Keloid & Hypertrophic Scars

1. Clinical Overview

Summary

Keloid and hypertrophic scars represent aberrant wound healing characterized by excessive fibroproliferative responses and abnormal collagen deposition. These pathological scars arise from dysregulation of the normal wound healing cascade, resulting in raised, firm, often symptomatic lesions that cause significant cosmetic and functional morbidity.

Hypertrophic scars are raised, erythematous scars that remain confined within the boundaries of the original wound and typically exhibit spontaneous regression over 12-24 months. They result from excessive collagen deposition during the proliferative phase of healing but retain normal wound remodeling mechanisms. [1,2]

Keloid scars extend beyond the original wound margins (resembling "claws" or "crab-like projections"), do not regress spontaneously, and demonstrate a marked propensity for recurrence after treatment (50-100% after excision alone). Keloids represent a benign fibroproliferative tumor with unique pathophysiological mechanisms including decreased fibroblast apoptosis, persistent TGF-β signaling, and failure of normal scar remodeling. [1,2,3]

Key Clinical Distinctions

Key Facts

• Epidemiology: Keloid prevalence 4-16% in darker-skinned populations vs 0.09% in Caucasians; hypertrophic scars affect up to 70% of burn patients [4,5]
• Pathophysiology: Chronic inflammation in reticular dermis with TGF-β1 overexpression, reduced fibroblast apoptosis, and excessive type I/III collagen deposition [6,7]
• Risk Factors: Fitzpatrick skin types IV-VI (15-20x increased risk), age 10-30 years, high-tension anatomical sites, genetic predisposition (familial clustering) [4,8]
• First-line treatment (Keloid): Intralesional corticosteroids (triamcinolone acetonide 10-40 mg/mL every 4-6 weeks); 50-100% response rate [9,10]
• First-line treatment (Hypertrophic): Silicone gel sheets (12+ hours/day for 2-6 months); pressure therapy for burn scars [11,12]
• Surgical principle: Excision alone results in high recurrence; must combine with adjuvant therapy (intralesional steroids, radiotherapy within 24-48h post-excision) [13,14]
• Recurrence rates: Keloid excision alone 50-100%; excision + adjuvant radiotherapy 10-25% [14,15]

Clinical Pearls

"Within vs. Beyond": The fundamental clinical distinction is anatomical extent—hypertrophic scars stay within the original wound, keloids invade normal skin beyond wound margins.

"Keloids Love Earlobes, Chest, and Shoulders": These high-tension, low-mobility sites (earlobes post-piercing, anterior chest, deltoid region) are classic keloid locations. Avoid unnecessary procedures in keloid-prone individuals.

"Never Excise Keloids Alone": Surgical excision without adjuvant therapy is essentially futile (50-100% recurrence). ALWAYS combine with intralesional steroids, radiotherapy, or both.

"Steroids First, Surgery Last": For keloids, exhaust non-invasive options (intralesional steroids, 5-FU, laser, cryotherapy) before considering surgery. Surgery should be reserved for refractory cases with adjuvant planning.

"Dark Skin, Young Age, Family History": The classic keloid patient is of African or Asian descent, aged 10-30 years, with a family history of keloids. Screen for keloid tendency before elective procedures.

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2. Epidemiology

Incidence and Prevalence

Hypertrophic Scars:

• Extremely common after traumatic wounds, surgery, and burns
• Affect 40-70% of surgical wounds [1]
• Up to 70% prevalence in major burn injuries [5]
• Peak incidence in first 2-3 months post-injury

Keloid Scars:

• Overall prevalence: 0.09% in Caucasian populations [4]
• African populations: 4-16% prevalence [4,5]
• Asian populations: 4-6% prevalence
• Hispanic populations: 2-4% prevalence
• No significant gender difference, though some studies suggest slight female predominance (1.5:1) [8]

Age Distribution

Ethnic and Genetic Predisposition

Ethnic Risk Stratification:

• African descent: 15-20× increased risk vs Caucasians [4,8]
• Asian descent: 5-7× increased risk
• Hispanic descent: 3-4× increased risk
• Caucasian: Baseline risk (lowest)

Genetic Factors:

• Family history positive in 15-20% of keloid patients [8]
• Autosomal dominant inheritance with incomplete penetrance and variable expression suggested
• HLA-DRB1 polymorphisms associated with keloid susceptibility in Afro-Caribbean populations [16]
• Specific genetic loci identified: chromosomes 2q23, 7p11, 15q21-22 [8]

Anatomical Site Predilection

High-Risk Sites (Keloid Formation):

Hypertrophic Scars:

• Can occur at any wound site
• More common over joints (flexor surfaces)
• Burn scars (especially deep dermal/full-thickness burns)

Common Triggers

Iatrogenic:

• Surgery (sternotomy, thyroidectomy, cesarean section)
• Ear/body piercing (earlobes most common)
• Vaccination (BCG, smallpox)
• Tattoos

Dermatological:

• Acne vulgaris (chest, back, jaw)
• Folliculitis (posterior neck, beard area)
• Chickenpox lesions

Traumatic:

• Burns (thermal, chemical, radiation)
• Lacerations
• Abrasions
• Insect bites

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3. Aetiology and Pathophysiology

Normal Wound Healing (Review)

Wound healing proceeds through four overlapping phases:

1. Haemostasis (minutes-hours): Platelet activation, fibrin clot formation
2. Inflammation (days 0-5): Neutrophil and macrophage infiltration, debris clearance
3. Proliferation (days 4-21): Fibroblast migration, collagen synthesis, angiogenesis, re-epithelialization
4. Remodeling (months-years): Collagen reorganization (type III → type I), myofibroblast apoptosis, scar maturation

In normal healing, the remodeling phase results in scar flattening, decreased vascularity, and collagen realignment.

Pathophysiology of Hypertrophic Scars

Hypertrophic scars represent a prolonged proliferative phase with delayed but eventual transition to remodeling. Key mechanisms include:

Cellular Mechanisms:

• Persistent myofibroblast activity (α-SMA positive cells)
• Prolonged inflammatory response (months instead of days)
• Increased TGF-β1 expression (stimulates collagen synthesis)
• Normal fibroblast apoptosis (eventually allows regression)

Extracellular Matrix:

• Excessive type III collagen deposition initially
• Gradual transition to type I collagen
• Parallel, organized collagen bundles (distinguishes from keloid)
• Eventual collagen degradation by matrix metalloproteinases (MMPs)

Histological Features:

• Thick, hypercellular dermis
• Parallel collagen fiber orientation
• Abundant myofibroblasts
• Minimal extension into subcutaneous tissue

Pathophysiology of Keloid Scars

Keloids represent a fundamentally dysregulated wound healing process with failure to transition to remodeling. This is not merely excessive healing but a distinct pathological entity with tumor-like characteristics. [6,7]

Cellular Mechanisms:

Exam Detail: 1. Chronic Reticular Dermal Inflammation:

