Comparison of the Efficacy of Combined Intralesional Steroid and Cryotherapy Versus Intralesional Steroid Alone in the Treatment of Keloid

By Sadia Abbasi¹, Atiya Rahman^1,2, Rehana Batool¹, Sara Shafqat^1,2, Sana Saleem¹, Sunaina Kumari¹

Affiliations

1. Department of Dermatology, PNS Shifa Hospital, Karachi, Pakistan
2. Department of Dermatology, Bahria University Health Sciences Campus, Karachi, Pakistan

doi: 10.29271/jcpsp.2025.10.1228

ABSTRACT
Objective: To compare the efficacy of combined intralesional triamcinolone acetonide (IL TAC) and cryotherapy versus IL TAC alone in the treatment of keloid.
Study Design: Randomised controlled trial.
Place and Duration of the Study: Department of Dermatology, PNS Shifa, Karachi, Pakistan, from July 2024 to February 2025.
Methodology: Patients with keloids were randomly divided into two groups, with 38 patients in each group. Group A received a combination of IL TAC and cryotherapy, while Group B received IL TAC alone. Both treatments were administered three times at 4-weekly intervals. Keloids were assessed using photographic record, the Vancouver Scar Scale (VSS), and the Patients Scar Assessment Scale (PSAS). Treatment efficacy was defined as a >75% reduction in the VSS score from baseline at the end of the treatment. Repeated measure ANOVA was used to compare the VSS score and the PSAS score within the groups, whereas the independent t-test was applied to compare the scores between the two groups. The Chi-square test was used to compare efficacy between the two groups.
Results: Most patients were young males, and keloids were most commonly observed on the chest. IL TAC alone was effective in 23 patients (60.5%), while the combination of IL TAC and cryotherapy was effective in 31 patients (81.5%). The difference was statistically significant (p = 0.038). Patient satisfaction was also higher in the combination therapy group.
Conclusion: IL TAC combined with cryotherapy is more efficacious than IL TAC alone in the treatment of keloid, resulting in higher level of patient satisfaction.

Key Words: Cryotherapy, Combination treatment, Efficacy, Intralesional triamcinolone acetonide, Intralesional steroid, Keloids.

INTRODUCTION

Keloids are dermal proliferations of fibrous tissue that most often arise at sites of cutaneous injury and have significant impact on quality of life. Although keloids occur in all populations, they are more prevalent among individuals with skin of colour.¹ Both keloids and hypertrophic scars develop due to exaggerated proliferation of dermal fibroblasts after skin injury, characterised by excess accumulation of collagen within the wound.^2,3 They have a reddish or purplish hue due to increased vascularity, and the scar tissue contains inflammatory cells such as lymphocytes and macrophages.⁴
 

There are many different treatments of keloids nowadays, such as surgical excision, laser, cryotherapy, radiotherapy, silicone gel, and corticosteroid injection.^1,5 Despite an array of treatment options, keloid remains difficult to treat. Intralesional triamcinolone acetonide (IL TAC) injection constitutes the first-line therapy for keloids.⁶ It reduces keloid size through different mechanisms, including inhibition of migration and phagocytosis of monocytes and leucocytes, potent vasoconstriction leading to diminished oxygen and nutrient supply to keloid tissue, reduction in alpha-globulin deposition, and inhibition of fibroblast and keratinocyte growth. Cryotherapy is also effective in reducing scar volume and has been used as a primary treatment for scars. Application of liquid nitrogen leads to freezing of the tissue, with resultant microcirculation ischaemic injury and tissue necrosis. It also improves the organisation of collagen bundles. It has also been used alone and in combination with other modalities, such as steroids.⁷ However, it has demonstrated better efficacy as part of combined regimens than when applied as a standalone treatment.^8,9

Pharmacological therapy, along with other treatments, is a primary treatment for keloids.^1,10 The most often utilised pharmacological treatment is intralesional steroid injections. The quest to find a viable, long-term, and efficacious treatment continues. IL TAC combined with cryotherapy has been found to be more effective than IL TAC alone in flattening keloid scars in small sample studies.¹⁰

Keloids continue to pose a significant challenge for both patients and clinicians. Keloids significantly impact quality of life, highlighting the need for effective and patient-satisfying treatment options. However, only a limited number of studies have explored this parameter, evaluating not just the treatment's efficacy but also patient satisfaction with the overall treatment plan. Thus, the study aimed to improve the level of evidence and to compare the efficacy between IL TAC combined with cryotherapy versus IL TAC alone in the treatment of keloid, simultaneously employing a validated, reliable tool to assess patient satisfaction with their treatment plan.

