HM Medical Clinic

Allwecare.nl

International Clinical Recommendations onScar Management Thomas A. Mustoe, M.D., Rodney D. Cooter, M.D., Michael H. Gold, M.D., F. D. Richard Hobbs,
F.R.C.G.P., Albert-Adrien Ramelet, M.D., Peter G. Shakespeare, M.D., Maurizio Stella, M.D.,
Luc Téot, M.D., Fiona M. Wood, M.D., and Ulrich E. Ziegler, M.D., for the International Advisory Panel
on Scar Management
Chicago, Ill., Nashville, Tenn., Adelaide, South Australia, and Perth, Western Australia, Australia, Birmingham and Salisbury, United Kingdom, Lau-sanne, Switzerland, Turin, Italy, Montpellier, France, and Wurzburg, Germany Many techniques for management of hypertrophic therapies showed early promise in small-scale scars and keloids have been proven through extensive use, trials, but these results have not been repeated but few have been supported by prospective studies withadequate control groups. Several new therapies showed in larger trials with long-term follow-up. Judg- good results in small-scale trials, but these have not been ment of efficacy has further been limited by repeated in larger trials with long-term follow-up. This the difficulty in quantifying change in scar ap- article reports a qualitative overview of the available clin- pearance, and by the natural tendency for scars ical literature by an international panel of experts using to improve over time. Thus, cutaneous scar standard methods of appraisal. The article provides evi-dence-based recommendations on prevention and treat- management has relied heavily on the experi- ment of abnormal scarring and, where studies are insuf- ence of practitioners rather than on the results ficient, consensus on best practice. The recommendations of large-scale randomized, controlled trials and focus on the management of hypertrophic scars and ke- loids, and are internationally applicable in a range of This article reports a qualitative overview of clinical situations. These recommendations support amove to a more evidence-based approach in scar man- over 300 published references using standard agement. This approach highlights a primary role for methods of appraisal and, where studies are silicone gel sheeting and intralesional corticosteroids in insufficient, expert consensus on best practices the management of a wide variety of abnormal scars. The from an international group with extensive ex- authors concluded that these are the only treatments for perience and interest in the treatment of scar- which sufficient evidence exists to make evidence-basedrecommendations. A number of other therapies that are ring. Although focusing primarily on the man- in common use have achieved acceptance by the authors agement of hypertrophic scars and keloids, the as standard practice. However, it is highly desirable that recommendations are internationally applica- many standard practices and new emerging therapies un- ble in a range of clinical situations.
dergo large-scale studies with long-term follow-up beforebeing recommended conclusively as alternative therapiesfor scar management.
(Plast. Reconstr. Surg. 110: 560, An initial systematic MEDLINE and EMBASE search (1996 through 2001) took place using the The management of hypertrophic scars and mesh terms "scar treatments," "surgery," "silicone keloids is characterized by a wide variety of gel sheeting," "intralesional corticosteroids," "ra- techniques. Many have been proven through diotherapy," "cryotherapy," "pressure therapy," extensive use over the past two decades, but and "laser therapy." In addition, a search on scar few have been supported by prospective studies evaluation methods took place and all review with adequate control groups, and in some articles on the management of hypertrophic cases even safety data are lacking. Many new scars and keloids were accessed in these data- From Northwestern University School of Medicine, Royal Adelaide Hospital and The Queen Elizabeth Hospital, Gold Skin Care Centre, University of Birmingham, Laing Burn Research Laboratories, Salisbury District Hospital, Burn Centre, CTO, Burns Unit University HospitalLapeyronie, Chirurgische Universitatsklinik, Burns Unit, and Royal Perth Hospital and Princess Margaret Children's Hospitals. Received forpublication March 20, 2001; revised December 6, 2001.

Vol. 110, No. 2 / SCAR MANAGEMENT RECOMMENDATIONS bases. A secondary hand search of citations in the forms have been developed to help use this accessed articles was also conducted.
The authors provided additional review arti- cles, clinical studies, and recent unpublished PREVENTION OR TREATMENT data that revealed further useful cited refer- It is much more efficient to prevent hyper- ences in English and other languages. Those trophic scars than to treat them. Prevention references providing original data on the effi- implies using a therapy with the aim of reduc- cacy of scar management techniques were ing the risk of a problem scar evolving. The graded according to "hierarchy of evidence" transition to a treatment regimen takes place methods to reflect the reliability of data.1–3 The when a true hypertrophic scar or keloid, and drafts of the manuscript were reviewed by the not an immature scar, is diagnosed. Conceptu- chairman and panel during a series of telecon- ally and practically, treatment and prevention ferences and by e-mail.
regimens can be similar, and the following sec-tion presents the clinical data for both. Early diagnosis of a problem scar can considerablyimpact the outcome. The consensus of the au- Scar classification schemes need to be as clin- thors is that the most successful treatment of a ically relevant as possible, and the authors have hypertrophic scar or keloid is achieved when extended standard terminology for this article the scar is immature but the overlying epithe- lium is intact, although this is not as yet con-firmed in current literature.
A number of grading systems have been sug- gested over recent years.4–7 The most widely A comprehensive review of the clinical liter- used system is the Vancouver Scar Scale,8–10 ature published over the past 30 years on scar which provides an objective measurement of treatments was undertaken and the evidence burn scars and assists prognosis and manage- was graded for quality. An evaluation is pre- ment. Generic measurement tools and record sented for each modality. The efficacy of twoscar management techniques, silicone gelsheeting and injected corticosteroids, has been demonstrated in randomized, controlled trials.
Scar Classification Comparison between treatment modalities and between clinical studies is difficult, as de- Mature scar—A light-colored, flat scar.
fining an adequate response to therapy re- Immature scar—A red, sometimes itchy or painful, and slightly elevated scar in the process of remodeling. Many mains a relatively neglected area. A mild partial of these will mature normally over time and become flat, response, which may still leave a cosmetically and assume a pigmentation that is similar to the unacceptable scar, is accepted as a therapeutic surrounding skin, although they can be paler or slightlydarker.
success in most studies. Scars never disappear Linear hypertrophic (e.g., surgical/traumatic) scar—A red, and in many cases only partial response is raised, sometimes itchy scar confined to the border of the original surgical incision. This usually occurs within weeksafter surgery. These scars may increase in size rapidly for The variability in efficacy and recurrence 3–6 months and then, after a static phase, begin to rates between studies is striking and makes sin- regress. They generally mature to have an elevated, slightly gle uncontrolled studies impossible to evalu- rope-like appearance with increased width, which isvariable. The full maturation process may take up to 2 ate. There are some good reasons for this vari- ability. First, differentiating hypertrophic scars Widespread hypertrophic (e.g., burn) scar—A widespread from keloids can be problematic. Second, red, raised, sometimes itchy scar that remains within theborders of the burn injury.
