Approach

The existing evidence to support the ideal treatment of keloids is weak.[24][25]​ A number of review articles have been published summarizing consensual algorithms for keloid scar management, with most of them emphasizing the need for combined multidisciplinary therapeutic regimens.[17][26]​ This is pertinent given the wide heterogeneity of scar features, as well as the different therapeutic goals and objectives that patients present with.[17][27]​​​

Initial treatment

The first-line treatment will depend on the site, size, etiology, and history of previous treatments. In general terms, single, small keloid scars can be treated with nonsurgical modalities, whereas large, bulky, or multiple lesions should be assessed for surgery and adjuvant therapy.[17][28]​​ Patient preference is a strong determining factor as well, so the number and size of presenting scarring should not preclude consideration of surgery.[17]

Nonsurgical local therapy may include corticosteroids, antitumor agents, laser therapy, or cryotherapy. Treatments may be combined or used sequentially to improve efficacy and minimize adverse effects. Examples of combinations include intralesional fluorouracil plus corticosteroid injections, laser therapy plus corticosteroid injections, or laser therapy plus intralesional fluorouracil. Preferred options are not well defined due to limited evidence. Take an individualized approach after discussing treatment options and goals with the patient.

See also Patient discussions.

Corticosteroids

Corticosteroids can be administered as an intralesional or sublesional injection or as a topically applied tape, and may be used in combination with other treatments. Corticosteroid tapes can be used as monotherapy in patients with thin scars. Bulkier lesions require a more reinforced approach, involving either induction with injectables or combination with other modalities. Benefits of a combined approach include enhanced efficacy and minimization of corticosteroid-associated adverse effects.[29][30]

Corticosteroids have a number of different actions including:[31][32]

  • Inhibition of leukocyte/monocyte migration and phagocytosis.

  • Vasoconstriction which reduces the delivery of oxygen and nutrients to the skin/scar.

  • Antimitotic effect through inhibition of fibroblast proliferation (by virtue of decreasing mitogenic factors including transforming growth factor beta-1 [TGF-beta 1], vascular endothelial growth factor, and insulin-like growth factor-1) and induction of cellular degeneration.

  • Decrease of collagen synthesis and enhancement of collagen degradation; this occurs through the reduction of levels of alpha-2 macroglobulin and alpha-1 antitrypsin (which are both potent collagenase inhibitors).

Corticosteroid injections

The most commonly used injectable corticosteroid is triamcinolone (as the acetonide salt). Despite the popularity of corticosteroid injections for the treatment of keloid and hypertrophic scars, little conclusive evidence exists to support definitive treatment protocols. The frequency of administration varies widely in the literature and ranges from 1- to 8-week intervals between each injectable treatment.[33][34]​​​​​​​ A survey among 102 international plastic surgeons concluded that the most popular interval between injections is 3-4 weeks (31%), closely followed by 4-5 weeks (26%).[35]​ Some proposed protocols also recommended using different doses depending on the volume/dimensions as well as location of the scar.[36][37][38]​​​​​ Response rates to triamcinolone injections vary considerably from 50% to 100% regression; recurrence rates are estimated to be 33% at year 1 posttreatment and 50% after 5 years.[33]

  • Intralesional injection: the most popular technique for injection into the substance of the keloid. Small diameter needles (ranges between 25 and 30 Gauge) in conjunction with Luer lock or insulin syringes with an integrated needle have been advocated in order to withstand the pressure encountered during injection into stiff scars. Several authors have advised that the needle should be inserted into the papillary dermis (where collagenase is produced) and the substance administered while slowly withdrawing the needle, while others support targeting the mid-dermis level in order to avoid irreversible epidermal atrophy, which is more likely with superficial injection. The principle of inserting the needle within the keloidal lesion (as opposed to neighboring healthy skin) to avoid the development of an iatrogenic keloid has not been substantiated with evidence in the literature.

  • Sublesional injection: an alternative technique to deliver corticosteroid to a keloid scar at the level of deep dermis in an attempt to mitigate the shortcomings of the intralesional technique. The first publication on this method employed light and electron microscope exam and showed that the positive changes in histologic appearance appeared earlier compared to those achieved with the intralesional approach with a similar pattern of adverse effects including atrophy, depigmentation, and telangiectasia.