METHODOLOGY

This randomised controlled trial was carried out in the Department of Dermatology, PNS Shifa, Karachi, Pakistan, from July 2024 to February 2025. Ethical approval was obtained from the Ethical Review Committee of the PNS Shifa Hospital, Karachi, Pakistan (ERC/2024/DERM/83), and the study was registered in the Iranian Registry of Clinical Trials (IRCT registration No. 79955). After obtaining written informed consent, a total of 76 patients of either gender, aged between 18 and 60 years, with single or multiple keloids measuring no more than 10 cm in the largest diameter, were included in the study. For patients with multiple keloids, only the largest keloid was included in the study. The sample size was calculated using OpenEpi calculator, taking the prevalence of keloids as 5.2%,¹⁰ keeping margin of error 5% and a 95% confidence interval. The calculated total sample size was 76, that is, 38 individuals per group. Patients with secondarily infected keloids, inflammatory skin diseases, psychiatric illnesses, history of bleeding disorders or poor wound healing, lactating or pregnant women, immunodeficiency, and diseases aggravated by cold (Raynaud’s disease, cryoglobulinaemia and cold urticaria) were excluded.

Patients were randomly divided into two groups using the lottery method. At each session, patients in Group A received cryotherapy with liquid nitrogen until a 1mm halo of freeze appeared, which took around 10-20 seconds. After that, the keloid was injected aseptically using a 30-gauge needle with 0.1 mL per cm² of triamcinolone acetonide (TAC, 40mg/mL), ensuring no more than 1mL was administered per lesion. Patients in Group B received IL TAC alone, following the same injection protocol. Both groups received therapy at weeks 0, 4, and 8 and were assessed every 4 weeks for treatment response. The patients were treated until the lesions flattened completely or until a maximum of three treatment sessions was reached. At 12 weeks, the final treatment response was recorded for patients who had received treatment at week 8.

Patients’ demographic data—including name, age, gender, education, socio-economic status, body mass index (BMI), duration of disease, and location of keloids—were recorded in a pre-designed patient proforma. Serial photographs of patients’ keloids were taken during the course of treatment. Patients’ scar was assessed by Vancouver Scar Scale (VSS), a semi-quantitative tool that measures improvement in scar tissue across four parameters: colour, pliability, vascularity, and height.¹¹ Scar height was measured precisely in millimetres using a ruler. Scar vascularity and pigmentation were evaluated by ocular inspection. Scar pliability was assessed subjectively by palpation. Efficacy was defined as a >75% reduction in the VSS from baseline at the end of treatment.

Apart from objective assessment by the VSS, patients’ perception of improvement was evaluated using Patient Scar Assessment Scale (PSAS). The PSAS measures pain, itching, colour, stiffness, thickness, and irregularity on a 1–10 scale. Patients also rated overall satisfaction, with total scores ranging from 6 to 60.¹²

Statistical Package for the Social Sciences (SPSS) version 26 was used for data analysis. Mean ± SD was calculated for quantitative data, whereas qualitative data were expressed as frequencies and percentages. Repeated measure ANOVA was used to compare the VSAS score and the PSAS score within the groups, whereas the independent t-test was used to compare the VSAS score and PSAS score between the two groups. The Chi-square test was applied to compare efficacy between the two groups, and a p-value of <0.05 was considered statistically significant.

RESULTS

A total of 76 patients having keloids were included. The mean age of patients in Group A was 30.29 ± 6.50 years, and in Group B was 30.29 ± 5.80 years. Most patients were males in both groups, and keloids were commonly observed on the chest. The baseline data in both groups were almost similar, with no statistically significant difference, with a p-value was >0.05, as shown in Table I.

