prevention and treatment of excessive dermal scarring

PREVENTION AND TREATMENT OFEXCESSIVE DERMAL SCARRING

Ingrid E. Roseborough; Mark A. Grevious, MD; and Raphael C. Lee, MD, ScDChicago, Illinois

Today, wound management to avoid excessive scar formation is increasingly important, espe-cially in populations with Fitzpatrick 3 or higher skin pigmentation. Medical science and industrialdevelopment are devoting more effort toward understanding and offering better therapy to con-trol scars. However, advances in scar management have been hampered by the confusing orambiguous terminology. There is no consensus on what amount of post-traumatic skin scar for-mation is "normal" and what should be considered "hypertrophic". In the World Health Organiza-tion's ICD-9, there is no diagnostic code for hypertrophic scar-only keloid is listed.' Yet, themedical and scientific literature distinguishes them as different conditions. Our experience sug-gests that the diagnosis of keloid disease is greatly over-rendered. For black patients, an elevat-ed scar seems, by default, diagnosed as keloid by most. This confusion results in inappropriatemanagement of scar formation, and occasionally contributes to decision making related to elec-tive or cosmetic surgery. Given that patients are expecting better outcomes from wound caretoday than in the past, this review article attempts to capture the essential biological factors relat-ed to wound scar production and discusses treatment options and indications used by theauthors. (J Nati MedAssoc. 2004;96:108-116.)

Key words: hypertrophic scar * keloid*management + anti-inflammatory

TERMINOLOGYIn the medical literature, hypertrophic scar is

generally described as an overgrowth of scar tissuethat remains within the boundaries of a wound(Figure 1).2 The wound boundary grows wider asmore scar tissue forms. Currently, no objectivediagnostic criteria have been formulated to indicatewhen a scar can be considered hypertrophic.Keloid scars are densely collageneous, nonencap-sulated, benign connective tissue neoplasms (Fig-

© 2004. From the Department of Surgery; Departments of Medi-cine, Organismal Biology, and Anatomy; Pritzker School of Medi-cine; The University of Chicago, Chicago, IL. Send correspon-dence and reprint requests for J Natl Med Assoc. 2004;96:108-116 to: Raphael C. Lee, MD, ScD, Section of Plastic Surgery,MC6035, Department of Surgery, University of Chicago, Chicago,IL 60637; phone: (773) 702-6302; fax: (773) 702-1634; e-mail:[email protected]

ure 2).3 The size and shape of a keloid scar have lit-tle correlation to the extent of the skin wound.Large, disfiguring tumors can often result fromminimal skin trauma. Keloid scars, unlike hyper-trophic scars, have a genetic etiology.A commonly taught but confusing concept is that

keloids can be distinguished from hypertrophic scarsby extension of the scar beyond the wound border.This concept, per se, implies that a scar starts out as ahypertrophic scar and later becomes a keloid when ithas exceeded some vaguely defined wound bound-ary. Such a classification scheme sets the stage forconfusion, particularly when one of the disorders isclassified as a heritable disease. Scientists investigat-ing pathologic scarring suggest that there are signifi-cant phenotypic differences between hypertrophicand keloid scars which may not be clinically obviousuntil they invade surrounding tissues.4 Therefore,while keloid scars are by definition hypertrophic,only a small percentage of large scars can be trulyclassified as keloid.

108 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 96, NO. 1, JANUARY 2004

WOUND-HEALING BACKGROUNDIn order to discuss hypertrophic and keloid scar

pathogenesis and treatment, a review of the perti-nent aspects of wound-healing is essential. Wound-healing is a very complex process that is tightlyregulated to achieve wound repair. The process canbe categorized into three distinct phases that havevery different objectives: inflammation, prolifera-tion, and maturation. Following the initial tissueinjury, inflammatory mediators, known ascytokines, are released from the injured tissue cellsand wound blood clot, and thereafter initiate theinflammatory phase.5 The amount of bloodreleased, the extent of devitalized tissue, and thebacterial content largely control the intensity of theinflammatory process. The length of time beforewound closure is a critical factor of wound inflam-mation, as the wound does not become sterile untilit regains an epithelium.6

