Meta-analysis of Treatments for Keloid and Hypertrophic Scars

Abstract

I wanted to do something a little different with this article, as we get alot of questions regarding Keloid scars and measure of management and treatment, so I put together this Article.

So what is a Keloid or hypertrophic scar? Keloid and hypertrophic scars are the dermatological equivalent of guests who overstay their welcome. They arise from disordered wound healing, refuse to follow normal biological rules, and have an irritating tendency to recur just when everyone thought the matter was settled.

Given the steady stream of new devices, injectables and protocols marketed to both clinicians and patients, we decided to step back and ask a simple question: what does the actual evidence say works, and for whom?

To answer this, we undertook a structured, evidence‑weighted meta‑analysis of the current literature on keloid and hypertrophic scar management, drawing on systematic reviews, meta‑analyses, randomised trials and high‑quality observational studies. We also considered how this evidence aligns with current NHS advice and NICE‑aligned practice in the UK.

As with most things in scarring, the answer is not a single miracle treatment, but a hierarchy of options where combination therapy, realistic counselling and specialist escalation consistently outperform simplistic approaches.

Executive summary

Keloid and hypertrophic scars are fibroproliferative disorders of wound healing that can cause pain, itch, restriction of movement, and substantial psychosocial burden. Across the published evidence base, no single treatment is consistently curative, relapse is common, and combination therapy usually outperforms monotherapy.

The strongest, most repeatable signal across comparative studies is that intralesional corticosteroid plus an adjunct (most commonly 5‑fluorouracil, bleomycin, cryotherapy, or botulinum toxin A) tends to improve clinical scar scores and reduce recurrence compared with steroid alone. For resistant or bulky keloids, excision plus adjuvant radiotherapy provides the lowest reported recurrence in many series, but requires specialist governance due to radiation risk.

UK-facing advice (NHS) recognises that keloids cannot usually be “removed” permanently, and lists steroid injections, silicone dressings or gels, cryotherapy, and laser therapy as options, while noting that surgery alone is not usually recommended because of high recurrence.

Scope and question

Question: In people with keloid or hypertrophic scars, which treatments improve scar appearance and symptoms, and which reduce recurrence?

Population: Keloid scars and hypertrophic scars (any aetiology).

Interventions: Intralesional therapies (triamcinolone acetonide, 5‑fluorouracil, bleomycin, botulinum toxin A), cryotherapy (surface or intralesional), silicone gel or sheeting, pressure therapy, laser and light devices, surgery ± adjuvant radiotherapy.

Comparators: Placebo, no treatment, or alternative active treatment.

Outcomes: Scar height, pliability, pigmentation/erythema, pain/itch (patient reported), Vancouver Scar Scale (VSS) or POSAS, and recurrence.

Methods

Search strategy and data sources

A structured literature search was undertaken using PubMed, MEDLINE, Cochrane Library and key dermatology and plastic surgery journals. Search terms included combinations of: keloid scar, hypertrophic scar, intralesional steroid, 5‑fluorouracil, bleomycin, cryotherapy, silicone gel, laser, radiotherapy, and recurrence.

Priority was given to systematic reviews, meta‑analyses and network meta‑analyses published in the last 10–15 years, supplemented by recent randomised controlled trials and high‑quality narrative reviews where higher‑order synthesis was unavailable.

Inclusion criteria

• Human studies involving keloid or hypertrophic scars

• Comparative studies or systematic syntheses of treatment modalities

• Outcomes including scar height, validated scar scales (VSS or POSAS), symptom burden (pain or itch), or recurrence

• Peer‑reviewed publications

Exclusion criteria

• Case reports with fewer than five patients

• Non‑English language papers without reliable translation

• Animal or in‑vitro studies (used only for mechanistic context, not outcome analysis)

Analytical approach

Because outcome measures, follow‑up duration and recurrence definitions vary significantly across studies, a single pooled quantitative effect size was not statistically defensible across all modalities. Instead, we applied an evidence‑weighted qualitative meta‑analysis, ranking interventions according to consistency of benefit, magnitude of effect, and reproducibility across independent datasets. This is a structured evidence synthesis drawing on:

1. meta-analyses, network meta-analyses, and systematic reviews where available, and

2. controlled trials and observational series where higher-level synthesis was not feasible.

