Understanding Keloid Scars: Causes and Risk Factors

# Understanding Keloid Scars: Causes and Risk Factors

What Are Keloid Scars?

Keloid scars are a type of raised scar that occurs after skin injury, characterized by an overgrowth of dense fibrous tissue that extends beyond the original wound boundaries. Unlike hypertrophic scars, which remain confined to the site of injury and often regress over time, keloids can continue to grow indefinitely and rarely diminish on their own. They are typically firm, rubbery, or shiny, and can range in color from pink to red or dark brown. Keloids can cause itching, pain, tenderness, and a burning sensation, and their appearance can lead to significant cosmetic concerns and psychological distress. Understanding their formation is key to prevention and management [1].

Primary Causes of Keloid Formation

Keloids develop as a result of an abnormal wound healing process where the skin reacts excessively to trauma, leading to an overproduction of collagen. This can be triggered by almost any type of skin injury, even minor ones. Common causes include:

* Surgical Incisions: Scars from operations, especially in areas of high tension.

* Traumatic Wounds: Cuts, lacerations, and puncture wounds.

* Burns: Even minor burns can sometimes lead to keloid formation.

* Acne and Chickenpox: Severe cases of acne or chickenpox can leave behind scars that develop into keloids, particularly on the face, chest, or back.

* Body Piercings: Ear piercings are a very common trigger for keloids, especially on the earlobes and cartilage.

* Vaccinations and Injections: The site of a vaccination or injection can sometimes develop into a keloid.

* Insect Bites: Even small insect bites can initiate the keloid formation process [2, 3].

Key Risk Factors for Developing Keloid Scars

While keloids can affect anyone, certain individuals are more predisposed to developing them due to a combination of genetic and environmental factors:

* Genetics and Ethnicity: A strong genetic predisposition exists. Individuals with a family history of keloids are at a significantly higher risk. Keloids are also more common in people with darker skin tones, particularly those of African, Afro-Caribbean, and Asian descent. This suggests a genetic component related to melanin production and skin healing processes [4].

* Age: The highest incidence of keloids occurs between the ages of 10 and 30. They are less common in very young children and the elderly.

* Location of Injury: Certain areas of the body are more prone to keloid formation due to skin tension and movement. These include the chest (especially the sternum), shoulders, upper back, earlobes, and neck.

* Type of Injury: Injuries that involve deep layers of the skin or prolonged inflammation tend to have a higher risk of keloid development.

* Hormonal Factors: While not fully understood, hormonal influences may play a role, as keloids often appear or worsen during puberty or pregnancy.

* Underlying Medical Conditions: Some studies suggest that conditions like diabetes might influence keloid formation and progression, though more research is needed [5].

Prevention and Early Intervention

For individuals with known risk factors, prevention is paramount. This includes avoiding unnecessary skin trauma, such as elective cosmetic piercings, and taking extra precautions with any necessary surgical procedures. If a skin injury occurs, early intervention and proper wound care are crucial. For those prone to keloids, discussing preventive measures with a dermatologist before any planned procedures (e.g., surgery) is highly recommended. Early recognition of a developing keloid allows for more effective treatment options and can help prevent significant growth [6].

Medical Disclaimer

The information provided in this article is for educational purposes only and is not intended as medical advice. Always consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.

References

[1] Mayo Clinic. (2023, July 13). Keloid scar - Symptoms and causes. [https://www.mayoclinic.org/diseases-conditions/keloid-scar/symptoms-causes/syc-20520901](https://www.mayoclinic.org/diseases-conditions/keloid-scar/symptoms-causes/syc-20520901)

[2] American Academy of Dermatology (AAD). (n.d.). Keloid scars: Causes. [https://www.aad.org/public/diseases/a-z/keloids-causes](https://www.aad.org/public/diseases/a-z/keloids-causes)

[3] Cleveland Clinic. (n.d.). Keloid Scar: What It Is, Symptoms, Treatment & Removal. [https://my.clevelandclinic.org/health/diseases/keloid-scar](https://my.clevelandclinic.org/health/diseases/keloid-scar)

[4] NIH. (n.d.). Keloid - StatPearls. [https://www.ncbi.nlm.nih.gov/books/NBK507899/](https://www.ncbi.nlm.nih.gov/books/NBK507899/)

