Jahani et al.[3] showed a successful treatment in a case of refractory keloid with fractional CO2 laser, followed by intralesional and topical triamcinolone who had not responded to intralesional triamcinolone acetonide, pulsed dye laser, and cryotherapy individually. A study by Kraeva et al.[4] showed excellent cosmetic results sustained at 22 months post-treatment with combination therapy of fractionated CO2 laser and laser-assisted drug delivery with topical triamcinolone acetonide ointment in an African-American man (Fitzpatrick VI).

Significant improvement in VSS was noted by Lee et al.[5] where keloid was treated in combination with fractional erbium glass laser, followed by ablative fractional carbon dioxide laser. Laser treatment was immediately followed by the administration of superficial cryotherapy and intralesional triamcinolone injection.

Verapamil is a calcium channel blocker that stimulates procollagenase synthesis in keloids leading to depolymerization of actin filaments, alteration of the shape of cells, and reduced fibrous tissue production.[6] A study by Margaret Shanthi et al.[7] where patients received 1 ml of either verapamil (2.5 mg) or triamcinolone (40 mg) intralesionally every three weeks showed that injection verapamil has lesser side effects compared to triamcinolone, is much cheaper and has a rapid beneficial effect than other modalities.[7,8]

Triamcinolone acetonide is the first line of management for keloid with a recurrence rate of up to 50% and various side effects.[9] Combination therapies are emerging and increased knowledge in this area may potentially lead to the development of novel therapeutic options for keloid with better efficacy and less recurrence. Limited studies have been found in studies regarding the efficacy of injection verapamil as monotherapy and combination therapy in the treatment of keloid. Hence, we conducted this study and enrolled 24 patients with keloid fitting into inclusion criteria.

In this study, the mean age was 26.7 years in Group 1 and 25.6 years in Group 2. Other studies had similar results, with most patients in the age group of 20–30 years. Males outnumbered females in this study in both groups (ratio of 7:1). Eighty-eight percent of patients were male and 12% were female. Other studies showed variable gender distribution.

The mean duration of keloid was 2.83 years in the fractional CO2+ triamcinolone group and 2.45 years in the verapamil + triamcinolone group. A majority of patients (22, 92%) had presternal keloid and two patients (8%) had keloid on the shoulder. Our study excluded face and earlobe keloids. The distribution of the site of keloid varied in various studies ranging from face, neck, chest, and limbs. In this study, 83% of patients had spontaneous onset of keloid, 12% developed keloid following acne, and one patient developed following varicella infection. Whereas in most of the studies, keloid had developed following trauma or surgery. Of the total patients, at presentation 11(45.8%) had pruritus, 10(41.6%) had pain, and one patient had a burning sensation over the keloid. The two studied groups showed no significant difference regarding demographic data and clinical profile [Table 1].

Improvement was noted in height and pliability after four weeks (one sitting) of treatment in both the groups but was more remarkable in triamcinolone + verapamil group. In a study by Margaret Shanthi et al. comparing the effectiveness of intralesional triamcinolone vs verapamil, the median time of reduction of VSS was lesser with the triamcinolone group, whereas the verapamil group was found to have lesser side effects and easier to inject.[7] In a study by Srivastava et al.[10] comparing intralesional triamcinolone, intralesional verapamil, and fractional CO2 laser individually, the response was earliest with the triamcinolone group, followed by verapamil and then CO2 laser. The verapamil group was free from adverse effects and easier to inject[10] and has long term stable effects.[11] In another combination study by Fayed et al.,[12] CO2 laser + intralesional triamcinolone showed better improvement (75%) compared to that of CO2 laser + intralesional verapamil (55%) but with more adverse effects in the former.

The occurrence of pain while injecting the drugs was higher with intralesional triamcinolone + verapamil compared to fractional CO2 laser + intralesional triamcinolone. This was comparable with a study by Fayed et al. [12] which showed more injection site pain in the verapamil group compared to triamcinolone after CO2 laser and with a study by Shah et al.[13]

Limitation

Limitations of the study are the small sample size and short duration of follow-up. Longer follow-up is needed to assess the longevity of the results.

Conclusion

This study reveals that intralesional verapamil with intralesional triamcinolone acetonide shows better clinical improvement when compared to fractional CO2 laser with intralesional triamcinolone acetonide in terms of faster reduction of height and pliability. There was no significant improvement in pigmentation with either group and the side effects profile was similar in both groups. None of the patients had a recurrence of keloid till the end of the study in either group.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence (AI)

This is an original article and is not generated or assisted by any AI tools.

Funding Statement

Nil.