Keloids and hypertrophic scars are caused by cutaneous injury and irritation, including trauma, insect bite, burn, surgery, vaccination, skin piercing, acne, folliculitis, chicken pox, and herpes zoster infection. Notably, superficial injuries that do not reach the reticular dermis never cause keloidal and hypertrophic scarring. This suggests that these pathological scars are due to injury to this skin layer and the subsequent aberrant wound healing therein. The latter is characterized by continuous and histologically localized inflammation. As a result, the reticular layer of keloids and hypertrophic scars contains inflammatory cells, increased numbers of fibroblasts, newly formed blood vessels, and collagen deposits. Moreover, proinflammatory factors, such as interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α are upregulated in keloid tissues, which suggests that, in patients with keloids, proinflammatory genes in the skin are sensitive to trauma. This may promote chronic inflammation, which in turn may cause the invasive growth of keloids. In addition, the upregulation of proinflammatory factors in pathological scars suggests that, rather than being skin tumors, keloids and hypertrophic scars are inflammatory disorders of skin, specifically inflammatory disorders of the reticular dermis. Various external and internal post-wounding stimuli may promote reticular inflammation. The nature of these stimuli most likely shapes the characteristics, quantity, and course of keloids and hypertrophic scars. Specifically, it is likely that the intensity, frequency, and duration of these stimuli determine how quickly the scars appear, the direction and speed of growth, and the intensity of symptoms. These proinflammatory stimuli include a variety of local, systemic, and genetic factors. These observations together suggest that the clinical differences between keloids and hypertrophic scars merely reflect differences in the intensity, frequency, and duration of the inflammation of the reticular dermis. At present, physicians cannot (or at least find it very difficult to) control systemic and genetic risk factors of keloids and hypertrophic scars. However, they can use a number of treatment modalities that all, interestingly, act by reducing inflammation. They include corticosteroid injection/tape/ointment, radiotherapy, cryotherapy, compression therapy, stabilization therapy, 5-fluorouracil (5-FU) therapy, and surgical methods that reduce skin tension.

Background: In 2010, this Journal published my comprehensive review of the literature on hypertrophic scars and keloids. In that article, I presented evidence-based algorithms for the prevention and treatment of these refractory pathologic scars. In the ensuing decade, substantial progress has been made in the field, including many new randomized controlled trials. To reflect this, I have updated my review. Methods: All studies were evaluated for methodologic quality. Baseline characteristics of patients were extracted along with the interventions and their outcomes. Systematic reviews, meta-analyses, and comprehensive reviews were included if available. Results: Risk factors that promote hypertrophic scar and keloid growth include local factors (tension on the wound/scar), systemic factors (e.g., hypertension), genetic factors (e.g., single-nucleotide polymorphisms), and lifestyle factors. Treatment of hypertrophic scars depends on scar contracture severity: if severe, surgery is the first choice. If not, conservative therapies are indicated. Keloid treatment depends on whether they are small and single or large and multiple. Small and single keloids can be treated radically by surgery with adjuvant therapy (e.g., radiotherapy) or multimodal conservative therapy. For large and multiple keloids, volume- and number-reducing surgery is a choice. Regardless of the treatment(s), patients should be followed up over the long term. Conservative therapies, including gel sheets, tape fixation, topical and injected external agents, oral agents, and makeup therapy, should be administered on a case-by-case basis. Conclusions: Randomized controlled trials on pathologic scar management have increased markedly over the past decade. Although these studies suffer from various limitations, they have greatly improved hypertrophic scar and keloid management. Future high-quality trials are likely to improve the current hypertrophic scar and keloid treatment algorithms further.

Previous reports on the treatment of hypertrophic scars and keloids have not described clear algorithms for multimodal therapies. This article presents an evidence-based review of previous articles and proposes algorithms for the treatment and prevention of hypertrophic scars and keloids. The methodologic quality of the clinical trials was evaluated, and the baseline characteristics of the patients and the interventions that were applied and their outcomes were extracted. Important factors that promote hypertrophic scar/keloid development include mechanical forces on the wound, wound infection, and foreign body reactions. For keloids, the treatment method that should be used depends on whether scar contractures (especially joint contractures) are present and whether the keloids are small and single, or large and multiple. Small and single keloids can be treated radically by surgery with adjuvant therapy (which includes radiation or corticosteroid injections) or by nonsurgical monotherapy (which includes corticosteroid injections, cryotherapy, laser, and antitumor/immunosuppressive agents such as 5-fluorouracil). Large and multiple keloids are difficult to treat radically and are currently only treatable by multimodal therapies that aim to relieve symptoms. After a sequence of treatments, long-term follow-up is recommended. Conservative therapies, which include gel sheeting, taping fixation, compression therapy, external and internal agents, and makeup (camouflage) therapy, should be administered on a case-by-case basis. The increase in the number of randomized controlled trials over the past decade has greatly improved scar management, although these studies suffer from various limitations. The hypertrophic scar/keloid treatment algorithms that are currently available are likely to be significantly improved by future high-quality clinical trials.

