At a glance......
- 1 Pathology of Hypertrophic Scars
- 2 Causes of Keloid Scar
- 3 Diagnosis of a Keloid Scar
- 4 Treatment of Keloid Scar
- 5 Others Treatment of Keloid Scar
- 5.1 Corticosteroid Administration
- 5.2 Adhesive tape support/silicone gel sheeting
- 5.3 Compression Therapy
- 5.4 Pressure Therapy
- 5.5 Stabilization Therapy
- 5.6 Radiotherapy
- 5.7 Laser Therapy
- 5.8 Laser and Light-Based Therapy
- 5.9 Fluorouracil (5-FU)
- 5.10 Other Therapies
- 5.11 Interferon
- 5.12 Bleomycin
- 5.13 Imiquimod 5% cream
- 5.14 Tranilast
- 5.15 Botulinum toxin A (BTA)
- 5.16 Photodynamic Therapy (PDT)
- 5.17 Recombinant TGF-β3, Justiva (avotermin)
- 5.18 Tamoxifen
- 5.19 Tacrolimus
- 5.20 Epidermal growth factor
- 5.21 Hydrogel scaffold
- 6 Surgery of Keloid Scar
- 7 References
Keloid Scar is also known as keloid disorder and keloidal scar, is the formation of a type of scar which, depending on its maturity, is composed mainly of either type III (early) or type I (late) collagen. It is a result of an overgrowth of granulation tissue (collagen type 3) at the site of a healed skin injury which is then slowly replaced by collagen type 1. Keloids are firm, rubbery lesions or shiny, fibrous nodules, and can vary from pink to the color of the person’s skin or red to dark brown in color.
Keloid scar dermal benign fibro-proliferative growth that extends outside the original wound and invades adjacent dermal tissue due to extensive production of extracellular matrix, especially collagen, which caused by overexpression of cytokines and growth factors. Although many attempts were made to understand the exact pathophysiology and the molecular abnormalities, the pathogenesis of keloid scar is yet to be determined. Even though there are several treatment options for keloid scars include a combination of medical and surgical therapies like a combination of surgical removal followed by cryotherapy or intralesional steroid therapy, the reoccurrence rate is still high despite the present treatment. This paper reviews literature about keloid scar formation mechanism, the most recent therapeutic options including the ones under research.
A keloid scar is benign and not contagious, but sometimes accompanied by severe itchiness, pain, and changes in texture. In severe cases, it can affect movement of skin. Keloid scars are seen 15 times more frequently in people of African descent than in people of European descent.
Pathology of Hypertrophic Scars
Although there is a defined clinical distinction between hypertrophic scars and keloid scars these two disorders may lie within a spectrum of the same pathophysiologic process. Wound healing is divided up into three phases (inflammatory, proliferative, remodeling). The scar is formed in the last phase (remodeling phase).
There are increased numbers of myofibroblasts in hypertrophic scars. Transforming growth factor beta stimulates differentiation of both local and bone fibroblasts into myofibroblasts, which then creates tension on the wound. Certain pro-inflammatory mediators are unregulated in keloid scars. These include tumor necrosis factor-alpha, interleukin-1 alpha, interleukin-1 beta, and interleukin-6. Some experts believe that these mediators are more sensitive to being released in response to trauma in patients predisposed to hypertrophic and keloid scarring.
Burn wounds can be divided into superficial (partial thickness) and deep (full thickness). The majority of partial thickness burn wounds heal without hypertrophic scarring. Deep wounds stimulate dermal fibroblasts to produce collagen and inflammatory mediators like transforming growth factor-beta 1 (TGF-beta1). TGF-beta1 further stimulates fibroblasts to deposit elastin and collagen.
