• ✓Elucidating the pathophysiology of scars and keloids
• ✓Develop effective preventive and therapeutic methods for scars and keloids
• ✓Creating a world where there are no patients suffering from scars and keloids

The Scar/Keloid Clinic and Laboratory of Nippon Medical School

Keloids and hypertrophic scars are red scars that grow continuously so that they rise above the surface of the original wound. Keloids tend to be more deleterious than hypertrophic scars because they also relentlessly spread sideways. These pathological scars can be very itchy, painful, and disfiguring. Moreover, if they are located near a joint, they can contract, thereby restricting joint mobility. Common causes include surgery, burns, and trauma but also minor injuries such as highly inflamed acne (known as folliculitis) and piercings. Keloids in particular are especially common in people of Asian and African descent, which suggests that they are at least partly driven by genetics.

Our studies and those of others show that pathological scars are caused by continuous heavy inflammation that starts soon after wounding: while a short early burst of moderate inflammation is needed for normal wound healing, it is ongoing and excessive in pathological scars. The inflammation in turn hyperactivates fibroblasts in the wound/scar. While these cells are important for laying down the extracellular connective fibers and materials (especially collagen) that repair wounded skin, their activity does not abate in pathological scars: instead, the fibroblasts continue to churn out copious amounts of extracellular material long after the wound has closed. This generates large twisted bundles of collagen (called keloidal collagen) that cause the scar to thicken and stiffen.

If left untreated, keloids in particular but also hypertrophic scars near joints can become huge and greatly affect the quality of life of the patient. However, simple surgical removal of these scars is often futile, especially if they are keloids, because they very often grow back in and around the surgical scars, resulting in even worse scars. Moreover, current non-surgical therapies on their own often have weak effects at best, especially with large scars.

To improve the outcomes of patients with pathological scars, we established our Scar/Keloid-specialized Clinic in the Department of Plastic, Reconstructive, and Aesthetic Surgery at Nippon Medical School in Tokyo, Japan in 2005. In the ensuing years, we have treated approximately 2,000 new scar/keloid patients annually. Around the same time, we also consolidated our Scar/Keloid Research Laboratory: therein, we conduct (i) clinical research with the medical data of the thousands of scar patients who have been treated in our Clinic to date and (ii) basic research with keloid tissue and cell culture, genetic analyses, animal models, and computer modelling.

Below, we will describe some of our most seminal studies. Part A discusses the studies that elucidated the various factors and mechanisms that initiate and promote the relentless growth of these quite mysterious scars. Part B describes our studies searching for the most effective clinical techniques. The studies in Parts A and B have together helped us to develop highly effective multi-pronged therapeutic and preventative algorithms for scars of all types, locations, and sizes. As a result, even highly aggressive keloids can now be cured: patients no longer have to endure their scars or undergo multiple rounds of weak and sometimes painful therapies. These studies have also laid the foundation of our current research, which continues to unravel the mechanisms that induce (or prevent) pathological scarring. Our ultimate objective is to manipulate these mechanisms with new drugs and non-surgical techniques so that pathological scars can be treated or even prevented in a rapid and non-invasive manner.

A. Identification of the pathological features of keloids and hypertrophic scars and the factors that promote their growth

A1. All keloids and hypertrophic scars display chronic inflammation in the reticular layer of the dermis

The skin consists of three layers, namely, the epidermis, papillary dermis, and reticular dermis. Keloids and hypertrophic scars only develop when the dermal reticulum (the deepest layer) is damaged or inflamed. This explains why surgery, which generally involves a full-thickness incision in the skin, is a common cause of pathological scars. For the same reason, ear piercing can cause the ball-like keloids that grow on the ears. Subcutaneous injections that aim to induce local skin inflammation can also generate pathological scars. For example, the BCG vaccination in childhood can cause the dumb-bell-like keloids that run down the upper arm (note that current coronavirus vaccines are delivered in the muscle and thus are very unlikely to induce the dermal inflammation that initiates keloids). Other causes of dermal inflammation can also generate keloids, including highly inflamed acne (folliculitis): this can lead to keloids of the chest, jaw, neck, and shoulders in young people. Keloids and hypertrophic scars can also occasionally arise from shallow abrasions if the wounds become infected and the inflammation spreads to the reticular dermis.

