Table 2.
Systematic ranking of topical treatments reviewed in this article, ranked according to their Oxford Levels of Evidence (LOE), as defined by the Oxford Centre for Evidence Based Medicine [60–62]
| References | Sample size/Country of Origin | Study type | Treatment, assessment and follow-up | Outcome—positive or negative findings? | Level of evidence |
|---|---|---|---|---|---|
| Berman et al. [10] | n = 20, USA | Double-blind, randomised, placebo controlled clinical trial | 5 % imiquimod following excision of melanocytic nevi, visual analogue scale used to assess appearance of post-surgical wounds by clinicians and patients. 8 weeks follow-up | Negative/neutral—worse cosmesis evaluation at 8 weeks compared with base cream | 2 |
| Martin-Garcia and Busquets [76] | n = 6, Puerto Rico | Open-label trial | 5 % imiquimod following earlobe keloid excision. Recurrence defined as regrowth of scar tissue surpassing initial excision wound. 8 weeks treatment, 16 weeks follow-up | Positive—prevented recurrence following excision, however, one keloid reoccurred and one responded better to steroids | 4 |
| Stashower [105] | n = 4, USA | Case study | 5 % imiquimod following earlobe keloid shave excision. Recurrence and symptoms assessed visually by lead clinician and patient questionnaire (scar scale utilised not defined). 6 weeks treatment, 12 months follow-up | Positive—no recurrence after 12 months in all 8 keloid lesions | 4 |
| Berman and Kaufman [12] | n = 12, USA | Case study | 5 % imiquimod following earlobe keloid excision, symptoms assessed by clinician (scar scale utilised not defined) 2 months treatment, 24 weeks follow-up | Positive—no recurrence after 24 weeks in patients who completed full follow-up (2 patients lost) | 4 |
| Chuangsuwanich and Gunjittisomram [33] | n = 45, Thailand | Case study | 5 % imiquimod following keloid excision from various sites, recurrence assessed by clinician. 8 weeks treatment, 24 weeks follow-up | Positive—greatest rate of recurrence on chest wall, but earlobe recurrence was least | 4 |
| Cacao et al. [23] | n = 9, Brazil | Case study | 5 % imiquimod following trunk keloid excision. Symptoms assessed by clinician (scar scale utilised not defined) 8 weeks treatment, 20 weeks follow-up | Negative/neutral—all but one keloid excised from the chest/trunk recurred | 4 |
| Berman et al. [11] | n = 20, USA | Randomised case–control study | 5 % imiquimod following keloid shave excision. Symptoms assessed by clinician (scar scale utilised not defined) 6 weeks treatment, 6 months follow-up | Positive—reduction in keloid recurrence vs base cream control, however, not enough patients to determine statistical significance | 4 |
| Prado et al. [93] | n = 15, Chile | Case–control study | 5 % imiquimod following breast surgery, assessed via the Manchester Scar Scale. Treatment duration varied, 24 weeks follow-up | Positive—improvement in treated scar compared with untreated | 4 |
| Malhorta et al. [73] | n = 2, India | Case study | 5 % imiquimod following keloid excision. Symptoms assessed by clinician (scar scale utilised not defined). 8 weeks treatment and 12 weeks follow-up | Negative/neutral—keloids recurred within 12 weeks of stopping imiquimod treatment | 5 |
| Patel and Skinner [89] | n = 60, USA | Case study | 5 % imiquimod following earlobe keloid excision. Symptoms assessed by clinician (scar scale utilised not defined). 8 weeks treatment 24 weeks follow-up | Positive—only one recurrence after 24 weeks | 4 |
| Stewart and Kim [106] | n = 10, USA | Retrospective case study | Topical mitomycin C following head and neck keloid revision surgery. Recurrence and symptoms assessed by clinician (scar scale utilised not defined). Treatment varied, follow-up 7–14 months | Positive—only one keloid reoccurred | 4 |
| Bailey et al. [6] | n = 10, UK | Case study | Topical mitomycin C following head and neck keloid shave excision. Patient and clinicians rated symptoms on 10-point analogue scale (scar scale utilised not defined). 6 months follow-up | Positive—only one patient dissatisfied with the response | 4 |