Causes of Keloid Scar
Most skin injury types can contribute to keloid scarring. These include:
- acne scars
- chickenpox scars
- ear piercing
- surgical incision sites
- vaccination sites
According to the American Osteopathic College of Dermatology (AOCD), an estimated 10 percent of people experience keloid scarring. Men and women are equally likely to have keloid scars. Those with darkly pigmented skin, such as African-Americans, are more prone to keloids.
Symptoms of Keloid Scar
Keloids occur from the overgrowth of scar tissue. Symptoms occur at a site of previous skin injury.
The symptoms of keloids can include:
- a localized area that is flesh-colored, pink, or red in color
- a lumpy or ridged area of skin that’s usually raised
- an area that continues to grow larger with scar tissue over time
- an itchy patch of skin
Keloid scars usually have the following characteristics
- Raised above the skin.
- Hairless and has a shiny appearance.
- Continues to grow even after the wound heals.
- Has a hard and rubbery texture.
- Can be itchy.
- Maybe painful to the touch.
- Lumps may appear on it.
- Red or purple in color when new, but then turns pale over time.
- Constant exposure may darken them.
- Could affect movement if the scar is tight and occurs near a joint.
Keloid scars tend to be larger than the original wound itself. They may take weeks or months to develop fully.
- While keloid scars may be itchy, they’re usually not harmful to your health. You may experience discomfort, tenderness, or possible irritation from your clothing or other forms of friction. In rare instances, you may experience keloid scarring on a significant amount of your body. When this occurs, the hardened, tight scar tissue may restrict your movements.
- Keloids are often more of a cosmetic concern than a healthy one. You may feel self-conscious if the keloid is very large or in a highly visible location, such as an earlobe or on the face. Sun exposure or tanning may discolor the scar tissue, making it slightly darker than your surrounding skin. This can make the keloid stand out even more than it already does. Keep the scar covered when you’re in the sun to prevent discoloration.
Diagnosis of a Keloid Scar
- There is no particular test for a keloid scar. It is diagnosed from the clinical story (a slow-growing overgrowth of a scar, usually in a dark-skinned person), with the scar growing beyond the location of the original skin damage.
- Occasionally a keloid scar can mimic other skin tumors.
- Very rarely, a skin tumor like a dermatofibroma or a soft tissue sarcoma can be mistaken for a keloid scar or vice versa.
- In that case, a biopsy will need to be taken by a specialist. A biopsy is a procedure where a sample of tissue is taken for further analysis.
- The biopsy will be looked at under a microscope and a specialist (histopathologist) will be able to see the typical microscopic features of a keloid scar: a swirling nodular pattern of collagen fibers.
- Note: a biopsy is hardly ever necessary because the history – ie the patient’s story – and the appearance of the skin growth are very typical of a keloid scar.
Treatment of Keloid Scar
Treatment can be difficult and isn’t always successful.
Scars can never be completely removed but can be made less visible.
- Steroid injections directly into the scar – this may help to flatten small early ones
- Apply steroid – impregnated tape for 12 to 24 hours a day
- Apply silicone gel – sheeting on healing skin (not open wounds) for 12 hours a day, for at least 3 months. Silicone gels or sheets are available from some pharmacies.
- Use pressure bandages – to provide long-term compression.
- Other medicines may improve keloids – These include verapamil, fluorouracil, bleomycin, and interferon alfa-2b shots. They are not as well studied as corticosteroid shots, but your doctor may recommend trying one. They are most likely to work when used with another treatment.
- Imiquimod – Imiquimod (1-[2-methylpropyl]-1H-imidazo[4,5-c]quinolin-4-amin) belongs to the family of imidazoquinolines. Imiquimod induces TNF-alpha, IFN-alpha and IFN-gamma, IL-1, IL-4, IL-5, IL-6, IL-8, and IL-12 and alters the expression of markers for apoptosis.
