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HYPERTROPHIC SCAR AND KELOID

Complete Plastic Surgery Viva Guide

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1. DEMOGRAPHY & EPIDEMIOLOGY

• Most common site of keloid: Sternal/presternal region
• Most common site for minor keloid: Earlobe (after ear piercing)
• Most common race affected: Black Africans (incidence 4-16x higher than Caucasians); also Asians and Hispanics
• Least common sites: Face (central), palms, soles, genitalia
• Age: Young adults (peak 10-30 years); rare in infancy and old age
• Sex: Equal in both; some studies suggest slightly higher in females (due to ear piercing)
• Worldwide prevalence: 4.5-16% in darkly pigmented skin populations vs. <1% in Caucasians

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2. BASIC DEFINITIONS & DIFFERENCES

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3. CAUSES / ETIOLOGY

Genetic Factors

• Autosomal dominant inheritance with incomplete penetrance (familial keloids documented)
• HLA associations: HLA-B14, HLA-B21, HLA-DRB1*15 associated with keloid susceptibility
• Chromosome 2q23 locus implicated in familial keloids
• Multiple genes involved: NEDD4, CYP1B1, HMGA2 mutations reported

Environmental / Triggering Factors

• Trauma - most common trigger: surgery, burns, lacerations, abrasions, piercings
• Infections: acne pustules (chest/back keloids), folliculitis, chickenpox
• Vaccinations: BCG vaccination - a classic cause of deltoid keloids
• Tension: wounds perpendicular to Langer's lines, wound under high tension
• Hormones: puberty and pregnancy worsen keloids (hormonal influence); testosterone implicated
• Location: certain anatomic sites are inherently high risk (see below)

High-Risk Sites (Viva Key)

• Sternum (presternal region)
• Anterior chest/shoulders/deltoid
• Neck
• Deltoid/upper arm
• Earlobes
• Scalp (after burns)

Pathogenesis (Molecular)

1. TGF-β1 and TGF-β2 (profibrotic cytokines) - overexpressed → stimulate fibroblasts → excess collagen I, III
2. TGF-β3 (antifibrotic) - reduced in keloids
3. IL-6, IL-8, IL-10, VEGF - elevated → promote fibroblast proliferation and angiogenesis
4. PDGF (Platelet-Derived Growth Factor) - stimulates fibroblast mitosis
5. Apoptosis failure: keloid fibroblasts are resistant to apoptosis (p53 dysfunction, overexpressed bcl-2)
6. Mechanical stress: tension activates mechanoreceptors → TGF-β pathway activation
7. MAPK/ERK pathway: activated in keloid fibroblasts
8. Wnt signaling pathway: aberrantly activated
9. Mast cells: increased number; mast cell-derived histamine causes pruritus + stimulates fibroblast proliferation

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4. CLINICAL FEATURES

Hypertrophic Scar

• Raised, red/pink, firm scar within wound boundaries
• Appears within weeks of injury
• Associated with linear scars, burns, areas of skin tension
• Usually regresses spontaneously over 12-18 months
• May cause itching and discomfort during active phase
• No clawlike extensions

Keloid

• Firm, rubbery, pink-to-purplish nodule extending beyond wound margins
• Clawlike (cheloid) prolongations - pathognomonic
• Never regresses spontaneously
• Actively growing edge (peripheral) + inactive dense centre
• Surface is smooth, glossy, thinned
• Symptoms: pruritus (MC), pain, burning sensation
• May be tender to touch; rarely ulcerates or forms sinus tracts
• Sternal keloids can be large; earlobe keloids often "dumbbell-shaped" when lobule is pierced

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5. CLASSIFICATION

A. Mustoe International Classification (2002, most widely used)

B. Based on Etiology

• Post-traumatic (surgical, accidental injury)
• Post-inflammatory (acne, folliculitis, chickenpox)
• Spontaneous (rare - appears without obvious trauma)

C. Japan Scar Workshop (JSW) 2015 Scar Scale (JSS 2015)

• Score 0-5: Mature scar
• Score 6-15: Hypertrophic scar
• Score 16-25: Keloid
• Scores based on risk factors (genetics, site, race) + clinical features (height, color, symptoms)

D. Vancouver Scar Scale (VSS) - for objective severity grading

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6. INVESTIGATIONS

When to Investigate & What to Do

A. Clinical Assessment

• Usually clinical diagnosis is sufficient
• VSS scoring for objective documentation
• Photography for baseline and follow-up

B. Dermoscopy

• Helps distinguish active vs. quiescent scar
• Active keloid: visible vessels, erythema at periphery

C. Ultrasound

• High-frequency ultrasound (20 MHz): measures scar thickness; useful for monitoring treatment response
• Identifies extent of dermal involvement

D. MRI

• For giant/deep keloids to assess extent and plan surgery

E. Histopathology / Biopsy

• Atypical clinical presentation
• Suspicion of malignancy (carcinoma en cuirasse, DFSP, desmoplastic melanoma can mimic keloid)
• Rapid unexpected growth
• Ulceration, bleeding not explained by trauma
• No history of trauma at site

• Classic clinical appearance in known keloid-prone individual - biopsy itself can trigger/worsen keloid formation
• Avoid incisional biopsy at high-risk sites if diagnosis is clear

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7. BIOPSY - HOW TO TAKE, PATHOLOGY, IHC

How to Take

• Punch biopsy (3-4mm) preferred over incisional biopsy to minimize new wound
• Take from the active edge (advancing margin) - most cellular and informative
• Handle with care - use minimal trauma technique
• In known keloid-prone patient - if biopsy is truly needed, plan surgical excision of the entire lesion at the same time

Cells of Origin

• Fibroblasts (activated myofibroblasts are the primary cell)
• Mast cells (increased)
• Macrophages
• Endothelial cells (neovascularization)

Histopathology (KEY VIVA TABLE)

IHC Findings

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8. MANAGEMENT

Overview - General Principles

"No single proven best therapy exists; combination therapy is superior to monotherapy; keloids require adjuvant therapy after any surgery; hypertrophic scars have better outcomes."