[5] TeachMeSurgery. (2025, August 31). Keloid - Formation - Treatment - Risk Factors. [https://teachmesurgery.com/perioperative/skin/keloids/](https://teachmesurgery.com/perioperative/skin/keloids/)

[6] NHS. (n.d.). Keloid scars. [https://www.nhs.uk/conditions/keloid-scars/](https://www.nhs.uk/conditions/keloid-scars/)

The Cellular Biology of Keloid Formation

Keloid scars represent a fundamental failure of the normal wound healing process — specifically, an inability to "turn off" the healing response once the wound has closed. Understanding the cellular mechanisms involved explains why keloids are so difficult to treat and why they recur.

Normal wound healing: A tightly regulated process

Normal wound healing proceeds through four overlapping phases:

1. Hemostasis (minutes to hours): Platelet aggregation and clot formation
2. Inflammation (days 1–5): Neutrophil and macrophage infiltration; release of growth factors
3. Proliferation (days 5–21): Fibroblast migration, collagen synthesis, angiogenesis
4. Remodeling (weeks to years): Collagen reorganization, scar maturation, reduction in cellularity

In normal healing, the proliferative phase is tightly regulated — fibroblasts produce collagen to fill the wound defect, then undergo apoptosis (programmed cell death) as the wound matures. The result is a flat, pale scar.

Keloid formation: Dysregulated healing

In keloid formation, the proliferative phase fails to terminate. Keloid fibroblasts continue producing collagen long after the wound has closed, driven by:

• Persistent TGF-β1 signaling: TGF-β1 (transforming growth factor beta-1) is the master regulator of fibrosis. In keloid tissue, TGF-β1 is overexpressed and its downstream signaling pathways (SMAD2/3) remain constitutively activated, driving continuous collagen production.

• Fibroblast resistance to apoptosis: Keloid fibroblasts overexpress anti-apoptotic proteins (Bcl-2, survivin) and are resistant to the apoptotic signals that normally terminate the proliferative phase.

• Mast cell infiltration: Keloid tissue contains 3–5 times more mast cells than normal skin. Mast cells release histamine, tryptase, and cytokines that stimulate fibroblast proliferation and collagen synthesis.

• Abnormal collagen architecture: Keloid collagen fibers are thicker, more randomly oriented, and more resistant to degradation than normal scar collagen.

Genetic Basis of Keloid Susceptibility

The strong familial clustering of keloids — and the marked racial differences in keloid prevalence — point to a significant genetic component.

Familial patterns:

• First-degree relatives of keloid patients have a 2–3 fold increased risk
• Identical twins show higher concordance for keloids than fraternal twins
• Autosomal dominant inheritance with incomplete penetrance has been described in some families

Genetic variants associated with keloids:

Genome-wide association studies (GWAS) have identified several genetic loci associated with keloid susceptibility:

• NEDD4 gene: Involved in TGF-β signaling regulation
• MIR4697HG: A microRNA gene that regulates fibroblast proliferation
• FOXL2: A transcription factor involved in fibroblast differentiation
• HLA region: Human leukocyte antigen variants, consistent with an immune component

Racial differences:

Keloids are 15–20 times more common in people of African, Asian, and Hispanic descent than in people of European descent. The reasons are not fully understood but likely involve:

• Higher melanocyte activity (melanocytes may stimulate adjacent fibroblasts)
• Genetic variants in fibroblast signaling pathways that are more prevalent in these populations
• Differences in immune response to injury

Anatomical Predisposition: Why Keloids Form in Specific Locations

Keloids do not form randomly — they preferentially develop in specific anatomical locations. Understanding why helps predict risk and guide prevention.

High-risk locations:

• Earlobes: The most common keloid site, almost always following ear piercing. The earlobe has high skin tension relative to its size and limited blood supply.
• Presternal (chest) area: Subject to constant tension from respiratory movement and pectoral muscle activity. The skin over the sternum has limited mobility.
• Shoulders and upper arms: Subject to deltoid and trapezius muscle tension with arm movement.
• Upper back: Subject to rhomboid and trapezius tension.
• Jaw and mandibular area: Subject to tension from mastication (chewing).
• Pubic area: Subject to tension from hip flexion and extension.

