|Year : 2013 | Volume
| Issue : 1 | Page : 22-27
Comparative study of the 80% trichloroacetic acid multiple puncture technique versus botulinum toxin type A in the treatment of keloid scars
Department of Dermatology and Andrology, Al-Zahraa University Hospital, Abbasiya, Cairo, Egypt
|Date of Submission||01-Apr-2013|
|Date of Acceptance||06-May-2013|
|Date of Web Publication||23-Jun-2014|
MD, Department of Dermatology and Andrology, Al-Zahraa University Hospital, 11351 Heliopolice
Source of Support: None, Conflict of Interest: None
Keloid is one of the most challenging clinical problems encountered in wound healing. Although there are numerous treatment modalities, none of them have shown excellent therapeutic results.
The aim of the study was to evaluate the efficacies of 80% trichloroacetic acid (TCA) and botulinum toxin type A in the treatment of patients with keloid scars.
Thirty keloid patients were divided into two groups (each consisting of 15 patients). In group A, keloid scars were punctured using a punch instrument previously dipped in 80% TCA, whereas in group B keloid scars were injected intralesionally with botulinum toxin type A (2.5 U/cm3;). All patients underwent three to five therapeutic sessions 1 month apart, and follow-up for 1 year. The therapeutic response was determined according to the scores on the Vancouver scar scale and a self-assessment scale for pain and pruritus.
In group A, the mean scores on the Vancouver scar scale before and after treatment were 9.73±1.33 and 4.94±2.44, respectively, with a total improvement of 49%. In group B, the mean scores on the Vancouver scar scale before and after treatment were 9.05±1.34 and 4.68±2.67, respectively, with a total improvement of 48%. Comparison between mean values obtained on the Vancouver scar scale in groups A and B after treatment showed a statistically nonsignificant difference. Group B showed better improvement as per the self-assessment score. Most common side effects were reported in group A and were in the form of hyperpigmentation (33.3%), hypopigmentation (6.7%), and mixed pigmentation (6.7%). Relapses occurred in 26.7% of patients in group A, whereas no relapses occurred in group B.
The 80% TCA multiple puncture technique is better than botulinum toxin type A in the treatment against keloids.
Keywords: botulinum toxin type A, keloids, trichloroacetic acid
|How to cite this article:|
Ghonaim N. Comparative study of the 80% trichloroacetic acid multiple puncture technique versus botulinum toxin type A in the treatment of keloid scars. Egypt J Dermatol Venerol 2013;33:22-7
|How to cite this URL:|
Ghonaim N. Comparative study of the 80% trichloroacetic acid multiple puncture technique versus botulinum toxin type A in the treatment of keloid scars. Egypt J Dermatol Venerol [serial online] 2013 [cited 2017 Dec 18];33:22-7. Available from: http://www.ejdv.eg.net/text.asp?2013/33/1/22/135110
| Introduction|| |
Keloid is a benign hyperproliferative growth of dermal fibroblasts, which extends beyond the borders of the original wound; it does not regress spontaneously and tends to recur after excision 1. This proliferative scar is characterized by an increased activity of transforming growth factor β, platelet-derived growth factors, and vascular endothelial growth factor, together with altered collagen turnover 2. Itching and pain are common presentations in keloids and are associated with abnormalities in small nerve fiber function 3.
Several therapeutic strategies have been attempted to prevent or attenuate keloid formation, but most of them have failed to eradicate it 4.
Trichloroacetic acid (TCA) is an established peeling agent that is used for superficial and medium-depth peel. Application of TCA to the skin causes precipitation of proteins and coagulative necrosis of cells in the epidermis and necrosis of collagen in the papillary to upper reticular dermis 5. The peel depth varies according to its concentration 6; higher concentrations can reach deeper depths and modify deeper scars 7.
Botulinum toxin type A (BTX-A) is a potent agent blocking the release of acetylcholine, which normally transmits impulses at motor end plates of the muscles 8.
BTX-A prevents contraction of muscles and skin near the keloid tissue, which decreases tensile force during the course of traumatic cicatrization. It also suppresses the secretomotor function and trophic effect of the cell and influences cellular apoptosis and cellular proliferation, which maintains the balance of cellular dynamics 9.