In Group A, at baseline, the VSAS was 11.26, which reduced to 5.26 at week 12, indicating a significant reduction in the VSAS (p <0.001). Similarly, in Group B, the VSAS decreased from 11.34 at baseline to 6.95 at week 12, showing a significant reduction (p <0.001), as shown in Table II and Figure 1 and 2. Although both treatment plans were effective, patients receiving a combination of cryotherapy and IL TAC were found to have better results. IL TCA alone was effective in 23 (60.5%) patients, and a combination of IL TCA and cryotherapy was effective in 31 (81.5%) patients, as shown in Table I. No side-effects, including secondary bacterial infection, erosion, or post-cryotherapy blister formation, were recorded in any of the patients.

Interestingly, subjective assessment using PSAS revealed patient satisfaction in both groups after the first treatment session, which continued throughout the study period. However, a more noticeable reduction in scores from week 4 onwards was seen in Group A compared to Group B. Significant statistical difference was observed between Groups A and B (p <0.001), as shown in Table II.

Table I: Baseline characteristics of patients and the efficacy of treatment.

Baseline characteristics of patients	Group A (n = 38)	Group B (n = 38)	p-values
Age (mean ± SD)	30.29 ± 6.50	30.29 ± 5.80	>0.99*
BMI (mean ± SD)	25.04 ± 3.58	25.76 ± 3.8	0.427*
Duration of disease (mean ± SD)	10.61 ± 4.25	10 ± 4.02	0.526*
Gender       Female       Male	12 (31.6%) 26 (68.4%)	13 (34.2%) 25 (65.8%)	>0.99**
No. of keloids       Single       Multiple	16 (42.1%) 22 (57.8%)	14 (36.8%) 24 (63.15%)	0.815**
Location       Abdomen       Back       Chest       Others	8 (21.1%) 13 (34.2%) 15 (39.5%) 2 (5.3%)	9 (23.7%) 11 (28.9%) 15 (39.5%) 3 (7.9%)	0.935**
Efficacy       Yes        No	31 (81.6%) 7 (18.4%)	23 (60.5%) 15 (39.4%)	0.038**
*Independent t-test. **Chi-square test.

Table II: Comparison of the VSS and the PSAS in patients with keloids.

Groups	Baseline	Week-4	Week-8	Week-12	p-values
VSS
Group A (n = 38)	11.26 ± 1.20	9.8 ± 1.23	7.26 ± 1.13	5.26 ± 1.36	<0.001***
Group B (n = 38)	11.34 ± 1.04	10.08 ± 1.48	8.55 ± 2.14	6.95 ± 1.8	<0.001***
p-values	0.761*	0.153*	0.002*	<0.001*
PSAS
Group A (n = 38)	28.97 ± 6.47	17.92 ± 4.49	13.63 ± 3.88	9.42 ± 3.57	<0.001**
Group B (n = 38)	29.34 ± 6.67	24.24 ± 2.94	20.37 ± 2.78	17.21 ± 2.60	<0.001***
p-values	0.808*	<0.001*	<0.001*	<0.001*
*Independent t-test. ***Repeated measures of ANOVA.

Figure 1: Before-and-after photographs of a patient in Group A.

Figure 2: Before-and-after photographs of a patient in Group B.

DISCUSSION

Keloids burden healthcare systems and impact functional and psychological well-being of individuals. Failures and recurrences continue despite different therapies, highlighting the necessity of an efficient management strategy. IL TAC injections are commonly used to treat both keloids and hypertrophic scars. Depending on the size and location of scars, the injectable dosage varies from 10 to 80 mg/mL, with the number of sessions ranging from one to eight.¹³

Keloids most frequently develop in young men during the second and third decades of life.^3,6,7,14 Local data supports this, as a study conducted in Pakistan reported that the majority of study participants were in their thirties,¹⁴ which closely aligns with the present study’s findings. However, that study employed intralesional steroid and 5-fluorouracil (5-FU) and used the Patient and Observer Scar Assessment Scale (POSAS) for evaluating improvement. The validity and reliability of POSAS have been questioned by some authors.¹⁵ To address this incongruity, the present study employed the VSS for objective scar assessment and used the PSAS for patients’ overall satisfaction.

