5-Fluorouracil

5-fluorouracil (5FU) has been successfully used for the treatment of keloid and hypertrophic scars since 1989103. 5FU inhibits the proliferation of fibroblasts as a pyrimidine analogue. The response rate in keloids is approximately 50%104. Studies have demonstrated that even lower concentrations of 5FU in combination with intralesional corticosteroids can effectively reduce the recurrence rate after surgical removal of ear keloids105.

In a prospective study with a total of 69 patients, the combination of TAC (40 mg/ml) : 5FU (50 mg/ml) (1 : 9) once per week for 2 months, injected strictly intralesionally, and in part, additional use of a dye laser was shown to be superior to exclusive weekly injection of TAC 40 mg/ml57. In a further double-blind, prospective study of 40 patients with keloid and hypertrophic scars, better results in terms of a reduction of size and redness were seen with the combination TAC (40 mg/ml) : 5FU (50 mg/ml) (1 : 9) in comparison with the injection of TAC 40 mg/ml alone106. Strictly intralesional injection of a combination of 5FU (50 mg/ml) and TAC (40 mg/ml) (1 : 3) for the treatment keloids was examined in a retrospective study with either 5FU/TAC/excision or TAC/excision in a total of 102 patients, with the combination of 5FU/TAC/excision proving superior to TAC/excision107. The authors follow a similar dosing regimen with excellent results and a minimal side-effect profile.

Based on the currently available study data, the use of 5FU for the treatment of keloids represents a relatively safe approach. Side-effects include pain at the injection site, hyperpigmentation, skin irritation and ulceration (Figure 6). Listed contraindications include anaemia, leukopoenia, thrombocytopoenia, pregnancy, bone marrow depression and infection. Systemic side-effects have not been observed to date. Based on the updated German Guidelines for the therapy of pathological scarring, treatment of refractory keloids with 5FU can be considered23.

Bleomycin

Bleomycin sulfate is thought to inhibit collagen synthesis via decreased stimulation by TGF-β1108. A number of studies demonstrate significant improvement in hypertrophic scar and keloid height and pliability, as well as reduction in erythema, pruritus, and pain after administering three to five intralesional injections (via multiple needle puncture or jet injections) of bleomycin (1.5 IU/ml)108–110. Occasionally, development of de- or hyperpigmentation and dermal atrophy has been noted. Clinicians should be aware of its toxicity; however, systemic toxic effects of intralesionally administered bleomycin (e.g. lung fibrosis) appear to be rare100. Bleomycin may therefore represent a promising agent for the therapy of keloids and hypertrophic scars, but further investigation and efficacy trials are necessary in order to include this agent in future treatment protocols.

Conclusions

Scarring following surgery or trauma remains difficult to predict and both physicians and their patients are highly concerned with minimising scar appearance and value even small improvements in scarring as clinically meaningful. Most existing prophylactic and therapeutic strategies have been proven through extensive use, but few have been supported by well-designed prospective studies with adequate control groups.

Despite recent scar reduction techniques such as lasers, intralesional 5FU, and botulinum toxin A, the treatment of post-procedural complications remains challenging. It is still preferable to try and prevent scarring by minimising risk factors as much as possible. Each proceduralist should be aware of the knowledge of healing mechanisms and skin anatomy, as well as an appreciation of suture material and wound closure. The authors therefore propose correct supervision of surgical teaching techniques in order that these basic principles remain adhered to.