  • A number of different techniques can be employed to minimize discomfort, including local anesthetic creams or injections before corticosteroid administration. Some clinicians add lidocaine to the corticosteroid to give a 50/50 dilution. Lidocaine has a local anesthetic effect but will not reduce the pain of the injection (though it may make the subsequent pain more tolerable). It is also thought that lidocaine has local effects on fibroblasts, causing reduced collagen production and inhibiting cell proliferation.[39][40]

  • Complications of intralesional corticosteroid injections are common (reported in up to 63%) and include skin thinning, atrophy of the subdermal fat, telangiectasia, plaque formation, and pigmentary changes.[35] Systemic adverse effects are possible and can lead to adrenal suppression and Cushing syndrome. One systematic review confirmed 18 cases of Cushing syndrome after intralesional triamcinolone administration; 80% of cases occurred in children, and most after administration of more than 40 mg of triamcinolone within a period of 1 month.[35] Systemic hormone imbalance may also develop, which can result in water retention and menstrual irregularities in susceptible women.[24]

Corticosteroid tape

Topically applied corticosteroid tape (e.g., flurandrenolide) is indicated for:[41]

  • First-line treatment of small keloids

  • Adjunctive treatment following either corticosteroid injection or surgical intervention

Once corticosteroid injections have reduced the thickness of the pathologic scar to a couple of millimeters, corticosteroid tape can be a patient-friendly way to continue corticosteroid delivery to the affected skin.

The delivery of a corticosteroid using a tape formulation was first described in the literature in 1967.[42]​ Percutaneous corticosteroid delivery acts through the combined effect of the barrier component, which creates a semiocclusive environment of controlled hydration, and the corticosteroid component, which has the well-known effect of hampering fibroblast proliferation and decreasing the amount of collagen in the scar. The two components act synergistically to enhance vasoconstriction within the scar.

The tape is applied to the index scar with minimal overlap to neighboring skin and needs to be changed regularly. Follow-up is recommended after an initial trial of 3 months in order to assess clinical response.[21]

​One trial reported no systemic adverse effects after application of flurandrenolide, a moderate-potency corticosteroid tape, to scars up to 5% total body surface area for at least 6-8 weeks.[43] A separate observational study reported no systemic complications following at least 12 months of tape application in a mixed adult and pediatric cohort.[44]

Topical corticosteroids

Evidence to support the use of topical corticosteroids (e.g., creams, ointments, lotions) as monotherapy for keloid scars is very weak, and they should not be recommended routinely.[45] In one prospective observational study, a triamcinolone lotion was applied on scars, with an adjacent part of the lesion left untreated to act as the comparison area. Assessment on a 4-point scale (including parameters for color, elevation, texture, itch, and pain) found a response rate of 44.4% for the group of 9 keloid patients after a maximum follow-up period of 7 months.[46] Another case series investigating the response to fluocinolone cream included 12 patients with keloids: 2 patients showed clearance, 7 showed significant response, and 3 showed poor or no response, with no author speculation about the reasons for the variable response.[47]

Antitumor agents

Antitumor agents used for keloid treatment include fluorouracil, bleomycin, and mitomycin. Although some guidelines recommend antitumor agents as second-line options for refractory keloids, others suggest they should be considered as part of first-line therapy to help prevent recurrence.[28][45]​​

Fluorouracil is a pyrimidine analog, which interferes with DNA synthesis by blocking thymidine. It is also thought to inhibit type I collagen gene expression and the effects of TGF-beta.[48]​ It is used as an intralesional injection in the management of keloids.

The clinical effectiveness of intralesional fluorouracil seems to be similar to corticosteroids, with recurrence rates of up to 47%.[49] One randomized controlled trial (RCT) compared intralesional fluorouracil to triamcinolone injections in 44 keloidal patients. Both treatments were equally effective in reducing keloid volume, but the adverse effects in the fluorouracil group (pain and superficial ulceration) were significantly worse.[50] In another comparative trial of 30 patient with keloids, triamcinolone injection significantly improved volume reduction compared with intralesional fluorouracil, and fluorouracil was associated with more adverse effects (although this difference was nonsignificant).[51]

The addition of intralesional fluorouracil to triamcinolone injection is believed to ameliorate the combined adverse effect profile because of the decreased dose requirement of each agent. In one meta-analysis of intralesional injections for hypertrophic and keloid scars, the combination of intralesional triamcinolone and fluorouracil injection was more effective than triamcinolone alone in terms of patient assessment, observer assessment, scar height after treatment, as well as erythema score.[30]

A very small number of studies have employed intralesional fluorouracil in combination with laser therapy or as a postoperative adjunct.[52][53][54]​​​ The consensus in the literature suggests that the addition of intralesional fluorouracil to other scar management modalities - including intralesional corticosteroids and pulse dye laser - improved efficacy versus each treatment alone.[29]

Bleomycin and mitomycin are alternative injectable treatments to flatten keloids, but not commonly used.