The present study was conducted as a trial to evaluate the efficacy of 80% TCA as against that of BTX-A in the treatment of keloid scars.
| Patients and methods|| |
This study was conducted on 30 patients with keloid scars at varying regions and of varying sizes and durations who selected from the dermatology outpatient clinic of Al-Zahraa University Hospital between April 2010 and April 2012. Any patient with an old or a recent keloid lesion at any region of the body and aged between 16 and 55 years were eligible to be enrolled in the study. Patients with hypersensitivity to albumin, with hepatic, cardiac, renal diseases, with diabetics, or who were pregnant or lactating were excluded from the study.
All patients were subjected to the following examinations: complete history taking – including personal history (age, sex, occupation, and residence) and history of the disease (duration, course, associated pain, pruritus, and previous medications).
Dermatological examination, including:
- The Vancouver scar scale: This scale assesses the scar on four domains: vascularity, pigmentation, pliability, and height. The scores range from 0 to 14. The maximum score is 14, indicating the worst result; a score of zero indicates normal skin 10. Height of the scar was measured using ultrasonography (a superficial probe with frequency 7 MHz) before every session and 1 month after the last session to determine the degree of scar reduction. In group A height ranged from 5.7 to 13.2 mm, whereas in group B it ranged from 4 to 13.6 mm.
- Self-Assessment score, including evaluation of pain and pruritus: It is a verbal descriptor scale using which the patient is asked to verbally indicate his or her level of pain and pruritus, represented as none, mild, moderate, or severe, and numbered 0–3 11,12.
Patients were divided into two groups:
Group A: This group consisted of 15 patients whose keloids were punctured with a 2–4 mm punch instrument previously dipped into 80% TCA. On average, 4 punctures/cm3 of skin were made.
Group B: This group consisted of 15 patients who were injected intralesionally with BTX-A (50 IU/ml) at a dose of 2.5 U/cm3, with a maximum dose of 100 U/session.
All patients had to provide written informed consent before being included in the study. Each patient underwent 3–5 sessions at 1-month intervals. A local anesthetic was applied before each session and the patients were followed up through photographs.
Assessment of clinical response
Clinical response was judged according to the scores obtained on the Vancouver scar scale and was based on reduction in vascularity, height, and pigmentation and softening of the scar, as well as according to the scores on the self-assessment scale evaluating decrease in pain and pruritus.
Data are presented as percentage, mean, and SD. Percentages were compared using the χ 2-test, linear correlations, and statistical program at 0.05, 0.01, and 0.001 level of P.
| Results|| |
This study was conducted on 30 patients with keloid scars and comprised 20 men and 10 women patients ranging in age from 16 to 51 years (mean±SD 32.40±2.53).
They were divided into two groups: A and B. The duration for which the lesion had been present in the patients ranged from 0.9 to 7 years. The most commonly affected regions were the chest, upper back, ear lobe, occipital area, arm, and forearm.
[Table 1] shows the results of the Vancouver scar scale before and after treatment in both groups with respect to vascularity, pliability, height, and pigmentation. Vascularity and pigmentation were better in group B, whereas height and pliability were better in group A.
|Table 1: Results of the Vancouver scar scale before and after treatment in both groups|
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In group A the range of height before and after treatment was 5.7–13.2 mm (mean 9.67±2.57 mm) and 0–6.6 mm (mean 2.41±2.20 mm), respectively, whereas in group B the range was 4–13.6 mm (mean 7.25±2.62 mm) and 1.6–9.5 mm (mean 4.88±2.25 mm), respectively [Figure 1].
Complete flattening occurred in 26.7% in group A, whereas no flattening occurred in group B.
[Table 2] shows the results of the self-assessment score as regards pain and pruritus. Improvement in both pain and pruritus was better in group B, and the difference was statistically significant.
|Table 2: Results of self-assessment score before and after treatment in both groups|
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The mean values of the Vancouver scar scale in group A before and after treatment were 9.73±1.33 and 4.94±2.44, respectively, and those in group B were 9.05±1.34 and 4.68±2.67, respectively [Figure 2].
|Figure 2: Mean Vancouver scar scale before and after treatment in both groups.|
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The mean total improvement in group A and group B was 49 and 48%, respectively.