there is a tremendous range between the scar Minor keloid—A focally raised, itchy scar extending over that becomes hypertrophic in the first few normal tissue. This may develop up to 1 year after injury months and then completely resolves with little and does not regress on its own. Simple surgical excisionis often followed by recurrence. There may be a genetic or no treatment and the more severe hypertro- abnormality involved in keloid scarring. Typical sites phic scar that becomes permanently disfigur- include earlobes.
ing. Length of follow-up, heterogeneity of the Major keloid—A large, raised (⬎0.5 cm) scar, possibly painful or pruritic and extending over normal tissue. This scars, and the lack of controls can either over- often results from minor trauma and can continue to estimate or understate the benefit of treat- spread over years.
ment, but more often the former. Third, ke-

PLASTIC AND RECONSTRUCTIVE SURGERY, August 2002 loids often do not recur for 6 months to as long mg/ml), and up to 63 percent of patients ex- as 2 years, and so length of follow-up is critical.
perience side effects that include skin atrophy, Very few studies on keloids have adequate fol- depigmentation, and telangiectasias.29 Topical low-up. These limitations must be kept in mind steroid creams have been used with varying in evaluating any of the therapies below.
success,30 but absorption through an intact ep-ithelium into the deep dermis is limited. A prospective, randomized study shows that top- Surgical excision of hypertrophic scars or ical steroids do not reduce scar formation in keloids is a common management option postburn deformities.31 when used in combination with steroidsand/or silicone gel sheeting. However, exci- Silicone Gel Sheeting sion alone of keloids results in a high rate of Silicone gel sheeting has been a widely used recurrence (45 to 100 percent).11–14 clinical management option for hypertrophic Combining surgery with steroid injections scars and keloids since the early 1980s.32–37 De- reduces the recurrence rate of keloids to less spite initial skepticism, there is now good evi- than 50 percent, with the combination of sur- dence of its efficacy and silicone gel sheeting gery and perioperative radiation therapy re- has now become standard care for plastic sur- ducing recurrence to 10 percent.11,15 However, geons. Results from at least eight randomized, this combination approach is usually reserved controlled trials and a meta-study of 27 trials38 for abnormal scars resistant to other demonstrate that silicone gel sheeting is a safe and effective management option for hypertro- Hypertrophic scarring resulting from exces- phic scars and keloids.39–48 Totally occlusive sive tension or wound complications, such as dressings (e.g., polyethylene films) and semi- infection or delay in healing, can be treated occlusive dressings, such as polyurethane films, effectively with surgical excision combined have not shown evidence of efficacy, and evi- with surgical taping and silicone gel sheeting.
dence of the effectiveness of other materials Scars that are subject to tension require sub- such as glycerin and other non–silicone-based stantial physical support. The authors agreed dressing is mixed.49–51 that the most effective way of splinting scars is Silicone gel sheeting may be especially useful by surgical closure with intradermal sutures for in children and others who cannot tolerate the at least 6 weeks and, when tension is substan- pain of other management procedures. Sili- tial, for up to 6 months. Surgical techniques, cone products vary considerably in composi- such as W-plasty and Z-plasty, improve the ap- tion, durability, and adhesion. To date, most pearance and mobility of contracted burn scars conclusive trials have been undertaken on but are not appropriate for immature hyper- pure adherent silicone gel sheeting. It is not known whether these results are transferable toother fabric/polyurethane dressings with sili- cone adhesive or to nonadherent silicone Despite relatively few randomized, prospec- products.52 Some formulations of silicone oil tive studies, there is a broad consensus that have been shown to be effective on minor hy- injected triamcinolone is efficacious and is pertrophic scars, although these studies have first-line therapy for the treatment of keloids limitations in their design.33,53 and second-line therapy for the treatment ofhypertrophic scars if other easier treatments Pressure Therapy have not been efficacious.15,17–23 Despite their Pressure therapy has been used in the man- use in scar management since the mid-1960s, agement of hypertrophic scars and keloids their principal mechanism of action remains since the 1970s.54 It has been standard therapy unclear.24,25 Response rates vary from 50 to 100 for hypertrophic burn scars and is still first-line percent, with a recurrence rate of 9 to 50 per- therapy in many centers.55–61 cent.18 Results are improved when corticoste- It is generally recommended that pressure roids are combined with other therapies such be maintained between 24 and 30 mmHg for 6 as surgery11,13,26 and cryotherapy.27,28 to 12 months for this therapy to be effective; Intralesional corticosteroid injection is asso- however, this advice is largely empiric.18,62 ciated with significant injection pain, even with There are mixed reports on long-term compli- standard doses of insoluble triamcinolone (40 ance, but it remains a significant issue, as ef-

Vol. 110, No. 2 / SCAR MANAGEMENT RECOMMENDATIONS fectiveness seems to be related directly to the high-energy short-pulsed carbon dioxide lasers duration of pressure.63–65 and scanned continuous-wave carbon dioxide The evidence supporting the speed of scar lasers were effective in postsurgical hypertro- maturation and enhancement of cosmetic out- phic/keloidal, traumatic, acne, and varicella come is variable. For example, in a prospective scars.75,76 Scanning carbon dioxide lasers have randomized study in 122 burn patients, pres- been used to debride burn wounds, but with- sure garments did not increase the speed of out clinically improved scar outcome.77 How- wound maturation or decrease the duration of ever, these early reports have not been widely substantiated, and currently carbon dioxide la-ser is not widely accepted for the treatment of keloids because of the high late recurrence Radiotherapy has been used as mono- therapy, and in combination with surgery, for Argon lasers were first used in the 1970s for hypertrophic scars and keloids. However, the management of keloids, but studies failed monotherapy remains controversial15,67 be- to show long-term improvements.73,78 They pro- cause of anecdotal reports of carcinogenesis duce more nonspecific thermal damage than following the procedure. Response to radio- carbon dioxide lasers and are associated with therapy alone is 10 to 94 percent, with a keloid higher levels of keloid recurrence.76 recurrence rate of 50 to 100 percent.11,13 Such More recent wavelength-specific lasers (yttri- high recurrence rates are understandable, um-aluminum-garnet and pulsed-dye lasers) given the resistance of these cases to other have been used to selectively ablate blood ves- management options. Best results have been sels. Neodymium:yttrium-aluminum-garnet la- achieved with 1500 to 2000 rads over five to six sers have response rates between 36 and 47 sessions in the early postoperative period.68,69 percent.79 In a recent study of 17 patients with There have been mixed results from radiother- keloids, nearly 60 percent of keloids were flat- apy after surgical excision of keloids, with a tened following one session of neodymium: significant objective response reported in 25 to yttrium-aluminum-garnet laser treatment.