• Persistent inflammatory infiltrate (T-cells, mast cells, macrophages) in deep reticular dermis [6]
• Continuous release of pro-fibrotic cytokines (TGF-β1, IL-1, IL-6, PDGF)
• Mast cell degranulation with histamine and tryptase release (drives fibroblast proliferation)

2. Fibroblast Dysfunction:

• Decreased apoptosis: Keloid fibroblasts resist programmed cell death (unlike normal fibroblasts post-healing) [7]
• Increased proliferation: Higher mitotic rate, longer survival
• Altered phenotype: Overexpress collagen I, III, and fibronectin
• Autonomous growth: Can proliferate in culture without exogenous growth factors

3. Growth Factor Dysregulation:

• TGF-β1 overexpression: Most critical mediator; stimulates collagen synthesis and inhibits degradation [6,7]
• PDGF elevation: Promotes fibroblast chemotaxis and proliferation
• VEGF increase: Drives angiogenesis (accounts for erythema)
• Reduced TGF-β3: (Anti-scarring isoform) decreased in keloids

4. Defective Matrix Remodeling:

• Reduced MMP activity: Matrix metalloproteinases (MMP-1, MMP-2, MMP-9) decrease collagen degradation
• Increased TIMP expression: Tissue inhibitors of MMPs further block collagen breakdown
• Net result: Collagen accumulation without degradation

Extracellular Matrix:

• Massive type I and type III collagen deposition
• Disorganized, whorled collagen bundles (hallmark histological feature)
• Thick, hyalinized "keloidal collagen" (glassy, eosinophilic on H&E)
• Abundant glycosaminoglycans (dermatan sulfate, chondroitin sulfate)

Molecular Mechanisms:

Exam Detail: Genetic Factors:

• Familial clustering suggests genetic predisposition [8,16]
• HLA-DRB1*15 association in Afro-Caribbean populations [16]
• Candidate genes: NEDD4, FOXF2, AHNAK (chromosome 2q23)

Epigenetic Modifications:

• DNA hypermethylation of tumor suppressor genes
• Histone acetylation changes affecting collagen gene expression
• MicroRNA dysregulation (miR-21, miR-152 upregulated; suppress collagen degradation)

Mechanical Tension:

• High-tension sites promote keloid formation (earlobes, chest, shoulders)
• Mechanotransduction via focal adhesions and YAP/TAZ signaling
• Tension maintains myofibroblast phenotype and prevents apoptosis

Histological Comparison:

Why Keloids Don't Regress

The failure of keloid regression is multifactorial:

1. No fibroblast apoptosis: Cells that should die post-healing persist indefinitely [7]
2. Persistent TGF-β signaling: Continuous pro-fibrotic stimulus
3. Defective matrix degradation: Low MMP activity prevents collagen breakdown
4. Mechanical memory: High-tension sites maintain myofibroblast activation
5. Autonomous growth: Keloid fibroblasts proliferate independently of wound signals

Neurogenic Inflammation Hypothesis

Emerging evidence suggests neurogenic mechanisms contribute to keloid pathogenesis:

• Substance P (neuropeptide) elevated in keloid tissue
• Nerve growth factor (NGF) overexpression
• Mast cell-nerve fiber interaction drives inflammation
• May explain pruritus and pain in keloids [17]

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4. Clinical Presentation

Symptoms

Hypertrophic Scars:

• Pruritus (itching): Very common, often severe in active phase
• Tenderness: Mild to moderate, improves with maturation
• Tightness: Especially over joints (can restrict movement)
• Pain: Usually mild; worse with tension or trauma
• Timeline: Symptoms peak at 3-6 months, improve over 12-24 months

Keloid Scars:

• Pruritus: Severe, persistent (may last years)
• Pain/tenderness: Moderate to severe; worsened by pressure
• Burning sensation: Common complaint
• Hypersensitivity: To touch, clothing friction
• Psychological distress: Body dysmorphia, social anxiety, depression
• Timeline: Symptoms persist or worsen; no spontaneous improvement

Signs

Hypertrophic Scar Physical Examination:

Keloid Scar Physical Examination:

Classical Clinical Scenarios

Scenario 1: Earlobe Keloid Post-Piercing

• 18-year-old Afro-Caribbean female
• Ear pierced 6 months ago
• Progressive enlargement of firm, pink nodule extending beyond piercing site
• Tender, itchy, cosmetically distressing

Scenario 2: Acne Keloidalis (Chest/Back)

• 25-year-old African male
• History of severe acne vulgaris
• Multiple raised, firm, hyperpigmented scars on anterior chest
• Scars extend beyond original acne lesions
• Persistent pruritus

Scenario 3: Post-Sternotomy Hypertrophic Scar

• 55-year-old Caucasian male post-CABG
• Raised, red, linear scar along sternotomy incision
• Pruritic, mildly tender
• Scar confined to incision line (does NOT extend laterally)
• Improving gradually over 18 months

Scenario 4: Burn Hypertrophic Scarring

• 10-year-old child with 30% TBSA flame burn
• Thick, raised, erythematous scars over healed burn areas
• Severe pruritus, restricted shoulder movement (contracture)
• Scars remain within original burn boundaries

Examination Viva Scenarios

Exam Detail: Viva Question 1: "How do you distinguish a keloid from a hypertrophic scar clinically?"

Model Answer:

"The key distinction is whether the scar extends beyond the original wound boundaries. I would assess:

History:

• Timing: Hypertrophic scars develop within weeks post-injury and may regress over 1-2 years. Keloids develop months to years after injury and progressively enlarge without regression.
• Ethnicity: Keloids show strong ethnic predisposition (African, Asian descent), while hypertrophic scars have no ethnic association.
• Family history: Positive in 15-20% of keloid patients.
• Site: Keloids preferentially affect earlobes, chest, shoulders; hypertrophic scars can occur anywhere.

Examination:

• Extent: Hypertrophic scars are confined within the original wound. Keloids extend beyond wound margins with 'claw-like' projections into normal skin.
• Appearance: Keloids are often dome-shaped, lobulated, with irregular borders. Hypertrophic scars are linear (if surgical) or match the original wound shape.
• Regression: On serial examination, hypertrophic scars flatten over time; keloids do not.

If doubt remains, biopsy can confirm (though rarely necessary): hypertrophic scars show parallel collagen bundles, keloids show whorled, disorganized 'keloidal collagen'."

Viva Question 2: "A patient with known keloid tendency requires an appendicectomy. How do you counsel them regarding scar risk?"

Model Answer:

"I would counsel this high-risk patient as follows:

Pre-operative:

• 'You have a significant risk of keloid formation at the surgical site. We will take measures to minimize this risk, but keloids can still occur despite optimal technique.'
• Discuss alternative approaches if available (e.g., laparoscopic vs. open—laparoscopic may result in smaller scars but port sites can still keloid).
• Obtain informed consent documenting keloid risk.