Comparison between the mean value of the Vancouver scar scale in groups A and B after treatment gave a statistically nonsignificant result.
All patients underwent 3–5 sessions (according to Vancouver score improvement) within a 1-month interval [Figure 3], [Figure 4], [Figure 5] and [Figure 6].
|Figure 3: (a) Keloid scar before treatment: Vancouver score=6. (b) Trichloroacetic acid (TCA) multiple punctures. (c) The scar after three TCA sessions: Vancouver score=2 (66.7% improvement).|
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|Figure 4: (a) Keloid scar before treatment: Vancouver score=7. (b) The scar after five sessions of trichloroacetic acid treatment: Vancouver score=1 (85% improvement).|
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|Figure 5: (a) Keloid scar before botulinum toxin type A (BTX-A): Vancouver score=6. (b) Keloid scar after three sessions of BTX-A: Vancouver score=3 (50% improvement).|
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|Figure 6: (a) Keloid scar before botulinum toxin type A (BTX-A): Vancouver score=10. (b) Keloid scar after three sessions of BTX-A: Vancouver score=3 (70% improvement).|
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Side effects were reported in group A in the form of hypopigmentation in 6.7% of patients, mixed pigmentation in 6.7% of patients, and hyperpigmentation in 33.3% of patients. There was recurrence in 26.66% in group A, whereas no recurrence occurred in group B.
| Discussion|| |
Keloid is a benign growth of dense fibrous tissue developing from an abnormal healing response to a cutaneous injury 13. The exact etiology and pathophysiology are still poorly understood. There is no single therapeutic modality that can be considered the best across all keloid cases 14. The aim of this work was to evaluate the efficacy of the 80% TCA multiple puncture technique against BTX-A in the treatment of keloids. The efficacy was determined according to the scores obtained on the Vancouver scar scale and self-assessment scale.
The multiple puncture method was suggested in group A to penetrate the keloid scar with a high concentration of TCA (80%) using a 2–4 mm punch instrument according to the shape of the keloid.
The mean improvement in the Vancouver scar scale score in group A was 49% (vascularity, height, pliability, and pigmentation). There were significant differences in pliability and pigmentation and a highly significant difference in height, whereas there was no significant difference in vascularity improvement before and after treatment. According to the self-assessment score, pain and pruritus showed no improvement after treatment and the difference was statistically nonsignificant. Recurrence was observed in four cases (26.7%). In group B, the mean improvement in the Vancouver scar scale score was 48%. Height, pliability, and vascularity after treatment were significantly lower than before treatment. As regards pigmentation, the difference was statistically nonsignificant. Both pain and pruritus significantly improved after treatment. None of the patients showed recurrence.
This study is the first clinical trial to demonstrate the effectiveness of TCA in the treatment of keloids.
Earlier studies on TCA have mainly concentrated on its effects on atrophic scars, as TCA in high concentration produces increased dermal thickening and collagen volume 15.
TCA is one of the most widely used peeling agents utilized to create an injury of a specific skin depth. It stimulates growth of new epidermis and new collagen 16.
Keloid fibroblasts overproduce type I collagen, and these cells have a greater capacity to proliferate 17. Yonei et al. 18 stated that TCA-treated skin expresses interleukin-10 and this cytokine is probably involved in the regulation of type I collagen synthesis and degradation. It downregulates collagen I and upregulates collagenase protein in cultured dermal fibroblasts 19. They also indicated that expression of platelet derived growth factor-B after TCA treatment was significantly upregulated, and then immediately downregulated. The transiently increased platelet derived growth factor might be helpful for rapid wound repair.
Nilforoushzadeh et al. 20 reported that the suggested mechanism of TCA in scars is acceleration of cellular regeneration in the dermal and epidermal areas following induction of inflammation. When used in a controlled manner, TCA improves collagen and elastin in the skin. Penetrating the reticular dermis, the deep peel maximizes the regeneration of new collagen 21, hence the effect of TCA on keloid.