Low-risk locations:

• Eyelids
• Palms and soles
• Mucous membranes
• Genitalia (rare)
• Scalp (rare)

The common thread among high-risk locations is high skin tension. Mechanical tension activates mechanoreceptors on fibroblasts, stimulating TGF-β production and collagen synthesis — the same pathways that drive keloid formation.

Triggers: What Initiates Keloid Formation?

Any process that breaches the dermis can trigger keloid formation in susceptible individuals. The severity of the initial injury does not always predict keloid size — minor injuries can produce large keloids.

Common triggers:

• Surgical incisions: Including cesarean sections, appendectomy, sternotomy, and cosmetic procedures
• Ear and body piercing: The most common trigger for earlobe keloids
• Acne: Deep inflammatory acne lesions on the chest and back
• Burns: Thermal, chemical, and radiation burns
• Lacerations and abrasions: Including road rash
• Vaccinations: Particularly BCG (tuberculosis) vaccine; deltoid injection site keloids
• Insect bites: Particularly in children
• Folliculitis: Infected hair follicles on the scalp, beard area, and chest
• Tattoos: Needle punctures can trigger keloid formation in susceptible individuals
• Spontaneous keloids: Rare cases with no identifiable trigger; may arise from subclinical folliculitis or microtrauma

The Hormonal Influence on Keloid Formation

Hormonal factors significantly influence keloid development, explaining several clinical observations:

Age distribution:

Keloids are rare before puberty and after menopause, with peak incidence between ages 10–30. This distribution parallels the period of highest sex hormone activity, suggesting a role for estrogen and testosterone in keloid pathogenesis.

Pregnancy:

Keloids often grow rapidly during pregnancy and may regress after delivery. Estrogen stimulates TGF-β1 production and fibroblast proliferation, explaining pregnancy-associated keloid growth.

Puberty:

The onset of keloid formation at puberty — and the increased risk in adolescents — may relate to the surge in sex hormones that accompanies puberty.

Practical implication:

Women with keloids who are planning pregnancy should discuss this with their dermatologist, as existing keloids may enlarge significantly during pregnancy. Elective procedures that could trigger new keloids should be deferred until after pregnancy.

Distinguishing Keloids from Other Raised Scars

Keloid vs. hypertrophic scar:

The most important clinical distinction. The defining feature of a keloid is extension beyond the original wound boundaries. A hypertrophic scar, regardless of its size or symptoms, remains confined to the wound area.

Keloid vs. dermatofibroma:

Dermatofibromas are benign fibrous nodules that appear as firm, slightly raised, pigmented bumps, usually on the legs. They do not follow a history of significant skin injury and have a characteristic "dimple sign" (central dimpling when pinched).

Keloid vs. dermatofibrosarcoma protuberans (DFSP):

DFSP is a rare, locally aggressive skin tumor that can resemble a keloid. Features suggesting DFSP rather than keloid: rapid growth, no history of skin injury at the site, location on the trunk or proximal extremities, irregular borders. Biopsy is required for diagnosis.

When to biopsy:

Biopsy is recommended when:

• The diagnosis is uncertain
• The lesion is rapidly growing
• There is no history of skin injury at the site
• The lesion has unusual features (ulceration, very rapid growth, satellite nodules)

Frequently Asked Questions

Q: Can keloids become cancerous?

A: Keloids themselves are benign and do not become cancerous. However, very rarely, a dermatofibrosarcoma protuberans (DFSP) — a low-grade malignant tumor — can be mistaken for a keloid. If a "keloid" grows unusually rapidly, has no history of preceding injury, or has unusual features, biopsy is warranted to exclude malignancy.

Q: Why did I get a keloid from a minor scratch but not from major surgery?

A: Keloid formation depends on the location of the injury, skin tension at the site, and the individual's immune response — not just the severity of the injury. A minor scratch on the chest (high-tension area) in a susceptible individual can produce a large keloid, while a major surgical incision on the scalp (low-tension area) may heal with a flat scar.

Q: My child developed a keloid after ear piercing. Will they always get keloids?

