Trolamine-Containing Topical Emulsion: Clinical Applications ... - Cutis

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Drug Therapy Topicscan result in cell necrosis. After application oftrolamine-containing topical emulsion to skin inthis study, collagen synthesis and IL-1a secretionwere enhanced, capillary alterations were decreased,and CD34 expression and epithelial cell proliferationwere restored. It was concluded that applicationof trolamine-containing topical emulsion madeit possible to modulate fibroblast metabolism andsubsequent collagen synthesis in a way that may beadvantageous in limiting postradiation fibrosis. 5How may trolamine-containing topical emulsionmodulate the wound-healing process?Trolamine-containing topical emulsion has beenshown to promote the wound-healing process.Wound healing is a complex biologic process involvinga complex interaction between many cell types,a variety of mediating secretions, and immunologicphenomena. 4,5 The process can be divided into thefollowing 3 phases: (1) hemostasis and inflammation;(2) cell migration and proliferation; and (3) skinremodeling. 6,7 Transition from one phase to anotheris not abrupt because there is overlap of the biologicprocesses that occur during wound healing.The hemostasis and inflammation phase includesthe time of skin injury through days 4 to 6. 3-7 Immediatelyafter a cutaneous wound occurs, plateletshelp to form a fibrin plug while growth factors andcytokines are being released and recruited into thearea of the injury. Within 24 hours, the inflammatorystage of healing coincides with the arrival ofneutrophils, which are involved with phagocytosisTrolamine-ContainingTopical Emulsion 2,3Indications and Dermatologic UsesFull-thickness wounds aSuperficial wounds aFirst- and second-degree burns,including sunburn aDermal ulcers aGraft site management aRadiation dermatitis aMinor abrasions aPostoperative woundsaIndication approved by US Food and Drug Administration.and wound debridement. Monocytes, transformedinto macrophages, arrive within 48 to 96 hours andplay an important role in wound healing.Cell migration and proliferation, the secondphase of wound healing, occurs from day 4 throughday 14. 6,7 After an injury to the skin, the nuclearfactor-kB pathway is activated through cytokinereceptors IL-1 and tumor necrosis factor-a, amongother chemokines, adhesion molecules, and cytokinesproduced by local tissue cells and migratingleukocytes. Continued migration of inflammatorycells and macrophages into the wound space ultimatelyleads to granulation tissue formation and reepithelializationas the infiltrating cells perform thefollowing: (1) consumption of bacteria via phagocytosis;(2) secretion of collagenases, which modulateswound debridement; (3) release of growth factors,which promotes angiogenesis and further healing;(4) stimulation of the deposition of new collagenformation by fibroblasts; and (5) recruitment offibroblasts and keratinocytes by macrophages. 6,7The final stage of wound healing is skin remodeling,which occurs from day 14 through 1 year. 6,7 Inthis final stage of wound healing, collagen depositedby fibroblasts is formed into an organized network.Within the wound, there is interaction betweencollagen degradation and new collagen production,as overall collagen formation increases to accommodatethe new thicker collagen that is oriented alongthe stress lines within the wound. 6,7 The durationof skin remodeling correlates with the depth of thewound, with the process continuing over weeks insuperficial wounds and for up to one year or morein deep wounds, though replacement tissue is notcreated with the degree of organization equivalentto that found in uninjured skin.Trolamine-containing topical emulsion appearsto promote and expedite healing by increasing thenumber of macrophages recruited to the injury site,thereby decreasing the time needed for healing. 2,4,5Macrophages have been referred to as the “orchestraleaders” of wound healing because their role is todirect the course of the wound-healing process. 7They serve to complete the debridement initiatedby neutrophils and participate directly in the inflammatorycascade with the release of cytokines andgrowth factors, which produces a cytokine profileconducive to wound healing. 4,5,7Is trolamine-containing topical emulsion helpfulin the treatment of radiation dermatitis?Trolamine-containing topical emulsion has a historyof use for radiation dermatitis, with information onits mechanistic role already reviewed. 2,3,8,9 The use210 CUTIS ®
Drug Therapy Topicsof ionizing radiation to treat primary tumors andpalliate metastatic disease sometimes may lead toacute or chronic skin injury. These insults are consideredadverse effects and are not fully amelioratedby the development of more modern equipment or ofmore sophisticated therapeutic regimens intended tominimize skin toxicity. Even with modernized equipmentand techniques, radiation-induced cutaneousinjury continues to be a challenging side effect, sometimesassociated with discomfort and pain, and it maylimit the duration of treatment or dose delivered. 9In addition to interfering with the normal maturation,reproduction, and repopulation of epidermaland hair matrix cells, radiotherapy targets bothfibroblasts and cutaneous vasculature. 9 A radiationinducedinjury is considered a complex wound inwhich adverse structural tissue changes occur immediatelyand are characterized by DNA damage andalteration of cellular proteins and lipids. Repeatedexposure to radiation contributes both to directtissue injury and impairment of healing via inhibitionof granulation tissue formation, fibrogenesis,and angiogenesis. 9For acute radiation dermatitis, trolaminecontainingtopical emulsion appears to reducediscomfort and provide moisturization; however,as with other topical formulations, it has notbeen proven to be radioprotective. 8-11 In one study,trolamine-containing topical emulsion was shownto prevent treatment delays or interruptions due toradiation-induced skin toxicity. The study demonstratedthat the overall treatment time of chemotherapyand radiotherapy was reduced because themodalities could be administered simultaneouslyrather than sequentially. 8What other uses of trolamine-containing topicalemulsion have been reported to be effective?Treatment of actinic keratosis (AK), especially withphysical modalities such as cryotherapy, causes disruptionof epithelium. The impact of trolaminecontainingtopical emulsion on the healing time oftreatment sites after cryotherapy for AK was evaluatedin an investigator-blinded pilot study (N540). 2,12Study participants with symmetric involvement ofAKs on the dorsal hands, dorsal forearms, forehead,and cheeks were treated with liquid nitrogen cryotherapyfollowed by twice-daily application of trolaminecontainingtopical emulsion to all treated targetregions on one side of the body and a designatedpetrolatum-based ointment (nonmedicated whiteTime to Complete Healing, d141210864209.0711.36Dorsal Hands(n13)10.2513.12Dorsal Forearms(n8)9.4012.60Forehead(n10)8.5510.88Cheeks(n9)Target RegionTrolamine-containing topical emulsionNonmedicated moisturizerFigure 1. Mean time to complete healing of actinic keratosis site following cryotherapy and application of trolaminecontainingtopical emulsion or petrolatum-based ointment (nonmedicated moisturizer) to the dorsal hands, dorsalforearms, forehead, and cheeks. Reprinted from Del Rosso, 12 with permission from HMP Communications.VOLUME 81, MARCH 2008 211
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