100 percent of patients.18,70,71 These patients remained free of keloid scar- Radiotherapy is difficult to evaluate, as most ring at 18-month to 5-year follow-up.80 The re- studies are retrospective, do not define the maining seven patients required further laser term "recurrence," and use a variety of radia- treatment and intralesional corticosteroids to tion techniques with varying follow-up (6 to 24 flatten the keloids completely. Recurrence of months). In addition, there are no random- keloids occurred in three patients, all of whom ized, prospective studies with long-term follow- responded to further laser treatment. A recent up. Most investigators agree that radiotherapy study in 36 patients has shown that the pulsed should be reserved for adults and keloids resis- erbium:yttrium-aluminum-garnet laser is an ef- tant to other management modalities. Never- fective and safe treatment option for hypertro- theless, radiotherapy with informed consent phic and depressed scars.81 Further large com- remains a valuable therapeutic option and is parative studies with longer follow-up are now the most efficacious treatment available in se- vere cases of keloids, provided there is appro- Flashlamp-pumped pulsed-dye lasers have priate shielding of nonaffected tissues.
shown promise in elimination of erythema andflattening atrophic and hypertrophic scars.82–85 Laser Therapy Intense-pulsed-light-source devices are usually Laser therapy has been used for nonspecific considered in the same category as pulsed-dye destruction of tissue to produce less scarring, lasers. Improvements in appearance of hyper- but this has been largely discredited following trophic scars and keloids have been noted in mixed results in larger long-term trials with 57 to 83 percent of cases,82 with further im- carbon dioxide and argon lasers. Carbon diox- provements seen in combination with intrale- ide lasers showed early promise in the excision sional corticosteroids.86 A pilot study has sug- of keloids72 but failed to suppress keloid gested that laser treatment in combination growth and recurrence in later studies.73,74 with intralesional corticosteroids is effective in Two newer types of carbon dioxide laser are healing previously resistant keloids.87 A recent in use. Small noncontrolled studies, limited by study in 106 patients (171 anatomic sites) has lack of long-term follow-up, suggested that shown fast resolution of scar stiffness and ery-

PLASTIC AND RECONSTRUCTIVE SURGERY, August 2002 thema and improvement in quality of scarring ments that have an absence of randomized when preventive treatment with flashlamp- studies or some negative studies suggesting pumped pulsed-dye lasers is started within 2 lack of efficacy. These include topical vitamin weeks after surgery.88 However, a recent single- E,31,97,98 onion extract cream,99 allantoin- blind, randomized, controlled study in 20 pa- sulfomucopolysaccharide gel,100,101 glycosami- tients with hypertrophic scars showed no im- noglycan gel,102 and creams containing extracts provements in hypertrophic scars following from plants such as Bulbine frutescens and Cen- laser therapy.89 Laser therapy remains emerg- ing technology, with limited follow-up and a The second category includes classic thera- lack of controlled studies. Further studies are pies with anecdotal success but significant side required to define its role. However, many der- effects or lack of confirming studies. These matologists, and some of the authors, have include topical retinoic acid,104 colchicine,105 seen benefits in erythematous hypertrophic and systemic antihistamines.106 scars in speeding resolution, and perhaps im- The third category includes newer therapies proving long-term outcomes.
with anecdotal reports that do not yet have ahistory. Although these may develop into use- ful therapies in the future, the authors cannot Cryotherapy alone results in keloid flatten- make any recommendations at this time. These ing in 51 to 74 percent of patients after two or include skin equivalents that incorporate arti- more sessions, and it is beneficial for the man- ficial dermis constructs, cyclosporine,107 and agement of severe acne scars.90–93 Limitations include the delay of several weeks required for Other physical management options include postoperative healing and the commonly oc- hydrotherapy, massage, ultrasound, static elec- curring side effect of permanent hypopigmen- tricity, and pulsed electrical stimulation. Hy- tation. Other side effects include hyperpig- drotherapy is widely used in several European mentation, moderate skin atrophy, and pain.94 countries for the treatment of hypertrophic As a result, cryotherapy is generally limited to burn scars (using high pressure). Massage has management of very small scars.
been widely used by physical therapists, occu-pational therapists, and other allied health Adhesive Microporous Hypoallergenic Paper Tape care professions. However, further long-term The consensus of the authors was that apply- studies are required before recommendations ing paper tape with an appropriate adhesive to can be made regarding their efficacy.
fresh surgical incisions, and for several weeksafter surgery, was useful. The mechanism of Emerging Evidence benefit is unknown, but may in part be me-chanical (analogous to pressure therapy) and Three therapies provide emerging evidence occlusive (analogous to silicone gel therapy).
However, only two uncontrolled studies con-firm its efficacy.95,96 The authors also felt that • Interferon (interferon-␣, interferon-␤, and this treatment was less effective than more es- tablished treatments such as silicone gel, but it • Intralesional 5-fluorouracil15,116 could be used as preventive treatment in low- • Bleomycin injections117–120 risk patients, or before silicone gel use in freshincisions. Tape with an elastic component may Interferon-␣, interferon-␤, and interferon-␥ be useful for scars over mobile or complex have been shown to increase collagen break- surfaces, including joints.
down.109–111 Tredget et al. found that interfer-on-␣2b injections three times weekly resulted in significant mean rates of improvement of There are anecdotal reports on a number of hypertrophic scars versus control and also re- additional therapies, but there is no adequate duced serum transforming growth factor-␤ lev- published information on which the authors els that continued after treatment.114 Inter- can evaluate the efficacy and safety of these feron injections are reported to be significantly therapies or make recommendations. These better than triamcinolone acetonide injections therapies fall into three categories.
in preventing postsurgical recurrence of ke- The first category includes popular treat- loids (18.7 percent versus 58.5 percent recur-

Vol. 110, No. 2 / SCAR MANAGEMENT RECOMMENDATIONS rence).115 However, these painful injections and adding the transforming growth factor-␤3 may require regional anesthesia.
isoform. These approaches have shown efficacy Intralesional 5-fluorouracil has been used in animal models.125–127 Early human trials are successfully as monotherapy as well as in com- in progress for some of these strategies.
bination with intralesional corticosteroids to Another area of active research is interfer- treat hypertrophic scars and keloids.15,116 Phy- ence with collagen synthesis. Historically, pen- sicians experienced in its use show great enthu- icillamine and other nonspecific inhibitors of siasm for 5-fluorouracil. The rationale for its collagen synthesis were used as inhibitors, but use is sound, and it shows a lack of side effects.