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8.1 PREVENTION (First-Line Strategy)

1. Tension relief: Close wounds parallel to Langer's lines; use subcutaneous/fascial sutures to reduce skin tension
2. Silicone gel/sheets: Apply 2 weeks post-wound closure; 12-24 hours/day; for 12-24 weeks - first-line prophylactic and treatment option (Bailey & Love, Bailey)
3. Pressure garments: Start as soon as wound is closed; especially for burns; >25 mmHg pressure; worn 23 hrs/day
4. Taping: 3+ months post-closure; changes every 24-48 hours
5. Sunscreen SPF 50+: For 1 year post-op to prevent hyperpigmentation
6. Avoid: Nonessential surgery at high-risk sites in keloid-prone individuals
7. Avoid: Secondary intention healing in high-risk patients (delays healing >2-3 weeks → higher risk)

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8.2 NON-SURGICAL TREATMENTS

A. Intralesional Corticosteroids (ILCs) - Gold Standard First-Line

• Skin atrophy (inject only into scar tissue)
• Hypopigmentation (dose-dependent; commoner with higher concentrations)
• Telangiectasia formation
• Adjacent fat atrophy if injected beyond scar
• Pain during injection
• Cushingoid features if large amounts used

B. 5-Fluorouracil (5-FU) - Second Line / Combination

C. Bleomycin

D. Verapamil

E. Botulinum Toxin A

F. Silicone Gel/Sheeting

G. Pressure Therapy

• 25+ mmHg; worn 23 hrs/day; changed when worn
• Mechanism: reduces wound oxygen tension → decreases myofibroblast proliferation; collagen I & III reduction seen within 1 week
• Duration: Until scar maturation (6-18 months)

H. Emerging / Novel Agents

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8.3 LASER THERAPY

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8.4 CRYOTHERAPY

• Mechanism: Ice crystal formation → vascular disruption → fibroblast apoptosis → collagen destruction; also reduces TGF-β1
• Technique: Contact, spray, or intralesional needle cryoprobe
• Protocol: Three freeze-thaw cycles, 30-second sessions, every 3-4 weeks
• Best for: Small isolated keloids; earlobe keloids
• Side effects: Hypopigmentation (significant in dark skin - limit use), pain, blistering

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8.5 SURGICAL MANAGEMENT

Indications for Surgery

• Functional impairment (contracture limiting joint movement)
• Large hypertrophic scars after 1 year of conservative management
• Keloids refractory to 12 months of conservative therapy
• Diagnostic uncertainty (simultaneous biopsy + excision)
• Earlobe keloids (after ILC failure)
• Symptomatic lesions (severe pain/pruritus unresponsive to medical treatment)

Contraindications / Relative Contraindications to Surgery

• Active growing keloid (relative)
• No adjuvant therapy planned (excision alone → 50-100% recurrence for keloids)
• Patient unwilling to comply with prolonged post-op adjuvant treatment
• High-risk anatomic sites with no clear functional benefit
• Young patients with strong keloid history and small lesion (try conservative first)

Limitations

• Keloid surgery alone → 50-100% recurrence rate (always needs adjuvant)
• Cannot cure genetic predisposition
• Each new wound = new opportunity for keloid formation

Surgical Steps - Keloid Excision

1. Mark the lesion; plan excision margins
2. LA with lidocaine + adrenaline + TAC mixture (reduces bleeding + immediate antikeloid effect)
3. Intralesional excision (leave thin shell of scar to close over without creating raw wound bed) OR complete excision depending on size
4. Tension-free primary closure with subcuticular sutures (monofilament)
5. Immediate (within 24-48 hours) post-op adjuvant therapy: radiation OR ILC injection
6. Start silicone gel and pressure earring post-operatively

1. Simple scar resection + primary closure with:
   • Adjacent tissue undermining
   • Deep subcutaneous tensile reduction sutures
   • Z-plasty (gains length, reorients scar along relaxed skin tension lines)
   • W-plasty / geometric broken line closure (for facial scars)
   • V-Y, Y-V plasty
   • Local or free flaps (for large areas, severe contractures)
2. Post-op: taping for 3 months + silicone therapy

• Standard Z-plasty: 60° angles → 75% length gain
• 45° angles → 50% length gain; 30° angles → 25% length gain
• Transposes tissue, relieves tension, breaks up linear scar
• Used for: contractures across joints, reorienting scar along RSTL

• For widespread large hypertrophic scars
• Generates extra skin for reconstruction
• Serial excision over multiple sessions

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8.6 RADIATION THERAPY

• Theoretical carcinogenic risk (literature has NOT proven significant association)
• Not preferred in young patients, areas near gonads/thyroid
• Skin atrophy, telangiectasia as late effects
• Avoid in pediatric patients

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8.7 COMBINED / MULTIMODAL APPROACH

The NMS (Nippon Medical School) Protocol (Ogawa et al.): Surgery + immediate post-op radiation + ILC injections + silicone + pressure = best outcomes

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9. APPROACH TO A PATIENT (Practical Algorithm)

PATIENT PRESENTS WITH ABNORMAL SCAR
              ↓
Is it within wound margins? → YES → Hypertrophic Scar
                             NO → Keloid
              ↓
ASSESS: Size, site, symptoms, VSS score, age, race, patient expectations