If the wound-healing process is uncomplicated,the proliferation stage (also called "transitionalrepair stage") begins several days after the injury.7Platelet degranulation activates the coagulation cas-cade, and the resultant fibrin clot serves as a scaf-fold for the proliferation phase of wound-healing.5During the proliferative phase, the number and den-sity of fibroblasts in the extracellular matrixincrease, and the fibroblasts synthesize tissue com-ponents, such as proteoglycans, fibronectin, andcollagen. New vessels and epithelium are formed asrapidly as possible to maximize the tissue-replace-ment dynamics. All wound cells are maximallyactive and are sensitive to factors that regulate cellproliferation and protein biosynthesis. As the cellsproliferate, metalloproteases are simultaneouslyreleased into the extracellular fluid to activate amatrix breakdown process. The balance betweentissue degradation and biosynthesis permits remod-eling of the provisional tissue and also determinesthe net amount of scar tissue produced.

When enough provisional tissue is generated, aturn-off signal is received that initiates the finalstage of wound-healing, the maturation stage. Thisphase is characterized by cellular apoptosis and ashift in balance from scar remodeling toward scardegradation.89 The process is accompanied byextracellular matrix reorganization and reduction.Metalloproteases synthesized during the prolifera-tion stage continue to break down the extracellularmatrix at a rate largely determined by physical andbiochemical factors in the matrix.'0 The amount of

EXCESSIVE DERMAL SCARRING

extracellular matrix biosynthesis is controlled byneed for tissue strength and other operationalparameters. Mechanical stress is an important con-tributory parameter in net scar production.

The most important known determinates of scarproduction are the extent and duration of inflam-mation, the magnitude of mechanical tension act-ing on the scar, and the genetic phenotype of theindividual. Although other factors may be impor-tant and some are yet unknown-scar manage-ment fundamentally based on these three criticalparameters can be effective in limiting unnecessaryscar formation in most cases.

PATHOLOGICAL SCAR

Hypertrophic ScarsSeveral epigenetic causes for hypertrophic scar-

ring have been identified. Basically, factors thatincrease or prolong wound inflammation or woundtension predispose to hypertrophic scar formation.Such factors include wound infection, prolongedhealing by secondary intention, or immunologicallyforeign material present in the wound. Hypertrophicscars begin as the result of an injury to the deep der-mis. They are especially pronounced in wounds thathave a prolongation of the inflammatory and prolif-erative phases of wound-healing.7 The incidence ofhypertrophic scars following surgery is about40-70%, whereas it is higher (up to 91%) followingburn injury.6 Several reports conclude that there is asubstantially increased risk for hypertrophic scarringin burn wounds that take longer than 21 days to heal.6

Hypertrophic scarring also occurs as the result ofdynamic mechanical skin tension acting on the heal-ing wound." As a result of mechanical tension, scarslocated on certain areas of the body (e.g. sternum,deltoid, and upper back) are frequently hypertrophic,the typical appearance of which can be seen in Fig-ure 1. This anatomic dependency seems to correlatewith patterns of skin tension.'2 The natural history ofhypertrophic scars is that they regress with time afterinjury, leaving behind, however, an unsightly widegap ofthinned dermis between wound edges.A familial pattern in hypertrophic scarring is

not described, however populations with higherskin melanin content are known to have a higherincidence of hypertrophic scars. These populationsinclude people of African, Asian, and Hispanicdecent.'3 Hormonal influences are also known to bea factor, with hypertrophic scarring often initiated

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 96, NO. 1, JANUARY 2004 109


at the start ofpuberty or during pregnancy. Scar tis-sue cells are sensitive to the influences of the samegrowth factors that drive normal tissue growth anddevelopment. Schierle et al. report an increase intestosterone receptors in hypertrophic scars,'4which may contribute to the formation of thesescars during the adolescence.

