Mitomycin C in the Treatment of Keloids: A Case and Review

Mitomycin C (MMC) is an antineoplastic antibiotic. It is derived from the Streptomyces caespitosus bacterium, and functions as an antiproliferative agent, inhibiting DNA synthesis by cross-linking the strands of the double helix.¹ Recently, MMC has been used as an alternative topical and intralesional agent in the approach to hypertrophic scars and keloids. There is wide variability in the mode of usage and the success of this agent in the literature, and no large trials have been conducted regarding scars. Herein, we report a case, discussing our experience with MMC, and we review the prior usage of MMC in scar treatment.

A 27-year-old Caucasian female with a history of systemic lupus erythematosus (not on systemic medications) presented large and painful sternal keloids, recurring after two prior excisions despite treatment with intralesional triamcinolone, 5-fluorouracil, topical imiquimod, topical silicone gel, and pulsed-dye laser. The patient’s superior sternal keloid was re-excised, and in light of the patient’s unfavorable response to other agents, MMC was used adjunctively. The skin was extensively undermined to a distance of at least 3 cm on either edge of the wound. Intraoperatively MMC (0.4 mg/ml; total of 50 ml soaked on gauze) was placed on the wound edges for a period of four minutes and then the treated area was irrigated with saline. The wound was sutured with polyglycaprone and polydioxanone intradermal sutures. 6-0 fast-acting gut cuticular sutures were used.

Thereafter, the patient underwent pulsed-dye laser treatments at 2-month intervals. She tried to keep as much strain off the wound as possible, bending her shoulders forward in the post-operative period. Six months following the excision she remained asymptomatic, with marked improvement of the area that was excised. She also noted that at the superior edge of her inferior sternal keloid had flattened, which she attributed to the MMC application (Figure 2). At this point, the inferior sternal keloid was excised and treated in a similar manner with MMC intraoperatively.

For approximately 3 years postoperatively, the patient was relatively asymptomatic, without recurrence of the keloids. Four years after her excisions, the patient began to feel itching and burning in the affected area. Following a further discussion of the agent and demonstrating an understanding of its off-label use, the patient was injected with 0.4 cc of a solution of MMC containing 0.4 mg/5 ml solution, with microdroplets placed approximately 1 cm apart along the margins of the suture line. This treatment was repeated several months later, achieving symptomatic improvement. At the present time the patient has occasional flares of itching or pain in the treated area, mostly at the edges, and was most recently treated with intralesional triamcinolone injections (Figure 3).

Several in vitro and animal studies have attempted to characterize the effect of MMC on the healing wound.^1-3 Gray et al indicated that MMC delays wound healing by down-regulating the production of extracellular matrix proteins.² They concluded that if MMC is applied to the wound before the genetic induction of a proliferative phenotype (ie, without delay after surgery), it may be effective at inhibiting fibroblast proliferation and consequent healing.

In an initial trial using MMC for the prevention of keloid recurrence postoperatively, Talmi et al conducted eight keloid excisions and placed a saturated pledget with MMC over the wound prior to closure for 5 minutes.⁴ A concentration of 0.4 mg/ ml was used. The patients were followed monthly for six months and again at 14 months. The authors stated that all patients improved and there were no adverse effects. They indicated that in all cases, scar thickness was substantially reduced, although only 2/8 keloids showed complete remission. A limitation of this small study was the lack of controls. Stewart et al provided similar results using a 0.4 mg/5 ml concentration of MMC intraoperatively, reporting a 90% success rate and no recurrences at follow-up intervals ranging from 6-14 months.⁵ Again, no controls were used. Soon after, Sanders et al performed a study with the same concentration of MMC and the same time frame for topical application in patients with multiple keloids who served as their own controls.⁶ The authors excised 30 keloids in 15 patients. Excision was followed by intralesional corticosteroid injection at monthly intervals for 6 months, though this