they showed unacceptable toxicity. In recent It may warrant further investigation and wider years, several companies have looked for spe- use as an alternative to steroid injections in cific nontoxic inhibitors of collagen synthesis that could be applied locally. Animal trials have Bleomycin injections show evidence of effi- been promising.128 Overall, there has been a
cacy in managing surgical/traumatic hypertro- substantial effort in the pharmaceutical and phic scars.117,118 Patients with older scars resis- biotechnology industry to develop more effec- tant to intralesional corticosteroids showed tive antiscarring therapies, and it seems likely good response to bleomycin 0.01% injections that new therapies will be available within the every 3 to 4 weeks. A recent pilot study in 13 next 5 years.
patients showed complete flattening (six pa-tients) or significant flattening (⬎90 percent; six patients) of hypertrophic scars and keloids These recommendations are made primarily following administration of bleomycin (1.5 on the basis of the clinical evidence reviewed IU/ml) using a multiple-puncture method on above and reflect the practice of the authors the skin surface.119 Although published re- and have been summarized in simple manage- search is limited, there is considerable clinical ment algorithms (Figs. 1 and 2). Cost-effective- experience in using this modality in some Eu- ness of therapies is not assessed in this article.
ropean countries. The rationale for use ofbleomycin, which is another chemotherapeutic agent, is similar to that of 5-flourouracil. A Every effort must be made to prevent the comparative study of the two agents with ste- development of hypertrophic scars or keloids roids is warranted. Adverse effects have not after surgery or trauma. Excellent surgical been reported for this indication, although technique and efforts to prevent postsurgical side effects in the treatment of warts with bleo- infection are of prime importance.129 Special mycin include nail loss and Raynaud's attention should be given to high-risk patients (i.e., those who have previously suffered abnor- Bleomycin and intralesional 5-fluorouracil mal scarring or are undergoing a procedure have been used by some of the authors with with a high incidence of scarring, such as considerable success. Despite a strong theoret- breast and thoracic surgery). To our knowl- ical rationale, larger scale prospective studies edge, there has been no large-scale assessment with appropriate follow-up are needed before of scar outcomes and risk factors. Recom- these treatments can be considered as standard mended preventive techniques include the In addition, experimental animal studies suggest that there may be a role for transform- • Hypoallergenic microporous tape with elas- ing growth factor modulators.122–125 Transform- tic properties to minimize the risk from ing growth factor-␤ has been implicated in sev- shearing. Use of taping for a few weeks after eral scarring conditions including pulmonary surgery is standard practice for the majority fibrosis, glomerulonephritis, and cutaneous of the authors. Although there are no pro- scarring. There are three isoforms, and there is spective controlled studies documenting its some evidence that the ratio is critical for op- efficacy, the authors' consensus is that it is timizing scar outcome. In addition to blocking transforming growth factor-␤ effects with anti- • Silicone gel sheeting, which should be con- bodies, researchers have proposed blocking sidered as first-line prophylaxis. Use of sili- transforming growth factor-␤ activation by cone gel sheeting should begin soon after means of the mannose 6-phosphate receptor, surgical closure, when the incision has fully

PLASTIC AND RECONSTRUCTIVE SURGERY, August 2002 FIG. 1. Prevention of surgical/trauma scarring.
epithelialized, and be continued for at least 1 month. Silicone gel sheets should be worn Pain and itchiness are commonly reported for a minimum of 12 hours daily, and if symptoms associated with scarring. Evidence of possible for 24 hours per day, with twice- management methodologies for pruritus re- daily washing. Use of silicone ointments may mains anecdotal. Pulsed-dye lasers may have be appropriate on the face and neck re- value in reduction of itching, although more gions, although their efficacy in preventing cost-effective options are preferred at this scarring is unsupported by controlled trials.
stage. Other treatments, such as moisturizers, Concurrent intralesional corticosteroid in- silicone gel sheeting, systemic antihistamines, jections as second-line prophylaxis for more topical corticosteroids, antidepressants, mas- severe cases.
sage, and hydrotherapy have been shown to The effectiveness of alternative therapies is improve symptoms. Care should be taken with limited to anecdotal evidence. Patients at low hypersensitivity to moisturizing products such risk of scarring should maintain normal hy- giene procedures and be provided with coun-seling and advice if concerned about their scar.
Immature hypertrophic scars (red). Scar Classification and Patient History difficult to predict whether this type of scar will When patients present with a troublesome resolve or develop into a hypertrophic scar. In scar, appropriate therapy should be selected the authors' experience, the techniques de- on the basis of scar classification and patient scribed above in the Prevention section should history. Scar classification is the primary deci- be followed. If erythema persists for more than sion criterion for treatment selection. Patient 1 month, the risk of true hypertrophy increases history, however, provides important informa- and management should be as for a linear or tion about the risk of the scar worsening widespread hypertrophic scar as appropriate should treatment fail, about previous thera- (see below). These scars may benefit from a pies, and about the patient's likely compliance.
course of pulsed-dye laser therapy, although The degree of erythema has been identified as this therapy requires further long-term trials.
being of great importance in predicting the Linear hypertrophic (surgical/traumatic) scars activity of the scar and response to therapy.
(red, raised). Silicone gel sheeting should be

Vol. 110, No. 2 / SCAR MANAGEMENT RECOMMENDATIONS FIG. 2. Complete management algorithm.
used as first-line therapy, in line with results tonide, long-term placement of intradermal su- from randomized, controlled trials. If the scar tures, and subsequent corticosteroids. Specific- is resistant to silicone therapy, or the scar is wavelength laser therapy and cryotherapy have more severe and pruritic, further management been used by the authors but require further with corticosteroid injections is indicated. Ad- controlled studies.
ditional consideration may be given to other Widespread burn hypertrophic scars (red/raised). second-line therapies mentioned above for se- Widespread burn scars should be treated with first-line therapy of silicone gel sheeting and If silicone gel sheeting, pressure garments, pressure garments, although there remains lim- and intralesional corticosteroid injections are ited significant evidence for the efficacy of pres- not successful after 12 months of conservative sure garments. The treatment of burn scars is therapy, surgical excision with postoperative difficult and often requires a combination of application of silicone gel sheeting should be techniques including individualized pressure considered. An option for more severe scars is therapy; massage and/or physical therapy; sili- reexcision with layering of triamcinolone ace- cone gel sheeting; corticosteroids on particu- PLASTIC AND RECONSTRUCTIVE SURGERY, August 2002 larly difficult areas; and surgical procedures atic, quantitative reviews of the literature to such as Z-plasty, excision, and grafting or flap ensure optimal management of scarring. The coverage. A variety of adjunctive therapies such authors' recommendations are made on the as massage, hydrocolloids, and antihistamines basis of the best available evidence in the liter- to relieve pruritus are also used. Pulsed-dye la- ature, particularly randomized, controlled tri- ser may have a role.
als, supported by clinical experience. Many Minor keloids. The consensus view from the management techniques have limited data to literature and the authors is that first-line ther- support their use, and these recommendations apy for most minor keloids is a combination of support a move to a more evidence-based ap- silicone gel sheeting and intralesional cortico- proach in scar management.
steroids. If there is no resolution, surgical ex- Thomas A. Mustoe, M.D. cision with follow-up intralesional steroids and Division of Plastic and Reconstructive Surgery silicone gel sheeting is indicated. Localized Northwestern University School of Medicine pressure therapy such as ear clips on earlobe 675 North Saint Clair, 19-250 keloids has been shown to be helpful as second- Chicago, Ill. 60611 line adjunctive therapy in small trials.