| Chi et al. [30] | n = 12, Korea | Case study | Topical mitomycin C following earlobe keloid shave excision. Recurrence and symptoms assessed by clinician (scar scale utilised not defined). 12 months follow-up | Positive—only one keloid reoccurred | 4 |
| Gupta and Narang [53] | n = 20, India | Case study and literature review | Topical mitomycin C following earlobe keloid shave excision. Patient and clinicians rated symptoms on linear analogue scale (scar scale utilised not defined). 6–24 months follow-up | Positive—no keloid recurrence during follow-up period | 4 |
| Seo and Sung [98] | n = 9, Korea | Case study | Topical mitomycin C following keloid excision. Recurrence and symptoms assessed via Vancouver Scar Scale and patient satisfaction also rated. 6 months follow-up | Positive—six out of nine were satisfied, none were disappointed. Intralesional treatment aggravated the scar | 4 |
| Sanders et al. [96] | n = 15, USA | Case study—patients had multiple keloids and acted as their own untreated control | Topical mitomycin C following keloid excision, followed by intralesional TAC after 1 month. Recurrence and symptoms assessed by clinician (scar scale utilised not defined). 4–28 months follow-up | Negative/neutral—no difference in response with or without mitomycin C | 4 |
| Talmi et al. [110] | n = 8, Israel | Case study | Topical mitomycin C following keloid excision. Recurrence and symptoms assessed by clinician (scar scale utilised not defined) and patient satisfaction also rated. 2 months follow-up | Negative/neutral—patients satisfied with outcome, however, total disappearance was only seen in 2 patients | 4 |
| Draelos et al. [43] | n = 44, USA | Randomised controlled single-blinded trial—patient acted as own untreated control | Topical application of proprietary onion extract cream (Mederma®) (4 weeks, once daily) following surgery for seborrheic keratoses. Symptoms assessed by clinician using 4-point scale (scar scale utilised not defined). Follow-up 10 weeks | Positive—significant improvement in appearance compared with treated controls | 1 |
| Jenwitheesuk et al. [63] | n = 60, Thailand | Randomised, double-blinded placebo controlled trial | Topical application of silicone ± onion extract (Cybele scagel) following surgery, twice daily for 12 weeks. Symptoms assessed via Vancouver Scar Scale and patient satisfaction also rated. 12 weeks follow-up | Positive—using Vancouver Scar Scale, pain itch and pigmentation were improved in onion extract-treated group compared with control | 1 |
| Ho et al. [56] | n = 120, Hong Kong | Randomised controlled trial | Topical application of onion extract (Contratubex®) following laser tattoo removal (twice daily, vs no treatment). Symptoms and appearance assessed by clinician (scar scale utilised not defined). 3 months follow-up | Positive—significantly reduced the risk of scarring from 23.5 to 11.5 % | 2 |
| Hosunter et al. [59] | n = 60, Turkey | Randomised trial, three groups—onion extract, silicone or both treatments. | Onion extract (Contratubex®) on existing hypertrophic and keloid scars, four times per day. Symptoms and appearance assessed by clinician (scar scale utilised not defined). Follow-up 6 months | Negative/neutral—ineffective at improving scar height and itch. Best response was in combination with silicone gel | 2 |
| Draelos [42] | n = 60, USA | Randomised trial | Topical application of onion extract cream (Mederma®) following surgery for seborrheic keratoses. Symptoms and appearance assessed by clinician and patient (scar scale utilised not defined). Follow-up 10 weeks | Positive—improvement in scar appearance compared with untreated controls | 3 |
| Chuangsuwanich et al. [32] | n = 15, Thailand | Randomised blinded split-scar study | Topical application of onion extract (Cybele scagel) following skin graft. Symptoms assessed via Vancouver Scar Scale and patient satisfaction also rated. 12 weeks follow-up | Positive—improvement in scar scale results compared with untreated control | 3 |