Hypertrophic Scar Management by Stage:

Keloid Management by Type:

Specific Scenarios (Viva Gold):

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10. FOLLOW-UP & PROGNOSIS

Follow-Up Schedule

• Monthly for first 3 months (active treatment)
• Every 3 months for first year
• Every 6 months for 2nd year
• Keloids: Follow for minimum 2 years - recurrences may not appear until 6 months to 2 years post-treatment

Prognosis

Recurrence Rates (Keloid)

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11. RECENT EVIDENCE (PubMed 2023-2025)

• PMID 39447283 (Burns, 2024 Meta-Analysis): TAC + Botulinum toxin A combination significantly superior to TAC alone for both hypertrophic scars and keloids
• PMID 38347765 (J Burn Care Res, 2024 Systematic Review): Laser-assisted drug delivery (LADD) using fractional CO2 + TAC/5-FU is effective for hypertrophic scars and keloids
• PMID 38760539 (Aesthetic Plast Surg, 2024 Network Meta-Analysis): PDL and CO2 laser most effective laser modalities; PDL best for erythema, CO2 best for thickness
• 2024 Single-center study: 10 Gy single-fraction EBRT within 24 hours post-surgery → 0.81% recurrence rate (vs. 8.47% with 9.5 Gy)

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12. CRUX FLOWCHART - MANAGEMENT ALGORITHM

╔══════════════════════════════════════════════════════════════════╗
║           PATIENT WITH HYPERTROPHIC SCAR / KELOID                ║
╚══════════════════════════════════════════════════════════════════╝
                              │
              ┌───────────────┴───────────────┐
              ▼                               ▼
    HYPERTROPHIC SCAR                      KELOID
    (within margins,                  (beyond margins,
     may regress)                      never regresses)
              │                               │
    ┌─────────┴──────────┐          ┌─────────┴──────────┐
    ▼                    ▼          ▼                    ▼
  EARLY               LATE       MINOR               MAJOR
 (<6 mo)            (>6 mo)    (earlobe,            (sternal,
                               small)               large)
    │                  │          │                    │
    ▼                  ▼          ▼                    ▼
Silicone+          ILC TAC     ILC TAC 40          Silicone+
Pressure           10-40mg/mL  mg/mL q6-8wks       Pressure+
Observe            q4wks                           ILC TAC 40mg/mL
                   │          NO RESPONSE          │
                   ▼          after 12 mo          ▼
               Laser PDL      │               ILC + 5-FU +
               +/- CO2        ▼               Bleomycin/
                        SURGICAL EXCISION     Verapamil
                              +              (combination)
                        IMMEDIATE ADJUVANT    │
                        ─────────────────    NO RESPONSE
                        EBRT 10 Gy within     │
                        24-48 hrs             ▼
                              +          SURGERY +
                        ILC post-op      EBRT 10 Gy +
                              +          ILC post-op
                        SILICONE +            +
                        PRESSURE          SILICONE +
                              │           PRESSURE
                              ▼               │
                         FOLLOW-UP       FOLLOW-UP
                         Monthly x3      Monthly x3
                         then q3/12      then q3/12
                         for 1-2 yrs     for 2 yrs

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13. QUICK RECALL MNEMONICS

• Klaws beyond borders (keloid)
• Ever regresses? No (keloid never regresses)
• Late onset (months-years)
• Odd thick hyalinized collagen histologically
• Itching + pain (more in keloid)
• Dark skin (more common)

• Compression + silicone (first)
• Laser (second)
• Intralesional injections (TAC ± 5-FU)
• Pressure garments
• Surgery (last resort, ALWAYS with adjuvant)
• Radiation (adjuvant post-surgery for keloid)

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• Andrews' Diseases of the Skin (11e) - Keloid section
• Dermatology 2-Volume Set 5e (Bolognia) - Ch. 98
• Sabiston Textbook of Surgery - Prevention & Treatment of Hypertrophic/Keloid Scars
• Bailey & Love's Short Practice of Surgery (28e)
• Schwartz's Principles of Surgery (11e) - Burns chapter
• Mustoe TA et al. International Clinical Recommendations on Scar Management (2002)
• Recent PubMed Systematic Reviews (2024): PMIDs 39447283, 38347765, 38760539

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HYPERTROPHIC SCAR AND KELOID

Complete Plastic Surgery Theory Exam Guide

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1. DEMOGRAPHY & EPIDEMIOLOGY

• Most common site of keloid: Sternal/presternal region
• Most common site for minor keloid: Earlobe (after ear piercing)
• Most common trigger: Trauma (surgery, burns, piercings)
• Most common symptom: Pruritus
• Most common race affected: Black Africans (4-16x higher incidence than Caucasians); also Asians > Hispanics > Caucasians
• Least common sites: Central face, palms, soles, genitalia (palms and soles almost never affected)
• Age: Peak incidence 10-30 years; rare in infancy and old age; hormones of puberty worsen keloid tendency
• Sex: Equal sex distribution overall; females overrepresented due to ear piercing history
• Worldwide prevalence: 4.5-16% in darkly pigmented populations vs <1% in Caucasians
• Hypertrophic scars: Much more common than keloids; occur in any race; burn patients particularly prone (up to 70% after deep burns)