Understanding how keloids and hypertrophic scars start helps us to prevent these scars or catch them while they are small and easier to treat. To this end, we have launched a general information program to educate general practitioners and the public about pathological scars and how to limit them, including thorough cleaning of even minor abrasions and monitoring children for piercing-, vaccine-, and acne-induced keloids.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/28287424

A2. Half of all idiopathic keloids occur on the anterior chest while none occur in bony regions

Our analysis of data from 1,500 patients visiting our Scar/Keloid Clinic showed that in the Japanese population, 49% of large idiopathic keloids (i.e. those not caused by surgery or piercing) occur on the anterior chest. An analysis of the causes showed that the main cause of keloids on this region was folliculitis. Thus, children and young people should be monitored carefully if they have anterior chest folliculitis.

This analysis also showed that keloids are extremely rare on regions with bone immediately under the skin, namely, the scalp and shin. They also never occur on the upper eyelids.

These observations suggest that wounds on the anterior chest should be followed closely whereas injuries or surgery on non-susceptible areas require less attention.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/22332721

A3. Keloids, hypertrophic scars, and scar contractures tend to occur in areas that move frequently

The distinct keloid localization pattern described above may reflect the fact that the keloid-prone body regions undergo regular skin stretching due to body movements whereas the non-susceptible scalp and shin do not. With regard to the upper eyelid, its skin sags naturally and thus eye closing and opening does not induce stretching tension.
These findings suggest that local stretching mechanical force can promote pathological scar growth.

This notion is supported by two other findings. First, joints are highly prone to contractile hypertrophic scars: while hypertrophic scars generally subside spontaneously after a few years, they often will not do so if they are near a joint. Instead, these scars will continue growing to form contractile scars that impede joint movement. Second, keloids tend to adopt region-specific shapes that directly match the predominant directions of skin tension. For example, keloids on the anterior chest (which is constantly undergoing powerful left-right stretching due to arm movements) often develop a crab’s claw shape. Another example is shown by our computer simulation analysis, which modeled the mechanical force on a left-right-running dumb-bell-shaped shoulder keloid. This analysis showed that (i) the predominant stretching tension on the shoulder also ran in the left-right direction and (ii) while the normal skin bore moderate tension (green), the highly inflamed leading edges of the keloid balls exhibited enormous tension (red). Thus, it may be that stretching tension increased the inflammation at the leading edges of the two keloid balls, causing further collagen deposition in these regions and promoting the steady invasion of the keloid balls into the soft surrounding normal skin. This process may be exacerbated by the stiffening effect of the new collagen, which amplifies the force on the leading edges and leads to a vicious circle of mechanical force-driven inflammation and scar growth/invasion.

These observations explain for example why training in the gym can cause keloids on the chest or abdomen to deteriorate and why minor wounds near a joint can result in severe scar contractures. This knowledge has helped us to identify the body areas that are particularly at risk of pathological scarring and therefore require close attention during and after surgery.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/18362577

A4. Other risk factors for pathological scarring

The studies described above suggest that mechanical tension on wound/scar edges can induce and worsen pathological scarring. Our studies described below in A4a–c have identified a number of other risk factors for pathological scarring or its worsening. This information may help us to identify patients most at risk of heavy or worsening scarring as well as point to biological pathways that could be targeted therapeutically by drugs or non-invasive treatments.

A4a. Female hormones may promote susceptibility to keloids

It is well-known that women are more likely to be treated for keloids than men. Indeed, our analysis of data from 1,659 patients who visited our Scar/Keloid Clinic showed that keloid patients are 2–3 times more likely to be female than male. The prevailing view in the field is that this reflects social factors (e.g. women are more likely than men to seek medical attention for unappealing scars) rather than a genuine predisposition of females to keloids. However, when we analyzed the data of people who developed keloids in childhood, we observed that girls were three times more likely than boys to develop keloids and that this did not reflect greater medical attention. The possibility that female hormones could promote keloid formation is currently being researched further.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/31586308