Intra-operative risk reduction:

• Meticulous surgical technique: tension-free closure, fine sutures, minimal tissue trauma
• Lowest tension closure possible (undermining, layered closure)
• Consider running subcuticular suture to minimize suture marks
• Smallest acceptable incision

Post-operative prevention:

• Early silicone gel sheeting (start at 2-3 weeks post-op, once epithelialized)
• Pressure therapy if anatomically feasible
• Close monitoring: review at 2, 6, 12 weeks
• Early intervention if keloid develops: intralesional steroids at first sign of abnormal scarring (rather than waiting for established keloid)

Long-term:

• 'If a keloid does develop, we have multiple treatment options including steroid injections, which are the first-line therapy and effective in 50-100% of cases. Surgery alone is not recommended due to high recurrence risk.'

Emphasize realistic expectations while reassuring that preventive measures significantly reduce risk."

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5. Differential Diagnosis

Key Differentials

Clinical Red Flags (Exclude Malignancy)

• Rapid growth (weeks instead of months)
• Ulceration or bleeding
• Firm, fixed to deep structures
• Older age (> 50 years; unusual for keloids)
• Lack of trauma/wound history
• Satellite lesions (distant from scar)

Action: If atypical features present, biopsy to exclude malignancy (rare but documented: squamous cell carcinoma, basal cell carcinoma can arise in chronic scars [Marjolin's ulcer]; sarcoma can mimic keloid).

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6. Investigations

Clinical Diagnosis

Gold Standard: Clinical diagnosis based on history and physical examination. Investigations are rarely required.

Diagnostic Criteria (Keloid):

1. Scar extends beyond original wound boundaries
2. No spontaneous regression
3. Predilection for specific anatomical sites (earlobes, chest, shoulders)
4. Ethnic predisposition (if present)
5. Family history (if present)

Diagnostic Criteria (Hypertrophic Scar):

1. Scar confined within wound boundaries
2. Develops within weeks to months post-injury
3. May regress over 12-24 months
4. Common after burns, high-tension wounds

Histopathology (When Indicated)

Indications for Biopsy:

• Atypical presentation (concern for malignancy)
• Diagnostic uncertainty (differentials: sarcoidosis, DFSP, dermatofibroma)
• Research purposes

Hypertrophic Scar Histology:

• Collagen: Parallel bundles, organized
• Fibroblasts: Increased density, oriented parallel to epidermis
• Myofibroblasts: Present (α-SMA positive)
• Inflammation: Moderate, superficial dermis
• Boundary: Does not extend into subcutaneous fat

Keloid Histology:

• Collagen: Thick, whorled, disorganized bundles
• "Keloidal collagen": Hyalinized, eosinophilic, glassy appearance (pathognomonic)
• Fibroblasts: Markedly increased density, random orientation
• Myofibroblasts: Abundant (α-SMA positive)
• Inflammation: Chronic, deep reticular dermis (mast cells, lymphocytes)
• Boundary: Extends beyond original wound into normal dermis/subcutis

Additional Investigations (Rarely Needed)

Imaging:

• Ultrasound: Can assess depth, vascularity (rarely alters management)
• MRI: If concern for deep extension (e.g., desmoid tumor differential)

Functional Assessment (Contractures):

• Goniometry: Measure joint range of motion if contracture present
• Vancouver Scar Scale (VSS): Standardized scar assessment tool (pigmentation, vascularity, pliability, height)

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7. Management

General Principles

Key Concepts:

1. Hypertrophic scars often improve spontaneously; focus on symptom relief (silicone, pressure, massage) and prevention of contracture.
2. Keloids require active intervention; first-line is intralesional corticosteroids. [9,10]
3. Surgery alone is contraindicated for keloids (50-100% recurrence); always combine with adjuvant therapy. [13,14]
4. Prevention is paramount in keloid-prone individuals: meticulous surgical technique, early silicone therapy, avoid unnecessary procedures.

Management Algorithm

┌────────────────────────────────────────────────────────────────────┐
│                    PATHOLOGICAL SCAR MANAGEMENT                     │
├────────────────────────────────────────────────────────────────────┤
│                                                                     │
│  INITIAL ASSESSMENT                                                │
│  ├─ History: Wound timeline, ethnicity, family history             │
│  ├─ Examination: Extent (within vs. beyond wound), color, height   │
│  └─ Classification: Hypertrophic vs. Keloid                        │
│                                                                     │
├────────────────────────────────────────────────────────────────────┤
│                                                                     │
│  HYPERTROPHIC SCAR TREATMENT LADDER                                │
│  ═══════════════════════════════════════                           │
│                                                                     │
│  FIRST-LINE (0-6 months):                                          │
│  • Silicone gel sheets/gel (12+ hours/day for 2-6 months) [11,12] │
│  • Pressure therapy (burns: 20-30 mmHg, 23 hours/day for 6-12mo)  │
│  • Massage (5-10 min twice daily)                                  │
│  • Moisturization                                                  │
│                                                                     │
│  SECOND-LINE (if refractory):                                      │
│  • Intralesional corticosteroids (triamcinolone 10-20 mg/mL)       │
│  • Pulsed dye laser (585-595 nm; targets vascularity) [18]        │
│                                                                     │
│  THIRD-LINE (severe, symptomatic):                                 │
│  • Surgical excision (if functional impairment/contracture)        │
│  • Intralesional 5-fluorouracil (off-label)                        │
│                                                                     │
│  → Expect spontaneous improvement over 12-24 months                │
│                                                                     │
├────────────────────────────────────────────────────────────────────┤
│                                                                     │
│  KELOID TREATMENT LADDER                                           │
│  ═══════════════════════                                           │
│                                                                     │
│  FIRST-LINE:                                                       │
│  • Intralesional CORTICOSTEROIDS (triamcinolone 10-40 mg/mL)      │
│    - Inject directly into keloid (blanching endpoint) [9,10]      │
│    - Repeat every 4-6 weeks until flattening (may need 6+ cycles) │
│    - Response rate: 50-100% (flattening, symptom relief)           │
│    - Side effects: Atrophy, hypopigmentation, telangiectasia       │
│  • Silicone gel sheets (adjunct; continuous use)                   │
│                                                                     │
│  SECOND-LINE (refractory to steroids):                             │
│  • Intralesional 5-fluorouracil (50 mg/mL weekly for 8-12 weeks)  │
│    - Can combine with triamcinolone (synergistic effect)           │
│  • Cryotherapy (liquid nitrogen, 20-30 sec freeze-thaw cycles)     │
│    - Best for small (less than 1 cm) keloids                                │
│  • Pulsed dye laser (reduces vascularity, pruritus)                │
│                                                                     │
│  THIRD-LINE (large, refractory, or functionally impairing):        │
│  • SURGICAL EXCISION + ADJUVANT THERAPY:                           │
│    ├─ Excision (core excision or shave excision techniques)        │
│    ├─ IMMEDIATE adjuvant (choose one):                             │
│    │   • Adjuvant radiotherapy (10-20 Gy in 3-5 fractions within   │
│    │     24-48h post-excision; recurrence 10-25%) [14,15]          │
│    │   • Intraoperative intralesional triamcinolone (40 mg/mL)     │
│    └─ ONGOING adjuvant:                                            │
│        • Intralesional steroids (start 2-4 weeks post-op, monthly) │
│        • Silicone sheets (continuous use for 6-12 months)          │
│        • Pressure therapy (if anatomically feasible)               │
│                                                                     │
│  ⚠️  SURGERY ALONE = 50-100% RECURRENCE (CONTRAINDICATED)          │
│                                                                     │
│  EXPERIMENTAL/EMERGING:                                            │
│  • Intralesional verapamil (calcium channel blocker)               │
│  • Bleomycin injections                                            │
│  • Botulinum toxin (reduces tension)                               │
│  • Imiquimod cream (post-excision)                                 │
│  • Tacrolimus (calcineurin inhibitor)                              │
│                                                                     │
└────────────────────────────────────────────────────────────────────┘

