Causes of Keloids
Keloids result from aberrant wound healing in the reticular dermis following skin injury, characterized by chronic inflammation, excessive fibroblast proliferation, and pathologic collagen deposition that extends beyond the original wound boundaries. 1, 2
Primary Pathophysiologic Mechanism
Keloids develop when injuries penetrate to the reticular dermis layer of skin, triggering an abnormal healing cascade. Superficial injuries that do not reach the reticular dermis never cause keloid formation, which confirms this specific anatomic requirement. 2
The fundamental process involves:
- Chronic localized inflammation in the reticular dermis that fails to resolve normally 2
- Excessive fibroproliferative response with overgrowth of granulation tissue and collagen type III during healing 1
- Disorganized extracellular matrix formation due to dysregulation in inflammatory, proliferative, and/or remodeling phases of wound healing 3, 4
Triggering Injuries and Risk Factors
Common Precipitating Events
Any trauma that reaches the reticular dermis can trigger keloid formation:
- Body piercings (ears, nose, nipples, navel) - with keloid formation occurring in approximately 2.5% of ear piercings and higher rates with body piercings performed in professional shops (18.4% infection rate which can lead to keloid formation) 5
- Surgical incisions and trauma 2
- Burns 2
- Insect bites 2
- Infections: acne, folliculitis, chicken pox, herpes zoster 2
- Vaccinations and skin piercing procedures 2
Genetic Predisposition
There is a strong genetic component to keloid formation, with predisposition being genetically transmitted. 1 Patients with personal or family history of keloids face significantly elevated risk with any skin trauma. 6
Specific genetic factors include:
- Upregulation of proinflammatory genes (IL-1α, IL-1β, IL-6, TNF-α) in skin that is sensitive to trauma 2
- Chromosomal abnormalities in some cases 5
Biomechanical Contributing Factors
Mechanical forces play a crucial initiating and perpetuating role in keloid development:
- Mechanical stimulation leads to excessive fibroblast proliferation, ECM deposition, and secretion of pro-fibrotic factors 7
- Increased matrix stiffness from collagen deposition further activates the fibrotic phenotype of keloid fibroblasts, creating a self-perpetuating cycle 7
- Skin tension across wounds promotes keloid formation 3
Key mechanotransduction pathways involved include TGF-β/Smad, integrin signaling, YAP/TAZ signaling, and calcium ion pathways. 7
Inflammatory Dysregulation
Keloids represent inflammatory disorders of the reticular dermis rather than true skin tumors. 2
The inflammatory component involves:
- Continuous histologically localized inflammation in the reticular dermis 2
- Persistent presence of inflammatory cells, increased fibroblasts, newly formed blood vessels, and excessive collagen deposits 2
- Proinflammatory factor upregulation that promotes chronic inflammation and invasive keloid growth 2
Clinical Distinction
The intensity, frequency, and duration of reticular dermis inflammation determine whether scars become hypertrophic (confined to wound boundaries) versus keloid (extending beyond original injury). 2 Various external and internal post-wounding stimuli—including local, systemic, and genetic factors—shape the characteristics, quantity, and progression of pathologic scarring. 2