Keloids are irregular scars made from fibrous tissue that grows outside the original injury and often does not regress over time. They are common when the skin is injured, burned, cut during surgery, or even has minor damage such as acne or piercings, especially in individuals with a family history [1]. Keloids are cosmetically disfiguring and can be associated with pruritus, pain, and psychological distress, significantly affecting the quality of life [2]. The pathophysiology of keloid formation is complex and not fully elucidated. It has been found to occur because of prolonged inflammation, dysregulated fibroblast proliferation and excessive deposition of extracellular matrix component which include collagen type I and type III [3] Studies have shown that fibroblasts within the keloid tissue shows increased activity and heightened sensitivity to growth factors such as transforming growth factor-beta (TGF-β) and they show higher resistance to apoptosis [4]. These characteristics make keloids progress and recur despite treatment. Contemporary management of keloids includes surgical excision, laser therapy, cryotherapy, silicone gel sheets, radiotherapy, pressure therapy, and application of various pharmacologic agents. Because keloids have high recurrence rates, monotherapy does not work well for them. Therefore, intralesional therapy has emerged as a preferred line of approach for many patients [5]. Intralesional corticosteroids of triamcinolone acetonide have been extensively studied for the treatment of keloids. The mechanism of action of triamcinolone appears to reduce collagen synthesis, fibroblast proliferation, and decrease inflammatory responses in the scar tissue [6]. Although this line of treatment appears to be effective, monotherapy with corticosteroids results in variable responses and high recurrence rates. To enhance therapeutic outcomes, a combination of triamcinolone with Fluorouracil (5-FU), an antimetabolite chemotherapeutic agent, is useful. Fluorouracil (5-FU) acts as an anti-proliferative agent against fibroblasts by inhibiting thymidylate synthase enzyme, thereby disrupting DNA synthesis and inducing apoptosis in fibroblasts, which results in a decrease of scar volume and symptom relief [7]. Studies have shown that a combination of triamcinolone and 5-FU is more effective than when either one is used alone and shows fewer recurrences [8]. The other promising compound is hyaluronidase enzyme, which hydrolyzes the hyaluronic acid component of the extracellular matrix. By degrading hyaluronic acid, the enzyme helps to reduce tissue edema, improve drug diffusion, and normalize the fibrotic extracellular environment. When used in combination with triamcinolone, it leads to enhancement of steroid distribution in the scar and remodeling of the scar [9]. Some people say that this approach can help provide relief from pain and visible scars caused by hypertrophic scars and keloids [10]. Since there is no consensus on approach and because responses in patients differ, there should be research focused on comparing these approaches to see which has the best outcomes. The current study aimed to determine the efficacy of two intralesional methods with Triamcinolone plus 5-Fluorouracil or Triamcinolone plus Hyaluronidase for treating keloids.

This prospective study was done in the Department of Venereology and Leprosy at Osmania General Hospital, Hyderabad, Telangana. Institutional Ethical approval was obtained for the study. Written consent was taken from all the participants of the study after explaining the nature of the study in the vernacular language. Inclusion Criteria 1. Keloids formed spontaneously, after trauma, and inflammation 2. Keloids due to other causes and recurrences of the same. 3. Male and Female cases 4. Patients of all age Groups and willing to follow up. Exclusion Criteria 1. Patients who are pregnant and lactating 2. Patients with systemic illnesses like diabetes, hypertension, malignancy, and 3. psychological disorders 4. Patients on immunosuppressant drugs 5. Patients who are not willing to undergo regular follow-up After the patient selection based on the inclusion and exclusion criteria, the demographic data and detailed history were taken, followed by general and cutaneous examination. Basic investigations like complete blood picture, random blood sugar, clotting time, bleeding time, HIV I and II, and HbsAg were carried out at the commencement of therapy. The photographs of keloids were taken before the treatment was initiated and in subsequent visits during treatment. All the patients were counselled regarding the disease, course, and prognosis. They were informed about the need for regular and prolonged treatment. Approval for conduction of the study was obtained from the ethical committee. Regimen: Patients were divided into two groups based on regimens: Regimen A and Regimen B. Patients in Regimen A received a combination of intralesional 5-Fluorouracil (50mg/ml) and triamcinolone acetonide (40mg/ml) injection in the ratio of 3:2 using a 26G needle at 3 weeks interval till complete flattening or for a total of 6 treatment sessions. Patients in Regimen B received a combination of intralesional triamcinolone acetonide (40mg/ml) and hyaluronidase injection(1500IU/ml) in the ratio of 1:1 using a 26G needle at 3 3-week intervals for a total of 6 treatment sessions or till complete flattening. Patients were informed about the disease, treatment, and the need for follow-up. Informed consent was taken before the procedure. The keloid was cleaned with betadine and spirit swab and allowed to dry. With the help of a syringe (26 gauge) drug was injected 0.1 ml per cm² area or till the area injected blanches, maximum dose being 2 ml per session. Both groups were followed up for 6 months. Photographs were taken on the first day of treatment and during subsequent visits till completion of treatment. Improvement was assessed based on regression in size as well as the flattening of the lesion. Efficacy was assessed by reviewing pre- and posttreatment scores on the Patient and Observer Scar Assessment Scale (POSAS). Categories of Response: Response was defined as a percentage change in POSAS Observer score and POSAS Patient score at the start of treatment (0 months) and post-treatment (6 months). Table 1: Response Definition Percentage Change in POSAS Response 0-25 Poor 26-50 Fair 51-75 Good 76-100 Excellent Statistical Analysis: Patient confidentiality was maintained. Data was tabulated in an Excel sheet. Data was analyzed using SPSS 23 software. Results were expressed in numbers and percentages for each category. Categorical data was analyzed using chi square test to correlate between the groups.