Specific Treatment Modalities

1. Intralesional Corticosteroids (First-Line for Keloids)

Mechanism: Inhibits fibroblast proliferation, reduces collagen synthesis, promotes collagen degradation, decreases TGF-β1 expression, induces vasoconstriction (reduces inflammation). [9,10]

Protocol:

• Agent: Triamcinolone acetonide
• Concentration: 10-40 mg/mL (start with 10-20 mg/mL; increase if tolerated)
• Technique:
  • Intralesional injection (NOT subcutaneous)
  • Inject until keloid blanches (whitens)—indicates adequate distribution
  • Use 27-30 gauge needle
  • Multiple injection sites for large keloids
• Frequency: Every 4-6 weeks
• Duration: Continue until flattening achieved (typically 6-12 sessions; may need ongoing maintenance)
• Dosage limits: Maximum 20-40 mg per session (risk of systemic absorption)

Response Rate:

• 50-100% achieve flattening or symptom relief [9,10]
• Best results in small (less than 2 cm), recent keloids
• Reduces height by 50-90%, improves pruritus and pain

Side Effects:

• Local: Skin atrophy (most common), hypopigmentation, telangiectasia, pain at injection
• Systemic (rare, high doses): Cushingoid features, menstrual irregularities, hyperglycemia
• Tip: Co-inject with 1% lidocaine to reduce pain

2. Silicone Gel Sheets and Silicone Gel

Mechanism: Exact mechanism unclear; proposed mechanisms include hydration, occlusion, static electricity effects, increased collagenase activity, reduced TGF-β2 expression. [11,12]

Protocol:

• Application: Apply to clean, dry, healed scar (must be epithelialized; no open wounds)
• Duration: 12-24 hours per day for minimum 2-3 months (up to 6-12 months)
• Forms: Sheets (reusable, cut to size) vs. gel (easier for irregular areas, face)
• Wash: Sheets washed daily with mild soap, air dry

Evidence:

• Meta-analyses support efficacy for prevention and treatment of hypertrophic scars [11,12]
• Reduces scar height, erythema, and pruritus
• Effective for prevention in high-risk scars (burns, high-tension closures)

Side Effects:

• Minimal: Pruritus, rash, maceration (reduce wear time if occurs)
• Good patient compliance required (aesthetic concern wearing sheets)

3. Pressure Therapy

Mechanism: Reduces capillary perfusion, decreases local oxygen tension, inhibits fibroblast proliferation, promotes collagen remodeling.

Protocol:

• Indication: Primarily burn hypertrophic scars; post-excision keloids (if anatomically feasible)
• Pressure: 20-30 mmHg (sufficient to blanch scar)
• Duration: 23 hours/day for 6-12 months
• Devices: Custom pressure garments (Jobst, Tubigrip), pressure earrings (earlobe keloids), clips

Evidence:

• Standard of care for burn scar prevention and treatment [5]
• Reduces hypertrophic scar height and symptoms
• Best results when started early (less than 3 months post-injury)

Limitations:

• Requires excellent compliance (uncomfortable, hot, cosmetically undesirable)
• Not feasible for all anatomical sites (face, central chest)

4. Cryotherapy

Mechanism: Induces tissue necrosis, vascular damage, reduces fibroblast activity, promotes apoptosis.

Protocol:

• Technique: Liquid nitrogen spray or contact probe
• Freeze time: 10-30 seconds (freeze-thaw cycle)
• Frequency: Every 3-4 weeks
• Sessions: 3-6 treatments

Best for: Small (less than 1 cm) keloids; earlobe keloids

Response Rate: 50-70% reduction in keloid size after 3-6 sessions

Side Effects:

• Hypopigmentation (permanent; significant concern in darker skin)
• Pain, blistering
• Hyperpigmentation (can occur)

Note: Hypopigmentation risk limits use in darker-skinned patients (the very population at highest keloid risk)—counsel carefully.

5. Intralesional 5-Fluorouracil (5-FU)

Mechanism: Inhibits fibroblast proliferation, reduces collagen synthesis (antimetabolite; interferes with DNA/RNA synthesis).

Protocol:

• Concentration: 50 mg/mL (dilute from 50 mg/mL stock)
• Technique: Intralesional injection (similar to steroids)
• Frequency: Weekly for 8-12 weeks
• Combination: Often combined with triamcinolone (synergistic; "TAC-5-FU" protocol: 9 mg triamcinolone + 45 mg 5-FU per mL)

Response Rate: 45-75% achieve flattening with combination therapy

Side Effects:

• Hyperpigmentation (common; can be cosmetically concerning)
• Ulceration (if too superficial injection)
• Pain at injection site

Advantage: Reduced atrophy risk vs. steroids alone

6. Laser Therapy

Pulsed Dye Laser (PDL):

• Wavelength: 585-595 nm
• Target: Oxyhemoglobin (targets vascularity)
• Mechanism: Reduces erythema, decreases vascularity, promotes collagen remodeling
• Protocol: Sessions every 4-6 weeks for 3-6 treatments
• Best for: Erythematous, vascular hypertrophic scars; reduces pruritus [18]
• Limitations: Minimal effect on keloid size; mainly improves color and symptoms

Fractional CO2 Laser:

• Mechanism: Ablative laser creates microchannels, promotes collagen remodeling
• Best for: Mature, atrophic scars; limited role in keloids

Nd:YAG Laser:

• Wavelength: 1064 nm (deeper penetration)
• Target: Deeper dermal vessels, collagen
• Use: Thick keloids

Evidence: Lasers reduce erythema, pruritus, and pliability but have limited effect on keloid size as monotherapy. Best used as adjunct. [18]

7. Surgical Excision (ONLY with Adjuvant Therapy)

Critical Principle: Surgery alone for keloids results in 50-100% recurrence (often larger than original). [13,14]

Indications for Surgery:

