What is the pathophysiology behind keloid formation?

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Last updated: June 19, 2025View editorial policy

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From the Guidelines

Keloid formation is primarily driven by abnormal wound healing, where excessive collagen production continues beyond normal scar formation, triggered by tissue injury and dysregulation of growth factors like TGF-β, PDGF, and IGF-1. The pathophysiology of keloid formation begins with tissue injury, which triggers the standard wound healing cascade, but in keloid formation, this process becomes dysregulated. After injury, inflammatory cells release cytokines and growth factors that stimulate fibroblast proliferation and collagen synthesis. In keloids, fibroblasts demonstrate heightened sensitivity to these signals and continue producing collagen long after wound closure should have occurred.

Some key factors that contribute to keloid formation include:

  • Genetic factors, as keloids show familial tendencies and are more common in individuals with darker skin 1
  • Mechanical tension across wounds, which explains their frequent occurrence over high-tension areas like the chest, shoulders, and earlobes
  • Imbalance between collagen production and degradation, with reduced activity of matrix metalloproteinases (MMPs) that would normally break down excess collagen

Understanding this pathophysiology helps explain why keloids extend beyond the original wound boundaries and why they frequently recur after surgical excision. Prevention is the best strategy for managing keloids, especially in individuals with a history of keloid formation or a family history of keloids. According to recent studies, individuals with a personal or family history of keloids should be cautioned about the risk associated with scarification and other body modification processes 1.

The most recent and highest quality study on this topic is from 2017, which highlights the importance of prevention and cautious approach to body modifications in individuals with a history of keloids 1. In summary, keloid formation is a complex process involving abnormal wound healing, genetic factors, and mechanical tension, and prevention is key to managing this condition.

From the Research

Pathophysiology of Keloid Formation

The pathophysiology behind keloid formation is complex and involves an abnormal wound-healing process. Key factors include:

  • Excessive production of extracellular matrix (ECM) components, particularly collagen, leading to a disorganized fibroproliferative collagen response 2, 3, 4
  • Lack of control mechanisms self-regulating cell proliferation and tissue repair, resulting in the formation of nodular lesions that extend beyond the area of injury 5
  • Excessive expression of growth factors and cytokines, contributing to the development of keloids 3

Abnormal Wound-Healing Process

The abnormal wound-healing process underlying keloid formation is characterized by:

  • A disorganized extracellular matrix due to excessive fibroproliferative collagen response 2, 4
  • Uncontrolled cell proliferation and tissue repair, leading to the growth of keloids beyond the original wound margins 5
  • The formation of fibroproliferative dermal tumors with effusive accumulation of ECM components, particularly collagen 3

Genetic and Environmental Factors

Keloid formation is also influenced by:

  • Genetic susceptibility, with keloids occurring after dermal injury in genetically susceptible individuals 3
  • Environmental factors, such as tension across the lesion and inflammatory response, which can contribute to the development of keloids 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Keloids: a review of therapeutic management.

International journal of dermatology, 2021

Research

Keloids: The paradigm of skin fibrosis - Pathomechanisms and treatment.

Matrix biology : journal of the International Society for Matrix Biology, 2016

Research

Management of Keloids and Hypertrophic Scars.

American family physician, 2024

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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