A4b. Inflammatory cytokines exacerbate keloids

Inflammation in general is mediated in large part by small molecules called cytokines. We recently reported the details of an interesting case of a patient who developed Castleman’s disease, which is characterized by abnormal levels in the blood of a cytokine called interleukin-6. The patient had ear keloids that were small and relatively inactive until she developed Castleman’s disease: at that point, the keloids grew very rapidly and required surgery. This case suggests that inflammatory cytokines can worsen keloids. This supports the notion that inflammation plays a key role in both keloid formation and growth.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/28607862

A4c. Single nucleotide polymorphisms associate with severe keloids

The predominance of keloids in Asians and Africans suggests that these scars are partly driven by genetics. This is supported by our analysis of cells in the blood of patients treated at our Scar/Keloid Clinic, which showed that patients with severe keloids have a small mutation in the NEDD4 gene (known as rs8032158). We are conducting further studies to determine how this mutation could promote severe keloid growth.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/24496234

A5. Abnormal blood vessels may play a key role in keloid formation and growth

Our studies described above in A1–3 indicate that local mechanical tension can provoke or worsen wound/scar inflammation and excessive collagen deposition. How mechanical tension promotes pathological scarring is not yet clear but we speculate that abnormal blood vessel function may be a key mediator. An important role of blood vessels is to act as a dynamic barrier between tissues and the circulation. Thus, the endothelial cells that line the blood vessels usually adhere tightly to each other, thereby preventing cells and large molecules in the circulation from entering the tissues. However, if a tissue has been wounded, it sends signals to the nearby blood vessels, which causes their endothelial cells to pull away from each other, thus allowing cleaning and reparative inflammatory cells and molecules to enter. This process is called vascular permeabilization. Endothelial cells are known to be exquisitely sensitive to mechanical forces. We speculate that if these cells are subjected to strong, repetitive, and unending pulling, the vascular permeability after wounding does not return to normal. Consequently, inflammatory cells and factors continue to flow in and activate fibroblasts, which cannot stop depositing collagen. Several of our studies support this scenario, as follows.

A5a. High blood pressure worsens keloids

Our analysis of the data of patients treated at our Scar/Keloid Clinic showed that patients with severe keloids (i.e. many or very large keloids) were much more likely to have hypertension than patients with milder keloids. We believe that high blood pressure may worsen keloids because it adds to the mechanical tension on the endothelial cells.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/25728259

A5b. Keloids associate with decreased vascular endothelial cell function

When we analyzed patients with and without keloids, we observed that keloid patients had significantly poorer vascular endothelial function than the control patients. Notably, this was particularly true for patients whose keloids started before adolescence or at an older age. We speculate that the young-onset patients have genetic factors that predispose them to poor endothelial cell function at an early age while the older-onset patients have acquired diseases such as hypertension and diabetes that cause endothelial cell functions to deteriorate.

These findings suggest that drugs (e.g. anti-hypertensive medications) or treatments that improve endothelial function could (i) ameliorate or prevent pathological scarring and (ii) result in scar-less wound healing.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/29240273

A5c. Histology of keloids show a close spatial and temporal relationship between deranged blood vessels, fibroblasts, and keloidal collagen production

When keloids are cut into slices and examined under the microscope (a procedure known as histology), their reticular dermis is observed to contain so-called keloidal collagen, which is characterized by abnormally thick, twisting, translucent ropes of fused collagen fibers. Keloidal collagen is responsible for the bulkiness of keloids. The prevailing view in the field is that these collagen structures are the end-result of inflammation, which has caused the collagen to degrade. However, keloidal collagen is not seen in other diseases. Our recent histology studies showed that in fact (i) keloidal collagen is directly produced by fibroblasts, (ii) these fibroblasts all lie adjacent to the blood vessels, (iii) the blood vessels are abnormal (often occluded, narrowed, or disrupted and appear to spill cells and cell fragments into the reticular dermis), and (iv) keloidal collagen starts being produced very soon after keloid onset.

These studies support the notion that impaired blood vessels allow ongoing local inflammation, which causes nearby fibroblasts to directly produce keloidal collagen, which in turn induces keloids to expand beyond the original wound boundaries.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/28467018

A6. Keloid patients are normal in terms of blood vessel production

The redness of keloids is due to the abnormal abundance of blood vessels. New blood vessels are produced by precursor endothelial cells that circulate in the blood. Together with the fact that keloid is partly a genetic disease, our suspicion that abnormal blood vessel functions may mediate keloid development led us to ask whether keloid patients have fundamental defects in new blood vessel formation. However, we found that patients with and without keloids did not differ in terms of how well their precursor endothelial cells produced blood vessels under culture conditions. Thus, the excessive production of blood vessels in keloids is due to local conditions.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/31290139

A7. Can keloids be categorized into primary (congenital or idiopathic) and secondary (acquired) keloids?