Keloid ScarAlthough the diagnosis of keloid scar is often

inappropriately applied to hypertrophic scars, thetwo lesions can be differentiated at several levels.Unlike hypertrophic scars, the natural history ofkeloid scars is that they do not regress with timefollowing injury. Keloid tumors grow to reach acertain size and may remain that size indefinitely.Patients with keloid scars also have an associatedstrong family history of keloids; both autosomaldominant and autosomal recessive modes of trans-mission have been reported. Castagnoli et al.reported an association between keloid occurrenceand HLA-BWl6, BW 21, and BW35.'5 The bulk ofavailable evidence suggests that keloid scarring is agenetic anomaly.

The genetic basis for this disease is evidenced bythe aberrant behavior of fibroblasts cells explantedfrom scar tissue. Several investigators have demon-strated that the keloid fibroblasts exhibit abnormalregulation of apoptosis.8"l7 It has also been reportedthat keloid fibroblasts in vitro produce abnormallyhigh levels of collagen, fibronectin, and proteogly-cans, and display atypical responses to regulationby metabolic modulators, such as growth factorsand hydrocortisone.9 McCauley et al. also reportedincreased serum levels of inflammatory cytokinesin keloid patients.'6 Histologically, collagen bundlesare thicker and more abundant in keloid scars andform acellular node-like structures in the deep der-mis.'8 Several recent reports indicate that there is apersistence of inflammatory cells in keloid scarsbeyond that found in normal scars.'9

In addition to the possible genetic factors,keloid fibroblasts are also quite sensitive to epige-netic factors that modulate gene expression.20Strong relations exist between keloid formationand age and sex hormones, with younger peoplebeing more vulnerable.9 Keloids have been noted toenlarge during pregnancy and regress at the end ofpregnancy or following menopause.2'

Clinical ManagementThe first consideration in discussion of scar

treatment is prevention. In the surgical setting,events occurring during the management of theopen wound are important. Careful and meticuloushandling of tissues, evacuation of blood from thewound, accurate wound edge alignment during clo-sure, as well as precise suture placement, willreduce inflammation and, consequently, scarring.The choice of suture material is important becausesome sutures trigger more immune reaction thanothers. Monofilament absorbable synthetic bio-polymers produce the least reaction.22 Minimizingtension acting on the wound by aligning the inci-sion parallel with the natural skin lines (when pos-sible) or use of local flaps will also help to reducethe incidence ofpostsurgical hypertrophic scars.

Over the past two decades, a few fundamentallynew therapeutic approaches to scar managementhave been reported. These new techniques haveadded substantially to existing therapeutic approach-es and continue to enhance them. In the followingparagraphs, we will attempt to briefly summarizesome of these new concepts.

Inhibition of Scar GrowthAnti-Inflammatory Agents: The inhibition of

extracellular matrix and inflammatory protein pro-duction by corticosteroids is one of the most well-established approaches to scar management.20 Attherapeutic concentrations, the multiple effects ofcorticosteroids on scars include inhibition of colla-gen and other extracellular matrix protein synthe-sis, decreased cytokine production, and inhibitionof neovascularization. As corticosteroids decreasenew protein synthesis, the balance between matrixsynthesis and degradation is disrupted, allowingpreviously synthesized collagenase and other met-alloproteases to decrease the amount of scar tissue.

Long-acting synthetic glucocorticoids such astriamcinolone-are most commonly used for treat-ment of hypertrophic and keloid scars. Syntheticglucocorticoids, applied topically, are weakly solu-ble in water but well absorbed in the epidermis.With time, they slowly diffuse into the scar. Alter-natively, solutions of triamcinolone can be injectedin 10-40 mg/nL concentrations.2,23 Both methodsof delivery are effective in the majority of nonin-fected scars that exhibit symptoms such as pain andpruritis.24 However, the morbidity ofrepeated injec-tions on a monthly basis, fat atrophy, and the depig-


mentation of skin are major drawbacks to thesetreatments. Steroids are not often useful for treat-ment of older scars that are less metabolicallyactive and also are not routinely used as a scar pre-ventative immediately after wound closure becauseof concern about wound infection or dehiscence.