Nilforoushzadeh et al. 22 applied 50% TCA to destroy the hyperkeratotic tissue surrounding the margin of the ulcer on the plantar area and obtained satisfactory results.
BTX-A is a neurotoxin preventing smooth muscle contraction near the site of injury. It immobilizes the local muscles and reduces skin tension caused by muscle pull 9. Because of the decreasing tension in close proximity to the scar, local fibroblasts gradually change their functional status, causing them to proliferate slowly and synthesize less extracellular matrix, including collagen 23.
In-vitro experiments have shown that BTX-A caused a decrease in transforming growth factor-β1 protein. This cytokine regulates cellular growth and differentiation and causes excessive deposition of collagen 23.
The pain and itching that are characteristic of keloids are believed to be secondary to the abnormal function of small nerve fibers 3. The analgesic effects of BTX-A may be related to its capacity to disrupt vesicular transport. Perhaps other vesicle-mediated substances necessary for the generation of pain are also affected by BTX-A 24.
The results of the present study were in agreement with those of Xiao et al. 25 who treated 19 patients with hypertrophic scars with three intralesional injections of BTX-A (2.5 U/cm3 of lesion at 1-month intervals). At 6-month follow-up, all patients showed acceptable improvement in the scars and the therapeutic satisfaction was very high. The erythema, pruritus, and pliability scores after the injections were significantly lower than before the injections.
In contrast, Gauglitz et al. 26, who injected four keloid scars at doses varying from 70 to 140 Speywood units per session every 2 months for up to 6 months, found no regression of keloid after treatment. The difference in BTX-A response between the study by Gauglitz and colleagues and our study might be due to the different doses of injection and different time intervals.
The side effects reported were hyperpigmentation in 33.3% of patients, hypopigmentation in 6.7% of patients, and mixed pigmentation in 6.7% of patients. All were reported in group A.
Kimura et al. 27 indicated that TCA activates the local skin stress response system by inducing proopiomelanocortin-derived peptide such as adrenocorticotrophic hormone, melanocyte-stimulating hormone and cortisol in response to inflammation, which, in our study, led to hyperpigmentation. Hypopigmentation may be due to injury to melanocytes during the procedure.
| Conclusion|| |
The response to TCA in this study denotes that it can normalize all types of scars by reconstitution of the dermal structure. It effectively inhibits keloids and the results were better than those obtained on administration of BTX-A; however, the entire biological mechanism responsible for TCA has still to be determined. Considering the low cost of TCA in comparison with BTX-A, and its good results, the TCA multiple puncture technique is recommended for the treatment of keloids.
| References|| |
|1.||Kelly AP.Medical and surgical therapies for keloids.Dermatol Ther 2004;17:212–218. |
|2.|| Brissett AE, Sherris DA.Scar contractures, hypertrophic scars, and keloids.Facial Plast Surg 2001;17:263–272. |
|3.|| Lee SS, Yosipovitch G, Chan YH, Goh CL.Pruritus, pain and small nerve fiber function in keloids: a controlled study.J Am Acad Dermatol 2004;51:1002–1006. |
|4.|| Gupta S, Sharma VK.Standard guidelines of care: keloids and hypertrophic scars.Indian J Dermatol Venereol Leprol 2011;77:94–100. |
|5.|| Brody HJ.Variations and comparisons in medium-depth chemical peeling.J Dermatol Surg Oncol 1989;15:953–963. |
|6.|| Khunger N.Trichloroacetic acid. Step by step chemical peels 2009:1st ed..New Delhi, India:Jaypee Medical Publishers. |