• Large, pedunculated keloids (functional/cosmetic impairment)
• Refractory to medical therapy
• Patient preference (after counseling on recurrence risk)
• Functional impairment (contracture, pain)

Surgical Techniques:

• Core excision: Remove keloid center, leave thin rim (preserves skin integrity)
• Complete excision: Remove entire keloid with narrow margin
• Shave excision: Flatten keloid flush with skin (avoid deep excision)
• Tension-free closure: Undermining, layered closure (minimize tension)

MANDATORY Adjuvant Therapy (Choose ≥1):

1. Adjuvant Radiotherapy:

• Timing: Within 24-48 hours post-excision (critical window) [14,15]
• Dose: 10-20 Gy total in 3-5 fractions (various protocols: single 15 Gy dose, or 3-4 Gy × 5 fractions over 7-10 days)
• Mechanism: Inhibits fibroblast proliferation, induces apoptosis
• Recurrence rate: 10-25% (vs. 50-100% without radiotherapy) [14,15]
• Side effects: Erythema, hyperpigmentation, theoretical malignancy risk (very low; risk-benefit favors use in adults; avoid in children if possible)
• Contraindications: Pregnancy, children (less than 18 years—relative; weigh risk-benefit)

2. Intralesional Corticosteroids (Peri- and Post-operative):

• Intraoperative: Inject wound bed with triamcinolone 40 mg/mL after excision
• Postoperative: Begin intralesional steroids at 2-4 weeks post-op; continue monthly for 6-12 months

3. Pressure Therapy:

• Apply pressure dressing/garment immediately post-op
• Continue 23 hours/day for 6-12 months

4. Silicone Gel Sheets:

• Start once wound epithelialized (2-3 weeks post-op)
• Continue for 6-12 months

Combined Approach (Best Outcomes):

• Excision + immediate adjuvant radiotherapy (within 24-48h) + intralesional steroids (starting week 2-4) + silicone sheets (starting week 2-3)
• Recurrence rates: 10-20% with multimodal approach

8. Prevention Strategies

For Keloid-Prone Individuals:

Pre-operative:

• Avoid unnecessary surgery/procedures (piercings, cosmetic procedures)
• If surgery required: counsel on keloid risk, obtain informed consent
• Consider anatomical site (avoid high-risk sites if elective)

Intra-operative:

• Meticulous surgical technique:
  • Tension-free closure (undermining, layered closure)
  • Fine sutures (5-0, 6-0 for face; 4-0 for body)
  • Avoid excessive tension
  • Minimize tissue trauma (gentle handling, avoid cautery near wound edges)
  • Running subcuticular closure (minimize suture marks)

Post-operative:

• Early silicone therapy: Start at 2-3 weeks (once epithelialized) [12]
• Pressure therapy: If anatomically feasible
• Close monitoring: Review at 2, 6, 12 weeks
• Early intervention: If keloid develops, start intralesional steroids immediately (do not wait for established keloid)

For All Wounds (Prevention of Hypertrophic Scars):

• Moist wound healing (avoid desiccation)
• Prevent infection (appropriate antibiotics if indicated)
• Avoid prolonged inflammation (debridement of necrotic tissue, early grafting for burns)
• Minimize tension (appropriate wound closure)
• Early mobilization (prevent contracture)

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8. Complications and Prognosis

Complications of Scars

Physical Complications:

• Contracture: Especially hypertrophic scars over joints (restricted range of motion, functional impairment)
• Pruritus: Severe, persistent itching (can significantly impair quality of life)
• Pain: Chronic tenderness, hypersensitivity
• Ulceration: Rare; can occur in large, pedunculated keloids (trauma, friction)
• Infection: Secondary infection from scratching (excoriation)

Psychological Complications:

• Body dysmorphic disorder: Preoccupation with scar appearance
• Social anxiety: Avoidance of social situations, clothing to hide scars
• Depression: Impaired self-esteem, quality of life
• Impact on relationships: Avoidance of intimate relationships

Rare Complications:

• Malignant transformation: Extremely rare; squamous cell carcinoma (SCC) can arise in chronic scars (Marjolin's ulcer—classically burn scars; very rare in keloids)

Complications of Treatment

Intralesional Corticosteroids:

• Skin atrophy (most common; can be permanent)
• Hypopigmentation
• Telangiectasia
• Systemic effects (rare): Cushingoid features, menstrual irregularities

Cryotherapy:

• Hypopigmentation (permanent; major concern in darker skin)
• Hyperpigmentation
• Pain, blistering

Radiotherapy:

• Erythema, hyperpigmentation (common, transient)
• Theoretical malignancy risk (very low; benefit typically outweighs risk in adults)
• Contraindicated in children (relative), pregnancy (absolute)

Surgical Excision:

• Recurrence (50-100% without adjuvant therapy; often larger than original) [13,14]
• Infection
• Wound dehiscence
• Cosmetically worse scar

Prognosis

Hypertrophic Scars:

• Natural history: Spontaneous regression over 12-24 months in majority
• Treatment response: Good response to conservative measures (silicone, pressure, massage)
• Recurrence after excision: 10-20% (much lower than keloids)
• Long-term: Most improve significantly; residual mild elevation/dyspigmentation common
• Functional outcome: Good if contracture prevented/treated early

Keloid Scars:

• Natural history: Do NOT regress; progressive enlargement over months-years
• Treatment response:
  • "Intralesional steroids: 50-100% achieve flattening/symptom relief [9,10]"
  • "Surgery alone: 50-100% recurrence [13]"
  • "Surgery + adjuvant radiotherapy: 10-25% recurrence [14,15]"
  • "Surgery + multimodal adjuvant (steroids + radiotherapy + silicone): 10-20% recurrence"
• Recurrence pattern: Recurrent keloids often larger than original
• Long-term: Chronic condition requiring ongoing management; symptom control achievable; complete cure rare

Prognostic Factors (Keloid Recurrence):

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9. Evidence and Guidelines

Key Guidelines

1. International Clinical Recommendations on Scar Management (2002, updated 2014):

• Evidence-based consensus on scar prevention and treatment
• Recommends silicone gel sheeting as first-line for hypertrophic scar prevention
• Pressure therapy standard for burn scars [12]

2. British Association of Dermatologists Guidelines (Patient Information):

• Patient-focused guidance on keloid scars
• Emphasizes intralesional steroids as first-line
• Caution against surgery alone

3. American Academy of Dermatology (AAD) Guidelines:

• Intralesional corticosteroids first-line for keloids
• Combination therapies for refractory cases

Key Evidence

Intralesional Corticosteroids:

• Level I evidence: Cochrane review (2019) supports intralesional steroids for keloid treatment; response rate 50-100% [9]
• Level II evidence: Randomized trials show triamcinolone 10-40 mg/mL effective for flattening and symptom relief [10]

Silicone Therapy:

• Level I evidence: Meta-analyses (2013, 2020) demonstrate efficacy for prevention and treatment of hypertrophic scars [11,12]
• Mechanism: Likely hydration and occlusion effects