In this study, N=73 patients were included after they met the inclusion criteria. N=13 patients didn’t come for follow up or dropped in middle of treatment and hence N=60 patients were taken up for the study, 30 each in Regimen A and Regimen B. Regimen A consisted of combination of intralesional 5-Fluorouracil (50mg/ml) and triamcinolone acetonide (40mg/ml) injection in the ratio of 3:2. Regimen B consisted of combination of intralesional triamcinolone acetonide (40mg/ml) and hyaluronidase injection (1500IU/ml) in the ratio of 1:1. Table 2: Age-wise distribution of the cases in the study Age in years Regimen Total Percentage A B 11-20 4 14 18 30.0 21-30 13 7 20 33.3 31-40 7 6 13 21.7 41-50 3 2 5 8.3 51-60 2 1 3 5.0 61-70 1 0 1 1.7 Total 30 30 60 100 The distribution of males and females showed that in regimen A, there were 10 females and 20 males, and in regimen B, there were an equal number of males and females, n=15 each. Analysis showed no significant difference in gender wise distribution between the regimens. The occupational status of patients enrolled in the study, comparing Regimen A and Regimen B for keloid treatment. Among the 60 patients, students constituted the largest group (40%), followed by skilled labourers (20%) and unskilled labourers (13.3%). Housewives comprised 11.7%, and businessmen 8.3%. Professionals, retired individuals, and the unemployed made up smaller proportions, each contributing less than 5%. Both regimens had a relatively balanced distribution across most occupational groups, though students were more represented in Regimen B. Table 2 depicts the duration of keloid lesions among the study participants. The majority of patients (65%) had lesions lasting between 1–5 years, indicating this is the most common duration at presentation. Lesions of less than 1 year were seen in 20% of patients, with a higher proportion in Regimen B. Long-standing lesions of more than 10 years were reported in 8.3%, and only 6.7% had lesions lasting 6–10 years. This distribution suggests most patients seek treatment within the first five years, emphasizing the importance of early intervention in keloid management. Table 3: Duration of Lesion Duration in years Regimen Total % A B <1 3 9 12 20.0 1-5 22 17 39 65.0 6-10 3 1 4 6.7 >10 2 3 5 8.3 Total 30 30 60 100 Table 3 shows the duration of keloid in the cases of the study. A critical analysis of the table shows that the majority of patients, 65% had lesions lasting from 1 – 5 years. Lesions of the less than one year were seen in 20% of cases and they were higher in proportion in Regimen B. Long-standing lesions of more then 10 years were found in 8.3% cases and 6.7% had lesion lasting between 6 – 10 years. Figure 1 shows the distribution of keloid lesions based on anatomical location. The chest was the most frequently affected site, accounting for 52% of cases, possibly due to its susceptibility to trauma or surgical incisions. Multiple-site involvement, including the chest, shoulder, arm, and back, was observed in 15% of patients, reflecting widespread lesion occurrence in some individuals. Other commonly affected areas included the face and ear (12%), upper limbs (8%), abdomen and back (5% each), and lower limbs (3%). These findings highlight the variability in lesion site and potential influence on treatment outcomes. Figure 2 highlights the signs and symptoms reported by patients with keloids. Pain was the most frequently reported symptom, experienced by 65% of the participants. This was followed by discoloration (57%) and itching (53%). Cosmetic deformity was reported by 25% of patients, emphasizing the psychological and social impact of the lesions. Restriction of movement was the least common symptom, affecting only 3% of patients, suggesting that functional limitations are relatively rare but can occur depending on lesion location and severity. These symptoms underscore the multifaceted burden of keloid disease. Table 4: Predisposing Factor Predisposing factor Total Percentage Burn 1 2 Infection 35 58 Spontaneous 3 5 Surgical procedure 7 12 Trauma 14 23 Total 60 100 Table 4 depicts the predisposing factors for keloid formation. A critical analysis of the table showed that the most frequent