Study selection approach: Priority was given to peer-reviewed systematic reviews and meta-analyses (including network meta-analysis), supplemented by recent randomised trials and high-quality narrative reviews for context. Where keloids and hypertrophic scars were pooled together, results are interpreted with caution because disease biology and recurrence behaviour differ.

Limitations: Outcome measures and definitions of “response” vary widely, follow-up is often short, and recurrence reporting is inconsistent. This restricts true quantitative pooling across all modalities. Therefore, conclusions are presented as an evidence-weighted hierarchy rather than a single pooled effect size.

What the NHS and NICE say

NHS position

NHS patient guidance notes that keloid scars cannot usually be eliminated, but treatments can improve symptoms and appearance. Listed options include steroid injections or cream, silicone dressings or gels, cryotherapy, and laser therapy, while highlighting that surgery is not usually recommended because keloids commonly recur and can return larger.

NICE and NHS prescribing context

There is no single dedicated NICE guideline focused solely on keloid scar treatment. However, NICE-aligned prescribing resources (BNF/NICE wound management sections) recognise silicone gel and silicone gel sheeting as established modalities used to reduce or prevent hypertrophic and keloid scarring, particularly once skin is healed.

In practice, NHS pathways vary locally (for example, hospital leaflets and ICB policies often centre first-line management on intralesional steroid, silicone therapy, and referral for specialist options).

Results by treatment category

1) Silicone gel and silicone gel sheeting

What it is and how it works: Silicone gel and silicone gel sheeting are topical, occlusive therapies applied once the epidermis is fully healed. Their proposed mechanisms include hydration of the stratum corneum, reduction of transepidermal water loss, modulation of fibroblast activity, and reduction in capillary activity within immature scar tissue. Silicone does not penetrate deeply; its effect is primarily biophysical rather than pharmacological.

Efficacy and evidence: Systematic reviews suggest modest improvements in scar thickness, erythema and pliability, particularly in hypertrophic scars and in early intervention. For established keloids, benefits are inconsistent and generally limited. Evidence quality is low to moderate due to small sample sizes and heterogeneity.

Timeframe and outcomes: Improvement, where it occurs, is typically seen over 8–24 weeks of consistent daily use.

Recurrence: Silicone therapy does not meaningfully reduce recurrence of established keloids when used alone.

Clinical role: Best used as first-line conservative therapy, post-procedure prevention, or adjunctive support rather than definitive treatment.

2) Intralesional corticosteroid (triamcinolone acetonide, TAC)

What it is and how it works: Intralesional TAC suppresses fibroblast proliferation, reduces collagen synthesis, increases collagen degradation, and decreases inflammatory mediators within scar tissue. It also reduces glycosaminoglycan production, leading to flattening and softening of scars.

Efficacy and evidence: Across multiple controlled trials and reviews, TAC consistently reduces scar height, erythema, pain and pruritus. However, outcomes are variable and dose-dependent.

Timeframe and outcomes: Clinical improvement is usually observed after 2–3 injection sessions, spaced 4–6 weeks apart.

Recurrence: Reported recurrence rates range widely, often 30–50% or higher, particularly once treatment stops.

Limitations: Adverse effects include dermal atrophy, hypopigmentation, telangiectasia and pain at injection sites.

3) TAC plus 5-fluorouracil (5-FU)

What it is and how it works: 5-FU is an antimetabolite that inhibits fibroblast proliferation and collagen production. When combined with TAC, the steroid reduces inflammation and discomfort, while 5-FU targets abnormal fibroblast activity more directly.

Efficacy and evidence: Meta-analyses demonstrate superior flattening, improved scar scores and lower adverse-effect rates compared with TAC alone.

Timeframe and outcomes: Improvement is commonly seen within 1–3 months, with treatment courses lasting several sessions.

Recurrence: Recurrence rates are consistently lower than TAC monotherapy, often reported in the 10–30% range, depending on follow-up duration.

Clinical role: Widely regarded as one of the most effective non-surgical options for resistant keloids.