The inflammatory response can be regulated atseveral different physiological levels before, dur-ing, and after inflammatory gene expression.Before gene expression are transcription factors,such as NF-kB (Nuclear Factor-kB), that are acti-vated by cell injury. After gene expression areinducible enzymes, such as cyclooxygenases,which produce cytokines that orchestrate multicel-lular responses. Three common ways to controlinflammation include inhibition of the NF-kBpathways that signal inflammatory gene inductionthat regulates inflammation, inhibition of prosta-glandin production via cyclooxygenase (COX) reg-ulation, and inhibition of histamine synthesis. Themost widely used anti-inflammatory agents belongto the broad category of nonsteroidal anti-inflam-matory drugs (NSAIDs). They inhibit either theNF-kB pathway or COX activity, or both. It is note-worthy that corticosteroids exert a broad anti-inflammatory effect through inhibition of multipleinflammation transcription factors NF-kB, AP-1(activator protein- 1), and NF-AT (nuclear factor ofactivated T lymphocytes).25

NF-kB is a rapid-response transcription factorthat is involved in the cellular stress response.26 NF-kB is involved in the up-regulation of cell membranereceptors to inflammatory peptides. It is alsoinvolved in the production of cytokines, chemokines,and growth factors. NF-kB activation can be inhibit-ed by several different agents. These agents includecyclosporine, tacrolimus, antioxidants, and salicy-lates (including aspirin). Salicylic acid indirectlyinhibits NF-kB expression by blocking the enzymeswhich lead to dissociation of IkB (the inactivator ofNF-kB) from the NF-kB complex in the cytoplasm.This dissociation subsequently decreases the amountof inflammation.26 Aspirin not only inhibits the NF-kB pathway but also irreversibly inactivates bothCOX isoforms. Salicylates (2-5%) are commonlyused to control certain causes of dermatitis and areroutinely used in acne treatment products. Our expe-rience increasingly suggests that topical applicationof salicylates to painful and itching scars is a practi-cal approach to reducing inflammation. Topicalaspirin should be used under a physician's guidance,


Figure 1 1(a) Appearance of a hypertrophic surgicalscar located on the forearm of a womanwith Fitzpatrick 3 skin type at one-year post-operatively.

(b) High-resolution (1 ] MHz) ultrasound imagedemonstrates penetration of scar beneathskin. Ultrasound imaging is useful formeasuring scar dimensions.

because some patients-particularly asthmatics-may develop hypersensitivity. Vitamin D3 (Dovonex8),which is also used to treat dermatitis, is anotherinhibitor of NF-kB. The action of Vitamin D3 is dueto its affinity for the DNA promoter regions thattransduce the NF-kB dissociation signals. To date,one prospective uncontrolled study of topical sali-cylic acid has been reported by the senior author.Nonetheless, the number of physicians prescribingtopical anti-inflammatory agents is increasing. Ourpersonal clinical experience has been very encourag-ing of the effectiveness of topical 2% salicylic acid(AvosilO, Avocet Polymer Technologies, Chicago) inmannaging prritic;, growving scars.



Figure 2(a) Three-year-old, inflamed, and enlargingkeloid scar on lower back secondary to avaricella-zoster lesion.

(b) Characteristic spreading of keloidscarring can be appreciated in this patient.Scar began with folliculitis in center of chestand spread to the lateral chest over 14 years.Scar-spreading mimics wave propagation,leaving flat disfigured skin behind thethickened and tender scar wavefront.