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2. DEFINITIONS

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3. CAUSES / ETIOLOGY

3.1 Genetic Factors

• Autosomal dominant inheritance with incomplete penetrance and variable expressivity - familial keloids are well-documented across multiple pedigrees
• HLA associations: HLA-B14, HLA-B21, HLA-DRB1*15 confer susceptibility
• Chromosomal locus: 2q23 implicated in familial keloid pedigrees
• Key genes: NEDD4, CYP1B1, HMGA2 mutations identified in keloid-prone individuals
• Racial predisposition: Black Africans carry the highest genetic burden; certain African tribes show near-universal keloid formation after skin trauma

3.2 Environmental / Triggering Factors

• Trauma (most important trigger):
  • Surgical wounds
  • Burns and scalds - widest, most severe hypertrophic scars
  • Lacerations and abrasions
  • Ear/body piercing
  • Tattoos
• Infection: Acne vulgaris (classic cause of chest/back keloids), folliculitis, chickenpox, infected wounds
• Vaccination: BCG at deltoid - classic teaching point
• Mechanical tension: Wounds perpendicular to Langer's lines; wounds over mobile areas (shoulder, sternum, jaw)
• Hormonal influences: Puberty and pregnancy both worsen keloids; testosterone implicated; keloids may regress after menopause
• Prolonged wound healing: Wounds taking >2-3 weeks to heal (deep partial-thickness burns, infected wounds) have markedly higher scar hypertrophy risk
• Wound infection / prolonged inflammation: Prolongs inflammatory phase → excess cytokine release

3.3 High-Risk Anatomic Sites

• Sternum / presternal chest
• Anterior chest wall
• Deltoid / shoulders
• Neck
• Earlobes
• Scalp (after burns)
• Supra-pubic region

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4. PATHOGENESIS (Molecular Basis)

Normal Wound Healing (Brief Review)

1. Hemostasis (seconds to hours): platelet plug; fibrin clot; release of PDGF, TGF-β from platelets
2. Inflammation (hours to days): neutrophils then macrophages; clean debris; release IL-1, TNF-α, TGF-β
3. Proliferation (days to weeks): fibroblast migration + proliferation; collagen I and III synthesis; angiogenesis; re-epithelialization
4. Remodeling (weeks to years): collagen III → collagen I; MMPs degrade excess collagen; scar matures and softens

What Goes Wrong in Keloid / Hypertrophic Scar

Kischer-Brody Collagen Nodule Theory

• High-density fibroblasts
• Unidirectional collagen within each nodule
• Surrounded by an alpha-smooth muscle actin (α-SMA)-positive fibrous capsule

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5. CLINICAL FEATURES

5.1 Hypertrophic Scar

• Raised, red/pink, firm scar within the original wound boundaries
• Usually linear, following the wound
• Appears within weeks of injury
• Actively growing for months, then stabilizes

• Pruritus and burning during active growth phase
• Usually regresses spontaneously over 12-18 months
• If over a joint → contracture → functional impairment

• No clawlike extensions
• Stays within wound margins
• Regresses over time
• Lower recurrence after surgery

5.2 Keloid

• Firm, rubbery, pink-to-purplish, shiny nodule/plaque
• Extends beyond the original wound margins in all directions
• Clawlike (cheloid) projections - pathognomonic
• Surface is smooth, glossy, thinned from pressure
• Never regresses spontaneously
• Actively growing edge (peripheral zone) + less active dense center
• Small trauma → disproportionately large keloid

• Pruritus (most common) - from mast cell histamine release
• Pain and burning sensation
• Psychological distress and cosmetic disfigurement
• Rarely: ulceration, sinus tract formation, drainage

• Earlobe keloid: "Dumbbell" or lobulated shape after piercing; grows on both sides of lobe
• Sternal keloid: Large, butterfly-shaped, extends up to shoulders and across chest
• Acne keloid: Multiple small nodules over upper back and chest
• BCG keloid: Raised nodule at deltoid vaccination site (classic exam scenario)

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6. CLASSIFICATION

6.1 Mustoe International Classification (2002) - Most Widely Used Clinically

6.2 Japan Scar Workshop (JSW) 2015 Scar Scale (JSS 2015)

6.3 Vancouver Scar Scale (VSS) - Objective Severity Assessment

• Maximum score = 13; higher score = worse/more active scar
• Used to monitor treatment response and compare outcomes
• Part of standard documentation in burns and reconstructive centers

6.4 Patient and Observer Scar Assessment Scale (POSAS)

• Two components: Observer (clinician rates vascularity, pigmentation, thickness, relief, pliability, surface area) + Patient (rates pain, itch, color, stiffness, thickness, irregularity)
• More comprehensive than VSS; captures patient-reported outcomes

6.5 Classification by Etiology

• Post-traumatic (surgical, accidental)
• Post-inflammatory (acne, folliculitis, chickenpox)
• Post-burn
• Spontaneous (without obvious trauma - suggests strong genetic predisposition)

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7. INVESTIGATIONS

7.1 Clinical Assessment

• Usually clinical diagnosis is sufficient and investigations are targeted
• Thorough history: timing of onset, trigger, growth pattern, prior treatments, family history
• Examine: margins (within vs. beyond wound), consistency, tenderness, clawlike projections

7.2 When to Investigate

7.3 High-Frequency Ultrasound (20 MHz)

• Measures scar thickness in millimeters
• Maps vascularity
• Monitors response to treatment (non-invasive, repeatable)
• Can distinguish dermis from subcutaneous tissue involvement

7.4 When NOT to Investigate

• Classic clinical presentation in known keloid-prone individual - avoid biopsy (biopsy = new wound = may trigger new keloid)
• If diagnosis is clinically clear, investigations only add to cost with no benefit
• Routine blood tests are not indicated unless systemic disease suspected

