Hypertrophic scars and keloids are pathological scars that occur as a result of dermal injury and characterized by persistent inflammation and fibrosis and excessive deposition of collagen and other fibroblast-derived ECM proteins (Atiyeh, 2007; Verhiel et al., 2015).
Hypertrophic scars are often painful and pruritic; scar contractures may lead to decreased functionality and, if formed across joints, can restrict growth in the pediatric population (Shih et al., 2010; Hu et al., 2014; Hu et al., 2014). Furthermore, the unaesthetic appearance of hypertrophic scars, particularly if occurring in visible regions such as the face, can have devastating psychosocial effects (Lawrence et al., 2012).
When treating HTS, both functional and aesthetic improvement is the ultimate goal. Multiple therapeutic options have previously been described including pressure therapy (Carr-Collins, 1992), surgical revision, laser therapy, silicone garments, and adjuvant topical drug treatments (Liu et al., 2011).
Fractional lasers create zones of ablation at variable depths determined by the treatment settings. The unique fractional injury induces a molecular cascade including heat shock proteins and other factors that lead to a rapid healing response and prolonged neocollagenesis with subsequent collagen remodeling (Waibel et al., 2009).
Verapamil hydrochloride, a calcium channel blocker, has been found to, depolymerize actin filaments, alter cell shape and reduce fibrous tissue production via stimulation of procollagenase synthesis in normal human cultured fibroblasts, keloids and HTSs (Margaret Shanthi et al., 2008).
5-Fluorouracil (5-FU), a pyrimidine analogue, is an antineoplastic agent that inhibits normal RNA and DNA synthesis, resulting in re¬duction of thymidylate synthase activity. It inhibit signaling of TGF-β1 in collagen I production, induces fibroblast apoptosis of fibroblasts without ne¬crosis, and targets rapidly metabolizing and proliferating cells such as dermal wounds’ fibroblasts which are responsible for excessive collagen production (Haurani et al., 2009).
Effective topical delivery of any pharmaceutical agent requires the ability to penetrate the epidermis. Fractional laser therapy creates precise, uniform columns of tissue vaporization which in theory might help to facilitate drug delivery past the epidermal barrier (Haedersdal et al., 2010).
The aim of this study is evaluating the efficacy of the combination therapy of fractional carbon dioxide laser with topically applied verapamil hydrochloride or 5-flurouracil (5-FU) in the treatment of hypertrophic scars and keloids.
This is a randomized comparative single blinded prospective study that included 30 patients with no history of treatment for the scars in preceding 6 months prior to inclusion. Patients were randomized into three study groups, group I (CO2 laser followed by topical verapamil application), group II (CO2 laser followed by topical 5-flurouracil application), and group III (CO2 laser only). All patients received a course of four treatment sessions of laser therapy at one-month intervals. Photography, clinical improvement assessment by Vancouver scar scale (VSS) (Sullivan et al., 1990), patients′ symptoms and satisfaction assessment by Patient Scar Assessment Scale (Draaijers et al., 2004) were done for each patient before and one month after the last session. Skin biopsies were taken from some patients before and one month after the 4th session. The biopsies were assessed histopathologically and by immunohistochemical staining with TGF-β1.
The results of our study were as follows:
Compared to baseline, there was a significant reduction in the VSS one month after the last treatment session in all groups (P |