cause was infection in 58% of cases, followed by trauma in 23% of cases, followed by surgical procedures (12%), reflecting the role of dermal injury in abnormal scar formation. Spontaneous occurrence was relatively rare (5%), and burns were the least common cause (2%). These findings underscore the importance of preventive strategies in wound care to mitigate keloid risk, particularly following infections and physical injuries. The analysis of family history showed that 10% of cases had a positive family history of keloid formation, and 90% did not have any family history. Table 5: Response of patients to Regimens (POSAS Observer) Regimen A Regimen B Response Percent change Frequency Percentage Frequency Percentage Poor 0 – 25 2 7 0 0 Fair 26 – 50 15 50 14 47 Good 51 – 75 11 37 16 53 Excellent 76 – 100 2 7 0 0 Comparative Table 5 of patient responses to Regimens A and B, based on POSAS Observer scores, highlights differences in treatment efficacy. In Regimen A, 7% showed poor response (0–25% change), while none in Regimen B had a poor outcome. Fair response (26–50% change) was comparable between groups—50% in Regimen A and 47% in Regimen B. However, Regimen B had a higher proportion of good responses (53%) compared to Regimen A (37%). Notably, 7% of patients in Regimen A achieved excellent response (76–100% change), whereas none in Regimen B reached this level. This suggests Regimen B may be more consistent, but Regimen A shows potential for better outcomes in select cases. Table 6: Treatment Outcome in All Regimens Posas (Patient) Regimen A Regimen B Total Response Frequency % Frequency % Frequency % Poor 0 0 2 7 2 3 Fair 16 53 14 47 30 50 Good 13 43 14 47 27 45 Excellent 1 3 0 0 1 2 Total 30 100 60 100 60 100 Table 6 compares the treatment outcomes of patients using Regimens A and B based on the Patient POSAS (Patient and Observer Scar Assessment Scale). A critical analysis of the table shows that in Regimen A, the majority of patients (53%) had a fair response, 43% had a good response, 3% showed excellent improvement, and none had a poor outcome. In contrast, Regimen B showed 47% fair and good responses each, but 7% had a poor outcome, and none achieved an excellent result. Overall, Regimen A had slightly better outcomes, with a higher percentage of excellent responses and no poor outcomes, suggesting it may be more effective than Regimen B. Table 7: Duration of Lesion and Outcome Regimen A Regimen B Response Duration Range (years) Total % Duration Range (years) Total % < 1 1 - 5 6 - 10 >10 < 1 1 - 5 6 - 10 >10 Poor 0 0 1 1 2 7 0 0 0 0 0 0 Fair 0 12 2 1 15 50 0 10 3 1 14 47 Good 3 8 0 0 11 37 9 7 0 0 16 53 Excellent 0 2 0 0 2 7 0 0 0 0 0 0 Total 3 22 3 2 30 100 9 17 3 1 30 100 Table 7 shows the comparison of the two treatments based on the duration of lesions. The majority of patients had Fair" (50%) or "Good" (37%) response, while Regimen B showed a higher proportion of "Good" outcomes (53%) and no "Poor" or "Excellent" responses. For lesions under 1 year, Regimen B showed better outcomes (9 “Good” responses) than Regimen A (3 “Good”). Regimen A had two "Excellent" responses, both in the 1–5 years category. Overall, Regimen B showed slightly better outcomes, with no poor responses and higher "Good" response rates across all lesion durations. The analysis of side effects associated with Regimens A and B showed that Regimen A had more side effects (13%) compared to Regimen B (9%). Hyperpigmentation (10%) and pain with necrosis (3%) were only reported with Regimen A, while erythema, atrophy with hypopigmentation, and pain with infection (each 3%) were observed only in Regimen B. The total number of adverse effects was slightly higher in Regimen A (4 cases) than in Regimen B (3 cases). Overall, both regimens had minimal side effects, with different profiles, but Regimen B showed slightly better tolerability. The recurrence rate analysis found that only one case of recurrence (2%) occurred, and it was in Regimen A. Regimen B showed no recurrence (0%). The vast majority of patients (98%) had no recurrence, indicating that both regimens are effective in preventing lesion return, with Regimen B showing a slightly better outcome in terms of recurrence.

