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 2. (Continued )

Follow-Up Period

Level of Evidence

Reference Cointervention

Efficacy

Adverse Events

Margaret

None

12 months Verapamil, like triamcinolone, significantly improves all clinical parameters of the scars

Incidence of adverse events higher for triamcinolone (e.g., hypopigmentation)

Level 2

Shanthi and colleagues 38

None

24 weeks

Mean zero VSS scores in respect of scar height (T-12, V-21 weeks), vascularity (T-15, V-18 weeks) and pliability (T-15, V-21 weeks)

Adverse events verapamil 0/26,

Ahuja and

Level 2

Chatterjee 39

triamcinolone 6/22 (telangiectasia, skin atrophy)

None

90 days

Verapamil showed good-quality scarring (80% and 75.2%) vs control group (48% and 51.2%)

None

Level 3

Boggio and

colleagues 40

hypertrophic and keloid scars in only low amounts. Verapamil has been shown to augment decorin expres- sion in animal models, when added to triamcinolone. 33 The end result with both triamcinolone acetonide and calcium antagonists is to increase collagenase levels to achieve collagen degradation within the scar. How- ever, the way they act on the pathways to achieve this effect is different. 20 It would be interesting to investi- gate whether the two drugs can be combined to derive a synergistic response, with similar or better results and fewer side effects than monotherapy. The main limitation of this reviewwas the lack of high- quality studies on ef fi cacy of calcium antagonists in pathological scars. Most evidence that was reviewed consisted of nonrandomized controlled trials, uncontrolled open-label trials and case reports. These study designs tend to overestimate treatment ef fi cacy. Case reports and small trials were included in this review to provide a comprehensive overview, but no level of recommendation can be attached to them. Almost all of the studies that were reviewed were limited by the number of subjects that were enrolled (usually less than 50 subjects). The highest level of evidence, according to criteria published by the Oxford Centre of Evidence-Based Medicine Levels of Evidence, was found to be level 2 Primary Outcomes on Efficacy and Adverse Events

Primary Outcomes on Mechanism of Action

Verapamil is a prototypical phenylalkylamine, it is considered to be the fi rst calcium channel blocker to be used clinically. It blocks both L-type and T-type channels with higher af fi nity for depolarized channels than for resting channels. Currently, verapamil is used in clinical setting to terminate cardiac arrhythmias. 41,42 It is reported that calcium antagonists promote a change in cell shape from bipolar to spherical. The mechanism by which this is accomplished remains unknown. It might be possible that the calcium channel blocker behaves like a calmodulin inhibitor that causes cells to round up. A calcium-independent process with alteration or rearrangement of the actin cytoskeleton would be involved. Another possibility for cell round- ing is that the effect of calcium antagonists may be similar to that of cytochalasin B. It causes change of cell shape by disrupting the stress fi bers, and it induces collagenase and production of protease. 24,43,44 Verapamil induces procollagenase expression and increases collagenase; furthermore, it inhibits the synthe- sis of extracellular matrix molecules, including collagen, fi bronectin, and glycosaminoglycans. 28,29,31 – 33 It has been found that fi broblasts in keloids show elevated IL-6 and VEGF levels. Verapamil decreases production of both IL-6 and VEGF, leading to decreased cell proliferation and increased apoptosis. 30,31 Decorin, which inhibits fi broblast proliferation and migration, may be present in

DE RMATOLOG I C S URG E RY

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