The process of wound healing is a complex, dynamic, and highly regulated cascade of cellular and molecular events aimed at restoring tissue integrity. In most individuals, this process culminates in the formation of a flat, normotrophic scar that is functionally and aesthetically acceptable [1]. However, in a subset of the population, this intricate process is dysregulated, leading to the formation of excessive fibrotic tissue, clinically manifesting as either a hypertrophic scar (HTS) or a keloid. These entities represent a spectrum of fibroproliferative disorders of the skin that result in significant physical and psychological morbidity [2,3].

While often used interchangeably in lay terms, hypertrophic scars and keloids are pathophysiologically and clinically distinct. A hypertrophic scar is characterized by excessive collagen deposition that remains confined to the boundaries of the original wound. It typically arises within weeks of injury, may undergo a phase of rapid growth, and often demonstrates a tendency to regress spontaneously over time [4]. It presents as a raised, erythematous, and pruritic lesion. In contrast, a keloid is a more aggressive lesion that extends beyond the margins of the original wound, invading the surrounding normal skin. It does not regress and can continue to grow for years, often presenting as a firm, rubbery, hyperpigmented nodule with characteristic claw-like extensions [5,6].

The pathogenesis of abnormal scarring is multifactorial, involving a complex interplay between genetic predisposition, systemic factors, and local wound environment. Central to this process is the dysregulation of fibroblasts and their response to growth factors, particularly Transforming Growth Factor-beta (TGF-β). In keloid and HTS tissue, fibroblasts exhibit increased proliferation, reduced apoptosis, and an exaggerated production of extracellular matrix components, primarily type I and type III collagen, alongside decreased collagenase activity [7,8]. This imbalance between collagen synthesis and degradation leads to the net accumulation of fibrotic tissue. Genetic factors are believed to play a substantial role, as evidenced by the higher prevalence in certain ethnic groups, particularly those with darker skin pigmentation, and the frequent occurrence of a positive family history [9,10].

Several clinical risk factors have been implicated in the development of these lesions. Anatomical location is a well-established predictor, with areas of high skin tension, such as the presternal chest, shoulders, upper back, and earlobes, being particularly susceptible [11,12]. Wound-related factors, including the presence of infection, delayed epithelialization, and the presence of a foreign body, are known to promote a chronic inflammatory state that can drive abnormal fibroplasia [13]. Systemic factors such as younger age, particularly puberty and pregnancy due to hormonal influences, and certain endocrine disorders have also been linked to a higher risk. However, the majority of existing evidence is derived from retrospective analyses. Given the profound impact of abnormal scars on patient quality of life, a comprehensive understanding of these risk factors is essential for risk stratification, patient counseling, and the implementation of early prophylactic interventions. This prospective study aims to contribute to this understanding by systematically evaluating these factors in a specific cohort.

OBJECTIVE

The primary objective of this study is to prospectively identify the demographic, clinical, and surgical risk factors associated with the development of keloid and hypertrophic scar formation in patients undergoing surgical procedures at a tertiary care hospital. By systematically collecting pre-operative, intra-operative, and post-operative data, we aim to quantify the relative contribution of each factor to the risk of abnormal scarring.

A secondary objective is to describe the clinical characteristics of the resulting scars in our population, including their severity as measured by a standardized scar assessment tool. This will allow for a better understanding of the clinical burden of abnormal scarring in our setting. Ultimately, the findings of this study are intended to inform clinical practice by facilitating the identification of high-risk patients who would benefit most from early, targeted prophylactic measures, such as silicone gel sheeting, pressure therapy, or intralesional corticosteroid injections, thereby improving post-surgical outcomes.