Surgical excision without careful follow-up or use of other adjunctive measures will result in a high recurrence rate, and if the surgery is Editorial assistance has been provided by Jeremy Bray. A performed without careful attention to pre- small unrestricted educational grant was provided by Smith serving normal architecture, the resulting de- & Nephew Medical, Ltd., and used by the panel for coordi- formity after recurrence may be worse. It is nation and communication.
preferable to only partially excise the keloid rather than produce a deformity. The authors' 1. Guyatt, G. H., Sackett, D. L., Sinclair, J. C., et al.
experience is that excision of difficult recur- guides to the medical literature: IX. A method for rent keloids with grafting of skin taken from grading healthcare recommendations. J.A.M.A. 274: the excised keloid followed by immediate radi- ation therapy can be successful, but that the
2. Piantadosi, S.
David Byar as a teacher. Control. Clin. Trials 16: 202, 1995.
long-term risks of radiation must be carefully 3. Olkin, I.
Statistical and theoretical considerations in meta-analysis. J. Clin. Epidemiol. 48: 133, 1995.
Major keloids. Major keloids are a most chal- 4. Davey, R. B., Sprod, R. T., and Neild, T. O.
lenging clinical problem, and many are resis- erised colour: A technique for the assessment of burn tant to any treatment. Extensive counseling with scar hypertrophy. A preliminary report. Burns 25: 207,1999.
the patient is required before embarking on a 5. Powers, P. S., Sarkar, S., Goldgof, D. B., Cruse, C. W., and surgical solution because the recurrence rate is Scar assessment: Current problems and so high. For some patients, symptomatic treat- future solutions. J. Burn Care Rehabil. 20: 54, 1999.
ment with antihistamines and good hygiene 6. Beausang, E., Floyd, H., Dunn, K. W., Orton, C. I., and may be all that is possible. Radiation therapy Ferguson, M. W.
A new quantitative scale for clinical scar assessment. Plast. Reconstr. Surg. 102: 1954, 1998.
should be considered for treatment failures, 7. Yeong, E. K., Mann, R., Engrav, L. H., et al.
and innovative therapies such as bleomycin and burn scar assessment with use of a new scar-rating 5-flourouracil may have a future role, in addi- scale. J. Burn Care Rehabil. 18: 353, 1997.
tion to investigational strategies that interfere 8. Sullivan, T., Smith, J., Kermode, J., et al.
with transforming growth factor-␤ or collagen burn scar. J. Burn Care Rehabil. 11: 256, 1990.
9. Baryza, M. J., and Baryza, G. A.
The Vancouver Scar synthesis. These patients are best treated by cli- Scale: An administration tool and its interrater reli- nicians with a special interest in keloids. Ongo- ability. J. Burn Care Rehabil. 16: 535, 1995.
ing patient counseling and advice on preven- 10. Nedelec, B., Shankowsky, A., and Tredgett, E. E.
tion are essential components of this therapy.
ing the resolving hypertrophic scar: Comparison ofthe Vancouver Scar Scale and scar volume. J. Burn CareRehabil. 21: 205, 2000.
11. Berman, B., and Bieley, H. C.
Adjunct therapies to surgical management of keloids. Dermatol. Surg. 22: Management choices should depend on the patient's individual requirements and evi- 12. Darzi, M. A., Chowdri, N. A., Kaul, S. K., et al.
ation of various methods of treating keloids and hy- dence-based findings. There remains a signifi- pertrophic scars: A 10-year follow-up study. Br. J. Plast. cant need for further randomized, controlled Surg. 45: 374, 1992.
trials of all available scar therapies and system- 13. Lawrence, W. T.
In search of the optimal treatment of Vol. 110, No. 2 / SCAR MANAGEMENT RECOMMENDATIONS keloids: Report of a series and a review of the litera- 35. Carney, S. A., Cason, C. G., Gowar, J. P., et al.
ture. Ann. Plast. Surg. 27: 164, 1991.
gel sheeting in the management of hypertrophic scar- 14. Berman, B., and Bieley, H. C.
Keloids. J. Am. Acad. ring. Burns 20: 163, 1994.
Dermatol. 33: 117, 1995.
36. Branagan, M., Chenery, D. H., and Nicholson, S.
15. Urioste, S. S., Arndt, K. A., and Dover, J. S.
of the infrared attenuated total reflectance spectros- hypertrophic scars: Review and treatment strategies.
copy for the in vivo measurement of hydration level Semin. Cutan. Med. Surg. 18: 159, 1999.
and silicone distribution in the stratum corneum fol- 16. Sherris, D. A., Larrabee, W. F., Jr., and Murakami, C. S.
lowing skin coverage by polymeric dressings. Skin Phar- Management of scar contractures, hypertrophic scars macol. Appl. Skin Physiol. 13: 157, 2000.
and keloids. Otolaryngol. Clin. North Am. 28: 1057, 1995.
37. Suetake, T., Sasai, S., Zhen, Y.-X., and Tagami, H.
17. Rockwell, W. B., Cohen, I. K., and Ehrlich, H. P.
fects of silicone gel sheet on the stratum corneum loids and hypertrophic scars: A comprehensive review.
hydration. Br. J. Plast. Surg. 53: 503, 2000.
Plast. Reconstr. Surg. 84: 827, 1989.
38. Poston, J.
The use of silicone gel sheeting in the man- 18. Niessen, F. B., Spauwen, P. H. M., Schalkwijk, J., and agement of hypertrophic and keloid scars. J. Wound On the nature of hypertrophic scars and Care 9: 10, 2000.
keloids: A review. Plast. Reconstr. Surg. 104: 1435, 1999.
39. Su, C. W., Alizadeh, K., Boddie, A., and Lee, R. C.
19. Alster, T. S., and West, T. B.
Treatment of scars: A problem scar. Clin. Plast. Surg. 25: 451, 1998.
review. Ann. Plast. Surg. 39: 418, 1997.
40. Katz, B. E.
Silicone gel sheeting in scar therapy. Cutis 20. Murray, J. C.
Keloids and hypertrophic scars. Clin. Der- 56: 65, 1995.
matol. 12: 27, 1994.
41. Berman, B., and Flores, F.
Comparison of a silicone 21. Kelly, A. P.
