2017-18 HSC Section 4 Green Book

Reprinted by permission of Dermatol Surg. 2015; 41(12):1343-1350.

REVIEW ARTICLE

Mechanism of Action, Efficacy, and Adverse Events of Calcium Antagonists in Hypertrophic Scars and Keloids: A Systematic Review

Svenna Verhiel, MD, Andrzej Piatkowski de Grzymala, MD, and Rene van der Hulst, MD, PhD

BACKGROUND Pathological scars often cause major cosmetic and functional consequences, which make effective treatment important. Intralesional therapies are widely used, with corticosteroid injection considered to be first choice. An emerging and promising treatment option is the calcium antagonist verapamil.

OBJECTIVE To provide a comprehensive evidence-based review of current evidence on mechanism of action, efficacy, and adverse events of calcium antagonists in treatment of hypertrophic scars and keloids.

METHODS AND MATERIALS A Cochrane Library and PubMed search was performed for the literature per- taining to treatment with calcium antagonists in pathological scars. Articles were categorized into two groups: mechanism of action or efficacy and adverse events. RESULTS Six in vitro studies were included in the first subgroup. Calcium antagonists have been found to reduce extra cellular matrix production, induce procollagenase synthesis, and inhibit interleukin-6, vascular endothelial growth factor, and proliferation of fibroblasts. Eight studies with a median level of evidence of 3.5 (range: 2–4) were included in the second category. A good efficacy with no major side effects was reported for calcium antagonists. CONCLUSION Important methodological shortcomings of the available literature were identified. Interesting results have been reported, but further large scale, high-quality studies are needed to optimally evaluate efficacy of treatment with calcium antagonists.

The authors have indicated no significant interest with commercial supporters.

H ypertrophic and keloid scars are pathological scars as a result of dermal injury and exhibit exuberant, inde fi nite growth of collagen during wound healing. The principle clinical feature that distinguishes them is that keloids extend beyond the original wound and rarely regress, whereas hypertrophic scar remain con fi ned to the original wound and often regress spontaneously. 1 – 6 Keloid scarring is reported to be more common in darker skin, whereas hypertrophic scarring is more common in fair skin. 7 Hypertrophic and keloid scars often cause symptoms such as hypersensitivity, pruritus, or pain. Patients can be affected with major cosmetic, psychological, and social

consequences. 4,8,9 For this reason, effective treatment of pathological scars is important in clinical practice.

There is nouniformtreatment of excessive scars andoften multiple therapies are combined to achieve a better ef fi - cacy. Different options for treatment are excision, radiotherapy, cryosurgery, pressure therapy, laser ther- apy, topical silicone gel, silicone sheeting, topical retinoid acid, and imiquimod cream. 10 – 14 In addition, intrale- sional therapies are widely used, including a number of emerging and promising treatment modalities. Examples of these are corticosteroids, cryotherapy, 5- fl uorouracil, verapamil, bleomycin, interferons, andmitomycinC. 15 – 19

Department of Plastic, Reconstructive and Hand Surgery, Maastricht University Medical Center, Maastricht, the Netherlands

© 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-0512 · Dermatol Surg 2015;41:1343 – 1350 · DOI: 10.1097/DSS.0000000000000506

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