Residency · Residency · Dermatology
Keloids and Hypertrophic Scars: Prevention and Treatment
Introduction
Abnormal scarring is a significant clinical problem affecting millions of patients worldwide. Keloids and hypertrophic scars represent a spectrum of fibroproliferative disorders resulting from dysregulated wound healing. Distinguishing between these two entities is essential because their natural histories, recurrence rates, and treatment strategies differ substantially.
Distinguishing Keloids from Hypertrophic Scars
Keloids
Keloids by definition extend beyond the boundaries of the original wound and do not regress spontaneously. They may develop months to years after injury and carry a high recurrence rate of 50 to 80% after simple excision alone. They are more common in areas of high skin tension including the earlobes, deltoid, presternal area, and upper back. There is a genetic predisposition, with higher prevalence in individuals of African, Asian, and Hispanic descent. Symptoms include pruritus, pain, tenderness, and cosmetic disfigurement. Histology reveals thick, haphazardly arranged hyalinized collagen bundles (keloidal collagen) with increased fibroblast activity.
Hypertrophic Scars
Hypertrophic scars remain within the boundaries of the original wound and tend to regress spontaneously over 12 to 24 months, at least partially. They develop within weeks of injury, are more responsive to treatment, and have lower recurrence after excision. They are often associated with wounds crossing skin tension lines, burns, or wounds healing by secondary intention. Histology shows organized collagen bundles arranged parallel to the epidermis with nodular fibroblast proliferation.
| Feature | Keloid | Hypertrophic Scar |
|---|---|---|
| Extends beyond wound | Yes | No (stays within wound) |
| Spontaneous regression | No | Yes (over 12–24 months) |
| Onset after injury | Months to years | Weeks |
| Recurrence after excision | 50–80% (without adjuvant) | Lower |
| Genetic predisposition | Strong (African, Asian, Hispanic) | Less prominent |
| Histology | Thick, haphazard hyalinized collagen | Organized parallel collagen bundles |
| Common sites | Earlobes, deltoid, presternal, upper back | Any wound crossing tension lines |
Pathophysiology
Normal Wound Healing
Normal wound healing proceeds through four overlapping phases. Hemostasis (minutes) involves platelet aggregation and fibrin clot formation. Inflammation (days) brings neutrophils and macrophages with cytokine release (TGF-beta, PDGF, IL-6). Proliferation (weeks) involves fibroblast migration, collagen deposition, angiogenesis, and reepithelialization. Remodeling (months to years) features MMP-mediated collagen turnover, replacement of type III collagen by type I, and scar maturation.
Keloid/Hypertrophic Scar Pathogenesis
Excessive TGF-beta signaling is central, with increased TGF-beta1 and TGF-beta2 and reduced TGF-beta3 (which normally promotes scarless healing). Fibroblast abnormalities include faster proliferation, greater collagen production, and resistance to apoptosis. Reduced MMP activity impairs collagen degradation, leading to net collagen accumulation. Mechanical tension plays a significant role, as wounds perpendicular to RSTLs have higher tension and greater hypertrophic scar risk. Genetic factors include familial clustering and associations with HLA-DRB1*15 and single nucleotide polymorphisms in wound healing genes. Immune dysregulation is evident in the increased mast cells and T-helper 2 cytokines (IL-4, IL-13) in keloids, which may represent a localized autoimmune or autoinflammatory process.
<image>Comparison diagram showing keloid extending beyond wound margins with thick hyalinized collagen bundles versus hypertrophic scar confined to wound margins with organized parallel collagen bundles, including corresponding histologic patterns and clinical photographs</image>
Prevention Strategies
Surgical Technique
Aligning incisions along RSTLs minimizes tension. Atraumatic tissue handling with minimal electrosurgery and avoidance of excessive undermining preserves tissue viability. Layered, tension-free closure with deep dermal sutures offloads epidermal tension. Eversion of wound edges optimizes scar outcome. Early suture removal (5 to 7 days on the face) reduces suture track marks.
Postoperative Measures
Silicone-based products including silicone gel sheeting or topical silicone gel are the evidence-based first-line prevention. The mechanism involves hydration of the stratum corneum, reduced transepidermal water loss, and modulation of fibroblast activity. They should be applied for 12 to 24 hours per day for at least 2 to 3 months. Pressure therapy using pressure earrings for earlobe keloids after excision (20 to 30 mmHg) and pressure garments for burn scars provides mechanical suppression of scar growth. Paper tape or microporous tape offers simple, inexpensive tension reduction across the wound and should be continued for 8 to 12 weeks. The Embrace device is a silicone-based tension-offloading device with evidence for improved scar outcomes in high-tension closures. Sun protection is important because UV-exposed scars have increased risk of permanent hyperpigmentation.
Treatment Options
Intralesional Corticosteroids
Triamcinolone acetonide (TAC) at 10 to 40 mg/mL is the first-line treatment for both keloids and hypertrophic scars. It inhibits fibroblast proliferation, reduces collagen synthesis, promotes collagen degradation, and has anti-inflammatory effects. It should be injected into the scar (not beneath it) using a 25 to 27 gauge needle, which requires high injection pressure. Treatment frequency is every 4 to 6 weeks for 3 to 6 sessions. Response rate is 50 to 100% improvement, though recurrence is common after cessation. Side effects include atrophy, telangiectasia, and hypopigmentation (especially in darker skin).