Prostaglandins are a group of potent hormone-likesubstances that mediate a wide range of physiologicalfunctions,, such as control of blood pressure and con-traction of smooth muscle.27 The synthesis of prosta-glandins is also central to the inflammatory response.The most common strategy for prostaglandin synthe-sis blockade is pharmacological inhibition of cell-membrane-bound COX.2ICOX_ 1 is expressed consti-tutively throughout the body, especially in thestomach and kidneys. COX-2, however, is expressedconstitutively only in the brain and kidneys.8 COX2syntheis is highly inducible by activation of NF-kB,which occurs at sites of injury or infection and playsan important role in fibrosis. The adverse side effectsofCOX inhibition are minimized by the use of specif-ic COX-2 inhibitors, making them agents of choicefor prolonged usage. The therapeutic value of theseagents in rheumatologic disease is well established,but their potential value in the management of hyper-trophic scarring has been a more recent consideration.

Ou reore exeiec suget tha COX

inhibitors reduce symptoms of pruritus and mayinduce scar maturation and involution.29 Some popu-lar topical consumer scar treatment products derivefrom onion extract (i.e., Mederma%, Merz Pharma-ceuticals) which has anti-inflammatory properties.

Antihistamines are commonly used to controlsymptoms of scar pruritus, but they also seem toexert an antifibrotic effect on scars.30 Antihista-mines, particularly the HI blockers, inhibit theinflammatory response, resulting in reduced scarformation and increased comfort. The inflamedscar is scratched less, which will most likely reducethe scar growth rate. Antihistamines are also wellknown to inhibit collagen synthesis.3 Diphenhy-dramine (Benadryl9, Pfizer) and hydroxazine(AtaraxR, Pfizer) are the most commonly used anti-histamines for scar management. In the past fewyears, we have preferred the use of long-acting,nondrowsy formulations, such as loratadine (Clar-itinK, Schering) or fexofenadine (AllegraR, Aven-tis), which have the advantages of sustained actionand fewer CNS side effects.

Inhibitors of Gene Transcription: The anti-metabolites mitomycin-c and 5-fluorouracil inhibitproliferation of cells by blocking DNA synthesis andtranscription through competitive inhibition ofthymidylate synthesis.32 A single application in thefirst few days after wound closure seems to be effec-tive. Antimetabolite-induced apoptosis has also beendemonstrated in Tenon's capsule fibroblasts.33 Thus,these agents are likely to be helpful in scar control.

Growth Factor Inhibition: The TransformingGrowth Factor Beta (TGF-b) family of proteins iscentrally involved in regulating wound-healing.9'8TGF-b synthesis and release is activated by injury,and along with Platelet Derived Growth Factor(PDGF), it has a central and critical role in induc-tion of wound-healing. Binding of TGF-b to itsreceptor on fibroblasts causes fibroblast prolifera-tion, extracellular matrix structural protein synthe-sis, and TGF-b synthesis. Mannose-6-phosphateand several other disaccharides sterically limitTGF-b binding to its receptor and limit scar forma-tion in experimental wound-healing models.34

Accelerators of Scar Degradation RateWhile anti-inflammatory agents and growth fac-

tor inhibitors can limit scar production, strategies toaccelerate scar tissue degradation are also very use-ful. This approach may be the best for managementof older hypertrophic scars and older keloids. The


rate of tissue breakdown can be increased by bothpharmacologic and physicochemical means.

Occlusive Dressings: After elastic pressurewrap dressings of healing burn scars were observedby Larson et al.35 to be effective in the reduction ofscar hypertrophy, 20-204 mm Hg pressure gar-ments became the mainstay of scar prevention. Themechanism of action of pressure dressings isunknown, because they remain effective even whenthey lose elasticity and pressure after several weeksof daily use. Measurements show a decrease inwound metabolism with an increase in collagenaseactivity.36 Drawbacks to their use are primarily relat-ed to thermal insulation and movement restriction.