| Perez et al. [91] | n = 30, USA | Randomised, blinded comparative study | 0.5 % hydrocortisone, silicone and vitamin E lotion vs onion extract gel. Keloid and hypertrophic scars. Visual analogue scale used to assess appearance of post-surgical wounds by clinicians and patients. 4 months follow-up | Positive—both treatments more effective than placebo | 3 |
| Chanprapaph et al. [27] | n = 20, Thailand | Randomised split scar study | Onion extract gel (Erasé gel) on caesarean scars. Visual analogue scale used to assess appearance of post-surgical wounds by clinicians and patients. 12 weeks follow-up | Positive—reduction in mean scar height and symptoms compared with untreated side | 4 |
| Koc et al. [69] | n = 27, Turkey | Open, randomised comparative study | Onion extract (Contratubex®) (three times daily for 3 months) vs intralesional TAC on keloid and hypertrophic scars for 3 months. Symptoms and appearance assessed by clinician and patient (scar scale utilised not defined). 2 months follow-up | Positive—both intralesional TAC and Contractubex were effective, combination therapy was best | 4 |
| Karagoz et al. [65] | n = 45, Turkey | Randomised case–control study | Comparison of silicone gel (Scarfade®), silicone gel sheet (Epi-Derm™) and onion extract (Contratubex®) (twice daily) on post-burn scars. Symptoms assessed via Vancouver Scar Scale. Follow-up for 6 months | Negative/neutral—silicone products responded better than Contratubex® | 4 |
| Chung et al. [34] | n = 24, USA | Randomised double-blind split scar study | Comparison of topical petroleum ointment with onion extract cream (Mederma®) on fresh surgical wounds, three times daily for 8 weeks. Visual analogue scale used to assess appearance of post-surgical wounds by clinicians and patients. 12 weeks follow-up, telephone interview after 11 months | Negative/neutral—no difference on onion extract treatment compared with petroleum ointment | 3 |
| Beuth et al. [14] | n = 771, Germany | Retrospective multi-centre cohort study | Onion extract (Contratubex®) on post-burn scars and hypertrophic/keloid scars. Symptoms assessed via Vancouver Scar Scale. Follow-up varied | Positive—improved response compared with corticosteroid treatment, with less ADRs | 2 |
| Willital and Simon [116] | n = 1268, Germany | Observational, non-intervention study | Onion extract (Contratubex®) on a range of scars. Symptoms and appearance assessed by clinician and patient (scar scale utilised not defined). Follow-up 4–5 months | Positive—well tolerated, and improvement in scar conditions over follow-up period | 2 |
| Muangman et al. [79] | n = 63, Thailand | Retrospective case study | Topical application of onion extract (Cybele scagel), twice daily, on partial thickness burns. Symptoms assessed via Vancouver Scar Scale. 24 weeks follow-up | Positive—improves pliability, pigmentation, itch and pain over the study period | 3 |
| Campanati et al. [24] | n = 35, Italy | Open-label, controlled, non-randomised clinical trial | Topical application of allium cepa–allantoin–pentaglycan gel (Kaloidon gel) to established keloid and hypertrophic scars. Symptoms and appearance assessed by clinician and patient (scar scale utilised not defined). 24 weeks follow-up | Positive—reduced erythema compared with untreated scars. Overall appearance improved | 4 |
| Ocampo-Candiani et al. [87] | n = 61, Mexico | Randomised controlled trial | Onion extract (Contratubex®) following caesarean. Assessed using Patient and Observer Scar Assessment Scale (POSAS). follow-up 12 weeks | Negative/neutral—similar improvement in POSAS results over time with treatment and non-treatment, although Contratubex® was preferred | 3 |
| Yoon et al. [119] | n = 37, Korea | Randomised split-faced clinical trial | 1 or 5 % green tea (Camellia sinensis) solution, for acne. Twice daily application vs 3 % ethanol control. Visual analogue scale used to assess appearance of acne by clinicians and patients. 8 weeks study | Positive—severity of acne reduced over 8 weeks study | 4 |