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8. BIOPSY

8.1 When to Biopsy

• Atypical appearance or rapid unexpected growth
• Clinical suspicion of malignancy (carcinoma en cuirasse, DFSP, desmoplastic melanoma can all mimic keloid)
• Ulceration, bleeding without clear cause
• No history of trauma at lesion site
• Large irregular plaques in atypical locations
• Pre-treatment baseline in research/clinical trials

8.2 When NOT to Biopsy

• Classic keloid in a known keloid-prone patient (biopsy creates a new wound = risk of triggering or enlarging keloid)
• Always ask: "Will the biopsy result change my management?" - if no, avoid
• If biopsy is truly necessary, plan simultaneous complete excision of the lesion

8.3 How to Take the Biopsy

• Punch biopsy (3-4 mm): preferred - minimal new wound created
• Site: Take from the active edge (advancing peripheral margin) - most cellular and diagnostically informative; the center is hypocellular and dense
• Handling: Minimize trauma; direct formalin fixation for routine H&E; fresh tissue for special studies
• Technique: Gentle handling, avoid crushing; orient specimen for proper sectioning

8.4 Cells of Origin

8.5 Histopathology (Key Table - Dermatology 5e Bolognia, Table 98.3)

• No epidermal flattening
• No fibrosis in papillary dermis
• Tongue-like advancing edge as scar extends through reticular dermis
• Horizontal cellular fibrous band in upper reticular dermis with sharp demarcation
• Prominent fascia-like fibrous bands deep in scar (Dermatology 5e)

8.6 Immunohistochemistry (IHC)

8.7 Molecular/Genetic Findings

• Overexpression of TGF-β1, PDGF, VEGF, IL-6, IL-8
• Reduced TGF-β3 (antifibrotic isoform)
• Activated MAPK/ERK pathway
• Wnt signaling constitutively activated
• COX-1 and COX-2 overexpression → prostaglandin synthesis → fibroblast activation
• Elevated fibronectin and glycosaminoglycans (mucopolysaccharides) in keloid matrix
• Decreased collagenase (MMP-1, MMP-8) activity + increased TIMP expression

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9. MANAGEMENT

Overview

"Hypertrophic scars and keloids share broadly similar management strategies, but no single proven best therapy exists. Combination multimodal therapy is superior. Keloids require adjuvant therapy after any surgery - surgery alone produces 50-100% recurrence." (Sabiston Textbook of Surgery)

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9.1 PREVENTION - The Best Strategy

1. Tension relief: Close wounds parallel to Langer's relaxed skin tension lines (RSTL); use subcutaneous/fascial sutures to offload skin tension; geometric scar revision for unfavorably placed scars
2. Hydration and occlusion: Silicone products; moisturizing lotions; moisture-retentive dressings
3. Taping and pressure: Postsurgical taping for 3 months; pressure garments for wide wounds/burns

• Avoid unnecessary surgery at high-risk sites in keloid-prone individuals
• Avoid wounds that take >2-3 weeks to heal (deep burns, infected wounds) - use early grafting/flaps
• Apply silicone starting 2 weeks after wound closure
• Pressure garments: start as soon as wound is closed, before hypertrophy develops
• Sunscreen SPF 50+ for 1 year post-op to prevent hyperpigmentation

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9.2 CONSERVATIVE / NON-SURGICAL TREATMENTS

A. Silicone Gel Sheeting / Gel - First-Line for Both Conditions

B. Pressure Therapy

C. Intralesional Corticosteroids (ILC) - Gold Standard Pharmacological Treatment

• Skin/fat atrophy (most important - inject only within scar to avoid)
• Hypopigmentation (dose-dependent; concerning in darker skin tones)
• Telangiectasia formation at injection sites
• Cushing's syndrome (rare with small-volume intralesional use)
• Pain during injection (can premix with LA)
• Menstrual irregularities (with large volumes)

D. 5-Fluorouracil (5-FU) Intralesional

E. Bleomycin Intralesional

F. Verapamil Intralesional

G. Botulinum Toxin A (BotA)

H. Cryotherapy

I. Emerging / Novel Therapies

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9.3 LASER THERAPY

• Fractional CO2 laser creates microchannels through scar epidermis
• TAC or 5-FU applied immediately after → enhanced penetration into scar
• 2024 Systematic Review (PMID 38347765): LADD is effective for hypertrophic scars and keloids with good evidence

• PDL best for erythema/vascularity
• CO2 best for thickness and texture
• Combined PDL + CO2 often used in practice

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9.4 SURGICAL MANAGEMENT

Indications for Surgery

• Functional impairment (contracture limiting joint movement - urgent)
• Large hypertrophic scars unresponsive to 12 months of conservative management
• Keloids refractory to 12 months of conservative therapy
• Diagnostic uncertainty (biopsy + excision simultaneously)
• Symptomatic lesions (severe uncontrolled pain/pruritus)
• Earlobe keloids after ILC failure
• Large disfiguring keloids causing psychological distress

Contraindications to Surgery

• Active, rapidly growing keloid (relative - wait until stabilized if possible)
• No adjuvant therapy planned (excision alone for keloid = 50-100% recurrence - contraindicated without adjuvant)
• Patient unable/unwilling to comply with prolonged post-op adjuvant therapy
• High-risk anatomic site with no functional benefit
• Very young patient with strong keloid history and small, manageable lesion (try conservative first)

Limitations of Surgery

• Keloid excision alone → 50-100% recurrence (Sabiston)
• Cannot address underlying genetic predisposition
• Each surgical wound = new opportunity for scar formation
• No cosmetic improvement guaranteed without adjuvant treatment

Key Surgical Techniques

• Leave a thin shell of scar tissue to avoid raw wound bed
• Reduces risk of stimulating regrowth
• Less tension on closure
• Good for earlobe keloids particularly