In this study, the combined therapy was effective and statistically significant than IL TAC alone therapy, consistent with the findings of previous studies conducted on smaller scale. The effectiveness of IL TAC with cryotherapy was initially demonstrated by Hirshowitz et al. in 58 keloid patients, with 41 (71%) fully regressing.¹⁶ In a comparable trial, the combination therapy produced superior results, with 30 keloid lesions per group. IL TAC combined with cryotherapy showed excellent treatment response than IL TAC alone (66.7% vs. 43.3%).¹⁷ Similarly, Yosipovitch et al. conducted a controlled study comprising ten patients, comparing the efficacy of combined cryotherapy and intralesional corticosteroid injections versus each modality alone in treating keloids. The authors employed a visual analogue scale (VAS) to determine improvement in pain and itch. They found that the combined therapy significantly reduced keloid thickness compared to monotherapies (p <0.001).¹⁸

However, a study conducted in Dhaka revealed that both the combined therapy (intralesional steroid and cryotherapy) and IL TCA treatment were effective (90% versus 83.3%, respectively), with no statistically significant difference.² The age and maximum location of keloid observed were similar to those in the referenced study; however, the strength of TAC used in their study was 40 mg/mL, with a maximum dose of 2 mL, whereas in the present trial, no more than one mL of 40mg/mL triamcinolone was administered. The present study postulated that higher doses of IL TAC may potentially lead to greater scar reduction but carry the risk of local adverse events such as cutaneous atrophy, telangiectasia, and secondary infections. Furthermore, the referenced authors assessed keloid reduction objectively; they did not evaluate patient satisfaction with the different therapeutic modalities.

Apart from efficacy, additional aspects including anatomical location, treatment affordability, accessibility, safety profile, and recurrence rates should be considered while choosing a treatment modality. It is hypothesised that combining IL TAC with cryotherapy provides synergistic therapeutic benefits in the treatment of keloids. IL TAC may work in tandem with cryotherapy to enable keloid regression while preventing the subsequent fibrotic reaction.^18,19 IL TCA has also been combined with other therapeutic modalities such as 5-FU and botulinum toxin.^14,20,21 However, these options are more expensive and therefore unaffordable for many patients from developing economies. In addition, 5-FU has been associated with significant side effects. A study conducted in Pakistan showed that intralesional 5-FU combined with TAC was more effective in treating keloids than IL TCA alone. However, their methodology was different, administrating weekly injections for 8 weeks and assessing patients for efficacy and safety at the 4^th and 8^th weeks.²¹ Weekly hospital visits may be difficult for patients to manage. In addition, 5-FU has been associated with higher rates of side effects, such as itching, discomfort, dryness, restricted movement, and thereby cosmetic issues, thereby compromising patient satisfaction.^21,22

Saha and Mukhopadhyay in their study compared the efficacy of intralesional 5-FU and TAC in treating keloids over a prolonged period of time. Both treatments showed similar efficacy rate in terms of keloid size reduction and recurrence rates. However, 5-FU caused significantly more side effects, including pain, hyperpigmentation, and ulceration.²³ Likewise, surgical excision of keloid had not been successful, and there was a greater chance of keloid recurrence after-wards.^3,24 Better results had been achieved with radiotherapy after excision. Recurrence rates differed according to the kind of radiation: brachytherapy had a 15% recurrence rate, while electron beam and x-ray had a 23% recurrence rate.²⁵

The impairment of quality of life in individuals with keloids may be profound, encompassing significant physical dis-comfort, psychological distress, and functional limitations.²⁶ The current study has considered both the objective improvement of keloids and patient satisfaction with the treatment modality. Notably, this study also determined patient satisfaction with combination therapy. Before any significant reduction in keloid size was observed at week 4, patients receiving combined IL TCA and cryotherapy reported substantially higher satisfaction compared to those receiving IL TCA alone. This satisfaction progressively increased with subsequent injections.

With its remarkable safety and efficacy profile, the combi-nation of IL TAC and cryotherapy provides distinct benefits over alternative treatment approaches. Despite some limitations, including the absence of a follow-up period, these findings align with previous studies, suggesting that the combination of IL TAC with cryotherapy treatment can be a valuable option in clinical practice for managing keloids with minimal recurrence and side effects.

CONCLUSION

This study concluded that IL TAC combined with cryotherapy is more efficacious than IL TAC alone in the treatment of keloids. Both treatment modalities are well tolerated and resulted in patient satisfaction.

