NEWS, VIEWS & REVIEWS

Keloids have long been a distressing complication of wound healing. While keloids can be treated by corticosteroid injection or surgical excision, in many situations these two approaches are not adequate for complete scar control. We review new developments in the management of keloids and comment on the optimal dose and duration of each treatment.

For most patients with keloids, the goal is to stop keloid growth and decrease them in size as soon as is practically possible. With surgical excision, the recurrence rate of keloids is from 45-100 percent.² Using post-procedure intralesional corticosteroids decreases the risk of recurrence to 33-70 percent.³⁶ The question remains as to whether other treatments can cause an even greater decrease in the risk of recurrence.

One topical therapy that might possibly decrease keloid recurrence even more than corticosteroids is imiquimod.³⁰ Imiquimod is an immune response modulator that is hypothesized to act in several ways to prevent keloid recurrence: (1) it indirectly stimulates interferon-γ, which has been used to treat fibrosis¹³; (2) it downregulates TGF-β, which is important in the formation of keloids⁴³; (3) it downregulates the TH2 cell response that promotes fibrosis³⁵; (4) it increases apoptotic markers in keloidal tissues¹⁹; and (5) it induces matrix metalloproteinase, which can cleave collagen and prevent keloid growth.³⁷

It appears that using nightly imiquimod 5% cream post-operatively for 6-8 weeks^41,30 is more effective and leads to lower recurrence rates than using imiquimod only three times per week.³ In the study by Berman et al., imiquimod 5% was applied by patients every night only for the first two weeks and was thereafter applied only three times a week. This led to a recurrence rate of 37.5 percent (3/8 patients), much higher than the recurrence rate resulting from nightly application of imiquimod, which was 0 percent (0/8 patients)³ and 25 percent (2/8 patients).³⁰ Of note, all three studies measured recurrence rate six months or more after the surgical excision.

It is important to note that these studies were all done on earlobe keloids. One study by Cacao et al. has shown that even the nightly use of imiquimod is not effective in preventing the recurrence of trunk keloids. In this study, nine patients, all with keloids on the trunk, were treated with imiquimod 5% every night for eight weeks, beginning on the night of the surgery. After 12 weeks, keloids recurred in eight out of nine of the patients.⁶ Even though this is a small case series, these results discourage the use of imiquimod for keloids on the trunk. In a larger scale trial involving 35 patients with keloids in various regions of the body including the earlobes, shoulders and chest wall, the earlobe keloids were also found to have a lower recurrence rate (2.9%) compared with the recurrence rate of keloids on the chest wall or neck (83.3%).⁸ After imiquimod, keloids appear to be more responsive on low-tension regions such as the earlobe.

Based on the above studies, imiquimod 5% cream should be used as an adjunct to surgical excision only in the case of earlobe keloids. In this situation, it should be applied every night to the suture site beginning on the night of the surgery and continuing for a total of eight weeks.

The antineoplastic agent, 5-fluorouracil (5-FU), has been shown to inhibit collagen synthesis.¹ Studies have been designed to test whether adding 5-FU to corticosteroid injection leads to superior results. The first study, carried out by Fitzpatrick et al., showed great efficacy and decreased pain from injections when 0.1 mL of 10 mg/mL triamcinolone (TAC) was mixed with 0.9 mL of 50 mg/mL 5-FU.¹¹ This treatment was found to be efficacious only when delivered once weekly or once every two weeks.^11,14 Another study, though short in its follow-up period of 12 weeks, confirmed Fitzpatrick's data by showing that the combination of TAC and 5-FU leads to greater flattening and reduction of keloid size, along with a more noticeable decrease in induration and erythema.⁹

The evidence shows that 5-FU is best used not as monotherapy but as an adjunct to TAC and surgical excision. Nanda and