• For hypertrophic scars and small keloids with planned adjuvant
• Combine with:
  • Deep dermal/subcutaneous tensile reduction sutures
  • Adjacent tissue undermining
  • Subcuticular (continuous) closure
  • Z-plasty / W-plasty

1. Mark keloid margins; plan excision
2. Local anaesthetic: lidocaine 1% + adrenaline 1:200,000 mixed with TAC (premixed injection)
3. Intralesional excision or complete excision depending on size/shape
4. Tension-free closure with subcuticular 4-0 monofilament
5. Immediate post-op adjuvant within 24-48 hours: EBRT 10 Gy single-fraction OR ILC TAC 40 mg/mL
6. Post-op: pressure earring + silicone gel
7. Follow-up: monthly for 6 months; 3-monthly for 2 years

• Transposes triangular flaps
• Reorients scar along RSTL
• Breaks up linear scar → reduces tension
• Used for: contractures across joints, linear scars in unfavorable direction

• Serial excision + tissue expansion
• Flap reconstruction (preferred over graft for contracture release)
• Why flaps > grafts: Skin-pedicled flaps expand after surgery; grafts do NOT expand and can develop circular pathologic scars at margins
• Full-thickness graft preferred over split-thickness when graft must be used (less contracture, better texture)

1. Release contracture across joint completely
2. Reconstruct defect with:
   • Local flap (Z-plasty, Y-V, V-Y, propeller flap)
   • Regional flap
   • Free flap (for severe contractures)
   • Skin graft (second choice)
3. Post-op: splint in corrected position; physiotherapy; pressure garment; silicone

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9.5 RADIATION THERAPY

• Theoretical risk of radiation-induced malignancy - literature has NOT proven significant association (Sabiston)
• Skin atrophy and telangiectasia as late effects
• Avoid near gonads, thyroid, developing breast tissue in children
• Not preferred in pediatric patients
• Avoid during pregnancy

• Shin et al. compared surgery + ILC (15.4% recurrence) vs surgery + RT (14% recurrence) - comparable efficacy
• Choice depends on availability, patient preference, site

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9.6 MULTIMODAL / COMBINATION APPROACH

• Tension-reducing surgery
• Immediate post-op EBRT (within 24 hours)
• Post-op ILC injections
• Silicone gel therapy
• Pressure garments

• Surgery + TAC: 15-20% recurrence
• Surgery + radiation: 14-15% recurrence
• Surgery alone: 50-100% recurrence
• Surgery + TAC + radiation + silicone: <10% recurrence

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10. APPROACH TO A PATIENT (Practical Algorithm)

Step 1: Diagnose and Classify

PATIENT WITH ABNORMAL SCAR
         ↓
Q: Does scar extend beyond original wound margins?
    NO → Hypertrophic scar
    YES → Keloid

Q: Does scar regress over time?
    YES → Hypertrophic scar
    NO → Keloid (never regresses)

Step 2: Assess Severity

• Apply VSS scoring
• Photograph baseline
• Assess for functional impairment (contracture?)
• Assess for symptoms (pruritus/pain/burning)

Step 3: Management by Scenario

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11. FOLLOW-UP

Schedule

• Monthly: First 3-6 months (active treatment phase - ILC injections, monitoring)
• Every 3 months: For the first year
• Every 6 months: 2nd year

What to Monitor

• VSS/POSAS scores at each visit
• Photograph at each visit
• Scar thickness (ultrasound if available)
• Symptoms (pruritus, pain, burning - use VAS scale)
• Side effects of treatment (atrophy, hypopigmentation)
• Evidence of recurrence (increasing height, erythema, symptoms returning)

Patient Counseling Points

• Scar treatment is a long-term commitment (months to years)
• No treatment guarantees complete resolution
• Keloids will never disappear completely - goal is flattening and symptom relief
• Compliance with silicone and pressure therapy is critical to success
• Advise avoiding nonessential surgery at high-risk sites in the future
• Sun protection for 1 year post-treatment

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12. PROGNOSIS

Recurrence Rates for Keloid by Treatment (Summary)

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13. DIFFERENTIAL DIAGNOSIS

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14. CRISP CRUX FLOWCHART

╔══════════════════════════════════════════════════════════════════╗
║              HYPERTROPHIC SCAR / KELOID - MANAGEMENT            ║
╚══════════════════════════════════════════════════════════════════╝
                              │
              ┌───────────────┴────────────────┐
              ▼                                ▼
    HYPERTROPHIC SCAR                       KELOID
    (within margins)                    (beyond margins)
    May regress                         Never regresses
              │                                │
    ┌─────────┴─────────┐          ┌───────────┴───────────┐
    ▼                   ▼          ▼                       ▼
  EARLY               LATE      MINOR                  MAJOR
  (<6 mo)            (>6 mo)  (earlobe, small)       (large, sternal)
    │                   │          │                       │
    ▼                   ▼          ▼                       ▼
SILICONE +           ADD ILC    ILC TAC                SILICONE +
PRESSURE +           TAC        40mg/mL                PRESSURE +
TAPING               10-40mg/mL q6-8wks ×6            ILC TAC +
OBSERVE              q4wks                             5-FU (combo)
    │                   │          │                       │
    ▼ (>6 mo)           ▼ (>6 mo)  ▼ (NO RESPONSE         ▼ (NO RESPONSE
LASER PDL          LASER +       12 months)              12 months)
+/- CO2            ILC                │                       │
    │                   │             ▼                       ▼
    ▼ (>12 mo)          ▼ (>12 mo) SURGERY                SURGERY
SURGICAL            SURGICAL     (intralesional           (excision) +
REVISION            REVISION     excision) +              IMMEDIATE
(excision +         (excision +  ADJUVANT:                EBRT 10 Gy
Z-plasty/W-plasty)  Z-plasty)    ─────────               (within 24 hrs)
+                   +            EBRT 10Gy                +
POST-OP SILICONE    POST-OP      within 24 hrs            ILC post-op
+TAPING x3 months   SILICONE     OR ILC TAC post-op       +
                    +TAPING      +                        SILICONE +
                                 PRESSURE EARRING         PRESSURE
                                 + SILICONE                   │
                                                          FOLLOW-UP
                                                          Monthly x 3
                                                          Q3/12 x 1 yr
                                                          Q6/12 x 2 yrs
                                 │
                         CONTRACTURE?
                              ▼ YES
                    URGENT SURGICAL RELEASE
                    (Z-plasty / Flap)
                    + PHYSIO + PRESSURE