Both hydrogel and silicone gel sheeting havealso been used to control scar formation (Figure3).37-40 Like elastic garments, the mechanism ofaction has not been clearly defined. Several putativemechanisms have been reported in the literature,including: induction of scar hypoxia, increasedhydration of the epidermis covering the scar, andincreased scar temperature.4' 42 The effect does notdepend on the composition of the gel sheeting used.It is clear, however, that release of silicone into thescar is not the mode of action. Several reports haveshown that hydrogel sheeting is equally effective assilicone and has fewer adverse side-effects.4344Hydrogel sheeting has recently been approved bythe FDA as substantially equivalent to silicone fortreatment of hypertrophic scars. Hydrogels have theadded advantage of use as a hydration vehicle, aswell as a higher heat capacity for maintaining a con-tinuous elevation of scar temperature.39

Inducers of Scar DegradationCalcium Antagonists: Many organic calcium

channel blockers (i.e., verapamil) induce collage-nase production and scar tissue degradation. Theyinduce changes in fibroblast gene expression, result-ing in decreased collagen synthesis and increasedcollagenase production. These effects appear to bemediated by interruption of the basic cellular G-pro-tein signal transduction pathway that is critical toregulation of fibroblast behavior.45 This pathway canbe interrupted at multiple points by a wide range ofcommonly used drugs.46 Verapamil, injected into thelesion, has been shown to induce scar degradation inthe skin, fascia, and periocular tissue.47 Our personalexperience is that use of4-5% verapamil in a creambase applied topically on the scar avoids reboundscarring from the trauma of intralesional injections.


Figure 3Response to hydrogel application on ahypertrophic burn scar over 12 weeks ofusage. At the time of hydrogel (Avogel)application the patient was eight monthsafter grafting.

(a) Hypertrophic, inflamed skin graft scarsbefore hydrogel therapy.

(b) Placement of hydrogel sheet. The sheetwas held in place with elastic netting 10 14hours per day.

(c) Appearance of the scar at 12 weeks afterhydrogel sheet therapy, showingconsiderable improvement in scar size.



If injection is necessary, then alternating verapamilwith cortisone injections at monthly intervals seemsto generate an effective yet less robust response.

Additional agents which may induce scar degra-dation include other calcium channel blockers,calmodulin inhibitors (i.e., trifluoperazine), andspecific protein kinase C (PKC) inhibitors (i.e.,tamoxifen). These agents hold promise as treat-ment for older, noninflamed scars that are nolonger actively remodeling.

Apoptosis Inducers: The density of keloid scarfibroblasts does not decrease as the scar ages.Instead, keloids continue to produce thick collagenbundles in a nodular array. They also produce high

Figure 4. Overview of Scar Management Protocol at University of Chicago Scar Clinic

Scar Type: Immature Mature Ear Keloid WidespreadHypertrophic Hypertrophic Fibroma Keloid Disease(06 months) (>6 months)

Step 1: Scar evaluation and classification

Document scar symptoms Scar Symptom Survey

Measurement Baseline ultrasound of reference point; photographs

Step 11: Control inflammation _

Anti-inflammatory drug Topical 2% salicylic acid COX-2 inhibitor COX-2 inhibitor (p.o.);(p.o.). If pruritus If pruritus persists,persists, then then add topical 2%

add salicylic acid and/ornonsedating nonsedatingantihistamines antihistamines

Step III: Accelerate scar maturation

Occlusive barrier Hydrogel sheeting Hydrogel sheeting as appropriate

Step IV: Stimulate scar degradation

Calcium antagonist Usually unnecessary Topical 7% verapamil(cream base) q 24 hs

Step_V: Evaluate_progress _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Evaluate scar and symptoms q four-to-six weeks; follow progress with_______________________survey, ultrasound, photos; adjust treatment as necessary

Step VI: Surgery and other treatments

Surgery Surgical excision, if necessary, to accelerate May also considertherapeutic response surgery requires that scar alternative therapies

symptoms should be under good control (radiotherapy,I_cryotherapy)

Step VII: Postsurgical follow-up and additional therapyPrevention of recurrence Continue anti-inflammatory and hydrogel treatment strategy after

therapeutic response for four-to-six months. Follow up q six- tol 2 weeks

levels of the proteolytic enzyme Caspase-3.8 Sayahet al. proposed that the down-regulation of apopto-sis-related genes in fibroblasts could alter fibro-blast phenotype, leading to increased scar tissueproduction."7 A pharmacologic agent that couldblock the expression and ultimate production ofCaspase-3 could be very valuable in the treatmentof hypertrophic and keloid scars.

