2017-18 HSC Section 4 Green Book

HY P E R TROP H I C S CAR S AND K E LO I D S

TABLE 1. Details and Results of the Six Studies That Were Included in the First Category (Mechanism of Action of Verapamil in Hypertrophic Scars and Keloids)

Reference

Type of Study Description of Study

Main Result

Lee and Ping 28

In vitro study Effect of calcium antagonist on uniaxially oriented mammalian fibroblast- populated collagen matrices In vitro study Effect of calcium antagonist on human keloid fibroblasts, isolated from excised keloids In vitro study Comparison of fibroblasts isolated from keloids and control fibroblasts In vitro study Effect of calcium antagonists on human keloid fibroblasts, isolated from excised keloid In vitro study Effect of combined steroid and calcium antagonist injection of human hypertrophic scars (implanted in mice model) In vitro study Effect of calcium antagonist on skin fibroblasts isolated from normal human skin

Verapamil retards the incorporation of proline into the extra cellular matrix

Doong and colleagues 29

Calcium antagonists alter cell shape, depolymerize actin filaments, and induce procollagenase synthesis Keloid fibroblasts show elevated IL-6 expression Verapamil inhibits proline incorporation and production of IL-6 and VEGF, induces procollagenase synthesis and collagen degradation in keloid fibroblasts Calcium antagonist inhibits decorin reuptake, stimulates collagenase release, and inhibits fibroblast proliferation Verapamil induces alterations represented by morphological changes, low cytostolic calcium concentration, discrete reorganization of actin cytoskeleton, and increase of matrix metalloproteinase production

Xue and colleagues 30

Giugliano and colleagues 31

Yang and Huang 32

Boggio and colleagues 33

complete results. 24,37 Only one of these articles reported adverse events, which were not experienced. 24 Law- rence and colleagues found that at a mean follow-up of 28months, 22 of 40 keloids (55%) did not recur and 16 of 31 patients (52%) remained keloid free after excision followed by pressure earrings and intralesional verap- amil. They did not report side effects. The study did not use a control group. 34 D ’ Andrea and colleagues dem- onstrated that adjuvant verapamil helped reduce the incidence of keloid recurrence after surgical excision and silicone sheet application, with 54% complete results (vs 0% in control group) and 36%partial results (vs 18% in control group). Adverse events were not reported in this study. 35 One article showed a low incidence of side effects from intralesional verapamil, being tolerable pain caused by injection in 6 of 22 patients. They found a recurrence of fi ve keloids after surgical excision, with two keloids that were smaller than the original lesion and two lesions being hypertrophic scars. 36 A prospective ran- domized single-blinded controlled trial demonstrated

that intralesional verapamil was comparable to intrale- sional triamcinolone acetonide in the treatment of keloids. Triamcinolone not only achieved these effects faster but also had a higher incidence of adverse events than verapamil did. 38 The outcomes of Ahuja and Chatterjee 39 were similar, they found a comparable end result for intralesional verapamil and intralesional triamcinolone, with a faster effect but also more side effects in the triamcinolone group.One study used topical verapamil instead of intralesional verapamil and found better quality scarring for subjects that were treated with a verapamil containing gel compared with the control group, andnoadverse eventswere experienced. 40 Table 2 includes a summary of the results that were described.

Discussion

In this review, the available literature on calcium antagonists for the treatment of hypertrophic and keloid scars was summarized. The evidence that was found was categorized in two subgroups, mechanism of action and ef fi cacy and adverse events.

DE RMATOLOG I C S URG E RY

200