- Tacrolimus – Tacrolimus is an immunomodulator that inhibits TNF-alpha. Gli -1, an oncogene, has been found to be overexpressed in fibroblasts of keloids. Inhibition of this oncogene may restore the natural apoptosis process and decrease proliferation of the ECM protein. Rapamycin, a close analog of tacrolimus, was used in an in vitro study and was found to inhibit the gli -1 oncogene, thus giving a rationale to initiate clinical trials of topical tacrolimus and rapamycin.
- Sirolimus – Sirolimus is an inhibitor of the mammalian target of rapamycin (mTOR), a serine/threonine kinase that regulates collagen expression. By inhibiting mTOR, sirolimus blocks the response to IL-2 and decreases ECM deposition. Similar to rapamycin, sirolimus inhibits Gli -1 signal transduction. mTOR kinases form 2 distinct multiprotein complexes, mTORC1 and mTORC2. In an in vitro and ex vivo study, 2 compounds, KU-0063794 and KU-0068650, were demonstrated to be potent and highly selective competitive inhibitors of mTORC1 and mTORC2 compared with rapamycin, which inhibits mTORC1 alone. The compounds have shown promising antifibrotic activity, with apparent no toxicity in vivo.
Others Treatment of Keloid Scar
- Corticosteroid injections, ointments, and tapes/plasters effectively treat keloids and hypertrophic scars. In addition to their direct anti-inflammatory effect, we believe that the steroids also act by inducing vasoconstriction. This is supported by the fact that corticosteroid administration causes keloids to whiten: this suggests that the blood flow in the scar has been decreased by vasoconstriction.
- The vasoconstrictor effects of topical steroids seem to be mediated by their binding to classical glucocorticoid receptors, rather than by nonspecific pharmacological mechanisms. Moreover, corticosteroid administration rapidly reduces the itching and pain associated with keloids, possibly because the vasoconstriction prevents the perivascular delivery of the inflammatory factors that elicit these symptoms
Adhesive tape support/silicone gel sheeting
- Hydration and occlusion have been suggested in the literature to be the main mechanisms of action of topical adhesive tape (plastic or paper) and silicone materials (sheets, strips, gels, creams, sprays, and foams; available over the counter or custom-made). Accordingly, it seems that silicone, in particular, is not always required.
- In fact, silicone and non-silicone gel dressings may be equally effective in the treatment of hypertrophic scars [rx]; however, studies have shown that silicone gel and silicone gel sheeting (SGS) appear to provide an appropriate occlusion level to treat abnormal scars, in contrast to other materials, such as vaseline [rx].
- Among the different available silicone formats, although silicone gel and SGS have equivalent efficacy in the management of excessive scarring after an operation, silicone gel currently appears to be the preferred silicone therapy, due mainly to ease of use, as Mustoe and colleagues advocate [rx].
- Compression therapy reduces both the objective and subjective symptoms of keloids and hypertrophic scars. We speculate that it acts by occluding the blood vessels in the scar, thereby inhibiting the inflammatory signals coming from the blood vessels. An additional mechanism may be that it stabilizes the wound, thereby decreasing inflammation.
- Pressure therapy has gained popularity for the management of hypertrophic scars and keloids since the 1970s. To date, pressure garments are frequently being used for the prevention of excessive scar formation post-burn. However, their underlying mechanism of action remains poorly understood.
- Decreased collagen synthesis by limiting capillary perfusion and thus decreased oxygen supply to the scar tissue[rx]–[rx], as well as increased apoptosis rates of fibroblasts35, are being discussed. Pressure therapy is usually performed with pressure suits or bandages, sometimes with transparent plastic masks or pressure buttons in special locations.
- Recommendations for the amount of pressure and the duration of the therapy are merely based on empirical observations and support continuous pressure of 15–40 mmHg for at least 23 hours per day for more than 6 months while the scar is still active[rx]
- Since stretching wounds can evoke inflammation of the reticular dermis, wounds should be stabilized. Thus, prolonged external mechanical support using tapes, sheets, and/or garments is recommended for scar prevention. This is supported by our study, which showed that silicone gel sheets reduce the tension on the wound site.