Radiotherapy:

• Level II evidence: Systematic reviews show adjuvant radiotherapy reduces recurrence to 10-25% vs. 50-100% with surgery alone [14,15]
• Optimal timing: Within 24-48 hours post-excision (critical window)

5-Fluorouracil:

• Level II evidence: Randomized controlled trials show combination 5-FU + triamcinolone superior to triamcinolone alone (75% vs. 50% response rate)
• Advantage: Reduced atrophy risk

Pulsed Dye Laser:

• Level II evidence: RCTs demonstrate reduced erythema, pruritus, and pliability in hypertrophic scars [18]
• Limitation: Minimal effect on keloid size as monotherapy

Landmark Studies

1. Ogawa R. "Keloid and Hypertrophic Scars Are the Result of Chronic Inflammation in the Reticular Dermis." Int J Mol Sci. 2017;18(3):606. [PMID: 28287424]

• Established chronic reticular dermal inflammation as central mechanism in keloid pathogenesis [6]

2. Berman B, Maderal A, Raphael B. "Keloids and Hypertrophic Scars: Pathophysiology, Classification, and Treatment." Dermatol Surg. 2017;43 Suppl 1:S3-S18. [PMID: 27347634]

• Comprehensive review of pathophysiology and evidence-based treatment [1]

3. Mustoe TA, et al. "International Clinical Recommendations on Scar Management." Plast Reconstr Surg. 2002;110(2):560-571. [PMID: 12142678]

• International consensus on evidence-based scar management [12]

4. Ogawa R, et al. "Associations between Keloid Severity and Single-Nucleotide Polymorphisms." Plast Reconstr Surg. 2014;133(3):661-673.

• Genetic associations with keloid susceptibility [8]

5. Berman B, et al. "Adjunct Therapies to Surgical Management of Keloids and Hypertrophic Scars: A Systematic Review." Dermatol Surg. 2018;44(3):294-332.

• Systematic review of adjuvant therapies post-excision [13]

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10. Examination Focus

High-Yield Concepts for Exams

MRCS/FRCS (Plastics):

• Pathophysiology: Chronic reticular dermal inflammation, TGF-β1 overexpression, defective fibroblast apoptosis
• Surgical principle: Never excise keloids alone—50-100% recurrence; always use adjuvant therapy
• Adjuvant radiotherapy: 10-20 Gy within 24-48h post-excision reduces recurrence to 10-25%
• Burn scar management: Pressure therapy (20-30 mmHg, 23 hours/day, 6-12 months)

MRCP/Dermatology:

• Clinical distinction: Hypertrophic (within wound) vs. keloid (beyond wound)
• Ethnic predisposition: African > Asian > Hispanic > Caucasian (15-20× risk)
• First-line keloid treatment: Intralesional triamcinolone (10-40 mg/mL every 4-6 weeks)
• Silicone gel sheets: Evidence-based for hypertrophic scar prevention/treatment (12+ hours/day, 2-6 months)

Clinical Examination (PACES, OSCE):

• Identify scar type (hypertrophic vs. keloid) based on extent
• Risk factors: Ethnicity, age, family history, anatomical site
• Counseling: Realistic expectations, treatment options, recurrence risk
• Functional assessment: Contracture (goniometry), psychological impact

Viva Questions and Model Answers

Exam Detail: Viva 1: "What is the key pathophysiological difference between hypertrophic scars and keloids?"

Model Answer:

"Both represent excessive fibroproliferative responses with abnormal collagen deposition, but they differ fundamentally in their remodeling capacity and cellular mechanisms:

Hypertrophic scars:

• Prolonged proliferative phase but eventual transition to remodeling
• Normal fibroblast apoptosis occurs (delayed but present)
• Parallel, organized collagen bundles
• Confined to wound boundaries
• Regress over 12-24 months

Keloids:

• Failure to transition to remodeling phase—represent a distinct pathological entity
• Defective fibroblast apoptosis: Keloid fibroblasts resist programmed cell death, persisting indefinitely [7]
• Chronic reticular dermal inflammation with persistent TGF-β1 signaling [6]
• Defective matrix degradation: Low MMP activity, high TIMP expression—collagen accumulates without breakdown
• Whorled, disorganized 'keloidal collagen' (hyalinized, glassy on histology)
• Extend beyond wound boundaries
• Do not regress; progressive enlargement

In essence, hypertrophic scars are 'delayed healing,' while keloids are 'failed healing' with tumor-like autonomous growth."

Viva 2: "A 22-year-old Afro-Caribbean woman presents with a 2 cm painful keloid on her earlobe following piercing 8 months ago. She wants it removed. How do you manage her?"

Model Answer:

"I would approach this systematically:

Assessment:

• Confirm diagnosis: Keloid extending beyond piercing site, no spontaneous regression, typical site and ethnicity
• Assess symptoms: Pain, pruritus, psychological impact
• Examine for other keloids (keloid tendency)
• Ask about family history (genetic predisposition)

Counseling (Critical):

• 'This is a keloid—a benign overgrowth of scar tissue. Surgery alone has a very high recurrence rate (50-100%), often resulting in a larger keloid.'
• 'I recommend starting with non-surgical treatment first, which is effective in most cases.'

First-Line Treatment (Intralesional Steroids):

• Intralesional triamcinolone acetonide 10-20 mg/mL [9,10]
• Inject directly into keloid until it blanches (whitens)
• Repeat every 4-6 weeks
• Expect flattening, reduced pain/pruritus over 3-6 months (may need 6-12 sessions)
• Warn about side effects: skin thinning, lightening of skin color

Adjuncts:

• Silicone gel sheets (continuous use)
• Pressure earring (if tolerated)

If Refractory to Steroids:

• Consider combination therapy: Intralesional 5-FU + triamcinolone
• Cryotherapy (small keloid—suitable, but warn about permanent skin lightening)
• Pulsed dye laser (reduce redness)

Surgery (Last Resort):

• Only if medical therapy fails and patient strongly desires removal
• Mandatory adjuvant therapy:
  • Surgical excision (shave technique to minimize trauma)
  • Post-operative adjuvant radiotherapy (10-15 Gy within 24-48h; reduces recurrence to 10-25%) [14,15]
  • Intralesional steroids starting week 2-4 post-op, monthly for 6-12 months
  • Silicone sheets and pressure earring
• Counsel: 10-25% recurrence risk even with optimal adjuvant therapy

Follow-up:

• Review every 4-6 weeks during treatment
• Long-term monitoring (keloids can recur years later)
• Advise avoid further ear piercing

I would set realistic expectations: complete cure is difficult, but symptom control and size reduction are achievable in most cases with intralesional steroids."

Viva 3: "Why is adjuvant radiotherapy effective post-keloid excision, and what is the critical timing?"

Model Answer:

"Adjuvant radiotherapy is one of the most effective strategies to prevent keloid recurrence after surgical excision.

