Table 3.
Intralesional Injection (with or without intralesional corticosteroids)
| First author, year | Study design | Treatment | Duration | N | Outcome(s) | Follow-up time | Adverse events | Comments |
|---|---|---|---|---|---|---|---|---|
| Abou-Taleb, 2020 [51] | P | IL verapamil (2.5 mg/ml) | Q3wks until complete flattening or 6 sessions | 43 |
Significant decrease in mean VSS score (p < 0.001) Recurrence in 20.9% of cases |
Up to 3 months |
Post-procedure pain in 83.7% Post-procedure pruritus in 9.3% |
|
| Aggarwal, 2018 [52] | RCT |
Group 1: IL TAC (40 mg/ml) Group 2: IL hyaluronidase (HA) 1500 IU/ml + TAC 40 mg/ml (1:1) Group 3: IL verapamil (2.5 mg/ml) Group 4: RF Group 5: RF + IL TAC (40 mg/ml) |
Groups 1, 3, 5: q3wks for 8 sessions or complete flattening Group 4: q6wks for 4 sessions or complete flattening |
80 |
Complete clearance: 75% Group 1: 68.75% Group 2: 0% Group 3: 11.76% Group 4, 75% Group 5 (p < 0.001) |
5 months | Groups 1, 2, and 5: atrophy and pigmentary (least in group 2 (p value < 0.001)); telangiectasia (group 1), urticaria (groups 3); ulceration + secondary infection in groups 4 and 5 (35.29% and 25%) (p value < 0.001) | Clearance: height reduced to 1 mm or less |
| Ali, 2020 [53] | RCT |
Group A: IL 5-FU (50 mg/ml) Group B: IL 5-FU + IL TAC (40 mg/ml) (9:1) |
q1wk for 4weeks, then twice a month for 2 months then q1mo until flat or max of 3 months | 60 | Efficacy higher in group B (86.7% vs. 60% p = 0.020) | 6 months | Skin necrosis in an unspecified number of cases |
Effectiveness: more than or equal to 50% reduction in initial height Group B effectiveness was higher only in ≤ 40 years (p = 0.013) |
| Danielsen, 2016 [54] | DB, RCT, split scar controlled |
Group 1: excision + IL TAC (10 then 5 mg/ml) Group 2: excision + IL verapamil (2.5 mg/ml) |
Q1mo for 4 months | 14 | Higher recurrence verapamil-treated half 6/14 (p = 0.01) | 12 months | 4 subjects w/atrophy IL-TAC half | The study was terminated early due to superior results in group 1 |
| El Kamel, 2016 [55] | P | Keloidectomy with core fillet flap + IL verapamil (2.5 mg/ml) | q2wks for 3 months | 16 |
71.4% with no recurrence 14.3% recurrence at wound bed |
18 months |
Partial flat tip necrosis in 10.5% 14.3% hypertrophic scar at incision |
Earlobe keloids only |
| Gamil, 2020 [56] | RCT, intraindividual controlled |
Group 1: IL BTA (2.5 IU/cm3) one side of the body and IL TAC to other side Group 2: IL BTA + IL TAC |
q1mo for 3 sessions | 50 | Group 2 shows significantly greater reduction in keloid surface area vs IL TAC | 6 months |
Group 1: 11.5% pain w/injection, 7.7% skin atrophy Group 2: none |
Scar Evaluation Scale (SBSES) and color Doppler ultrasound (CDS) used to evaluate keloids |
| Hewedy, 2020 [57] | RCT |
Group A: IL TAC (20 mg/ml) + PRP 1 week afterwards Group B: IL TAC (20 mg/ml) |
IL TAC q3wks for 4 sessions | 40 | Statistically significant better improvement in VSS in group A than in group B after treatment (p = 0.026) | 3 months | Significantly higher atrophy and hypopigmentation in subjects of group B vs A (p = 0.01 and .014) | |
| Huu, 2019 [28] | P | IL bleomycin (15 units) | Q4wks for an average of 4 times | 120 | 14% recurrence at follow-up | 18 months | Hyperpigmentation in 56.7%, blistering in 78.3%, ulceration in 5.8% | VSS used to quantify treatment response |