ETHICAL  APPROVAL:
The study was approved by the Ethical Review Committee of the PNS Shifa Hospital, Karachi, Pakistan (ERC/2024/DERM/83).

PATIENTS’ CONSENT:
Written informed consent was taken from all the participants included in the study.

COMPETING INTEREST:
The authors declared no conflict of interest.

AUTHORS’ CONTRIBUTION:
SA: Conception, study design, data acquisition, data analysis, and interpretation, literature review, and drafting.
AR: Conception, study design, data analysis, and interpre-tation, and critical revision.
RB, SS, SS, SK: Data acquisition, analysis, literature review, drafting, and revision.
All authors approved the final version of the manuscript to be published.

REFERENCES

1. Walsh LA, WuE, Pontes D, Kwan KR, Poondru S, Miller CH, et al. Keloid treatments: An evidence-based systematic review of recent advances. Syst Rev 2023; 12(1):42. doi: 10.1186/s13643-023-02192-7.
2. Ahsan MQ, Sikder MAU, Khondker L. Efficacy of combi-nation of intralesional corticosteroid injection and cryotherapy versus intralesional corticosteroid injection alone in patients of keloid. J Pak Assoc Dermatol 2019; 28(4):474-81.
3. Ekstein SF, Wyles SP, Moran SL, Meves A. Keloids: A review of therapeutic management. Int J Dermatol 2021; 60(6): 661-71. doi: 10.1111/ijd.15159.
4. Latoni DI, McDaniel DC, Tsao H, Tsao SS. Update on the pathogenesis of keloid formation. JID Innov 2024; 4(6): 100299. doi: 10.1016/j.xjidi.2024.100299.
5. Jwa SJ, Won J, Suh YC, Lee WJ. Extralesional cryotherapy combined with intralesional triamcinolone injections after keloid excision. Arc Asthet Plas Surg 2023; 29(1):8-13. doi: 10.14730/aaps.2022.00598.
6. Qi W, Xiao X, Tong J, Guo N. Progress in the clinical treatment of keloids. Front Med (Lausanne) 2023; 10: 1284109. doi: 10.3389/fmed.2023.1284109.
7. Cohen AJ, Talasila S, Lazarevic B, Banner L, Gleason L, Malkani K, et al. Combination cryotherapy and intralesional corticosteroid versus steroid monotherapy in the treatment of keloids. J Cosmet Dermatol 2023; 22(3):932-6. doi: 10. 1111/jocd.15520. 
8. Bijlard E, Timman R, Verduijn GM, Niessen FB, Hovius SER, Mureau MAM. Intralesional cryotherapy versus excision with corticosteroid injections or brachytherapy for keloid treatment: Randomized controlled trials. J Plast Reconstr Aesthetic Surg 2018; 71(6):847-56. doi: 10.1016/j.bjps. 2018.01.033.
9. Liu AH, Sun XL, Liu DZ, Xu F, Feng SH, Zhang SY. Epidemiological and clinical features of hypertrophic scar and keloid in Chinese college students: A university-based cross-sectional survey. Heliyon 2023; 9(4):e15345. doi: 10.1016/j.heliyon.2023.e15345.
10. Jacobs C, Wilmink J. Combined versus single treatment regimens for keloid therapy using serial intralesional corticosteroid injections, surgical excision, silicone- and/or cryotherapy. JPRAS Open 2021; 29:157-66. doi: 10.1016/j. jpra.2021.05.011.
11. Shin HY, Park YJ, Choi WK, Sim HB, Lee SH, Lee AY, et al. Assessment of treatment modalities in patients with keloids: A vancouver scale comparison. Ann Dermatol 2024; 36(6):348-54. doi: 10.5021/ad.23.160.
12. Lahdenpera NI, Lindford A, Kautiainen H, Paloneva J, Hietanen K, Vuola J, et al. Translation and psychometric validation of the Finnish version of the patient scar assessment scale for use in patients with burn scars. Burns 2023; 49(5):1113-21. doi: 10.1016/j.burns.2022. 08.025.
13. Morelli Coppola M, Salzillo R, Segreto F, Persichetti P. Triamcinolone acetonide intralesional injection for the treatment of keloid scars: Patient selection and perspectives. Clin Cosmet Investig Dermatol 2018; 11: 387-96. doi: 10.2147/CCID.S133672.