Mechanism of Action:

• Radiotherapy (ionizing radiation) inhibits fibroblast proliferation by damaging DNA, preventing cell division
• Induces fibroblast apoptosis (keloid fibroblasts normally resist apoptosis—radiotherapy overcomes this) [7]
• Reduces TGF-β1 expression (key pro-fibrotic cytokine in keloid pathogenesis) [6]
• Decreases inflammatory cell infiltration (chronic inflammation drives keloid growth)
• Inhibits angiogenesis (reduces vascular supply to scar)

Critical Timing:

• Within 24-48 hours post-excision (ideally within 24 hours) [14,15]
• Why? This is the early proliferative phase when fibroblasts are most active and radiosensitive
• Delayed radiotherapy (> 72 hours) is significantly less effective—recurrence rates increase

Dosing:

• Total dose: 10-20 Gy
• Fractionation varies: Single 15 Gy dose, OR 3-4 Gy × 5 fractions over 7-10 days
• Electron beam or superficial X-ray (spares deep structures)

Evidence:

• Without radiotherapy: 50-100% recurrence after excision alone [13]
• With adjuvant radiotherapy: 10-25% recurrence [14,15]
• Level II evidence from systematic reviews supports efficacy

Side Effects:

• Acute: Erythema, hyperpigmentation (common, transient)
• Chronic: Hyperpigmentation (can be permanent), skin atrophy
• Theoretical malignancy risk: Extremely low (less than 0.01% lifetime risk); benefit-risk favors use in adults
• Contraindications: Pregnancy (absolute), children less than 18 years (relative; weigh risk-benefit)

Practical Approach:

• Coordinate with radiation oncology pre-operatively
• Schedule radiotherapy immediately post-op (within 24h)
• Combine with intralesional steroids starting week 2-4 for best outcomes

The key message: Timing is critical—radiotherapy must be given in the narrow window when fibroblasts are most active (first 24-48 hours) to prevent keloid recurrence."

Viva 4: "What is the role of TGF-β in keloid pathogenesis?"

Model Answer:

"TGF-β (transforming growth factor-beta) is the central mediator of keloid pathogenesis. [6,7]

Normal Wound Healing Role:

• TGF-β is essential for wound healing: stimulates fibroblast migration, proliferation, and collagen synthesis
• Three isoforms exist: TGF-β1 (pro-fibrotic), TGF-β2 (pro-fibrotic), TGF-β3 (anti-scarring)
• Normally, TGF-β levels decline as wound matures, allowing transition to remodeling phase

Keloid Pathophysiology:

• TGF-β1 overexpression: Persistently elevated in keloid tissue (does not decline post-healing) [6]
• TGF-β3 deficiency: Anti-scarring isoform reduced in keloids (imbalance favors scarring)

Effects of Elevated TGF-β1 in Keloids:

1. Increased collagen synthesis: Upregulates collagen I and III gene expression
2. Inhibits collagen degradation: Downregulates MMPs (matrix metalloproteinases) and upregulates TIMPs (tissue inhibitors of MMPs)
3. Promotes fibroblast proliferation: Drives continuous fibroblast division (tumor-like growth)
4. Inhibits fibroblast apoptosis: Keloid fibroblasts resist programmed cell death [7]
5. Stimulates myofibroblast differentiation: α-SMA positive myofibroblasts contract and deposit collagen
6. Drives chronic inflammation: Recruits inflammatory cells (mast cells, macrophages) that perpetuate TGF-β release (self-sustaining cycle)

Therapeutic Implications:

• Intralesional steroids work partly by reducing TGF-β1 expression [9]
• Radiotherapy decreases TGF-β1 levels [14]
• Future therapies: TGF-β receptor inhibitors, anti-TGF-β antibodies (experimental)
• Exogenous TGF-β3: Being investigated as anti-scarring therapy (Avotermin)

In summary, TGF-β1 overexpression creates a self-perpetuating pro-fibrotic environment that drives excessive collagen synthesis, inhibits degradation, and prevents normal wound remodeling—the hallmark of keloid pathophysiology."

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11. Patient and Layperson Explanation

What Are Keloids and Hypertrophic Scars?

When your skin is injured (from a cut, burn, piercing, acne, or surgery), your body heals the wound by forming a scar. Normally, scars flatten and fade over time. However, sometimes the healing process goes wrong, and the scar becomes raised, thick, and red. There are two main types of abnormal scars:

Hypertrophic Scar:

• A raised, thick scar that stays within the area of the original wound
• Often itchy and red at first
• Usually improves on its own over 1-2 years and flattens (though it may not disappear completely)
• Common after surgery, injuries, or burns

Keloid Scar:

• A raised, thick scar that grows beyond the original wound, spreading into normal skin (like a crab with claws)
• Often itchy, painful, or tender
• Does not improve on its own—it keeps growing slowly over time
• Much more common in people with darker skin (African, Asian, or Hispanic heritage)
• Can develop months or even years after the original injury

Why Do Keloids Happen?

The exact cause is not fully understood, but keloids occur when your body produces too much scar tissue during healing. Instead of stopping when the wound is healed, your skin cells keep making scar tissue, and it builds up into a thick lump.

Risk Factors:

• Darker skin: Keloids are 15-20 times more common in people of African descent
• Family history: Keloids often run in families
• Age: Most common between ages 10-30
• Location: Certain body areas are more prone (earlobes, chest, shoulders, upper back)
• Type of injury: Ear piercing, acne, surgery, burns

How Are They Treated?

For Hypertrophic Scars:

• Silicone gel sheets or gel: Applied to the scar for 12+ hours a day for several months. This helps flatten the scar and reduce redness.
• Pressure therapy: Wearing tight pressure garments (especially for burn scars) helps flatten the scar.
• Massage: Gently massaging the scar can help it soften.
• Time: Many hypertrophic scars improve on their own over 1-2 years.

For Keloid Scars:

• Steroid injections (first-line treatment): A doctor injects a steroid medicine (called triamcinolone) directly into the keloid every 4-6 weeks. This helps flatten the keloid and reduce itching and pain. It works in 50-100% of people, but it may take several months of treatment.

  • "Side effects: The skin may thin slightly or lighten in color where the injections are given."

• Silicone gel sheets: Used alongside steroid injections to help keep the scar flat.

• Cryotherapy (freezing): Liquid nitrogen is used to freeze the keloid. This can help shrink small keloids but may cause the skin to lighten permanently (which can be noticeable on darker skin).

• Laser treatment: Laser therapy can reduce redness and itching but does not usually shrink the keloid much on its own.

• Surgery (last resort):

  • Cutting out the keloid alone almost always results in the keloid coming back (often bigger than before)—this happens in 50-100% of cases.
  • "If surgery is needed, it must be combined with other treatments such as:"
    • Radiation therapy within 24-48 hours after surgery (reduces recurrence to 10-25%)
    • Steroid injections after surgery
    • Silicone sheets and pressure therapy
  • Even with these extra treatments, there is still a 10-25% chance the keloid will come back.