Keloids. Dermatol. Clin. 6: 413, 1988.
gel-filled cushion and silicone gel sheeting for the 22. Murray, J. C.
Scars and keloids. Dermatol. Clin. 11: 697, treatment of hypertrophic or keloid scars. Dermatol. Surg. 25: 484, 1999.
23. Griffith, B. H., Monroe, C. W., and McKinney, P.
42. Gold, M. H.
A controlled clinical trial of topical sili- follow-up study on the treatment of keloids with tri- cone gel sheeting in the treatment of hypertrophic amcinolone acetonide. Plast. Reconstr. Surg. 46: 145, scars and keloids. J. Am. Acad. Dermatol. 30: 506, 1994.
43. Cruz-Korchin, N. I.
Effectiveness of silicone sheets in 24. McCoy, B. J., Diegelmann, R. F., and Cohen, I. K.
the prevention of hypertrophic breast scars. Ann. vitro inhibition of cell growth, collagen synthesis and Plast. Surg. 37: 345, 1996.
prolyl hydroxylase activity by triamcinolone ace- 44. Agarwal, U. S., Jain, D., Gulati, R., et al.
tonide. Proc. Soc. Exp. Biol. Med. 163: 216, 1980.
sheet dressings for prevention of post-minigraft cob- 25. Ketchum, L. D., Smith, J., Robinson, D. W., et al.
blestoning in vitiligo. Dermatol. Surg. 25: 102, 1999.
treatment of hypertrophic scar, keloid and scar con- 45. Ahn, S. T., Monafo, W. W., and Mustoe, T. A.
tracture by triamcinolone acetonide. Plast. Reconstr. silicone gel for the prevention and treatment of hy- Surg. 38: 209, 1966.
pertrophic scars. Arch. Surg. 126: 499, 1991.
26. Tang, Y. W.
Intra- and postoperative steroid injections 46. Ahn, S. T., Monafo, W. W., and Mustoe, T. A.
for keloids and hypertrophic scars. Br. J. Plast. Surg. 45: silicone gel: A new treatment for hypertrophic scars.
Surgery 106: 781, 1989.
27. Hirshowitz, B., Lerner, D., and Moscona, A. R.
47. Gold, M. H.
The role of CICA-CARE in preventing ment of keloid scars by combined cryosurgery and scars following surgery: A review of hypertrophic and intralesional corticosteroids. Aesthetic Plast. Surg. 6: keloid scar treatments. Oral presentation at the An- nual Meeting of the American Academy of Dermatol- 28. Whang, K. K., Park, H. J., and Myung, K. B.
ogy, San Francisco, Calif., March 10 –15, 2000.
analysis of the combination of cryosurgery and in- 48. Borgognoni, L., Martini, L., Chiarugi, C., Gelli, R., and tralesional corticosteroid for keloid or hypertrophic Reali, U. M.
Hypertrophic scars and keloids: Immu- scars. Korean J. Dermatol. 35: 450, 1997.
nophenotypic features and silicone sheets to prevent 29. Sproat, J. E., Dalcin, A., Weitauer, N., and Roberts, R. S.
recurrences. Ann. Burns Fire Disasters 8: 164, 2000.
Hypertrophic sternal scars: Silicone gel sheeting ver- 49. Quinn, K. J.
Silicone gel in scar treatment. Burns 13: sus kenalog injection treatment. Plast. Reconstr. Surg. 90: 988, 1992.
50. Morris, D. E., Wu, L., Zhao, L. L., et al.
30. Yii, N. W., and Frame, J. D.
Evaluation of cynthaskin chronic animal models for excessive dermal scarring: and topical steroid in the treatment of hypertrophic Quantitative studies. Plast. Reconstr. Surg. 100: 674, scars and keloids. Eur. J. Plast. Surg. 19: 162, 1996.
31. Jenkins, M., Alexander, J. W., MacMillan, B. G., et al.
51. Baum, T. M., and Busuito, M. J.
Use of a glycerin-based Failure of topical steroids and vitamin E to reduce gel sheeting in scar management. Adv. Wound Care 11: postoperative scar formation following reconstructive surgery. J. Burn Care Rehabil. 7: 309, 1986.
52. Phillips, T. J., Gerstein, A. D., Lordan, V., et al.
32. Perkins, K., Davey, R. B., and Wallis, K. A.
randomized controlled trial of hydrocolloid dressing A new treatment for burn scars and contractures.
in the treatment of hypertrophic scars and keloids.
Burns Incl. Therm. Inj. 9: 201, 1983.
Dermatol. Surg. 22: 775, 1996.
33. Sawada, Y., and Sone, K.
Treatment of scars and ke- 53. Wong, T. W., Chiu, H. C., Chang, C. H., et al.
loids with a cream containing silicone oil. Br. J. Plast. cream occlusive dressing: A novel non-invasive regi- Surg. 43: 683, 1990.
men in the treatment of keloid. Dermatology 192: 329, 34. Chang, C. C., Kuo, Y. F., Chiu, H., et al.
silicone, modulates the effects of keratinocytes on fi- 54. Staley, M. J., and Richard, R. L.
Use of pressure to treat broblasts. J. Surg. Res. 59: 705, 1995.
hypertrophic burn scars. Adv. Wound Care 10: 44, 1997.
PLASTIC AND RECONSTRUCTIVE SURGERY, August 2002 55. Fricke, N. B., Omnell, M. L., Dutcher, K. A., Hollender, 76. Kantor, G. R., Wheeland, R. G., Bailin, P. L., et al.
L. G., and Engrav, L. H.
Skeletal and dental distur- Treatment of earlobe keloids with carbon dioxide la- bances in children after facial burns and pressure ser excision: A report of 16 cases. J. Dermatol. Surg. garment use: A 4-year follow-up. J. Burn Care Rehabil. Oncol. 11: 1063, 1985.
20: 239, 1999.
77. Sheridan, R. L., Lydon, M. M., Petras, L. M., et al.
56. Ward, R. S.
Pressure therapy for the control of hyper- ablation of burns: Initial clinical trial. Surgery 125: 92, trophic scar formation after burn injury: A history and review. J. Burn Care Rehabil. 12: 257, 1991.
78. Hulsbergen-Henning, J. P., Roskam, Y., and van Gemert, 57. Tredget, E. E.
Management of the acutely burned up- Treatment of keloids and hypertrophic scars per extremity. Hand Clin. 16: 187, 2000.
with an argon laser. Lasers Surg. Med. 6: 72, 1986.
58. Nedelec, B., Ghahary, A., Scott, P., and Tredget, E.
79. Abergel, R. P., Meeker, C. A., Lam, T. S., and Dwyer, Control of wound contraction: Basic and clinical fea- Control of connective tissue metabolism by tures. Hand Clin. 16: 289, 2000.
lasers: Recent developments and future prospects.