|7.|| Dewandre L Rubin MG.The chemistry of peels and a hypothesis of action mechanisms.Chemical peels: procedures in cosmetic dermatology 2009.New Delhi, India:Elsevier Inc.;1–12. |
|8.|| Fagien S.Botox for the treatment of dynamic and hyperkinetic facial lines and furrows: adjunctive use in facial aesthetic surgery.Plast Reconstr Surg 1999;103:701–713. |
|9.|| Chuang YC, Huang CC, Kang HY, Chiang PH, Demiguel F, Yoshimura N, et al..Novel action of botulinum toxin on the stromal and epithelial components of the prostate gland.J Urol 2006;175 Pt 1 1158–1163. |
|10.|| O’Connell DA, Diamond C, Seikaly H, Harris JR.Objective and subjective scar aesthetics in minimal access vs conventional access parathyroidectomy and thyroidectomy surgical procedures: a paired cohort study.Arch Otolaryngol Head Neck Surg 2008;134:85–93. |
|11.|| Gracely RH, Dubner R.Pain assessment in humans – a reply to Hall.Pain 1981;11:109–120. |
|12.|| Meshkinpour A, Ghasri P, Pope K, Lyubovitsky JG, Risteli J, Krasieva TB, et al..Treatment of hypertrophic scars and keloids with a radiofrequency device: a study of collagen effects.Lasers Surg Med 2005;37:343–349. |
|13.|| Atiyeh BS, Costagliola M, Hayek SN.Keloid or hypertrophic scar: the controversy: review of the literature.Ann Plast Surg 2005;54:676–680. |
|14.|| Butler PD, Longaker MT, Yang GP.Current progress in keloid research and treatment.J Am Coll Surg 2008;206:731–741. |
|15.|| Butler PE, Gonzalez S, Randolph MA, Kim J, Kollias N, Yaremchuk MJ.Quantitative and qualitative effects of chemical peeling on photo-aged skin: an experimental study.Plast Reconstr Surg 2001;107:222–228. |
|16.|| Coleman WP3, Brody HJ.Advances in chemical peeling.Dermatol Clin 1997;15:19–26. |
|17.|| Calderon M, Lawrence WT, Banes AJ.Increased proliferation in keloid fibroblasts wounded in vitro.J Surg Res 1996;61:343–347. |
|18.|| Yonei N, Kanazawa N, Ohtani T, Furukawa F, Yamamoto Y.Induction of PDGF-B in TCA-treated epidermal keratinocytes.Arch Dermatol Res 2007;299:433–440. |
|19.|| Reitamo S, Remitz A, Tamai K, Uitto J.Interleukin-10 modulates type I collagen and matrix metalloprotease gene expression in cultured human skin fibroblasts.J Clin Invest 1994;94:2489–2492. |
|20.|| Nilforoushzadeh MA, Jaffary F, Ansari N, Siadat AH, Heidari A, Adibi N.Treatment of recalcitrant diabetic ulcers using trichloroacetic.J Res Med Sci 2012;17:286–290. |
|21.|| Rendon MI, Berson DS, Cohen JL, Roberts WE, Starker I, Wang B.Evidence and considerations in the application of chemical peels in skin disorders and aesthetic resurfacing.J Clin Aesthet Dermatol 2010;3:32–43. |
|22.|| Nilforoushzadeh MA, Esfahani MH, Fesharaki MA, Siadat AH, HaftBaradaran E.Treatment of recalcitrant electrical burn ulcer with application of topical trichloroacetic acid and autologous cultured fibroblast.Cell Tissue Transplant Ther 2010;3:4. |
|23.|| Xiao Z, Qu G.Effects of botulinum toxin type a on collagen deposition in hypertrophic scars.Molecules 2012;17:2169–2177. |
|24.|| Binder WJ, Brin MF, Blitzer A, Schoenrock LD, Pogoda JM.Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study.Otolaryngol Head Neck Surg 2000;123:669–676. |
|25.|| Xiao Z, Zhang F, Cui Z.Treatment of hypertrophic scars with intralesional botulinum toxin type A injections: a preliminary report.Aesthetic Plast Surg 2009;33:409–412. |
|26.|| Gauglitz GG, Bureik D, Dombrowski Y.Botulinum toxin A for the treatment of keloids.Skin pharmacol physiol 2012;25:313–318. |
|27.|| Kimura A, Kanazawa N, Li HJ, Yonei N, Yamamoto Y, Furukawa F.Influence of chemical peeling on the skin stress response system.Exp Dermatol 2012;21 Suppl 1 8–10. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2]