- Silicone tape is better than paper tape as it prevents the epidermal injury caused by repeated taping. Moreover, silicone tape keeps the scar surface moist. These tapes can be kept in place until they detach naturally. The patient does not need to change the tape after taking a bath/shower.
- In our experience, patients generally keep silicone tape in place for about 1–2 weeks. The exception is in summer: perspiration can reduce tape adherence. However, if a patient has a clear history of pathological scars, then stabilization tapes should be exchanged for steroid plaster/tape.
- Superficial X-rays, electron beam and low- or high-dose-rate brachytherapy have been employed primarily as an adjunct to surgical removal of keloids, with overall good results in terms of reduced recurrence,[rx]–[rx]with the exception of one report.[rx] Radiation mediates its effects through inhibition of neovascular buds and proliferating fibroblasts, resulting in decreased collagen production.[rx]
- Electron beam irradiation should be started early (24–48 hours) after keloid excision. A total dose of usually 12 Gy divided into six to ten fractions applied daily or every second day is currently recommended by dermatologists.16 Side effects include hypo- and hyper-pigmentation, erythema, telangiectasia, and atrophy.[rx] Since radiation represents some risk in terms of carcinogenesis, particularly in areas such as the breast or thyroid, its use should be handled with caution.[rx]
- Various lasers have been evaluated in the past decades for the improvement of hypertrophic scars and keloids.[rx] However, current data is difficult to compare due to the different laser settings utilized. The most encouraging results have been demonstrated with the 585-nm pulsed dye laser (PDL), which was first described as promising for the treatment of younger hypertrophic scars and keloids in a milestone study by Alster et al published in the Lancet in 1995.[rx]
- It is thought that the PDL improves keloids or hypertrophic scars by inducing capillary destruction, which generates hypoxemia and in turn alters local collagen production.[rx]–[rx] Also, increased production of MMPs (eg, collagenase) has been described upon PDL treatment.[rx] Non-overlapping laser pulses at fluences ranging from 6.0 to 7.5 J/cm2 (7-mm spot) or from 4.5 to 5.5 J/cm2 (10-mm spot) are currently recommended for the treatment of hypertrophic scars and keloids.[rx] According to Alster and colleagues, two to six treatment sessions are necessary to successfully improve scar color, height, pliability, and texture.[rx]
Laser and Light-Based Therapy
- Many different lasers have been studied and utilized in the treatment of hypertrophic scars and keloids including CO2, Er: Y AG and PDL, among others [rx]. The vascular PDL (pulsed dye laser) 585–595 nm is a nonablative non-fractional laser that has been recognized as an excellent first-line treatment and especially preventive strategy for hypertrophic scars [rx].
- Indeed, the primary indication for PDL is to reduce erythema [rx]. The conventional short-pulsed dye laser (585 nm PDL) has been described as the most appropriate and effective system for the treatment of scars, with improvement in scar texture, color, and pliability, as well as minimal side effects [rx].
- Indeed, this type of laser improves the appearance of hypertrophic scars, keloids, erythematous scars and striae, and diminishes pruritus [rx,rx,rx].
- 5-FU is a chemotherapy drug, a pyrimidine analog with antimetabolite activity [rx], effective in the treatment of keloid scars [rx], especially during the first 5 years of appearance. Wound ulceration, hyperpigmentation and pain are potential complications of the treatment [rx,rx]. Weekly intralesional 5-FU injections (50 mg/ml) for 12 weeks resulted in reduction in scar size of at least 50% with no recurrence in 24 months [rx].
- The triple combination of 5-FU, corticosteroids and PDL is a successful multifaceted approach for the treatment of hypertrophic scars and keloids [rx] and it currently appears to be the most promising therapy for keloids [rx].