59. Agrawal, K., Panda, K. N., and Arumugam, A.
J. Am. Acad. Dermatol. 11: 1142, 1984.
expensive self-fabricated pressure clip for the ear lobe.
80. Kumar, K., Kapoor, B. S., Rai, P., and Shukla, H. S.
Br. J. Plast. Surg. 51: 122, 1998.
situ irradiation of keloid scars with Nd:YAG laser.
60. Linares, H. A.
From wound to scar. Burns 22: 339, J. Wound Care 9: 213, 2000.
81. Kwon, S. D., and Kye, Y. C.
Treatment of scars with a 61. Rayner, K.
The use of pressure therapy to treat hyper- pulsed Er:YAG laser. J. Cutan. Laser Ther. 2: 27, 2000.
trophic scarring. J. Wound Care 9: 151, 2000.
82. Alster, T. S.
Improvement of erythematous and hyper- 62. Tilley, W., McMahon, S., and Shukalak, B.
trophic scars by the 585 nm flashlamp pulsed dye laser.
tation of the burned upper extremity. Hand Clin. 16: Ann. Plast. Surg. 32: 186, 1994.
83. Alster, T. S., Kurban, A. K., Grove, G. L., et al.
63. Johnson, J., Greenspan, B., Gorga, D., et al.
ation of argon induced scars by the pulsed dye laser.
ance with pressure garment use in burn rehabilitation.
Lasers Surg. Med. 13: 368, 1993.
J. Burn Care Rehabil. 15: 180, 1994.
84. Alster, T. S., and Williams, C. M.
Treatment of keloid 64. Kealey, G. P., Jensen, K. L., Laubenthal, K. N., and Lewis, sternotomy scars with 585 nm flashlamp-pumped Prospective randomised comparison of two pulsed-dye laser. Lancet 345: 1198, 1995.
types of pressure therapy garments. J. Burn Care Re- 85. Dierickx, C., Goldman, M. P., and Fitzpatrick, R. E.
habil. 11: 334, 1990.
Laser treatment of erythematous/hypertrophic and 65. Rose, M. P., and Deitch, E. A.
The clinical use of a pigmented scars in 26 patients. Plast. Reconstr. Surg. 95: tubular compression bandage, Tubigrip, for burn scar therapy: A critical analysis. Burns Incl. Therm. Inj. 12: 86. Goldman, M., and Fitzpatrick, R. E.
Laser treatment of scars. Dermatol. Surg. 21: 685, 1995.
66. Chang, P., Laubenthal, K. N., Lewis, R. W., II, et al.
87. Connell, P. G., and Harland, C. C.
Treatment of keloid Prospective, randomized study of the efficacy of pres- scars with pulsed dye lasers and intralesional steroid.
sure garment therapy in patients with burns. J. Burn J. Cutan. Laser Ther. 2: 147, 2000.
Care Rehabil. 16: 473, 1995.
88. McCraw, J. B., McCraw, J. A., McMellin, A., and Betten- 67. Norris, J. E. C.
Superficial X-ray therapy in keloid man- Prevention of unfavorable scars using early agement: A retrospective study of 24 cases and liter- pulse dye laser treatments: A preliminary report. Ann. ature review. Plast. Reconstr. Surg. 95: 1051, 1995.
Plast. Surg. 42: 7, 1999.
68. Cosman, B., Crikelair, G. F., Ju, D. M., et al.
89. Wittenberg, G. P., Fabian, B. G., Bogomilsky, J. L., et al.
gical treatment of keloids. Plast. Reconstr. Surg. 27: 335, Prospective single-blind, randomised controlled study to assess the efficacy of the 585-nm flashlamp pumped 69. Brown, L. A., Jr., and Pierce, H. E.
Keloids: Scar revi- pulsed-dye laser and silicone gel sheeting in hyper- sion. J. Dermatol. Surg. Oncol. 12: 51, 1986.
trophic scar treatment. Arch. Dermatol. 135: 1049, 1999.
70. Levy, D. S., Salter, M. M., and Roth, R. E.
90. Layton, A. M., Yip, J., and Cunliffe, W. J.
irradiation in the prevention of keloids. A.J.R. Am. J. on intralesional triamcinolone and cryosurgery in the Roentgenol. 127: 509, 1976.
treatment of acne keloids. Br. J. Dermatol. 130: 498, 71. Edsmyr, F., Larson, L. G., Onyango, J., et al.
therapy in the treatment of keloids in East Africa. East 91. Ciampo, E., and Iurassich, S.
Liquid nitrogen cryosur- Afr. Med. J. 50: 457, 1973.
gery in the treatment of acne lesions. Ann. Ital. Der- 72. Bailin, P.
Use of the CO2 laser for non-PWS cutaneous matol. Clin. Sper. 51: 67, 1997.
lesions. In K. A. Arndt, J. M. Noe, and S. Rosen (Eds.), 92. Zouboulis, C., Blume, U., Buttner, P., and Orfanos, C. E.
Cutaneous Laser Therapy: Principles and Methods. New Outcomes of cryosurgery in keloids and hypertrophic York: John Wiley, 1983. Pp. 187–200.
scars: A prospective, consecutive trial of case series.
73. Apfelberg, D. B., Maser, M. R., White, D. N., et al.
Arch. Dermatol. 129: 1146, 1993.
ure of carbon dioxide laser excision of keloids. Lasers 93. Ernst, K., and Hundeiker, M.
Results of cryosurgery in Surg. Med. 9: 382, 1989.
394 patients with hypertrophic scars and keloids. Haut- 74. Norris, J. E.
The effect of carbon dioxide laser surgery arzt 46: 462, 1995.
on the recurrence of keloids. Plast. Reconstr. Surg. 87: 94. Rusciani, L., Rosse, G., and Bono, R.
apy in the treatment of keloids. J. Dermatol. Surg. Oncol. 75. Bernstein, L. J., Kauvar, A. N., Grossman, M. C., et al.
19: 529, 1993.
Scar resurfacing with high-energy short-pulsed and 95. Reiffel, R. S.
Prevention of hypertrophic scars by long- flash scanning carbon dioxide lasers. Dermatol. Surg. term paper tape application. Plast. Reconstr. Surg. 96: 24: 101, 1998.
Vol. 110, No. 2 / SCAR MANAGEMENT RECOMMENDATIONS 96. Davey, R. B., Wallis, K. A., and Bowering, K.
and Ghahary, A.
The antifibrogenic effects of lipo- contact media: An update on graft fixation and burn scar management. Burns 17: 313, 1991.
wounds. J. Interferon Cytokine Res. 19: 1413, 1999.