| Domingo et al. [40] | n = 4, USA | Randomised split-faced clinical trial | 2.5 % green tea (Camellia sinensis) cream for facial erythema and telangiectasia, twice daily. Symptoms and appearance assessed by clinician and patient (scar scale utilised not defined). 6 weeks study | Positive—no reduction in symptoms however, HIF-1a and VEGF expression was reduced | 4 |
| Maenthaisong et al. [72] | Review | Systematic review | Aloe Vera for burns—4 studies included, 371 patients utilising a range of assessments and follow-up periods | Negative/neutral—average healing time reduced, however, difficult to compare papers and methodology | 2 |
| Eshghi et al. [51] | n = 49, Iran | Randomised placebo controlled trial | Topical Aloe vera ointment for post-hemorrhoidectomy pain. Visual analogue scale used to assess response by clinicians Treatment three times daily for 4 weeks follow-up | Positive—reduced pain upon defecation and improved wound healing | 2 |
| Dat et al. [39] | Review | Systematic review—Cochrane review | Aloe vera for treating acute and chronic wounds—7 studies included, 347 patients utilising a range of assessments and follow-up periods | Negative/neutral—evidence that healing time is reduced, however, poor-quality trials make firm conclusions difficult | 2 |
| Khorasani et al. [67] | n = 30, Iran | Case–control study, each patient acting as their own control | Aloe vera compared to silver sulfadiazine for partial thickness burns, twice daily application. Assessment based on percentage area of wound healed over 24 days follow-up | Positive—reduction in average healing time and improved rate of re-epithelisation | 3 |
| Khoo et al. [66] | n = 122, Malaysia | Randomised double-blinded trial | 5 % topical vitamin E on fresh surgical scars, twice daily for 6 weeks (starting 2 weeks after surgery). Assessed using Patient and Observer Scar Assessment Scale (POSAS). 16 weeks follow-up | Negative/neutral—no difference between treated and untreated control | 2 |
| Zampieri et al. [120] | n = 428, Italy | Randomised singe-blinded case–control study | Topical vitamin E before (three times daily, for 15 days) and after (twice daily for 30 days) surgery in children, to prevent scarring. Symptoms assessed via Vancouver Scar Scale. Follow-up 6 months | Positive—no abnormal scarring and improved cosmetic outcome in test group compared to untreated control | 2 |
| van der Veer et al. [113] | n = 30, Holland | Randomised, double-blinded placebo controlled trial | Topical calcipotriol (vitamin D) following bilateral mammoplasty, twice daily for 3 months. Symptoms and appearance assessed by clinician (scar scale utilised not defined). 12 months follow-up | Negative/neutral—no difference in scar outcome measures | 2 |
| Atiyeh et al. [5] | n = 60, Lebanon | Various study types—case/control studies | MEBO® on facial wounds. Visual analogue scale used to assess response by clinicians. 6 months follow-up | Positive—improved cosmetic compared with topical antibiotic (fudicin) and untreated controls | 4 |
| Atiyeh et al. [4] | n = 66, Lebanon | Various study types—case/control studies | MEBO® following split thickness skin grafts, Visual Analogue Scale used to assess response by clinicians. 6–12 months follow-up depending on study | Positive—improved quality of scar compared with controls | 4 |
Articles identified for inclusion in this review are summarised according to year of publication, country and sample size, along with details of the study design, treatment used and condition, follow-up period and outcome measures. While many of the studies assessed in this review rated scar symptoms such as inflammation, erythema size, scar contour, dryness and pruritus, to determine response to treatment, in many cases these did not relate their findings to a published and recognised specific scar scale