This was a single-center, prospective observational study conducted in the Department of General Surgery and Dermatology at a tertiary care hospital in Tamil Nadu, India, over a period of one year, from September 2019 to August 2020. The study protocol was reviewed and approved by the Institutional Ethics Committee prior to commencement. The study adhered to the principles of the Declaration of Helsinki. The primary outcome measure was the development of a hypertrophic scar or keloid at the surgical site, diagnosed clinically and assessed for severity using the Vancouver Scar Scale (VSS) at the six-month follow-up visit. Patients scheduled for elective surgical procedures were screened for eligibility during the pre-operative assessment period. Informed written consent was obtained from all participants after a detailed explanation of the study's purpose, procedures, and follow-up requirements. Inclusion Criteria: Patients aged 18 to 65 years, undergoing a clean or clean-contaminated elective surgical procedure with a linear incision of a minimum length of 2 cm, and who were willing to comply with the follow-up schedule were included. Exclusion Criteria: Patients with a pre-existing dermatological condition at the surgical site (e.g., active infection, psoriasis), those on systemic immunosuppressive or chronic corticosteroid therapy, patients with a known diagnosis of a connective tissue disorder (e.g., Ehlers-Danlos syndrome), and pregnant or lactating women were excluded. Patients lost to follow-up before the six-month assessment were also excluded from the final analysis. Data Collection Procedure: Data was collected at three time points: pre-operatively, intra-operatively, and post-operatively. Pre-operative data included patient demographics (age, sex), detailed medical history focusing on any personal or family history of keloids or HTS, and Fitzpatrick skin phototype. The anatomical site of the planned surgery was recorded. Intra-operative data comprised the type of surgical procedure, the length of the incision, and the suture material used for skin closure. Post-operatively, patients were followed up at 1 week, 2 weeks, 1 month, 3 months, and 6 months. At each visit, the wound was assessed for signs of infection, and the time to complete wound epithelialization was noted. At the 6-month visit, a final clinical assessment was made to determine if the scar was normal, hypertrophic, or keloidal. The scar was then objectively scored using the VSS, which assesses vascularity, pigmentation, pliability, and height [14,15]. Statistical Data Analysis: Data was entered into a Microsoft Excel spreadsheet and analyzed using SPSS version 25.0 (IBM Corp., Armonk, NY). Descriptive statistics were used to summarize baseline characteristics; categorical variables were presented as frequencies and percentages, while continuous variables were summarized as mean ± standard deviation or median with interquartile range as appropriate. Univariate analysis using the Chi-square test (or Fisher's exact test for small cell counts) was performed to identify associations between potential risk factors and the primary outcome (development of abnormal scar). Variables with a p-value <0.10 in the univariate analysis were entered into a multivariate logistic regression model to identify independent predictors of abnormal scarring. A two-sided p-value <0.05 was considered statistically significant for the final analysis.

A total of 42 patients who met the inclusion criteria and completed the six-month follow-up were included in the final analysis. The mean age of the study participants was 38.5 ± 12.4 years (range 19-63 years). The study cohort consisted of 24 (57.1%) females and 18 (42.9%) males. The most common surgical procedure was abdominal surgery (n=14, 33.3%), followed by orthopedic procedures on extremities (n=10, 23.8%), and cardiothoracic or shoulder surgeries (n=8, 19.0%). A personal history of keloid or HTS was present in 9 (21.4%) patients, and a family history was reported by 11 (26.2%) patients. The majority of the cohort (n=28, 66.7%) had Fitzpatrick skin phototype IV or V.

Table 1: Baseline Demographic and Clinical Characteristics of Study Participants (N=42)

During the six-month follow-up period, 12 patients (28.6%) developed abnormal scarring; 7 (16.7%) developed hypertrophic scars and 5 (11.9%) developed keloids. The mean Vancouver Scar Scale (VSS) score for patients with an abnormal scar was 7.4 ± 2.1. Delayed wound healing (defined as epithelialization time > 14 days) was observed in 13 patients (31.0%), and clinical signs of post-operative wound infection occurred in 6 patients (14.3%). The univariate analysis of risk factors is summarized in Table 2.

Table 2: Univariate Analysis of Risk Factors for Abnormal Scar Formation

Table 3: Multivariate Logistic Regression Analysis for Independent Predictors of Abnormal Scarring

In the multivariate logistic regression model (Table 3), a personal history of keloid or HTS (Adjusted OR = 12.4, 95% CI: 2.8-54.6; p=0.001) was the strongest independent risk factor for post-surgical abnormal scar formation. This was followed by an anatomical location on the chest or shoulder (Adjusted OR = 6.8, 95% CI: 1.5-30.9; p=0.013). A positive family history remained a significant independent predictor (Adjusted OR = 4.1, 95% CI: 1.1-15.3; p=0.035). Although post-operative infection showed a strong trend, it did not reach statistical significance as an independent predictor in this model (p=0.065).