4) Intralesional 5-fluorouracil monotherapy

What it is and how it works5-FU interferes with DNA synthesis in rapidly dividing fibroblasts, reducing excessive collagen deposition.

Efficacy and evidenceSystematic reviews indicate meaningful reductions in scar height and symptoms, with fewer steroid-related side effects.

Timeframe and outcomesClinical response typically emerges over 4–12 weeks.

RecurrenceRecurrence rates are variable but comparable to or slightly better than TAC in some series.

5) Intralesional bleomycin

What it is and how it works: Bleomycin induces fibroblast apoptosis and inhibits collagen synthesis. It is delivered intralesionally in very low doses.

Efficacy and evidence: Meta-analyses suggest higher rates of scar flattening compared with TAC and 5-FU in selected studies, though high-quality randomised trials are limited.

Timeframe and outcomes: Visible improvement is often noted after 1–2 sessions, with progressive flattening over several months.

Recurrence: Reported recurrence rates are moderate to low, but long-term data are limited.

Governance considerations: Systemic toxicity risk necessitates strict dosing protocols and informed consent.

6) Cryotherapy (surface and intralesional)

What it is and how it works: Cryotherapy causes cellular injury and vascular damage within scar tissue, leading to necrosis and volume reduction. Intralesional cryotherapy delivers cold directly into the keloid core.

Efficacy and evidence: Systematic reviews show effective volume reduction and symptom relief, particularly for bulky lesions.

Timeframe and outcomes: Results evolve over weeks to months, often requiring multiple sessions.

Recurrence: Recurrence remains common unless combined with intralesional therapies.

7) Botulinum toxin A

What it is and how it works: Botulinum toxin A reduces muscle tension and may downregulate fibroblast activity through neuromodulatory pathways.

Efficacy and evidence: Network meta-analyses suggest improvement in validated scar scores, though recurrence data are limited.

Timeframe and outcomes: Symptomatic improvement may occur within 4–8 weeks.

Recurrence: Long-term recurrence rates remain uncertain.

8) Laser and light-based therapies

What it is and how it worksLasers such as pulsed dye laser target vascular components of scars, reducing erythema and fibroblast stimulation. Fractional lasers promote remodelling via controlled dermal injury.

Efficacy and evidenceConsistent benefit for erythema, texture and symptoms; variable efficacy for volume reduction.

Timeframe and outcomesGradual improvement over several sessions.

RecurrenceHigh if used alone for keloids.

9) Surgical excision with adjuvant radiotherapy

What it is and how it works: Surgical removal of keloid tissue followed by radiotherapy suppresses fibroblast proliferation during wound healing.

Efficacy and evidence: Meta-analyses consistently report the lowest recurrence rates of all modalities.

Timeframe and outcomes: Definitive structural correction occurs immediately post-excision; radiotherapy is delivered within days.

Recurrence: Often reported in the 5–15% range, depending on protocol.

Clinical role: Reserved for severe, recurrent or functionally impairing keloids within specialist services. (triamcinolone acetonide, TAC)

Evidence summary: effective symptom control, high recurrence, predictable adverse effects. TAC remains the most widely used intralesional therapy. Across multiple studies, it reliably reduces scar height and symptoms such as itch and pain. However, recurrence rates remain substantial, and adverse effects including dermal atrophy, hypopigmentation and telangiectasia are common with repeated dosing.

Clinical interpretation: TAC is a reasonable first‑line intralesional therapy but should rarely be considered a standalone long‑term solution.

Evidence‑weighted hierarchy of effectiveness

Rank	Intervention	Typical outcomes	Recurrence profile
1	Excision + adjuvant radiotherapy	Significant volume reduction, symptom relief	Lowest reported recurrence in literature
2	TAC + 5‑FU	Improved flattening, reduced itch and pain	Lower than TAC alone
3	Bleomycin (intralesional)	Marked flattening in selected cases	Moderate, data limited
4	TAC monotherapy	Symptom control	High
5	Cryotherapy ± TAC	Volume reduction	Variable
6	Laser adjuncts	Colour and texture improvement	High if used alone
7	Silicone gel/sheeting	Modest improvement	High

This hierarchy reflects consistency and reproducibility across studies rather than theoretical efficacy. Based on the aggregated evidence across systematic reviews, meta-analyses, and comparative trials:

1. Excision + adjuvant radiotherapy (specialist pathway; lowest recurrence in many series).

   
   

2. Combination intralesional therapy (most consistently: TAC + 5‑FU, with supportive signals for TAC + bleomycin, TAC + cryotherapy, and selected protocols including botulinum toxin A).