Can Keloids Be Prevented?

If you are prone to keloids:

• Avoid unnecessary piercings, tattoos, or cosmetic procedures
• If you need surgery, tell your surgeon about your keloid tendency so they can use special techniques to minimize scarring
• After any wound or surgery, use silicone gel sheets early (starting 2-3 weeks after healing) to reduce the risk of keloid formation
• Keep wounds clean and avoid infection (infections increase scarring)

What Should I Expect?

• Hypertrophic scars: Usually improve over time with or without treatment. With silicone and pressure therapy, most people see good improvement within 1-2 years.

• Keloid scars: Do not go away on their own and require active treatment. With steroid injections, most people see flattening and symptom relief over several months. However, keloids are difficult to cure completely, and long-term monitoring is often needed because they can grow back.

When Should I See a Doctor?

See a doctor if:

• You develop a raised, growing scar that spreads beyond the original wound
• Your scar is painful, itchy, or interfering with movement
• You are planning surgery and have a history of keloids (so your surgeon can plan preventive measures)
• You notice rapid growth, bleeding, or ulceration of a scar (rare but should be checked)

Important Takeaways

• Hypertrophic scars stay within the wound and often improve; keloids grow beyond the wound and do not improve without treatment
• Keloids are much more common in people with darker skin
• Steroid injections are the first-line treatment for keloids and work in most people
• Surgery alone for keloids almost always leads to recurrence—it must be combined with other treatments
• Prevention is key: avoid unnecessary procedures if you are keloid-prone, and use silicone therapy early after any wound

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12. References

Key Guidelines

1. Berman B, Maderal A, Raphael B. Keloids and Hypertrophic Scars: Pathophysiology, Classification, and Treatment. Dermatol Surg. 2017;43 Suppl 1:S3-S18. doi:10.1097/DSS.0000000000000819. PMID: 27347634

2. Slemp AE, Kirschner RE. Keloids and scars: a review of keloids and scars, their pathogenesis, risk factors, and management. Curr Opin Pediatr. 2006;18(4):396-402. doi:10.1097/01.mop.0000236389.41462.ef. PMID: 16914994

Epidemiology and Risk Factors

3. Arno AI, Gauglitz GG, Barret JP, Jeschke MG. Up-to-date approach to manage keloids and hypertrophic scars: a useful guide. Burns. 2014;40(7):1255-1266. doi:10.1016/j.burns.2014.02.011. PMID: 24767715

4. Marneros AG, Norris JE, Watanabe S, Reichenberger E, Olsen BR. Genome scans provide evidence for keloid susceptibility loci on chromosomes 2q23 and 7p11. J Invest Dermatol. 2004;122(5):1126-1132. doi:10.1111/j.0022-202X.2004.22327.x. PMID: 15140214

5. Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17(1-2):113-125. doi:10.2119/molmed.2009.00153. PMID: 20927486

Pathophysiology

6. Ogawa R. Keloid and Hypertrophic Scars Are the Result of Chronic Inflammation in the Reticular Dermis. Int J Mol Sci. 2017;18(3):606. doi:10.3390/ijms18030606. PMID: 28287424

7. Limandjaja GC, Niessen FB, Scheper RJ, Gibbs S. The Keloid Disorder: Heterogeneity, Histopathology, Mechanisms and Models. Front Cell Dev Biol. 2020;8:360. doi:10.3389/fcell.2020.00360. PMID: 32509777

8. Ogawa R, Okai K, Tokumura F, et al. The relationship between skin stretching/contraction and pathologic scarring: the important role of mechanical forces in keloid generation. Wound Repair Regen. 2012;20(2):149-157. doi:10.1111/j.1524-475X.2012.00766.x. PMID: 22332721

Treatment: Intralesional Corticosteroids

9. Sidle DM, Kim H. Keloids: prevention and management. Facial Plast Surg Clin North Am. 2011;19(3):505-515. doi:10.1016/j.fsc.2011.06.005. PMID: 21856539

10. Mustoe TA, Cooter RD, Gold MH, et al; International Advisory Panel on Scar Management. International clinical recommendations on scar management. Plast Reconstr Surg. 2002;110(2):560-571. doi:10.1097/00006534-200208000-00031. PMID: 12142678

Treatment: Silicone Therapy

11. Monstrey S, Middelkoop E, Vranckx JJ, et al. Updated scar management practical guidelines: non-invasive and invasive measures. J Plast Reconstr Aesthet Surg. 2014;67(8):1017-1025. doi:10.1016/j.bjps.2014.04.011. PMID: 24888226

12. O'Brien L, Jones DJ. Silicone gel sheeting for preventing and treating hypertrophic and keloid scars. Cochrane Database Syst Rev. 2013;(9):CD003826. doi:10.1002/14651858.CD003826.pub3. PMID: 24030657

Treatment: Surgery and Adjuvant Therapy

13. Berman B, Viera MH, Amini S, Huo R, Jones IS. Prevention and management of hypertrophic scars and keloids after burns in children. J Craniofac Surg. 2008;19(4):989-1006. doi:10.1097/SCS.0b013e318175f3a7. PMID: 18650723

14. Ud-Din S, Bayat A. Strategic Management of Keloid Disease in Ethnic Skin: A Structured Approach Supported by the Emerging Literature. Dermatol Surg. 2013;39(11):1631-1648. doi:10.1111/dsu.12308. PMID: 24010643

15. Ogawa R, Yoshitatsu S, Yoshida K, Miyashita T. Is radiation therapy for keloids acceptable? The risk of radiation-induced carcinogenesis. Plast Reconstr Surg. 2009;124(4):1196-1201. doi:10.1097/PRS.0b013e3181b5a3db. PMID: 19935302

Genetics

16. Brown JJ, Bayat A. Genetic susceptibility to raised dermal scarring. Br J Dermatol. 2009;161(1):8-18. doi:10.1111/j.1365-2133.2009.09258.x. PMID: 19416257

Neurogenic Mechanisms

17. Luo S, Benathan M, Raffoul W, Panizzon RG, Egloff DV. Abnormal balance between proliferation and apoptotic cell death in fibroblasts derived from keloid lesions. Plast Reconstr Surg. 2001;107(1):87-96. doi:10.1097/00006534-200101000-00014. PMID: 11176606

Laser Therapy

18. Manuskiatti W, Fitzpatrick RE. Treatment response of keloidal and hypertrophic sternotomy scars: comparison among intralesional corticosteroid, 5-fluorouracil, and 585-nm flashlamp-pumped pulsed-dye laser treatments. Arch Dermatol. 2002;138(9):1149-1155. doi:10.1001/archderm.138.9.1149. PMID: 12224975

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Last Updated: 2026-01-07
Evidence Level: High (18 PubMed citations)
Target Audience: MRCP, MRCS, FRCS (Plastics), Dermatology Postgraduate Examinations