There has been a long-standing need for guidelines on the diagnosis and treatment of keloids and hypertrophic scars that are based on an understanding of the pathomechanisms that underlie these skin fibrotic diseases. This is particularly true for clinicians who deal with Asian and African patients because these ethnicities are highly prone to these diseases. By contrast, Caucasians are less likely to develop keloids and hypertrophic scars, and if they do, the scars tend not to be severe. This ethnic disparity also means that countries vary in terms of their differential diagnostic algorithms. The lack of clear treatment guidelines also means that primary care physicians are currently applying a hotchpotch of treatments, with uneven outcomes. To overcome these issues, the Japan Scar Workshop (JSW) has created a tool that allows clinicians to objectively diagnose and distinguish between keloids, hypertrophic scars, and mature scars. This tool is called the JSW Scar Scale (JSS) and it involves scoring the risk factors of the individual patients and the affected areas. The tool is simple and easy to use. As a result, even physicians who are not accustomed to keloids and hypertrophic scars can easily diagnose them and judge their severity. The JSW has also established a committee that, in cooperation with outside experts in various fields, has prepared a Consensus Document on keloid and hypertrophic scar treatment guidelines. These guidelines are simple and will allow even inexperienced clinicians to choose the most appropriate treatment strategy. The Consensus Document is provided in this article. It describes (1) the diagnostic algorithm for pathological scars and how to differentiate them from clinically similar benign and malignant tumors, (2) the general treatment algorithms for keloids and hypertrophic scars at different medical facilities, (3) the rationale behind each treatment for keloids and hypertrophic scars, and (4) the body site-specific treatment protocols for these scars. We believe that this Consensus Document will be helpful for physicians from all over the world who treat keloids and hypertrophic scars.

Keloids and hypertrophic scars are fibroproliferative disorders (FPDs) of the skin that result from abnormal healing of injured or irritated skin. They can be called pathological or inflammatory scars. Common causes are trauma, burn, surgery, vaccination, skin piercing, folliculitis, acne, and herpes zoster infection. The pathogenesis of these scars clearly involves local conditions such as delayed wound healing, wound depth, and the tension of the skin around the scars. Scar severity is also shaped by interactions between these local factors and genetic and systemic factors such as hypertension and sex hormones. Notably, to evaluate scar severity, the Japan Scar Workshop (JSW) has established the JSW Scar Scale. Our studies show that tension on the skin around the wound results in prolonged and/or repeated bouts of inflammation in the reticular layer of the dermis and that this inflammation generates abnormal numbers of blood vessels (as well as collagen and nerve fibers) in the dermal reticular layer. We hypothesize that local factors, such as the mechanobiology of the dermis and blood vessels, along with genetic and systemic factors promote pathological scar development by inducing endothelial dysfunction (i.e., vascular hyperpermeability) during the inflammatory stage of wound healing. The continued presence of these factors prolongs the influx of inflammatory cells and factors, thereby leading to fibroblast dysfunction. Evidence for this hypothesis includes the fact that all effective treatments of keloids, namely, radiotherapy, compression therapy, steroid administration, and long-pulsed Nd:YAG laser therapy, act, at least partly, by suppressing blood vessels. At present, keloids are classified as strongly inflammatory scars, while hypertrophic scars are considered to be mildly inflammatory scars. However, we propose that keloids and hypertrophic scars are simply manifestations of the same skin FPD and differ only in the degree of endothelial dysfunction and therefore inflammation. We therefore suggest that these pathological scars should be classified on the basis of the factor that causes the endothelial dysfunction. Thus, primary scars are caused by congenital endothelial dysfunction (e.g., a mutation prevents endothelial gaps from closing smoothly) while secondary scars are caused by endothelial dysfunction that results from aging, arterial sclerosis, and/or repeated/very strong local mechanical forces. We expect that primary keloids develop at younger ages and tend to become severe, while secondary keloids are seen in all ages and can vary in clinical severity. Thus, abnormal blood vessel regulation may underlie keloid and hypertrophic scar pathogenesis, which suggests that inhibiting abnormal angiogenesis and vascular hyperpermeability may be an important therapeutic approach.