Treating Keloids With Intralesional 5-Fluorouracil and Triamcinolone Acetonide: Aren’t We There Yet?

Keloid scars are commonly encountered and can be difficult to treat in dermatological practice. In addition to being esthetically concerning to patients, they are commonly accompanied by pruritus or pain. Despite a wide array of therapeutic options available, from first-line options including silicone sheeting, pressure dressings, and triamcinolone acetonide (TAC) injections, to alternative options including intralesional 5-fluorouracil (5-FU), verapamil and bleomycin, cryotherapy, surgical excision, and lasers, keloid management remains clinically challenging. ¹ In many ways, the large number of options is a direct reflection of the absence of consensus regarding the best treatment for keloids.

While intralesional 5-FU and TAC have both been proven as effective monotherapy, there has been increased interest in their combined synergistic effects, particularly with respect to their mechanisms of action and complementary adverse effect profiles. The chemotherapy agent 5-FU is a pyrimidine analog that inhibits deoxyribonucleic acid synthesis by inhibiting thymidine synthase, effectively halting the proliferation of fibroblasts and the fibroblast-populated collagen lattice. ² Corticosteroids offer further inhibitory effects including suppression of fibroblast and keratinocyte proliferation, and reduction of inflammation. ³

This combination treatment is supported by evidence in which combination of 5-FU and TAC has been suggested to be superior to either monotherapy alone. In a recent meta-analysis, Ren et al ³ concluded that 5-FU in combination with TAC resulted in greater effectiveness, compared to TAC alone, as measured by keloid scar height. Furthermore, combination therapy resulted in both superior cosmetic outcomes and patient satisfaction. Correspondingly, a systematic review by Shah et al ⁴ found similar results with combination therapy compared to 5-FU monotherapy.

Additional benefits of combination therapy include reduced adverse effect profiles, owing to the lower concentrations required of each agent. A relatively safe drug, 5-FU has had no systemic toxicities reported with intralesional use of up to 2 mL of 50 mg/mL per session. Local adverse effects can include transient erythema, dyspigmentation, ulceration, and most notably, significant pain at the site of injection. ⁵ The addition of TAC has been found to substantially reduce this pain profile, as well as 5-FU-induced erythema and inflammation. ⁴ Additionally, common steroid-induced adverse effects are also reduced with the addition of 5-FU, namely telangiectasia, atrophy with hypopigmentation, and rebound recurrences. ⁴

From a practical standpoint, many combination dosages and treatment intervals have been examined, ⁴ but the optimal sequence remains unknown. Empirically, in the author’s practice, up to 2 mL of 50 mg/mL 5-FU are used to dilute down TAC to its desired concentration and patients are injected every 4 to 6 weeks. Dilution of TAC can be as low as 2.5 to 3.3 mg/mL for first-time treatment of small keloids at risky sites for iatrogenic atrophy and the concentration of TAC may be increased with subsequent treatments or started at 5 to 10 mg/mL for larger keloids at more forgiving anatomical sites.

Based on the current state of evidence, we propose that combination of intralesional 5-FU and TAC has been an underutilized treatment option, yet it holds potential. With increased awareness, dermatologists may increasingly consider the use of this therapy in their armamentarium for the effective treatment of keloid scars.