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15. QUICK-RECALL SUMMARY CARDS

Keloid vs Hypertrophic Scar (Key Differentiators)

Drug Doses Rapid-Fire

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• Dermatology 2-Volume Set 5e (Bolognia et al.) - Chapter 98
• Andrews' Diseases of the Skin (Clinical Dermatology)
• Sabiston Textbook of Surgery (19e/21e) - Chapter on wound healing
• Bailey & Love's Short Practice of Surgery (28e)
• Schwartz's Principles of Surgery (11e) - Burns chapter
• Mustoe TA et al. International Clinical Recommendations on Scar Management, Plast Reconstr Surg 2002
• PubMed 2024: PMIDs 39447283, 38347765, 38760539, 40773601

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Latest 2024-2025 Clinical Practice Guidelines & Evidence Update

Keloid and Hypertrophic Scar Management

---

Important note on "guidelines" status: As of 2025-2026, no single comprehensive international society clinical practice guideline has been published specifically for keloids/HTS in 2024-2025. The field continues to operate on the 2014 Mustoe International Consensus as its formal guideline foundation, supplemented by an important 2024 international e-Delphi consensus (KECORT), multiple high-quality systematic reviews and meta-analyses, and the December 2024 American Family Physician evidence-based review. All of these are synthesized below.

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1. THE 2024 KECORT e-DELPHI CONSENSUS

The Closest Thing to a New Guideline

Consensus Reached On (Formal Recommendations):

Consensus NOT Reached On (Still Controversial):

• Optimal TAC dosing concentration (10 vs 20 vs 40 mg/mL)
• Best method for prior local anesthesia
• Exact location within keloid to inject (center vs edge vs throughout)

Clinical impact: This is the first formal international consensus specifically addressing the practical aspects of ILC for keloids. It upgrades the previously variable practice to a more standardized protocol.

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2. AMERICAN FAMILY PHYSICIAN 2024 EVIDENCE-BASED REVIEW

The Most Current Comprehensive Clinical Summary

Key 2024 AFP Recommendations:

Viva-critical point: The 2024 AFP guideline now places botulinum toxin ABOVE 5-FU in the treatment hierarchy for the first time in a major review. This reflects accumulating meta-analytic data.

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3. MAJOR SYSTEMATIC REVIEWS & META-ANALYSES (2024-2025)

3.1 Radiotherapy After Keloid Excision - TIMING NOW CLARIFIED

Study A: "Should We Do Post-op Radiotherapy as Soon as Possible?" (Meta-Analysis)

• Population: 507 keloids across 8 observational studies
• Key finding: Radiation within 2 hours post-excision → 7% recurrence vs within 6 hours → 16% recurrence (p<0.01)
• For HDR brachytherapy specifically: 2-hr group 5% vs 6-hr group 16% (p<0.01)
• BED 30 Gy group (5%) outperformed BED 20 Gy (6%) and BED 15 Gy (26%)
• Keloids >5 cm had higher recurrence (10.4%) than <5 cm (9.9%)

New 2025 recommendation: Start radiation within 2 hours of surgery (previously consensus was "within 24 hours"). This updates prior guidance.

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Study B: "Post-Excisional Radiotherapy for Keloid - Meta-Analysis" (Largest to Date)

• Population: 10,745 keloid lesions from 106 studies (largest ever radiotherapy meta-analysis for keloids)
• Mean patient age: 35 years; equal gender distribution
• Recurrence rates by modality:

• No statistically significant difference between modalities (p >0.05)
• No significant difference between early (<24 hrs) vs late (>24 hrs) radiotherapy timing (p >0.05 across all subgroups)

Paradigm shift: This large-scale 2025/2026 meta-analysis contradicts the widely taught "within 24 hours" rule - all three modalities and both timing windows produce comparable recurrence and complication rates. Treatment choice can reflect physician preference and local availability. This is the largest and most definitive radiation study to date.

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3.2 Botulinum Toxin + Corticosteroid - Meta-Analysis Confirms Superiority

• Meta-analysis of randomized trials
• TAC + BotA combination significantly superior to TAC alone on Vancouver Scar Scale
• Pooled mean difference: -1.69 in scar severity scores (statistically significant)
• Supports the 2024 AFP recommendation elevating BotA in treatment hierarchy

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3.3 Surgical Outcomes for Major Keloids - New Data

• Systematic review and meta-analysis: 244 patients with major keloids across 10 studies
• All patients underwent surgical resection
• Coverage methods: skin grafts, perforator flaps, secondary intention, skin substitutes
• Overall recurrence rate: 21%
• Patients with wound coverage had lower recurrence than secondary intention
• Local flap + adjuvant radiotherapy = lowest recurrence + highest patient satisfaction

New recommendation for major keloids: Local perforator flap (rather than skin graft or secondary intention) combined with adjuvant radiotherapy gives best outcomes. Current guidelines lack sufficient guidance for this specific group - this meta-analysis partially fills that gap.