Keloids sometimes present a therapeutic challenge due to their chronic nature as well as cosmetic disfigurement and tendency to recur. They often occur in younger individuals and are usually found in cosmetically sensitive areas such as the earlobes or chest. In the current study, we found the demographic profile of our cohort aligns with the results of other similar studies in the literature [11-13]. This study found that about 60% of cases were under the age of 30 years, with a male preponderance of 58% of all cases would be due to the cosmetic disfigurement leading to dermatological consultations. We found that the chest is the common anatomical location of the keloids in this study, with 50% of all cases. These findings are consistent with studies of Berman et al. [14], Muir et al. [15], Bayat et al. [16], and Aggarwal et al [17]. The most commonly reported symptom was pain (65%), skin discoloration (57%), and itching (53%), which contrasts with earlier studies where cosmetic concerns predominated [18]. The most frequent cause of keloid in the patients of this study was infections in 58% of cases, followed by trauma in 23% of cases. This is in concordance with observations of Kelly et al. [18] and Murray et al. [19]. A positive family history of keloids was given by 10% of all cases in a similar study. Berman et al. [14] showed the presence of positive history in 4.5 – 16% of patients. Our regimen A (Triamcinolone + 5-Fluorouracil) used combination of intralesional 5-Fluorouracil (50mg/ml) and triamcinolone acetonide (40mg/ml) injection in the ratio of 3:2. Other studies have demonstrated the effectiveness of this combination in various ratios mostly used were from 3:1 to 9:1. Reinholz et al. [20] and Davison et al. [21], have reported good to excellent outcomes using this regimen with greater than 50% reduction in volume of keloid in majority of patients. In this study, we found 44% of patients were able to achieve >50% improvement on the POSAS observer scale and 47% on the patient scale. We also found that 7% of the patients were able to achieve >75% improvement, and there was symptomatic relief in all cases. These results are comparable to those of Khan et al. [22] and Khalid et al. [23], who found good to excellent responses in more than 80% of patients. Our regimen B received a combination of intralesional triamcinolone acetonide (40mg/ml) and hyaluronidase injection(1500IU/ml) in the ratio of 1:1. There is limited literature on this combination used for keloid treatment. The only published study by Aggarwal et al. [17] showed good responses in 68.75% of cases. Our study adds to this evidence with 53% of patients showing greater than 50% improvement on the POSAS observer scale and 47% on the patient scale, and complete symptomatic relief. Our study is one of the few studies that have comprehensively evaluated outcomes using both the POSAS scale and assessing detailed treatment efficacy. The evaluation of side effects showed that regimen A had mild adverse effects, which included pain, ulceration in 3%, and hyperpigmentation in 10% of cases. These adverse effects were less than those reported by Khalid et al. [23] and Darougheh et al. [24] could be due to proper postoperative care. Regimen B showed a favorable safety profile, with erythema (3%), atrophy with hypopigmentation (3%), and minor infection (3%). These rates are comparatively lower than the 18.75% adverse event rate reported by Aggarwal et al. [17]. The frequency of recurrence of keloids remains a significant concern. Khalid et al. [23] showed that the recurrence rate was 17.5% for triamcinolone + 5-FU. In this study, only one patient (2%) from regimen A experienced recurrence, and there were no reports of recurrence in regimen B.

In conclusion, we found that both regimens have been found to have significant efficacy and safety in the treatment keloids. Regimen A (Triamcinolone + 5-FU) remains a time-tested combination with consistent results, while Regimen B (Triamcinolone + Hyaluronidase), showed comparable outcomes with fewer adverse effects and no recurrence. This suggests it may serve as a viable alternative, especially in patients with poor tolerance to 5-FU or a higher risk of ulceration. Further studies with larger sample sizes and longer follow-up are recommended to substantiate these findings.