- Cryotherapy in combination with intralesional steroid (triamcinolone) has been the most popular classic treatment for both keloid and hypertrophic scars. It is also a very good way to heal small scars like acne scars. Moreover, the common side effect of cryotherapy is permanent hypopigmentation.
- Although it is used as multiple sessions every month, the least number of sessions the better chance for post-operative healing. Further, the success rates after 2 sessions are ranged from 30 to 75% either by using spray or contact cryosurgery with liquid nitrogen, and it is lower in keloid than in hypertrophic scars.[rx]
- Intralesional cryo-needle is the most effective method in treating keloid scar compared with contact and spray probes.[rx] Cryotherapy has been used to treat keloids either as a monotherapy or in combination with intralesional triamcinolone injection [rx]. Cryotherapy delivery methods include contact, sprays, or intralesional needles.
- In recent years, fat grafting/lipofilling [rx], stem cell therapy [rx], and electrochemotherapy [rx] have been used to treat burn scars, hypertrophic scars, and scar contractures. The effectiveness of these techniques remains unclear. Large-scale clinical trials on these techniques are expected.
- Moreover, it is likely that, in the next few years, a number of drugs that target specific molecules and thereby improve or prevent pathological scarring will be tested in clinical trials. These drugs may target molecules that participate in inflammation and angiogenesis in the reticular dermis.
- In particular, drugs that target mechanosensors may be highly effective given that pathological scars are sensitive to mechanical forces [rx].
- Interferon (IFN) subdermal injections are reported to be more efficient than triamcinolone acetonide injections in preventing postsurgical recurrence of keloids. However, these painful injections may require regional anesthesia [rx,rx,rx] and flu-like adverse effects are also common [rx].
- Interferon-α, β, and γ have been shown to increase collagen breakdown . Furthermore, IFN-α2b has been suggested to have antiproliferative properties [rx]. IFN-γ inhibits TGF-β and therefore fibrosis, via initial activation of Jak1, which in turn stimulates the negative regulator of collagen YB-1 (Y-box protein-1), which activates Smad7, eventually leading to TGF-β1 suppression [rx]. However, there is a study where IFN-γ failed to antagonize TGF-β-mediated fibrotic response in keloid-derived dermal fibroblasts [rx].
- In vivo, intralesional IFN-γ has been shown to be effective in improving the appearance of keloids and hypertrophic scars, and in reducing keloid recurrence after excision [rx], with variable treatment regimens. For instance, 0.01–0.1 mg, 3 times a week for 3 weeks [rx], or a unique weekly maximal dose of 0.05 mg for 10 weeks [rx]. IFN-α2b intralesional injection is usually used at 1.5 million IU twice daily over 4 days in keloids or three times weekly for hypertrophic scars [rx,rx]. Although IFN is an expensive form of therapy, it remains a promising therapeutic approach for excessive scarring [rx].
- Bleomycin induces apoptosis, inhibits collagen synthesis via decreased stimulation by TGF-β1 [rx], and is frequently used as an antitumor agent. It has also antibacterial and antiviral activity [rx]. Intralesional multiple jet injections of bleomycin 0.1 ml (1.5 IU/ml) at a maximum dose of 6 ml to avoid toxicity (cutaneous and less frequent pulmonary), 2–6 sessions within a month, may currently be indicated as a therapy for keloids and hypertrophic scars unresponsive to intralesional steroid injection [rx,rx], such as patients with old scars [rx]; however, its use is still uncommon.
- Bleomycin can be used as intralesional injections. The recommended dosage starts at 0.1 ml (1.5 IU/ml) and can go up to a maximum dose of 6 ml in order to prevent adverse effects which are usually cutaneous and less common pulmonary.[rx], [rx] For patients with old scars that do not respond to the intralesional steroid, the recommended treatment is between 2 and 6 sessions per month. Bleomycin usage is still uncommon in clinical practice.[rx]
Imiquimod 5% cream
- Imiquimod is an immune-response modifier and Toll-like receptor (TLR) agonist [rx], approved for the treatment of genital warts, basal cell carcinoma and actinic keratoses [rx].