   
   

3. Intralesional TAC monotherapy (first-line but recurrence common).

   
   

4. Cryotherapy and laser as adjuncts (symptom and appearance benefits; variable recurrence control).

   
   

5. Silicone gel or sheeting (best for prevention and early hypertrophic scars; modest benefit for established keloids).

Practical NHS‑aligned approach

Within UK practice, this evidence aligns with current NHS advice: conservative measures first, escalation where symptoms or functional impairment persist, and specialist referral for refractory disease. Importantly, patients should be counselled that control rather than cure is the realistic aim for most keloids.

1. Risk and prevention: avoid elective trauma in high-risk patients (piercings, tattoos), reduce wound tension, optimise aftercare.

2. First-line: silicone gel or sheeting once healed; consider early referral for symptomatic or progressive lesions.

3. Clinic-based therapy: intralesional TAC, escalating to combination TAC + 5‑FU or other adjuncts for resistant scars.

4. Specialist escalation: bulky, recurrent, or function-limiting keloids: consider surgical excision with adjuvant radiotherapy in an appropriate service.

What this means for aesthetic practice

For aesthetic clinics, the key governance points are:

• honest counselling: recurrence risk is material and should be consented explicitly

• preference for evidence-supported combinations over repeated monotherapy

• clear escalation pathways to dermatology or plastic surgery for lesions requiring surgery or radiotherapy

• documentation of symptom outcomes (itch, pain) and validated scar scales (VSS or POSAS) to avoid “it looks better” guesswork

References (peer-reviewed and guideline resources)

1. Sigrist RM (conference report context): BBC News report summarising RSNA presentation on filler complications (context only, not keloid data).

2. Zhang et al. The efficacy of bleomycin for treating keloid and hypertrophic scar: a meta-analysis. (PubMed ID: 32243056).

3. Jiang ZY et al. Efficacy and Safety of Intralesional Triamcinolone Versus Combination of Triamcinolone with 5‑Fluorouracil in Keloids and Hypertrophic Scars: systematic review and meta-analysis. (PubMed ID: 32342167).

4. King A et al. Intralesional 5‑Fluorouracil for Keloids: a systematic review. (2024).

5. Bijlard E et al. Intralesional 5‑Fluorouracil in keloid treatment. Acta Derm Venereol. 2015.

6. Acharya R et al. Randomised trial of intralesional triamcinolone vs triamcinolone + 5‑FU in keloids/hypertrophic scars. 2024.

7. Menon TSK et al. Intralesional triple combination vs triamcinolone monotherapy for keloids: comparative study. 2025.

8. O’Brien L, Jones DJ. Silicone gel sheeting for preventing and treating hypertrophic and keloid scars: systematic review. 2013.

9. Wang F et al. Efficacy of topical silicone gel in scar management: meta-analysis / systematic review. 2020.

10. De Decker I et al. Fluid silicone gels in prevention and treatment of scars: systematic review. 2022.

11. van Leeuwen MCE et al. Intralesional cryotherapy for the treatment of keloid scars: systematic review. 2015.

12. O’Boyle CP et al. Intralesional cryotherapy for hypertrophic scars and keloids: comprehensive review. 2017.

13. Fu S et al. Surgical excision combined with radiotherapy for keloids: meta-analysis (recurrence outcomes). 2024.

14. Gold MH et al. Assessing keloid recurrence following surgical excision and radiation therapy: systematic review context. 2020.

15. Lai IC et al. Comparative efficacy and recurrence risk of intralesional therapies for keloids: network meta-analysis. 2025.

16. Kim SW et al. Management of keloid scars: noninvasive and invasive treatments (guideline-style review). 2021.

17. NHS. Keloid scars: treatments and patient advice. (NHS website).

18. NICE/BNF. Wound management: specialised dressings (silicone gel and sheeting use).