Genetic Factors and Management of Hypertrophic Scarring

Causes and Risk Factors for Hypertrophic Scarring

Hypertrophic scars typically develop in response to injuries that penetrate the dermal layers, such as surgical incisions, burns, or traumatic wounds. Several intrinsic and extrinsic factors contribute to the formation of HTS, including:

• Genetic Predisposition: Specific genetic factors have been associated with an increased risk of developing HTS. For instance, research indicates alterations in genes related to collagen synthesis and remodeling, which are critical during wound healing (Bian et al., 2025). Variants in the PAK2 gene, known for its role in cellular signaling and proliferation, have been implicated in the pathogenesis of various fibrotic disorders, including HTS.
• Age and Ethnicity: Younger individuals and certain ethnic groups, particularly those with darker skin, are at a higher risk for developing hypertrophic scars. This is likely due to differences in skin structure and healing responses (Wang et al., 2018).
• Wound Characteristics: The tension on the wound, location, and depth of the injury are significant determinants of HTS formation. Wounds that are under tension or located in areas of high mobility (e.g., joints) are more likely to result in hypertrophic scars (Ghazawi et al., 2018).

Table 1: Key Risk Factors for Hypertrophic Scarring

Clinical Presentation and Diagnosis of Hypertrophic Scarring

Clinically, hypertrophic scars present as raised, firm, and red lesions that may be itchy or painful. They typically develop within weeks of the injury and can take several months to mature. The diagnosis of HTS is primarily based on clinical examination, although histopathological analysis may be used in atypical cases to differentiate HTS from keloids or other skin conditions.

Diagnostic Tools for Hypertrophic Scarring

• Visual Inspection: The appearance of the scar, including elevation, color, and texture, can provide immediate clues.
• Histology: A biopsy may reveal increased collagen deposition and fibroblast proliferation characteristic of HTS.
• Ultrasound: This imaging modality can assess the thickness and vascularity of the scar tissue.

Effective Treatment Options for Hypertrophic Scarring

Management of hypertrophic scars involves a multi-faceted approach tailored to the severity of the condition, patient preferences, and response to initial treatments. Options include:

• Pressure Garments: Custom-made pressure garments can help flatten hypertrophic scars by applying consistent pressure to the scar tissue, preventing excessive collagen deposition.
• Silicone Gel Sheets: These sheets are effective in reducing scar height and redness when applied to the scar for prolonged periods.
• Intralesional Corticosteroids: Corticosteroids can be injected directly into the scar to reduce inflammation and collagen synthesis. This treatment can be combined with pressure therapy for enhanced results (Ghazawi et al., 2018).
• Laser Therapy: Various laser treatments, such as pulsed dye laser or fractional CO2 laser, have shown efficacy in improving the appearance of hypertrophic scars by promoting collagen remodeling and reducing redness.
• Surgical Revision: In cases of severe scarring, surgical intervention may be warranted to excise the hypertrophic scar and allow for more aesthetically pleasing healing.

Table 2: Treatment Modalities for Hypertrophic Scarring

Role of Iron Traits in Hypertrophic Scarring Development

Emerging research has begun to unravel the complex relationship between iron metabolism and hypertrophic scarring. Iron plays a critical role in collagen synthesis and the overall healing process. Abnormalities in iron homeostasis, such as iron deficiency anemia (IDA), have been linked to impaired wound healing and potentially increased scarring (Bian et al., 2025).

Genetic Insights

A Mendelian randomization study indicated that elevated transferrin saturation (TFS) levels might have a protective effect against the risk of developing hypertrophic scars. This suggests that maintaining optimal iron levels may be beneficial in modulating scar formation (Bian et al., 2025). The inverse variance weighted (IVW) method highlighted a potential protective association, although results varied across different statistical methods.

Table 3: Genetic Factors and Iron Traits Associated with Hypertrophic Scarring

Future Directions in Hypertrophic Scarring Research

The field of hypertrophic scarring research is evolving, with several promising directions that warrant exploration. Future studies should focus on:

• Longitudinal Studies: Investigating the long-term outcomes of various treatment modalities for hypertrophic scars, including patient-reported outcomes.
• Genetic Studies: Further elucidating the genetic factors involved in scar formation could lead to targeted therapies that address the underlying mechanisms of hypertrophic scarring.
• Novel Therapies: Exploring the role of emerging technologies, such as gene therapy or stem cell treatments, in modulating scar formation and improving healing outcomes.

Conclusion

Hypertrophic scarring is a multifactorial condition influenced by genetic, environmental, and physiological factors. Understanding the role of iron traits and other genetic predispositions can provide valuable insights into the mechanisms underlying hypertrophic scarring and lead to more effective management strategies. Continued research is essential to develop targeted therapies that improve patient outcomes and enhance the quality of life for those affected by hypertrophic scars.

FAQ

What is hypertrophic scarring? Hypertrophic scarring is an excessive fibroproliferative response to skin injury, resulting in raised and thickened scars.

What causes hypertrophic scars? Factors influencing hypertrophic scars include genetic predisposition, age, ethnicity, wound tension, and injury characteristics.

How can hypertrophic scars be treated? Treatment options include pressure garments, silicone gel sheets, intralesional corticosteroids, laser therapy, and surgical revision.

Is there a genetic component to hypertrophic scarring? Yes, genetic factors, including specific gene variants, play a significant role in the risk of developing hypertrophic scars.

What is the role of iron in scar formation? Iron is crucial for collagen synthesis and wound healing, with research suggesting that optimal iron levels may reduce the risk of hypertrophic scarring.

References

1. Bian, D., Gong, H., & Shi, W. (2025). The causal effect of iron traits on risk of hypertrophic scarring: A two‐sample Mendelian randomization study. Journal of Cosmetic Dermatology. Retrieved from https://pubmed.ncbi.nlm.nih.gov/12046542/

2. Ghazawi, F. M., Zargham, R., Gilardino, M. S., Sasseville, D., & Jafarian, F. (2018). Insights into the pathophysiology of hypertrophic scars and keloids: How do they differ? Advances in Skin & Wound Care, 31(1), 582–595

3. Wang, Y., Beekman, J., Hew, J., & others. (2018). Burn injury: Challenges and advances in burn wound healing, infection, pain, and scarring. Advanced Drug Delivery Reviews, 123, 3–17. Retrieved from https://doi.org/10.1016/j.addr.2018.08.004