Cryotherapy
Intralesional cryotherapy (CryoShape needle) delivers liquid nitrogen directly into scar tissue via a specialized needle. It is more effective than spray cryotherapy, reducing keloid volume by 50 to 75% in a single session. It can be combined with intralesional TAC. Risk of hypopigmentation limits use in darker skin types.
5-Fluorouracil (5-FU)
Intralesional 5-FU at 50 mg/mL inhibits fibroblast proliferation. It is often combined with TAC in a mixture of TAC 40 mg/mL with 5-FU 50 mg/mL in a 1:9 ratio -- the so-called "keloid cocktail." Monthly injections are given for 3 to 6 sessions. Side effects include pain, hyperpigmentation, and rarely ulceration.
Surgical Excision
Keloids should never be excised without adjuvant therapy because the recurrence rate is 50 to 80% with excision alone. The combination approach uses excision plus immediate postoperative intralesional TAC plus adjuvant radiation or silicone. Core excision (intramarginal excision) removes the central bulk while leaving a peripheral shell of scar tissue to reduce tension and recurrence. Earlobe keloids respond best to excision plus adjuvant therapy, with recurrence below 20% when postoperative TAC or radiation is used.
Radiation Therapy
Adjuvant radiation within 24 to 48 hours of surgical excision is the most effective combination therapy, reducing recurrence to 10 to 20% compared to 50 to 80% with excision alone. Typically superficial X-ray (SXR) or electron beam therapy is used, with 3 to 4 fractions totaling 12 to 20 Gy. There is a theoretical concern for radiation-induced malignancy, which is generally considered low risk, but radiation should be avoided in children, breast tissue, and the thyroid region.
<image>Treatment algorithm flowchart for keloid management: initial assessment leading to first-line intralesional TAC, with escalation pathways to combination TAC/5-FU, surgical excision with adjuvant radiation or TAC, and emerging therapies including laser and biologics</image>
| Treatment | Mechanism | Efficacy/Response | Key Considerations |
|---|---|---|---|
| Intralesional TAC (10–40 mg/mL) | ↓Fibroblast proliferation, ↓collagen synthesis | 50–100% improvement | First-line; risk of atrophy, hypopigmentation |
| Intralesional 5-FU (50 mg/mL) | Inhibits fibroblast proliferation | Enhanced with TAC combination | "Keloid cocktail" (TAC:5-FU = 1:9) |
| Surgical excision + adjuvant | Debulks scar; adjuvant prevents recurrence | Recurrence <20% with adjuvant | NEVER excise without adjuvant therapy |
| Adjuvant radiation (12–20 Gy) | Destroys proliferating fibroblasts | Reduces recurrence to 10–20% | Within 24–48 hrs of excision; avoid in children |
| Silicone gel sheeting | Hydration, ↓TEWL, modulates fibroblasts | First-line prevention | Apply 12–24 hrs/day for ≥2–3 months |
| Intralesional cryotherapy | Direct tissue destruction | 50–75% volume reduction | Risk of hypopigmentation in dark skin |
| Pressure therapy (20–30 mmHg) | Mechanical suppression | Effective for earlobes, burns | Sustained use required |
Laser Therapy
The pulsed dye laser (PDL) at 585 to 595 nm reduces erythema, pruritus, and improves pliability through vascular disruption and collagen remodeling. Fractional CO2 laser improves scar texture and facilitates drug delivery (laser-assisted drug delivery of TAC or 5-FU). The Nd:YAG at 1064 nm addresses the vascular component in hypertrophic scars. Lasers are typically adjunctive and rarely curative alone for established keloids.
Emerging and Investigational Therapies
Bleomycin (intralesional) inhibits collagen synthesis but involves painful injection and risk of flagellate hyperpigmentation. Botulinum toxin reduces wound tension and modulates TGF-beta expression, with promising early results. Dupilumab (anti-IL-4/IL-13) is a rational target given Th2 cytokine involvement, with promising case reports. Imiquimod 5% cream applied to the excision site postoperatively reduces keloid recurrence to approximately 25%.
<image>Clinical before-and-after series showing treatment outcomes: earlobe keloid before and after surgical excision with postoperative radiation therapy, and presternal keloid before and after combination intralesional triamcinolone and 5-FU injection therapy</image>
Key Clinical Pearls
Keloids extend beyond wound boundaries and do not regress, while hypertrophic scars stay within wound limits and often self-resolve. Silicone gel sheeting is the best evidence-based preventive measure and should be applied for at least 2 to 3 months postoperatively. Keloids should never be excised without adjuvant therapy, as combination with intralesional TAC or adjuvant radiation is essential to prevent recurrence. The intralesional TAC/5-FU combination ("keloid cocktail") is more effective than TAC alone for refractory keloids. Earlobe keloids have the best surgical outcomes, while presternal and deltoid keloids have the highest recurrence rates.
References
- Gauglitz GG, Korting HC, Pavicic T, et al. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17(1-2):113-125.
- Ogawa R. Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis. Int J Mol Sci. 2017;18(3):606.
- Hietanen KE, Jarvinen TA, Huhtala H, et al. Treatment of keloid scars with intralesional triamcinolone, 5-fluorouracil, and leucovorin: a systematic review. Acta Derm Venereol. 2019;99(1):4-13.
- Jones ME, Hardy C, Ridgway J. Keloid management: a retrospective case review on a new approach using surgical excision, platelet-rich plasma, and in-office superficial photon X-ray radiation therapy. Adv Skin Wound Care. 2016;29(7):303-307.