14. Naseem S, Paracha MM, Sagheer F, Qayyum A, Noor SM. Comparison of efficacy of intralesional triamcinolone acetonide versus combination of intralesional triamcinolone with 5-fluorouracil in treatment of keloids: A randomized controlled trial. J Postgrad Med Ins 2022; 36(4):207-12. doi: 10.54079/jpmi.36.4.3053.
15. Liu X, Nelemans PJ, Van Winden M, Kelleners-Smeets NW, Mosterd K. Reliability of the patient and observer scar assessment scale and a 4-point scale in evaluating linear facial surgical scars. J Eur Acad Dermatol Venereol 2017; 31(2):341-6. doi: 10.1111/jdv.13805.
16. Hirshowitz B, Lerner D, Moscona AR. Treatment of keloid scars by combined cryosurgery and intralesional corticosteroids. Aesthetic Plast Surg 1982; 6(3):153-58. doi: 10.1007/BF01570635.
17. Sharma S, Bhanot A, Kaur A, Dewan SP. Role of liquid nitrogen alone compared with combination of liquid nitrogen and intralesional triamcinolone acetonide in treatment of small keloids. J Cosmet Dermatol 2007; 6(4):258-61. doi: 10.1111/j.1473-2165.2007.00344.x.
18. Yosipovitch G, WidijantiSugeng M, Goon A, Chan YH, Goh CL. A comparison of the combined effect of cryotherapy and corticosteroid injections versus corticosteroids and cryotherapy alone on keloids: A controlled study. J Dermatolog Treat 2001; 12(2):87-90. doi: 10.1080/ 095466301317085363.
19. Ogawa R. The most current algorithms for the treatment and prevention of hypertrophic scars and keloids: A 2020 update of the algorithms published 10 years ago. Plast Reconstr Surg 2022; 149(1):79e-94e. doi: 10.1097/PRS. 0000000000008667.
20. Rasaii S, Sohrabian N, Gianfaldoni S, Hadibarhaghtalab M, Pazyar N, Bakhshaeekia A, et al. Intralesional triamcinolone alone or in combination with botulinium toxin A is ineffective for the treatment of formed keloid scar: A double blind controlled pilot study. Dermatol Ther 2019; 32(2):e12781. doi: 10.1111/dth.12781.
21. Khalid FA, Mehrose MY, Saleem M, Yousaf MA, Mujahid AM, Rehman SU, et al. Comparison of efficacy and safety of intralesional triamcinolone and combination of triamcinolone with 5-fluorouracil in the treatment of keloids and hypertrophic scars: Randomised control trial. Burns 2019; 45(1):69-75. doi: 10.1016/j.burns.2018.08.011.
22. Bijlard E, Steltenpool S, Niessen FB. Intralesional 5-fluorouracil in keloid treatment: A systematic review. Acta Derm Venereol 2015; 95(7):778-82. doi: 10.2340/000 15555-2106.
23. Saha AK, Mukhopadhyay M. A comparative clinical study on role of 5-flurouracil versus triamcinolone in the treatment of keloids. Indian J Surg 2012; 74(4):326-9. doi: 10.1007/ s12262-011-0399-y. 
24. Mohamed R, Elawadi AA, Al-Gendi R, Al-Mohsen S, Wani S, Wafa A. The outcome of postoperative radiation therapy following plastic surgical resection of recurrent ear keloid: A single institution experience. J Egypt Natl Canc Inst 2022; 34(1):4. doi: 10.1186/s43046-022-00105-8.
25. Mankowski P, Kanevsky J, Tomlinson J, Dyachenko A, Luc M. Optimizing radiotherapy for keloids: A meta-analysis systematic review comparing recurrence rates between different radiation modalities. Ann Plast Surg 2017; 78(4): 403-11. doi: 10.1097/SAP.0000000000000989.
26. Sitaniya S, Subramani D, Jadhav A, Sharma YK, Deora MS, Gupta A. Quality-of-life of people with keloids and its correlation with clinical severity and demographic profiles. Wound Repair Regen 2022; 30(3):409-16. doi: 10.1111/ wrr.13015.