Bleomycin is used in the management of various malignancies and works by inducing tissue sclerosis. According to one meta-analysis, intralesional bleomycin significantly improves keloid and hypertrophic scars compared with triamcinolone, fluorouracil, and cryotherapy combined with triamcinolone.[55]

Mitomycin is a Streptomyces derivative that possesses antineoplastic and antiproliferative properties. In one meta-analysis, topical application of mitomycin on the surgical wound (3-5 minutes every 3 weeks) resulted in a recurrence rate of 16.5% (95% CI: 7.9 to 31.3).[56]

Laser therapy

Laser modalities are becoming more popular in scar management. In general, flatter keloids are more suitable for laser therapy because the beam can reach an adequate depth of penetration.[21] Two main technologies are employed:

  • Vascular lasers: these work by destroying blood vessels within a scar, thereby causing local ischemia, as well as by downregulating TGF-beta 1 expression.[57][58]​​​

    • One review on laser applications for keloid and hypertrophic scarring concluded that the optimal laser is currently the 585 nanometer (nm) pulsed dye laser (PDL), although the Q-switched 532 nm frequency laser is also promising; early use of laser modalities in susceptible patients is recommended.[59]​ A systematic review of eight RCTs concluded that PDL may improve overall scar appearance compared with conventional treatment modalities.[60]

    • A comparative, randomized split-scar trial compared the effectiveness of PDL (595 nm) versus Nd:YAG laser (1064 nm) modalities in 20 patients with hypertrophic or keloid scars.[61] One month after the last treatment, both modalities produced statistically significant improvements based on Vancouver scar scale assessments (P <0.001), with no significant differences between the two modalities.[61]

    • The long pulsed Nd:YAG vascular modality should be considered in patients with pigmented skin (Fitzpatrick types IV to VI) to avoid issues with pigmentation changes associated with more superficial wavelengths including PDL therapy.[62]

  • Resurfacing lasers (e.g., Er:YAG, carbon dioxide): aim to improve the texture and bulk of scarring by creating controlled damage to the scar and inciting a remodeling cascade in the skin.

    • These can be divided into ablative (i.e., removing the epidermis) and nonablative (i.e., leaving the epidermis intact), as well as fractional (i.e., those generating zones of microthermal injury with intervening islands of intact skin, inducing a healing response and scar remodeling) and nonfractional or full beam.[25]

Evidence to support laser-based devices for treatment of keloids is considered early, and further research is warranted to ascertain the strength and longevity of results.[57][63] A review of laser therapy for management of keloids reported a 22% recurrence rate following Er:YAG laser therapy at 8 months’ follow-up.[64] After 6 months, recurrence rates following Nd:YAG laser therapy differed based on the keloid site, from 25% over the scapula to 53% for anterior chest lesions. Carbon dioxide laser treatment was associated with recurrence appearing as early as 2 weeks and as late as 3 years posttreatment.[64]

In general, fully ablative modalities are not recommended for pathologic scars, as they are associated with high recurrence rates.[65]

Laser-assisted corticosteroid delivery

In clinical practice, lasers are used in combination with injectables on the basis of good synergistic effects.

In one small study, PDL combined with corticosteroid injections yielded a 60% improvement in height, 40% improvement in erythema, and 75% improvement in pruritus.[66]

Another study used carbon dioxide laser ablation/excision followed with intralesional triamcinolone injections at 3-4 weekly intervals over 6 months, and noted a significant increase in keloid recurrence in patients who did not regularly attend follow-up sessions for corticosteroid administration.[67]

Fractional carbon dioxide-assisted corticosteroid delivery is gaining in popularity. In one Chinese study of 41 patients with refractory keloids, treatment with eight sessions of fractional carbon dioxide treatment alongside topical triamcinolone application resulted in significant improvement in all components of the patient and observer scar assessment scale.[68]