We have observed that some patients are highly susceptible to keloid formation: they develop them in childhood and the keloids are often severe and very difficult to treat. By contrast, other patients who develop keloids only do so in adulthood after surgery, serious injuries, and/or the advent of vascular diseases such as hypertension; moreover, these keloids are often relatively unaggressive and easy to treat. This suggests that some patients have an inherent constitution that promotes keloid formation: this constitution may relate to vascular function and/or inflammation and the factors that shape it may be largely genetic. Such cases could be considered to be primary (congenital or idiopathic) keloid cases. The second type of keloid patients may be those where vascular dysfunction or inflammation arises only after other conditions develop; as such, these cases could be considered to be secondary (acquired) keloid cases.

This classification system may be helpful when determining the treatment strategy for individual patients. Thus, primary keloids require early diagnosis, early aggressive treatment, close follow-up, and assiduous attention to small injuries by the patient. By contrast, a more relaxed approach can be taken with secondary keloid cases. We are currently establishing this classification system for clinical use.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/27959277

B. Treatment of pathological scars

When we established our Scar/Keloid Clinic in 2005, the treatment options for pathological scars in Japan and elsewhere were limited and dismal outcomes were frequent. Surgery often led to worse scarring, corticosteroid injections were painful and made little headway with large scars, and other treatment options had mild or unreliable effects. Patients were faced with enduring their keloids.

Today, our extensive clinical experiences with and research on pathological scars have led to highly effective treatment algorithms that mean even congenital keloids and contractile hypertrophic scars, the most aggressive of the pathological scars, can be cured. Our key discoveries are described below.

B1. Development of the Nippon Medical School Protocol for curing keloids, hypertrophic scars and scar contractures

Japan has particularly extensive long-term experience with managing pathological scars due to the atomic bombings in World War II, which led to many patients with post-burn keloids, some of whom are still alive today. This together with the keloid-proneness of ethnic Asians means that Japanese physicians were and are in a unique global position in terms of understanding pathological scars. Nonetheless, we recognized in 2005 that there was still a huge need for clear evidence-based guidelines on diagnosing and treating pathological scars. Therefore, we sought in 2006 to consolidate the experience of Japanese clinicians, researchers, and other medical personnel such as paramedics by establishing the Japan Scar Workshop, which meets annually. Around the same time, we established our Scar/Keloid Clinic and Laboratory.

The Japan Scar Workshops and our research and many years of experience in treating patients with scars/keloids have led to many new insights and discoveries into how to manage all types of scars, no matter how aggressive, big or small, where they are located, or what type of functional or aesthetic problem they cause. This led us to create the Nippon Medical School Protocol in 2021. This Protocol describes the mechanisms by which pathological scars arise and explains how to use this knowledge to eliminate and prevent them. It discusses in detail how to apply the main components in the scar/keloid armamentarium, which include silicone tape and gel sheets for fixing wounds and scars; steroid tapes, plasters, and injections; a large array of finely honed surgical techniques; postoperative radiation; laser therapy; makeup therapy; and close long-term follow-up.

While our Protocol was optimized for Japanese patients, our experience with a growing body of non-Japanese patients suggests that it is also effective in other ethnicities. Thus, the Nippon Medical School Protocol may be suitable as the foundation of a standard international prevention/treatment algorithm for pathological scars.

Reference：https://pubmed.ncbi.nlm.nih.gov/32741903/

B2. Development of the Japan Scar Workshop Scar Scale for diagnosing keloids and hypertrophic scars

While hypertrophic scars and keloids are both the result of excessive fibroblast activity in the skin and resemble each other in many ways, they do have some differences. In particular, unless hypertrophic scars are near a joint, they are significantly less aggressive than keloids and can resolve spontaneously. This means that hypertrophic scars generally require less assertive treatment than keloids. However, it can be difficult to distinguish between these two pathological scar forms. The lack of an objective way to differentiate keloids from hypertrophic scars has also hampered global harmonization regarding these scars: for example, western physicians, who predominantly see Caucasian patients (who have low susceptibility to pathological scars), often tend to describe any raised scar as a keloid whereas African physicians tend to describe scars that show relatively mild invasion into the adjacent normal skin as hypertrophic scars.