This prospective study confirms that the development of keloids and hypertrophic scars following surgery is a common occurrence, affecting nearly one in four patients in our cohort. The most critical finding is the overwhelming importance of a patient's intrinsic predisposition to abnormal scarring. A personal history of keloid or HTS was the single most potent predictor, increasing the risk of developing a similar lesion at a new surgical site by over twelve-fold. This finding is consistent with a substantial body of literature identifying prior scarring as the most significant clinical indicator of a systemic fibroproliferative tendency [10,16]. The genetic underpinnings of this predisposition are further emphasized by the finding that a positive family history independently doubled the risk, reinforcing the concept of a heritable component in the pathogenesis of these disorders [17]. These results underscore the critical need for a thorough history-taking process before any elective surgery. For a patient with a positive personal or family history, the physician is no longer discussing a generic risk but is instead managing a highly probable outcome, necessitating a frank discussion about prophylactic options. The second major finding of our study highlights the crucial role of the local wound environment. Surgeries on the chest and shoulder were associated with a significantly increased risk of abnormal scarring. This observation is widely supported and is primarily attributed to the high resting skin tension in these regions, which leads to persistent mechanical stress on the healing wound [11,18]. This tension activates mechanotransduction pathways in fibroblasts, promoting their differentiation into myofibroblasts and leading to sustained extracellular matrix production [19]. While post-operative infection and delayed wound healing were significant in our univariate analysis, they did not maintain significance as independent predictors in the multivariate model. This is likely because these factors often coexist, with infection leading to delayed healing. The resultant prolonged inflammatory phase creates a cytokine milieu (rich in TGF-β, PDGF, and IL-6) that is profoundly profibrotic, effectively acting as a local accelerant for scar formation [20,21]. In the context of a patient with an already high genetic risk, a localized infection can be the "second hit" that triggers an aggressive keloidal response. Our study did not find a statistically significant association between skin phototype and abnormal scarring, although there was a trend. This finding stands in contrast to the well-documented higher prevalence of keloids in darker-skinned populations [9]. This discrepancy is almost certainly due to the limited sample size and the fact that our study population was relatively homogenous, with most patients (66.7%) already having Fitzpatrick phototypes IV or V. Since a significant portion of our cohort belonged to higher phototypes, our sample was likely underpowered to detect a difference when comparing to lighter-skinned individuals. Similarly, while younger age and female sex are often cited as risk factors, our study did not demonstrate a significant association, potentially due to the sample size limitations. The hormonal influences of puberty and pregnancy, which are known to stimulate collagen production, may not have been adequately represented in our adult cohort [22]. The clinical implications of our findings are clear. The pre-operative identification of high-risk patients (those with a personal or family history and/or surgery on high-tension sites) allows for the implementation of a proactive management strategy. This could include pre-operative intralesional corticosteroid injections at the wound margins, the use of prophylactic silicone gel sheeting from the time of suture removal, and close post-operative surveillance for early signs of hypertrophy to allow for prompt intervention [23]. For such high-risk patients, meticulous surgical technique aimed at minimizing tension (e.g., layered closure, deep dermal sutures) and the avoidance of infection are of paramount importance. Our study provides prospective data from a specific Indian population, reinforcing the universal nature of these risk factors and confirming their applicability in a tertiary care setting. LIMITATIONS OF THE STUDY The primary limitation of this study is its relatively small sample size, which is a common constraint for prospective studies within a single center over a limited timeframe. This small sample size limited the statistical power to detect the independent effects of several risk factors, such as skin type and post-operative infection, and precluded a more detailed subgroup analysis. The follow-up period of six months, while adequate for the assessment of hypertrophic scars, may be insufficient for the definitive diagnosis of some keloids, which can have a delayed onset and continue to evolve for years. A longer follow-up would provide a more complete picture of final scar outcomes. Furthermore, the study population, while diverse in age and surgical procedures, was ethnically homogenous, drawn from a specific region of South India. This limits the generalizability of the findings to more heterogeneous populations. Finally, the diagnosis of keloid versus hypertrophic scar, while based on clinical criteria, retains a degree of subjectivity, and the assessment of the scar using the VSS, though validated, is an observer-dependent measurement. ACKNOWLEDGEMENT We would like to express our sincere gratitude to the Department of General Surgery and the Department of Dermatology for their unwavering support and for providing the necessary infrastructure to conduct this study. We are deeply indebted to all the patients who participated in this research and willingly committed to the follow-up schedule; this work would not have been possible without their cooperation. We also thank our colleagues in the Department of Community Medicine for their valuable guidance on the statistical analysis used in this manuscript.

In conclusion, this prospective observational study reaffirms that the development of keloid and hypertrophic scars following surgery is a significant and common complication. The most critical predictors are a patient's inherent predisposition, manifested by a personal or family history of abnormal scarring, and the anatomical location of the surgical wound, with high-tension areas like the chest and shoulder being particularly vulnerable. These factors are non-modifiable; therefore, the key to management lies not in treating the established scar but in its prevention. A comprehensive pre-operative assessment that specifically elicits a history of abnormal scarring is not optional but essential for risk stratification.

Patients identified as high-risk should be managed with a proactive, multi-modal prophylactic approach. This begins with patient education about their elevated risk and continues with meticulous surgical technique to minimize tension and the risk of infection. Early initiation of prophylactic therapies, such as silicone gel sheeting, should be standard practice for these individuals. Future research should focus on larger, multi-center prospective cohorts to validate these findings and explore novel biomarkers for risk prediction. Additionally, investigating the efficacy of different combination prophylactic protocols in high-risk patients can pave the way for more personalized and effective strategies to combat this challenging clinical problem.

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