One retrospective study of 70 keloids treated with 2940 nm ablative fractional erbium laser in combination with topical betamethasone under occlusion showed a recurrence rate of 22% after a mean follow-up period of 8 months.[69] Interestingly, one split side study with a very similar design (2940 nm laser and occluded topical betamethasone) failed to show any statistically significant difference compared with intralesional injection.[70]

One 12-week single-blind study of patients with keloid and hypertrophic scars comparing intralesional triamcinolone injection (group 1), intralesional triamcinolone plus fluorouracil injection (group 2), and intralesional triamcinolone plus fluorouracil injection plus three sessions of PDL treatment (group 3) concluded that the overall efficacy of groups 2 and 3 were similar, but group 3 produced better results (15% vs. 40% vs. 70% good to excellent improvement for each group according to blinded observers).[52]

Cryotherapy

The aim of cryotherapy is to induce a freeze-thaw cycle that will induce cell death and cause scar regression.

Cryotherapy can be delivered via contact probes or spray formulations. The most popular method involves an intralesional needle probe, which produces rapid freezing from the core of the scar outwards. One literature review concluded that the evidence supporting intralesional cryotherapy is low.[71]

Clinical experience suggests that intralesional cryotherapy can be considered especially for pedunculated keloids, with scar volume reduction rates reported to range from 51% to 67% after a single treatment. Adverse effects include pain, prolonged healing, and hypopigmentation; rates of recurrence have been reported to be around 24%.[71]

Surgery

Surgical techniques can be largely divided into intralesional (debulking) and extralesional (radical resection). Surgery should be ideally combined with adjuvant therapies given that the risk of recurrence following surgery alone has been reported to be in the region of 45% to 100%.[72][73]

A number of services offer intralesional (or intramarginal) excision of keloids. This represents a partial excision technique using incisions within the peripheral borders of the keloid scar to a variable depth and wound closure via approximation of the peripheral rims.

There are cellular and histologic arguments to support an extralesional as opposed to the widely practiced intralesional approach; most of the evidence converges toward the fact that intralesional excision leaves behind less apoptotic and more actively fibrogenic fibroblastic populations, explaining the higher recurrence rates following intralesional excision.[74]

A number of parameters have been proposed as key factors for an optimal surgical result including:[21]

  • Adequate scar excision. The scar is ideally removed extralesionally down to a deeper tissue layer, which for an area like the chest would be the deep fascia. It is important to remove the subcutaneous layer of fat in order to allow the visualization of fascial layers and subsequent undermining. In certain situations, total excision is not practical due to the size and location of the scar (e.g., risk of causing deformity in the helical rim) and the core excision method is used; this involves removing the reticular dermal keloid component and using the epidermal and papillary dermal component as a flap. For the management of very large scars, tissue expansion or flap closure may be considered.

  • Undermining. This is an important step in order to slide and approximate layers of tissue and minimize tension during closure.

  • Tension relieving deep closure. This aspect incorporates the use of deep fascial suture placement. This ensures reduction of tension in the fascial and dermal layers as well as minimization of dead space, which plays a key role in preventing collections. A polydioxanone suture material is recommended in order to maintain tensile strength in the wound/scar for at least 3 months.[73]

  • Dermal approximation using Z-plasty closure. This aims to disperse superficial tension along the wound, particularly over considerable lengths and/or on high tension areas of the body (e.g., the anterior chest).

Postoperative therapy

Radiation therapy is the preferred postoperative adjunct treatment for adults, and referral is recommended.

  • Radiation therapy has both antiproliferative and anti-inflammatory actions, both of which are likely to be important in the treatment of keloid scarring. Various types of radiation may be used for the treatment of keloids, including electrons, superficial/orthovoltage x-rays, and brachytherapy.

  • Radiation therapy is effective for the adjuvant treatment of keloids soon after excision. The evidence for this approach consists of retrospective case series, small RCTs, and comparative cohorts. Most of these studies have flaws, including variable doses and numbers of treatments, the treatment of different keloid sites and hypertrophic scars in the same studies, small patient numbers, short follow-up, and unclear outcomes.[75]

  • It is generally accepted that the radiation therapy must be started as soon after the surgery as possible (e.g., within 24-48 hours), and that the treatment course should not last more than 1 week.[21] However, there is considerable variation in the dose and numbers of treatments (fractions) used in various centers.[75]