To overcome these issues, the Japan Scar Workshop created the JSW Scar Scale (JSS) in 2011, with a revised version being published in 2015. This scale is based on the known risk factors for aggressive pathological scar growth, including ethnicity, body region, age at onset, and whether the scar only grows upwards or also spreads into the normal skin. The scores run from 0 to 25, with scores of 0–5, 5–15, and 15–25 indicating mature scars, hypertrophic scars, and keloids, respectively. 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 Japan Scar Workshop also established a committee that, in cooperation with international experts in various fields, prepared a Consensus Document on keloid and hypertrophic scar treatment guidelines in 2019. This Document describes (i) the diagnostic algorithm for pathological scars and how to differentiate them from clinically similar benign and malignant tumors, (ii) the general treatment algorithms for keloids and hypertrophic scars at different medical facilities, (iii) the rationale behind each treatment for keloids and hypertrophic scars, and (iv) the body site-specific treatment protocols for these scars. This Consensus Document, which formed the basis of our Nippon Medical School Protocol, is helpful for physicians from all over the world who treat keloids and hypertrophic scars.

Reference：https://pubmed.ncbi.nlm.nih.gov/31890718/

B3. Key discoveries in our quest for treatments that can cure even keloids

We will describe below a few of our most important discoveries in our long search for evidence-based treatments for pathological scars.

B3a. Long-term corticosteroid tape and plaster use can be very effective for small/moderately sized pathological scars

Steroids have long been known to dampen the inflammation and fibroblast activity in keloids. One way to deliver steroids is to continuously cover keloids with steroid-containing tape or plaster. This approach has become a mainstay in our therapeutic algorithms for pathological scars, partly because we in Japan have access to two types of steroid tape/plasters. The first, a fludroxycortide tape (Drenison®), is accessible elsewhere in the world but it is a relatively weak steroid preparation. The second is available only in Japan on prescription by Japanese physicians (as mandated by Japanese Pharmaceutical Affairs Law): it is a deprodone propionate plaster (Eclair®), which is a strong steroid preparation. Our routine initial approach with small or moderately sized keloids in adults is to apply the strong steroid plaster. Thus, the plaster is cut so that it does not contact normal skin as much as possible and it is changed every day. Many keloids and hypertrophic scars will flatten after six months to several years of this treatment, depending on how long the scars have grown. Once the scar has softened and flattened to the point that the patient cannot feel it with eyes closed, the frequency of plaster application is reduced. The scar may still be red at this point but it will gradually fade and the scar will eventually acquire a more normal skin tone and become less noticeable. The plaster should not be continued if only redness remains because it will thin the skin and cause additional reddening.

Children can be treated with the weaker tape. The tape and especially the plaster also play a key role in ensuring that pathological scars do not recur after surgical resection: these tapes/plasters should be affixed as soon as the slightest hardening or growth is observed in or around the surgical scar.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/29799565

B3b. Development of a less painful and more effective steroid injection method

Another way to apply steroids to pathological scars is by injection (Kenacort®). However, this approach was limited by the fact that the injection can be quite painful. We have established a method that is both much less painful and more effective. Thus, in the past, the drug was injected directly into the hard core. However, not only does this increase the pressure in the scar (which causes pain), the drug is contained within part of the hard core, which makes it less effective. Our approach is to mix the drug with a local anesthetic and then, using the finest needle possible, inject the mixture little by little into the bottom and edges of the scar from the soft surrounding area. It is often sufficient to inject once every 1–3 months, and the flattening effect can be augmented by using steroid tape. Indeed, if the steroid tape is used correctly, only a few injections will be needed in many cases.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/31890718

B3c. Silicone gel sheeting can ameliorate pathological scars by diverting local mechanical forces

Since local mechanical forces can promote pathological scar formation and progression, methods to block these forces can have therapeutic value. One such method is to apply a silicone gel sheet to the scar. Our computer simulation analysis showed that this approach effectively shifts the force to the edge of the silicone gel sheet, thereby reducing the force on the scar itself. This approach is also useful for wounds that may be at risk of turning into pathological scars.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/18362577