97. Havlik, R. J.
Vitamin E and wound healing: Safety and 114. Tredget, E. E., Shankowsky, H. A., Pannu, R., et al.
efficacy reports. Plast. Reconstr. Surg. 100: 1901, 1997.
Transforming growth factor-beta in thermally injured 98. Baumann, L. S., Spencer, J., and Klein, A. W.
patients with hypertrophic scars: Effects of interferon effects of topical vitamin E on the cosmetic appear- alpha-2b. Plast. Reconstr. Surg. 102: 1317, 1998.
ance of scars. Dermatol. Surg. 25: 311, 1999.
115. Berman, B., and Flores, F.
Recurrence rates of excised 99. Jackson, B. A., Shelton, A. J., and McDaniel, D. H.
keloids treated with postoperative triamcinolone ace- study evaluating topical onion extract as treatment for tonide injections of interferon alfa-2b injections.
postsurgical scars. Dermatol. Surg. 25: 267, 1999.
J. Am. Acad. Dermatol. 37: 755, 1997.
100. Scalvenzi, M., Delfino, S., and Sammarco, E.
116. Fitzpatrick, R. E.
Treatment of inflamed hypertrophic matological scars: Improvement after application with scars using intralesional 5-FU. Dermatol. Surg. 25: 224, an allantoin and sulphomucopolysaccharide-based gel. Ann. Ital. Dermatol. Clin. Sper. 52: 132, 1998.
117. Bodokh, I., and Brun, P.
Traitement des chéloïdes par 101. Magliaro, A., Gianfaldoni, R., and Cervadoro, G.
infiltrations de Bléomycine. Ann. Dermatol. Venereol. Treatment of burn scars with a gel based on allantoin 123: 791, 1996.
and sulfomucopolysaccharides. G. Ital. Dermatol. Vene- 118. Larouy, J. C.
Traitement des chéloïdes: trois méth- reol. 134: 153, 1999.
odes. Nouv. Dermatol. 19: 295, 2000.
102. Boyce, D. E., Bantick, G., and Murison, M. S.
119. Espana, A., Solano, T., and Quintanilla, E.
of ADCON-T/N glycosaminoglycan gel in the revision in the treatment of keloids and hypertrophic scars by of tethered scars. Br. J. Plast. Surg. 53: 403, 2000.
multiple needle punctures. Dermatol. Surg. 27: 23, 103. Widgerow, A. D., Chait, L. A., Stals, R., and Stals, P. J.
New innovations in scar management. Aesthetic Plast. 120. Smith, E. A., Harper, F. E., and LeRoy, E. C.
Surg. 24: 227, 2000.
phenomenon of a single digit following local intra- 104. Janssen de Limpens, A. M. P.
The local treatment of dermal bleomycin sulfate injection. Arthritis Rheum. hypertrophic scars and keloids with topical retinoic 28: 459, 1985.
acid. Br. J. Dermatol. 103: 319, 1980.
121. Epstein, E.
Persisting Raynaud's phenomenon follow- 105. Peacock, E. E., Jr.
Pharmacologic control of surface ing intralesional bleomycin treatment of finger warts.
scarring in human beings. Ann. Surg. 193: 592, 1981.
J. Am. Acad. Dermatol. 13: 468, 1985.
106. Topol, B. M., Lewis, V. L., Jr., and Beneviste, K.
122. O'Kane, S., and Ferguson, M. W.
use of antihistamine to retard the growth of fibroblasts growth factor beta s and wound healing. Int. J. Biochem. derived from human skin, scar and keloids. Plast. Re- Cell Biol. 29: 63, 1997.
constr. Surg. 68: 227, 1981.
123. Yamada, H., Tajima, S., Nishikawa, T., Murad, S., and 107. Duncan, J. L., Thomson, A. W., and Muir, L. F. K.
Pinnell, S. R.
Tranilast, a selective inhibitor of col- Topical cyclosporin and T-lymphocytes in keloid scars.
Br. J. Dermatol. 124: 109, 1991.
lagen synthesis in human skin fibroblasts. J. Biochem. 108. Lawrence, W. T.
Treatment of earlobe keloids with (Tokyo) 116: 892, 1994.
surgery plus adjuvant intralesional verapamil and 124. Nakamura, K., Irie, H., Inoue, M., Mitani, H., Sunami, pressure earrings. Ann. Plast. Surg. 37: 167, 1996.
H., and Sano, S.
Factors affecting hypertrophic scar 109. Tredget, E. E., Wang, R., Shen, Q., Scott P. G., and development in median sternotomy incisions for con- genital cardiac surgery. J. Am. Coll. Surg. 185: 218, mRNA and protein in hypertrophic scar tissues and fibroblasts: Antagonism by IFN-alpha and IFN-gamma 125. O'Kane, S., and Ferguson, M. W.
in vitro and in vivo. J. Interferon Cytokine Res. 20: 143, growth factor betas and wound healing. Int. J. Biochem. Cell Biol. 29: 63, 1997.
110. Granstein, R. D., Rook, A., Flotte, T. J., et al.
126. Cowin, A. J., Holmes, T. M., Brosnan, P., and Ferguson, trolled trial of intralesional recombinant interferon-␥ Expression of TGF-beta and its receptors in in the treatment of keloidal scarring. Arch. Dermatol. murine fetal and adult dermal wounds. Eur. J. Derma- 126: 1295, 1990.
tol. 11: 424, 2001.
111. Pittet, B., Rubbia-Brandt, L., Desmoulieve, A., et al.
127. Tyrone, J. W., Marcus, J. R., Bonomo, S. R., Mogford, fect of gamma interferon on the clinical and biological J. E., Xia, Y., and Mustoe, T. A.
Transforming growth evolution of hypertrophic scars and Dupuytren's dis- factor beta3 promotes fascial wound healing in a new ease: An open pilot study. Plast. Reconstr. Surg. 93: animal model. Arch. Surg. 135: 1154, 2000.
128. Kim, I., Mogford, J. E., Witschi, C., Nafissi, M., and 112. Larrabee, W. F., Jr., East, C. A., Jaffe, H. S., et al.
Mustoe, T. A.
Inhibition of prolyl 4-hydroxylase re- tralesional interferon gamma treatment for keloids duces scar elevation in a rabbit model of hypertrophic and hypertrophic scars. Arch. Otolaryngol. Head Neck scarring. Wound Repair Regen. 9: 139, 2001.
Surg. 116: 1159, 1990.
129. Harahap, M.
Surgical Techniques for Cutaneous Scar Re- 113. Takeuchi, M., Tredget, E. E., Scott, P. G., Kilani, R. T., vision. New York: Marcel Dekker, 1999.

Source: http://www.allwecare.nl/media/Studies/2001_-_Thomas_A._Mustoe_-_International_Clinical_Recommendations_on_Scar_Management.pdf