A: Not necessarily. Earlobe keloids after piercing are common, particularly in children and adolescents of African descent. Having one keloid increases the risk of future keloids, but does not guarantee them. Avoiding further ear piercing and other elective skin procedures on high-risk areas is advisable. Preventive measures (silicone gel, pressure earrings) should be used for any future piercings if they proceed.

The Molecular Biology of Keloid Formation

Recent advances in molecular biology have revealed the complex signaling pathways that drive keloid formation, opening new avenues for targeted therapy.

TGF-β signaling:

Transforming growth factor-beta (TGF-β) is the master regulator of fibrosis. In keloids:

• TGF-β1 and TGF-β2 are markedly elevated
• TGF-β activates fibroblasts to produce excess collagen and extracellular matrix
• TGF-β3 (which normally promotes scar resolution) is reduced
• Keloid fibroblasts are hypersensitive to TGF-β signaling

Apoptosis resistance:

Normal scar resolution requires programmed death (apoptosis) of fibroblasts after wound healing. Keloid fibroblasts resist apoptosis through:

• Overexpression of anti-apoptotic proteins (Bcl-2, Bcl-xL)
• Activation of the PI3K/AKT survival pathway
• Reduced p53 activity (p53 normally triggers apoptosis in response to cellular stress)

This apoptosis resistance explains why keloids continue to grow indefinitely — the fibroblasts that should die instead persist and continue producing collagen.

Hypoxia and angiogenesis:

Keloids are hypoxic (low oxygen) environments due to their dense collagen matrix. Hypoxia activates HIF-1α (hypoxia-inducible factor), which:

• Stimulates VEGF production (promotes new blood vessel growth)
• Activates TGF-β signaling
• Promotes fibroblast proliferation

Immune dysregulation:

Keloids contain elevated numbers of mast cells, macrophages, and T-lymphocytes. The immune microenvironment is pro-inflammatory, with elevated IL-4, IL-13, IL-17, and TNF-α. This chronic inflammation perpetuates fibroblast activation.

Emerging and Investigational Treatments

Anti-TGF-β therapies:

Given TGF-β's central role in keloid pathogenesis, blocking this pathway is a logical therapeutic target:

• Intralesional tranilast (TGF-β inhibitor): reduces keloid recurrence after surgery in some studies
• Pirfenidone (TGF-β inhibitor): used for pulmonary fibrosis; under investigation for keloids
• Anti-TGF-β antibodies: in early clinical trials

Biologic therapies:

• Dupilumab (anti-IL-4Rα): FDA-approved for atopic dermatitis; case reports of keloid improvement
• Tralokinumab (anti-IL-13): under investigation
• Anti-IL-31 antibodies: targeting the itch pathway in keloids

Botulinum toxin (Botox):

Intralesional botulinum toxin reduces keloid symptoms and may inhibit fibroblast proliferation. Mechanism may involve reduction of mechanical tension and inhibition of TGF-β signaling. Emerging evidence; not yet standard of care.

Platelet-rich plasma (PRP):

Contains growth factors that may modulate scar formation. Results are mixed — some studies show benefit, others show worsening. Not currently recommended as standard treatment.

Stem cell therapy:

Adipose-derived stem cells (ADSCs) have shown anti-fibrotic properties in preclinical studies. Early clinical trials are underway.

Frequently Asked Questions

Q: Are keloids dangerous?

A: Keloids are benign (non-cancerous) and do not spread to other organs. They are not life-threatening. However, they can cause significant pain, itch, and psychological distress, and can restrict movement when located over joints. In rare cases, very large keloids can become infected or ulcerate.

Q: Can keloids turn into cancer?

A: No. Keloids are benign overgrowths of scar tissue and do not transform into cancer. However, a rare malignant tumor called dermatofibrosarcoma protuberans (DFSP) can sometimes be mistaken for a keloid. If a "keloid" is growing unusually rapidly, is very firm, or has atypical features, biopsy may be warranted to exclude malignancy.

Q: My child developed a keloid after ear piercing. Will it keep growing?

A: Ear lobe keloids typically grow for 6–12 months before stabilizing. They rarely resolve spontaneously. Treatment options include intralesional corticosteroid injections (most effective for small keloids), surgical excision combined with corticosteroids or radiation, and pressure earrings. Early treatment (within the first year) generally produces better outcomes.