B3d. Postoperative radiotherapy and skin stretch-disrupting surgical techniques hugely reduce keloid recurrence rates

Large keloids can generally only be debulked by surgery. However, surgery by itself associates with atrociously high recurrence rates (45–100%). This can be prevented by applying another vital component in our pathological scar armamentarium, namely, postoperative radiotherapy. On the basis of our experience, we have established finely tuned postoperative radiotherapy regimens for specific body sites that use as little radiation as needed. For example, after keloid resection, anterior chest and earlobe wounds receive 18 and 8 Gy delivered over 3 and 1 days, respectively. Routine application of these regimens has seen our keloid recurrence rates drop to 10%. Moreover, since all patients are assiduously followed up after surgery and are treated with steroid plaster when the slightest sign of recurrence is observed, patients no longer have to fear that their keloid will ever become problematic again.

Since mechanical stretching tension promotes keloid growth, we also use surgical techniques that disrupt this tension. One of these techniques is the Z-plasty, where a linear wound that runs in the main direction of stretching tension is sutured in a zigzag pattern. This effectively disrupts the stretching tension. It is particularly useful for wounds on the anterior chest and shoulder, where tension is strong.

We also routinely apply a type of stitching technique called subcutaneous/fascial tensile reduction suturing. This involves placing sutures in the tough connective tissue under the skin: this strongly pulls the wound edges together and means that all of the sutures we use to close the overlying skin layers, including the dermis (where pathological scars start growing), encounter very little stretching tension.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/31840001

B3e. Large keloids can be completely resected by using flap surgery

Sometimes keloids are so big that their surgical excision leaves such a large wound that the edges cannot be pulled together and sutured. In such cases, we cut the nearby normal skin so that we get a loose flap of skin (often still attached to its feeding blood vessels) that we then turn around like a puzzle piece to cover most of the wound. The flap can then be stitched to the wound edges with little tension. The wound left by lifting the flap itself is also small enough to stitch shut without any tension. This surgery always requires postoperative radiotherapy on both the flap-covered wound and the flap donor wound because these patients tend to be highly prone to keloids and could therefore develop keloids in both areas.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/27757357

B3f. There is a large array of surgical methods for keloids, hypertrophic scars, scar contractures, and mature scars

We use a wide variety of surgical techniques to improve not only hypertrophic scars, keloids, and scar contractures but also mature scars. Some mature scars can be quite visible because the wounds had reached the reticular dermis and the inflammation phase was prolonged and/or more potent for some reason (e.g. genetics or location on a tense body site). Some scars can also form pits (atrophic scars) because of excessive collagen degradation in the last stage of wound healing (called the remodeling phase). All of these scars can be improved by well-timed and judiciously chosen surgical techniques, which include z-plasties, w-plasties, split-thickness skin grafting, full-thickness skin grafting, local flaps (including the square flap method and the propeller flap), and expanded flaps, distant flaps, regional flaps, and free flaps.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/30891462

B3g. Laser treatment can further improve conservatively treated keloids and hypertrophic scars

When some keloids and hypertrophic scars undergo conservative treatment with, for example, steroid plasters, their ridges and hardness disappear but they remain quite red and visible. In these cases, laser treatment that reduces the number of blood vessels can be used. These lasers include the Nd:YAG and Dye lasers. However, at present, these treatments are not covered by health insurance in Japan.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/25587506

B3h. Oral medications can reduce the symptoms of keloids and hypertrophic scars

Keloids and hypertrophic scars can be extremely itchy due to the presence of many mast cells, which release histamine. Allergies are also characterized by heavy mast cell activity. It has been shown that an anti-allergic agent called tranilast (Rezaben®) can improve the itchiness of pathological scars, particularly in patients with large or multiple keloids and hypertrophic scars. This may reflect the fact that these patients have an inherent body-wide tendency to excessive inflammatory responses: since tranilast is taken orally, it dampens the mast cells all over the body. In severe cases of pathological scar itching, anti-allergic agents containing steroids can also be effective.

Reference：https://www.ncbi.nlm.nih.gov/pubmed/31890718