| Ismail, 2020 [58] | RCT |
Group A: IL BTA (2.5 U/cm3) Group B: IL 5-FU (50 mg/ml) |
Q1mo until flattening or 6 sessions | 69 |
Greater flattening group A vs group B (p = 0.04) 8.8% vs 31.4% recurrence group A vs B (p < 0.05) |
Up to 3 months |
Group A: hypopigmentation in 5.9% Group B: hyperpigmentation in 14.3% and hypopigmentation in 2.9% |
6 patients had multiple keloids and received different treatments in different lesions |
| Khan, 2019 [59] | RCT |
Group A: IL bleomycin (1.5 IU/ml) Group B: IL TAC (40 mg/ml) |
q4wks for 6 months | 164 |
Decrease in POSAS score was significantly larger in group A Efficacy 82% vs 70% group A vs B (p = .0069) |
None |
Group A: hyperpigmentation in 70%, and ulceration in 27% Group B: atrophy in 70%, hypopigmentation in 29%, and telangiectasias in 21% |
POSAS score used to quantify treatment response Efficacy: greater than 50% reduction in the POSAS score from baseline |
| Khare, 2012 [60] | P | Excision with 5-FU to excision margin and the wound bed vs. IL TAC | IL TAC q2wks | 60 | Recurrence rate with excision and 5-FU was 3.57% vs IL TAC 21.9% | 1 year | Excision and 5-FU group with superficial necrosis in 11%, dehiscence in 7%, and local infection in 4% | Earlobe keloids |
| Khattab, 2020 [61] | P | IL verapamil (2.5 mg/ml) vs PDL then IL verapamil (2.5 mg/ml) | Q3 weeks for up to 8 sessions or flattening | 40 (56 keloids) | PDL + verapamil showed a statistically significant greater reduction in height (p = 0.003) and pliability (p = 0.025) | 24 weeks |
Increase size, pain, purpura, hyperpigmentation, and depigmentation AE more frequent in PDL + verapamil (25%) compared to IL verapamil (5.36%) |
VSS |
| Pruksapong, 2017 [62] | RCT |
Control group: IL TAC (10 mg/m)l 7 days after suture removal Toxin group: BTA (1.5 μ/cm) 7 days after suture removal |
Control group only: additional injections at 1, 3, and 6 months | 25 (50 keloids) | VSS score in control group significantly lower than the toxin group at 6th month follow-up (5.33 ± 1.87 vs. 4.11 ± 1.96, p = 0.010) | 6 months | Not stated | |
| Rasaii, 2019 [63] | DB, RCT, intraindividual controlled |
Group A: IL TAC (20 mg/ml) + placebo Group B: IL TAC + IL BTA (20 U/ml) |
q4wks for 3 sessions | 40 | No significant difference in therapeutic efficacy between groups | 1 month | Not stated | VAS used to quantify treatment response |
| Reinholz, 2020 [64] | P | IL 5-FU (50 mg/ml) + IL TAC (40 mg/ml) (3:1) | q4wks for 4 treatments | 50 |
All parameters in the patient score revealed significant improvement after treatment Keloid height and volume were reduced by 59.3% and 53.1% DLQI score showed improvement in QOL |
12 months | Hyperpigmentation (36%), telangiectasia (24%), ulceration (20%), hyperpigmentation (12%) |
Inclusion criteria included resistant to treatment after 3× cryotherapy + TAC Treatment response monitored by digital photography, three-dimensional phase shift rapid in vivo measurement of skin (PRIMOS) software, ultrasound and standardized questionnaires (POSAS, DLQI) |
| Sadeghinia, 2012 [65] | DB, RCT |
Group A: IL TAC (40 mg/ml) Group B: 5-FU solution (50 mg/ml) dripped after 40 punctures per 5 mm2 (tattoo method) |
q4wks for 12 weeks | 40 |