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3.4 Comprehensive Pathophysiology & Management Review (2025)

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3.5 Dupilumab for Keloids - Caution Flagged

• Systematic review: 3 case reports + 3 case series = 15 patients total
• Results: variable - some significant improvement, some no change, some worsening
• Grade D recommendation (insufficient evidence to recommend)
• Proposed mechanism of worsening: dupilumab may promote Th17 differentiation → paradoxical worsening in some keloids
• Current status: do not recommend dupilumab as standard therapy for keloids; use only in refractory cases with monitoring

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3.6 Comprehensive Keloid Management Update 2025-2026

New 4-Category Treatment Algorithm Based on Keloid Morphology:

Postoperative Radiation - Updated Evidence Table (2025):

Emerging Therapies with 2024 Evidence:

• Regenerative therapies (2024 systematic review): PRP, stromal vascular fraction, stem cell-conditioned medium - effective with minimal side effects, can combine with standard treatments
• Adipose-derived stem cell extracellular vesicles: Significantly prevent hypertrophic scar formation (2024 SR)
• Electrical stimulation / Extracorporeal shockwave (2024 scoping review): Early evidence for pain and appearance improvement; not yet clinical standard
• Targeted molecular therapies: TGF-β inhibitors, PI3K/Akt/mTOR inhibitors actively investigated

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3.7 The Largest Therapeutic Systematic Review to Date (2026)

• 162 studies included; searched through April 2025
• Evaluated: ILC, optical therapy, radiation, 5-FU, bleomycin, verapamil, excision surgery, cryotherapy, topical treatments, multi-drug regimens, stem cells, RNA microneedles
• Key conclusions:
  1. Sole/inadequate treatment = major risk factor for recurrence
  2. Combination therapy (ILC + surgery + laser + radiation) is superior to single modality for reducing recurrence
  3. Corticosteroid and excision remain the critical benchmarks against which new treatments are measured
  4. Anti-fibroblast growth strategies are essential alongside physical interventions
  5. No gold standard exists; personalized, combination approach is the standard of care

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3.8 Laser Therapy Update (2025)

• Comparative systematic review of clinical trials for atrophic, hypertrophic, and keloid scars
• ~404 patients, 506 treated scar sites
• Fractional CO2 broadly adopted in clinical practice globally

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4. CURRENT STANDARD OF CARE - CONSOLIDATED 2025 RECOMMENDATIONS

Treatment Hierarchy (Updated 2025)

FIRST-LINE (all keloids/HTS):
├── Silicone gel/sheets (prevention & treatment)
├── Pressure garments (especially burns/widespread HTS)
└── Intralesional TAC 40 mg/mL (KECORT 2024):
    • Max 80 mg/month
    • 25-27G needle, 1 mL syringe
    • q4 weeks
    • Endpoint = blanching
    • Do NOT inject subcutaneously

SECOND-LINE (if inadequate response or combination from outset):
├── TAC + Botulinum Toxin A [2024 AFP: BotA now SUPERIOR to 5-FU]
├── TAC + 5-FU (9:1 ratio, 50 mg/mL 5-FU)
├── TAC + Bleomycin 1.5 IU/mL (darker skin types)
├── Cryotherapy (± TAC combination)
└── Pulsed Dye Laser (PDL) ± CO2 Laser

SURGERY (keloids only with mandatory adjuvant):
├── Excision + adjuvant radiotherapy
│   [JPRAS 2026 meta-analysis: X-ray/brachytherapy/EBRT comparable]
│   [Within 2 hours appears better than 6 hours - Aesthetic Plast Surg 2025]
│   [10 Gy single-fraction EBRT: 0.81% recurrence for ear keloids]
│
├── Major keloids: Local flap + adjuvant RT
│   [Aesthet Surg J 2025: best outcomes vs graft or secondary intention]
│
└── Post-excision ILC 10-14 days post-surgery
    [AFP 2024: superior to intraoperative injection]

EMERGING (not yet standard):
├── PRP / Stem cell therapies (2024 SR: promising)
├── Electrical stimulation / Shockwave (preliminary)
├── Dupilumab (Grade D - insufficient evidence; risk of worsening)
└── RNA interference / nanogels / TGF-β inhibitors (investigational)

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5. WHAT HAS CHANGED FROM PRIOR GUIDELINES (DELTA 2014 → 2024-2025)

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6. COMPLETE REFERENCE LIST (2024-2025)

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7. WHAT REMAINS CONTROVERSIAL / UNRESOLVED (2025)

1. Optimal ILC concentration (10 vs 20 vs 40 mg/mL) - no consensus
2. Radiation timing: 2-hr meta-analysis says sooner is better; 10,745-lesion meta-analysis says timing doesn't matter significantly
3. Role of dupilumab - variable results; needs RCTs
4. Best coverage method for major keloids after excision - insufficient controlled data
5. How to standardize outcome measurement - VSS, POSAS, Patient-reported outcomes all used differently
6. Optimal laser parameters - PDL vs CO2 vs fractional varies widely
7. No RCTs exist for most combination therapy regimens

Bottom line for exams: The field in 2024-2025 is moving toward protocolized ILC (KECORT 2024), BotA as the preferred second agent, and combination therapy as the standard with surgery + radiotherapy for refractory keloids. There is no single comprehensive practice guideline yet - the closest is the KECORT 2024 consensus + AFP 2024 review.