1. Al-Attar A, Mess S, Thomassen JM, Kauffman CL, Davison SP. Keloid pathogenesis and treatment. Plast Reconstr Surg. 2006;117(1):286–300. 2. Berman B, Bieley HC. Keloids. J Am Acad Dermatol. 1995;33(1):117–123. 3. Lee JY, Yang CC, Chao SC, Wong TW. Histopathological differential diagnosis of keloid and hypertrophic scar. Am J Dermatopathol. 2004;26(5):379–84. 4. Ghazawi FM, Zargham R, Gilardino M, Sasseville D. Insights into the pathophysiology of keloids: Facts and controversies. Clin Dermatol. 2020;38(6):613–623. 5. Manuskiatti W, Fitzpatrick RE. Treatment response of keloidal and hypertrophic sternotomy scars: Comparison among intralesional corticosteroid, 585-nm flashlamp-pumped pulsed-dye laser, and combined treatment. Arch Dermatol. 2002;138(9):1149–55. 6. Darzi MA, Chowdri NA, Kaul SK, Khan M. Evaluation of various methods of treating keloids and hypertrophic scars: A 10-year follow-up study. Br J Plast Surg. 1992;45(5):374–79. 7. Fitzpatrick RE. Treatment of inflamed hypertrophic scars using intralesional 5-FU. Dermatol Surg. 1999;25(3):224–32. 8. Manuskiatti W, Fitzpatrick RE. Intralesional corticosteroid with 5-FU for keloid therapy: A combination approach. Dermatol Surg. 2002;28(1):25–31. 9. Park TH, Seo SW, Kim JK, Chang CH. Clinical application of triamcinolone with hyaluronidase for hypertrophic scars and keloids: A pilot study. Ann Plast Surg. 2013;71(5):484–88. 10. Adigun CG. Topical and intralesional therapies for hypertrophic scars and keloids. Dermatol Ther. 2020;33(6): e14234. 11. Bush J, So K, Mason T, Occleston NL, O'Kane S, and Ferguson MW. Therapies with emerging evidence of efficacy: avotermin for the improvement of scarring. Dermatology research and practice. 2010 3; 2010:690613. 12. Jalali M, and Bayat A. Current use of steroids in the management of abnormal raised skin scars. The Surgeon. 2007; 1;5(3):175-80. 13. Tredget EE, Nedelec B, Scott PG, Ghahary A. Hypertrophic scars, keloids, and contractures: the cellular and molecular basis for therapy. Surgical Clinics of North America. 1997; 1;77(3):701-30. 14. Berman B, Bieley HC. Adjunct therapies to surgical management of keloids. Dermatol Surg. 1996 Feb;22(2):126-30. 15. Muir IF. On the nature of keloid and hypertrophic scars. Br J Plast Surg. 1990 Jan;43(1):61-9. 16. Bayat A, Arscott G, Ollier WE, Ferguson MW, McGrouther DA. Description of site-specific morphology of keloid phenotypes in an Afrocaribbean population. Br J Plast Surg. 2004 Mar;57(2):122-33. 17. Aggarwal A, Ravikumar BC, Vinay KN, Raghukumar S, Yashovardhana DP. A comparative study of various modalities in the treatment of keloids. Int J Dermatol. 2018 Oct;57(10):1192-1200. 18. Kelly AP. Keloids. Dermatol Clin. 1988 Jul;6(3):413–24. 19. Murray JC. Scars and keloids. Dermatol Clin. 1993 Oct;11(4):697-708. 20. Reinholz M, Guertler A, Schwaiger H, Poetschke J, Gauglitz GG. Treatment of keloids using 5-fluorouracil in combination with crystalline triamcinolone acetonide suspension: evaluating therapeutic effects by using non-invasive objective measures. J Eur Acad Dermatol Venereol. 2020 Oct;34(10):2436-2444. 21. Davison SP, Dayan JH, Clemens MW, Sonni S, Wang A, Crane A. Efficacy of intralesional 5-fluorouracil and triamcinolone in the treatment of keloids. Aesthet Surg J. 2009 Jan-Feb; 29(1):40-46. 22. Khan MA, Bashir MM, Khan FA. Intralesional triamcinolone alone and in combination with 5-fluorouracil for the treatment of keloid and hypertrophic scars. J Pak Med Assoc. 2014 Sep;64(9):1003-07. 23. Khalid FA, Mehrose MY, Saleem M, Yousaf MA, Mujahid AM, Rehman SU, Ahmad S, Tarar MN. 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 Feb;45(1):69-75. 24. Darougheh A, Asilian A, Shariati F. Intralesional triamcinolone alone or in combination with 5-fluorouracil for the treatment of keloid and hypertrophic scars. Clin Exp Dermatol. 2009 Mar; 34(2):219-23.