  • The largest and best-described case series is that of Ogawa et al., in which various cohorts of patients were treated with different doses and numbers of fractions.[76] Up to 2002, they used 15 Gy in 3 fractions for all keloid sites (n=249). They found that earlobe keloids were well controlled with 6% recurrence at 2 years, but that there was a high recurrence rate (40%) with other sites. From 2003 to 2012 the dose was "risk-adapted," so that sites at a high risk of recurrence (e.g., scapular, anterior chest wall, suprapubic) were treated with a higher dose of 20 Gy in 4 fractions, and earlobes (at low risk of recurrence) were treated with a lower dose of 10 Gy in 2 fractions (n=644). This led to a reduction in recurrence of high-risk sites to 13% and preservation of low recurrence rates to earlobes, although auricular sites still had a relatively high risk of 21% recurrence. From 2008 to 2012 there was some modification in surgical technique, in particular the auricular excision technique was changed from wedge excision to core excision, leading to reduction in auricular keloid recurrence rate to 9%. From 2013 to 2017 the radiation therapy fractionation was shortened to 8 Gy in 1 fraction to earlobes, 18 Gy in 3 fractions to high recurrence sites, and other sites to 15 Gy in 2 fractions, with a recurrence rate overall of 9.3% (n=494).[76]

  • The use of radiation therapy as a primary treatment (i.e., without full surgical excision) is less established, but there is some evidence to show that the use of higher doses than those used after excision can be effective.[77]

  • The adverse effects of radiation therapy tend to be minor, with acute skin redness and peeling, leading to changes in pigmentation and telangiectasia (mainly in patients pretreated with corticosteroid injections).[76] There is a theoretical risk of radiation-induced carcinoma which is dependent on age, body site, radiation therapy dose, and technique.[78] A typical value would be 0.02% lifetime risk of skin cancer for radiation therapy to an earlobe keloid.[76]

Corticosteroid tape or injection may be used as an adjunct following radiation therapy to treat residual inflammation. In select cases, corticosteroids may be used as an alternative to radiation therapy following surgical excision.[17][21]​​​ This may be done if radiation therapy is contraindicated, if a patient declines radiation therapy, or for keloids on certain areas of the body (e.g., earlobes). However, a specialist should be consulted because corticosteroids alone may not be sufficient to prevent recurrence after surgery. In practice, a nonsurgical approach is often preferred if radiation therapy is not appropriate.

A very small number of studies describe antitumor agents as postoperative adjuncts, but data are scarce and this is not routinely recommended.[54][56]

Other historical therapies

Silicone-based therapy

  • Silicone-based therapy comes in various compositions (e.g., gel, spray, or gel sheets). The aim is to treat for increasing periods of time as tolerated, with eventual continuous use. Typical use ranges from several weeks to 6 months.[45] ​Sheets are considered more potent in maintaining skin hydration, which is one of the theories accounting for the beneficial effects of these adjuncts on scarring.

  • Clinical experience suggests that silicone sheets have only short-term benefits, represent a significant daily commitment for patients, and should not be considered as a definitive modality to treat keloid scars. Nevertheless, these products may be considered as part of a strategy to prevent hypertrophy in high-risk individuals.[29]

  • In one Cochrane review, trials evaluating silicone gel sheeting as a treatment for keloid or hypertrophic scars showed improvements in scar thickness and scar color, but the trials were of poor quality and highly susceptible to bias.[79]​ One subsequent Cochrane review examined silicone gel sheeting for treatment of keloids only; two eligible RCTs were identified, but evidence was insufficient to determine efficacy due to risk of bias, indirectness, and imprecision.[80]

  • Two small studies failed to demonstrate that silicone dressings were more effective than nonsilicone dressings or paper tape for scar treatment or prevention.[81][82]

Pressure therapy

  • Recommended by some guidelines as a conservative, mainly preventative option.[21][28]​ However, supportive evidence is limited and pressure therapy is no longer commonly used in clinical practice for keloid treatment.[75]

  • Pressure is thought to work by causing local tissue hypoxia and needs to be maintained for a prolonged period of time to be effective.

  • Clips are commonly used for earlobe lesions, whereas elastic garments, with or without localized padding, are designed to deliver pressure of around 24 mmHg to the scar (these are most helpful for hypertrophic scars covering a large surface area).

  • A small number of observational studies have reported success for prevention of postsurgical recurrence of ear keloids.[83] 

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