- Imiquimod stimulates interferon and TNF-α, which increases collagen breakdown and reduces fibroblast-mediated collagen production, respectively [rx]. The cream is applied on alternate nights for 8 weeks after surgery. Adverse effects include irritation and hyperpigmentation [rx]. Although many clinical studies suggest the beneficial effect of imiquimod in the prevention of postsurgical keloid recurrence [rx–rx], it still remains questionable [rx].
- Tranilast (N-(3,4-dimethoxy cinnamoyl) anthranilic acid) is an anti-allergic drug that inhibits the release of histamine and prostaglandins from mast cells, a H1 receptor antagonist [rx]. It also suppresses collagen synthesis of keloids and hypertrophic scar-derived-fibroblasts by downregulating TGF-β1 [rx]. This drug is approved in Japan and Korea for the treatment of hypertrophic scarring [rx].
- Mitomycin C (MMC), a derivative of Streptomyces caespitosus that was isolated in 1958 by Wakaki, is an antibiotic agent with antineoplastic and antiproliferative activities, which has been used as a therapeutic agent to treat pterygium since1963.[rx]
- MMC inhibits DNA, RNA and protein synthesis by alkylating and crosslinking DNA at guanine adenosine nucleotides. MMC has been shown to decrease the DNA synthesis and density cultured keloid fibroblasts in vitro. It has been also shown to suppress fibroblast proliferation and thereby reduce the formation of scars in vitro and in vivo.[rx]
Botulinum toxin A (BTA)
- BTA immobilizes local muscles, reduces skin tension caused by a muscle pull, and thus, decreases microtrauma and subsequent inflammation.[rx] Reduction of the tensile force during the course of cicatrization and effective regulation of the balance between fibroblast proliferation and cellular apoptosis[rx] may represent a novel therapeutic option for the aesthetic improvement of post-surgical scars.
- Indeed, Gassner and colleagues could demonstrate that botulinum toxin injections into the musculature adjacent to the wound (15 U of BTA (Botox, Allergan, Irvine, CA, USA) per 2 cm intraoperative length) within 24 hours after wound closure resulted in enhanced wound healing and less noticeable scars compared with placebo.[rx] By injecting BTA 4–7 days prior to surgery, we have seen similar results using a slightly reduced dose regime, depending on the respective anatomic location (risk of severe asymmetry if injecting only one side of the musculus frontalis, brow ptosis).
Photodynamic Therapy (PDT)
- Topical PDT has been used extensively in treating superficial basal cell carcinoma, actinic keratosis, and Bowen’s disease. Very recently, PDT has been suggested as a novel therapeutic approach for the treatment of keloids. The potential underlying mechanism is currently unknown. However, the photodynamic reaction generates reactive oxygen species, which in turn leads to cell apoptosis, membrane and mitochondrial damage, and activates various signaling molecules such as tumor necrosis factor-α.
- PDT has been demonstrated to reduce type I collagen synthesis and fibroblast proliferation in vitro, which may be responsible for the improvement seen clinically.[rx],[rx] Ud-Din et al recently demonstrated in 20 patients that three treatments of PDT (37 J/cm[rx]) at weekly intervals were effective in reducing pruritus and pain, and in increasing pliability of symptomatic keloids.
- Also, when applied postoperatively after excision of keloids, no recurrence rates were seen at 9-month follow-up, with the exception of one patient.[rx] Based on this small amount of data available, PDT represents a promising, noninvasive treatment which produces a good cosmetic outcome with minimal side effects. However, more studies are needed to further evaluate the optimal PDT treatment regime for this indication.