Low-dose ionizing radiation is a well establishedmethod of therapy for hypertrophic scarring andkeloids.4'849 The primary mechanism of radiation-induced scar control seems to be apoptosis of prolif-erating cells in the scar tissue.50 Low-dose ionizingradiation is most often reserved as the method of last


resort for the treatment of intractable keloid scars.This therapy utilizes 15-20 Gy of ortho-voltage radi-ation divided into five to six treatments. Althoughradiation therapy alone is not adequate, if used inconjunction with surgical intervention, reduction inrecurrence may reach 25%, compared with a recur-rence rate ofup to 80% with surgery alone.

Surgical Revision: The most common indica-tions for surgical removal of scars are the following:large scars that are unlikely to be completely man-aged by medical therapy in a reasonable timeframe,scars that harbor painful furuncles, and scar contrac-tures that hamper musculoskeletal function.5'Although the outcome of surgery may be desirablein the short postoperative term, surgical revision ofhypertrophic or keloid scars is followed by a highrecurrence rate.23 Adjunctive measures to reduceinflammation, skin tension, and other factors areessential to reduce recurrence. Our observationsindicate that most patients with scars large enoughto require surgical excision require both systemicCOX-2 inhibitors and long-acting HI antihistaminesto induce scar degradation and reduce recurrence.The protocol for patients that require elective surgi-cal excision is to identify effective scar control med-ications beforehand, then to restart the medicationsimmediately following surgery. Gentle surgical tech-nique is also critically important, because inflamedscar tissue produces a tremendous scar response totrauma. The use of lasers and other burning tech-niques for scar removal is very controversial.

SUMMARYDespite recent scientific progress, scar-related

disfigurement and disability remain major ongoingmedical problems. Stripped of the conflicting andconfusing terminology, hypertrophic and keloidscarring can be essentially reduced to inflamma-tion-mediated dermal fibrosis. This suggests thatthere is much insight into effective managementthat can be gleaned from the medical literature per-taining to dermatological and rheumatologic condi-tions which also have a large inflammatory geneexpression component.

With these concepts in mind, the authors havedesigned several scar management protocols whichare under clinical evaluation. Under these proto-cols, summarized in Figure 4, patients with scarsthat are actively enlarging or prurtic are treatedwith either topical salicylates and oral COX-2medications to control the scar inflammation. The


oral COX-2 inhibitors are reserved for patientswith scars thicker than 2 centimeters or whosewidespread scarring is such as that seen in keloiddisease. The use of topical verapamil (5-10%) hasshown great promise in inducing degradation ofolder inactive scars and reduced the need for surgi-cal intervention. Transepidermal delivery of thesetopical agents has been enhanced by the applica-tion of an occlusive barrier, such as hydrogel sheet-ing (Avogel , Avocet Polymer Technologies). Ourstratified approach to scar management has result-ed in the ability to effectively treat scar conditionsthat have been refractory to conventional therapy.We hope that this experience will lead to more-effective therapeutic options for these patients.

In this article, we have attempted to briefly sum-marize and place into a conceptual framework thevarious existing and emerging therapies for hyper-trophic scar disorders. We hope that this reviewwill encourage development and consistent use ofless ambiguous terminology and more effectivetherapeutic strategies in the future.

ACKNOWLEDGEMENTThe authors wish to acknowledge the excellent

support and assistance from Beverly Meiner, RN,and the staff of the University of Chicago Physi-cian Group clinics. Dr. Lee receives financial sup-port from Avocet Polymer Technologies, Inc.

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prevention and treatment of excessive dermal scarring