Patient self-assessment, induration, pruritus were significantly better (p < .05) in Group B Better results were found for group B group (p < .05) per observer assessment |
44 weeks | None | |
| Sagheer, 2016 [66] | RCT |
Group A: IL 5-FU (50 mg/ml) Group B: IL TAC (40 mg/ml)+5-FU (1:9) |
Monthly for 6 months | 60 | Group A with efficacy in 10 (33.3%) cases vs. 22 (73.3%) group B (p = 0.002.) | 6 months | Not stated | Efficacy: 51–100% improvement (flattening and decrease in size of lesion |
| Saha, 2012 [67] | RCT |
Group F: IL 5-FU (50 mg/ml) Group T: IL TAC (40 mg/ml) |
Frequency unspecified, until satisfactory result | 44 | Both modalities of treatment were equally effective | Up to 1 year | Group F: ulceration, hyperpigmentation | |
| Saki, 2019 [68] | RCT, intraindividual controlleld |
IL TAC (20 mg/ml) + cryotherapy Vs IL verapamil (2.5 mg/ml)+ cryotherapy |
q3wks until flattening or 8 sessions | 30 | Statistically better improvement in height and pliability in the triamcinolone-receiving group compared with the verapamil-receiving group (P < 0.001). | 24 weeks |
TAC: hyperpigmentation and hypopigmentation Verapamil: hyperpigmentation |
Scar evaluation at each stage was done by serial photographic records as well as by Vancouver Scar Scale |
| Saleem, 2017 [69] | RCT |
Group A: IL 5-FU (50 mg/ml) + TAC (40 mg/ml) Group B: IL TAC (40 mg/ml) |
q4wks until flattened or period of 12 weeks | 100 | Mean reduction in VSS was −71.18 (±8.69) in group A as compared to −50.80 (±8.59) in group B (p = 0.001) | 12 weeks | No serious adverse effects | |
| Shaarawy, 2015 [70] | DB, RCT |
Group A: IL TAC (10 mg/ml) Group B: IL BTA (5 IU/cm3) |
Group A: q4wks for six sessions or complete improvement Group B: q8wks for 3 sessions or complete improvement |
24 | Significant decrease in the volume (p < 0.01), softening (p < 0.01) and decrease in height (p < 0.01), no significant difference between groups | None | Group A: skin atrophy and telangiectasia 25% | |
| Srivastava, 2017 [71] | SB, RCT |
Group A: IL TAC (40 mg/ml) Group B: IL 5-FU (50 mg/ml) Group C: IL TAC (40 mg/ml) + IL 5-FU (50 mg/ml) (1:9) |
q3wks for 24 weeks or resolution | 60 | There was a reduction in VSS all three groups | none | Telangiectasias and skin atrophy most frequently in group A. Skin ulceration was a common problem in group B | Resolved: when a total score of 2 or less was achieved on Vancouver Scar Scale (VSS) |
| Velurethu, 2017 [72] | P | IL 5-FU (50 mg/ml) + IL TAC (40 mg/ml) + IL HA (1500 units) | q4wks until complete flattening or a maximum six sessions | 50 (60 keloids) |
Significant improvement of POSAS at 12 weeks for all patients 65% with complete flattening after 4 sessions 2 recurrences at 6 months |
6 months–1 year | Skin ulceration (13%), hypopigmentation (23%) | |
| Wilson, 2013 [73] | P | Excision w/ POD 9 IL 5-FU (50 mg/ml) and IL BTA (50 IU/ml) | Once | 80 | Recurrence rate of 3.75% | 17–24 months | Pruritus (10%), pain (8.75%), burning (5%), hyperpigmentation (2.5%), dehiscence (1.25%), late scar widening (13.75%) |
P prospective trial, SB single blind, DB double blind, RCT randomized controlled trial, IL intralesional, TAC triamcinolone acetonide, yo year old, mo month, qnwks every n weeks, HA hyaluronidase, IU international unit, 5-FU = 5-fluorouracil, BTA botulinum toxin A, PRP platelet-rich plasma, PDL pulsed-dye laser