Recombinant TGF-β3, Justiva (avotermin)
- In 2009, Ferguson and colleagues summarized the results of three double-blind, placebo-controlled trials in a milestone study published in the Lancet:[rx] Intradermal avotermin (recombinant, active, human TGF-β3, Justiva) was administered in healthy subjects to both margins of 1 cm, full-thickness skin incisions, before wounding and 24 hours later and was judged to be effective by lay observers and clinicians.
- Even though the investigators acknowledged their commercial interests in TGF-β3, adherence to established standards in this translational investigation and the rigorous nature of the statistical analysis in a well-powered series of studies provided strong evidence for the benefits of Justiva in this setting. However, in spring 2011, Justiva failed to hit its primary and secondary endpoints in a pivotal Phase III trial.
- In light of these findings, the company regrettably concluded that the efficacy of Justice may be insufficient to demonstrate significant benefit when tested in a broad population of scar revision patients.[rx] To date, the clinical future of recombinant TGF-β3 remains uncertain.
UV-A1 (340–400 nm) Light Therapy
- It is a potential noninvasive option to treat keloid scars. The mechanism of action of ultraviolet light therapy appears to be related to an increase in the collagenase activity. A higher dosage is better than a lower one, and the best response appeared at average 25 dosages.[rx]
- The control of collagen production and wound healing has been shown to be affected by the renin-angiotensin system locally. According to Ardekani et al, local application of captopril on New Zeland white rabbits successfully stopped hypertrophic scarring. This group recently reported the first treated human case.[rx]
Calcium channel blockers
- Like verapamil enhance scar tissue degradation through stimulating collagenase production. They cause changes in the gene expression of the fibroblasts, thereby resulting in decreased collagen production with increased collagenase synthesis. Verapamil cream applied on the keloid scar appears to prevent rebound scarring from intralesional injections.[rx]
- Other agents that may enhance scar degradation are calmodulin inhibitors (e.g. trifluoperazine) and protein C kinase inhibitors (tamoxifen). These agents are promising to treat noninflamed older scar with no active remodeling.[rx]
- It is an immune response modulator through increasing expression of tissue necrotic factor alpha, gamma and alpha interferons (IFN-α, g), and interleukin 1, 6, 8, 12.[rx] In addition, imiquimod also acts as a Toll-like receptor (TLR) agonist,33 and shows promising results in a few reported cases.[rx] Imiquimod (Aldara) cream 5% concentration is used topically to treat different dermatological diseases like warts.[rx], [rx]
|Verapamil||Usually intralesional 2.5 mg/ml [rx], but also topical 7% cream [rx].|
|It is a calcium antagonist that decreases collagen production in the ECM and stimulates
collagenase synthesis, reducing fibrotic tissue production [rx].
|Topical retinoic acid
|Clinical studies suggest that it lightly diminishes the size and symptoms of keloids, but it should not be
considered first-line therapy [rx]
|Hyaluronic acid||Controversial results: While some argue it may prevent excessive scarring [rx], others [rx] defend the
|Radiofrequency||Although collagen fibril changes have been reported, significant clinical improvement is still lacking
|Dermatography||Microsurgical needle tattooing provides camouflage pigmentation and induces scar atrophy via the
cutting action of the needles.
|Dyspigmentation and textural abnormalities of large scars can be reduced with dermatography [rx].|
|Pentoxifylline||This anti-fibrinolytic drug, popularly used to manage the peripheral vascular disease, inhibits burn scar
fibroblasts in vitro [rx]
|Fibrostat||Putrescine 50 mmol/l|
|Colchicine||Alters cytoskeleton and the mitotic phase of the cell cycle. Inhibits inflammation and may prevent
keloid recurrence [rx]
|Mitomycin C||Appears to prevent scar tissue formation, but not keloid recurrence [rx]|
|Ultraviolet light||UVA1 increases collagenase activity [rx]|
|Epicatechin gallate||Catechins are a type of polyphenolic compound with in vitro antioxidant and anti-inflammatory
|Anogeissus latifolia||It is a deciduous tree native to India whose bark is used in tanning and contains leucocyanin and ellagic
acids. It has antimicrobial and healing properties [rx]
|Butea monosperma||It is the bark of a tropical evergreen, with antioxidant and wound healing properties [rx]|
|Curcumin||It blocks fibroblast proliferation [rx]|
|MEBO||=Moist Exposed Burn Ointment.
Contains multiple herbs with beta-sitosterol [rx].
|Mederma skin gel||Onion extract gel with scarce scientific evidence yet, although onion extracts are gaining popularity in
the literature [rx,rx]
|Contractubex gel||Contains onion extract with heparin and allantoin [rx]|
|Vitamin E||May actually worsen scars or cause contact dermatitis [rx]|
|Promising preclinical studies [rx], but more research warranted|
- Tamoxifen, a synthetic nonsteroidal antiestrogen used to treat breast cancer, has been shown to inhibit proliferation of keloid fibroblasts and their collagen synthesis in monolayer cultures. Hu et al demonstrated that tamoxifen exhibits a dose-dependent and reversible inhibition of contraction of adult human dermal fibroblast in vitro.
- Tacrolimus is an immunomodulator that inhibits TNF-alpha. Gli -1, an oncogene, has been found to be overexpressed in fibroblasts of keloids. Inhibition of this oncogene may restore the natural apoptosis process and decrease proliferation of the ECM protein. Rapamycin, a close analogue of tacrolimus, was used in an in vitro study and was found to inhibit the gli -1 oncogene, thus giving a rationale to initiate clinical trials of topical tacrolimus and rapamycin.
Epidermal growth factor
- Epidermal growth factor (EGF) is a growth factor produced by platelets, macrophages, and monocytes and is activated by binding with the EGF receptor present on keratinocytes and fibroblasts. It acts by stimulating keratinocyte proliferation and altering fibroblast activity, resulting in reduced healing time and improved tensile strength of scars. It has been found to be involved in wound healing. It is up-regulated early in the fetal period and is thought to be an important cytokine in scarless fetal healing.
Hydrogel scaffold is approved for used in Europe for improvement of wound healing and scarring and is available as an injectable porcine gelatin-dextran hydrogel scaffold. Its approval is for injection of incisional sites immediately prior to closure. It is thought to function as a lattice for fibroblast adherence, leading to more regulated and organized distribution, with improved wound healing outcome.
- Freeze it. This is called cryotherapy. It is best used for small keloids, such as from acne. Cryotherapy can lighten the skin.Freezing early keloids with liquid nitrogen to stop them growing
- Laser treatment to reduce redness – but this won’t make the scar smaller
- Surgery to remove the keloid, sometimes followed by radiotherapy for the most severe cases. It is effective about 70% of the time
- Surgery followed immediately afterwards with steroid injections at the site of the removed scar
- Interferon injections – recent studies of interferon injections have shown promise in reducing the size of keloids, although it’s not certain how long the effects will last
- Fluorouracil injections – this chemotherapy agent, injected alone or together with steroids, has been used as a treatment for keloids
- Dermal fillers can be used to ‘plump’ any scars that are pitted. However, results are usually temporary
- Skin needling – rolling a small device covered in hundreds of tiny needles across the skin is reported to be helpful but results vary and repeat treatments are often needed.
- Topical treatment – Some doctors like to use sheeting made out of silicone to apply on the keloid or even hypertrophic scars. “The dressing provides pressure on the wound and helps keep more moisture within the skin, which both help to get rid of them,” Khosh says
Surgery of Keloid Scar
- Surgery – If the keloid is larger than normal, your best bet is to minimize the scar through surgery, thus creating a new scar, says Umar. From there, the doctor injects steroids into your new scar to prevent it from growing again.
- Laser Some doctors use lasers to diminish the look, but both doctors say that they find this method to be the least effective way of getting rid of keloids, especially ones formed from a surgical procedure.