Genetics of Keloid Disorder

Keloid disorder has a fascinating and very diverse presentation. This disorder can present itself as a single spot on the skin of the affected individual, or it can involve several areas of the skin. In some cases, presentation is limited to one or few small lesions of the skin; either round or linear; in other cases, keloids can appear as large nodules, conglomerate of nodules, or appear as very large patches.
Such a diverse presentation is most likely associated with a complex genetics, involving more than one gene. Unfortunately, we have no knowledge as to how the vast and varied presentations of this disorder can correlate with any particular set of genetic abnormalities. This has been topic of several studies, none of which have provided any solid evidence for any particular genetic abnormality that can explain development of this condition.

Most keloids develop in genetically predisposed individuals as a consequence to variety of injuries to the skin. These triggering factors include acne, chicken pox, vaccination, body piercing, surgical wound, burns, etc. Although reported in individuals from almost all ethnic backgrounds, the disease is more common among two distinct and genetically distant populations; Africans / African Americans and Asians. The only groups of individuals who may be spared from developing keloids are albinos, making the case for a relationship between melanin (skin pigment) production and susceptibility to keloid formation, at least among dark-skinned individuals. Most keloid patients, especially Africans and African Americans have a positive family history of keloids. Development of keloids among twins also lends credibility to existence of a genetic susceptibility to develop keloids.

The variable presentation of the disease is perhaps due to multi gene inheritance, with certain individuals perhaps having only one mutations or one genetic abnormality and present with minimal keloidal disease, to those who have inherited two or more genetic mutations, whereby the disease appears in its most severe form.

Much more research needs to be done to determine the genetic cause of keloid disorder. Lack of progress in keloid disorder is in part due to lack of a lobbying group for this condition. Although quite common, keloid has not captured the interest of research community. This needs to change. I encourage you to join www.Keloid Research and help to form a strong lobbying group to push the research in this disorder.

If you have keloid, or know of someone who does, please also visit www.Keloid and participate in a keloid study.


Age of Onset of Keloid Disorder

Age distribution of keloid is not well documented. Based on clinical observations, various authors have reported keloid to be commonly seen between the ages of 10 and 30.

Although keloids can occur at any age, they tend to develop more rapidly during and after puberty. Epidemiology and age of onset of keloid has never been properly studied. Our current understanding is solely based on observation or citations of very old medical literature. According to recent studies, which include very large number of keloid patients, a 10-year-old boy with earlobe keloid was the youngest. In Another study, the age of onset of keloid was determined by taking a keloid history from the patients. The age reported for first keloid development in this study varies from 5 to 52 years, although most patients (50%) reported onset of their first keloid between 10 and 19 years. Similarly when individuals with multiple keloids were asked to recall onset age of each lesion, participants reported the largest number of keloids (46%) appearing between 10 and 19 years.

Our own recent IRB approved keloid survey was launched in November 2011 with the goal of capturing detailed information about this disorder directly from patients [] . As of June 1, 2013, 990 patients with keloid disorder had completed this survey. 770 adult or parent responders hve provided the age when they (or thier child) developed their first keloid. Distribution of age of onset of keloid from this survey is shown in the graph below.
The preliminary results of this survey suggests that the age of onset of keloid for majority of patients ranges between 5 to 25 years and not what is commonly believed to be between 10 to 30, and in a large majority of patients, this is a true pediatric disorder with 62% of responders reporting that they developed thier first keloid at age of 17 or younger.

If you have keloid, I urge you participate in this study survey. Your participation will help us to better understand not only the age on onset and age distribution of keloid, but also numerous other aspects of this disorder.

Keloid in Children

Although keloids can occur at any age, they tend to develop more rapidly during and after puberty.
Treating keloids is a challenge, more so in children. We were lucky to be able to manage this particular child’s keloids. Treating her keloids took almost a year and several rounds of cryotherapy, which is naturally painful for a very young child.
Almost a year later, her earlobes are free of keloids. We continue with applying pressure magnetic discs to her earlobes, to keep them flat and prevent another recurrence.
I urge parents who have any history of keloid disorder themselves, or in their relatives, not to pierce their child’s ears. African Americans have to be even more careful when choosing to have their daughter’s ears pierced.

Iatrogenic Keloid

The onset of a keloid is triggered by a minor wound in the skin. In surgically removing a keloid, a much bigger wound is induced by the surgeon. This new and larger wound will obviously result in formation a much larger keloid.
The unfortunate fact is that majority of keloid patients do not draw any benefit from surgery. Furthermore, removing a large keloid leaves a wound that the surgeon cannot easily close. In performing such procedures, in order to close the wound at the site of an excised keloid, some surgeons use another surgical procedure known as skin grafting. Skin grafting involves removing a piece of normal skin from another part of the body and transplanting it to the wound that cannot be otherwise closed.

Removing normal appearing skin for purpose of skin grafting in a keloid patient can result in formation of a new keloid at the site where the graft is taken from, one that is caused solely by that act of a surgeon. In medicine, this is called “iatro-genic”. Iatros in Greek language means “doctor”. This is to be distinguished from worsening of a keloid after surgery and also developing a keloid at the site of a surgical wound for a medically necessary procedure.

Below is case of a Iatrogenic thigh keloid. This gentleman had a large keloid under his chin. Surgeon decided to do a wide excision and close the keloid site with a skin graft that he took from the thigh, causing a totally new keloid, one that this patient did not have before.
The next image is Iatrogenic keloid in lower abdomen. This gentleman had a keloid behind his ear. Surgeon decided to do a wide excision and close the keloid site with a skin graft that he took from his lower abdomen, causing a totally new keloid, one that this patient did not have before.
If you have keloid, I urge you participate in this study survey. Your participation will help us to better understand not only the true rate of efficacy of surgery in keloid, but also numerous other aspects of this disorder

Keloid Infection

As Keloids grow in size, they can develop secondary complications such as bleeding and infections. A sudden onset appearance of pain in a Keloid is most often due to an infection in the Keloid tissue. An infected Keloid will need to be attended to urgently. Such infections cause pain, discomfort as well as risk of causing a systemic and rarely blood stream infections.

An infected Keloid is tender, painful and warmer than the surrounding normal skin. A course of oral antibiotics can usually resolve this complication. Once a Keloid becomes infected, it always runs the risk of re-infection. Quite often, in patients who have multiple Keloids, it is a particular Keloid that gets infected all the time. Large Keloids near the groin areas are more prone to develop infection. The image below depicts a keloid that is acutely infected with pus oozing from the edges. Antibiotics alone are not enough for such a keloid. The necrotic and infectious material has to be drained from this kind of keloid to allow antibiotics to work.
BLEEDING: Large Keloids, when caught and pulled during the sleep, can bleed. Any excessive pulling on a large Keloid can result in a skin tear and bleeding. Spontaneous bleeding is rare in keloids, yet it is often seen in cases of massive Keloids that have been treated with radiation therapy. Radiation can cause chronic damage to the skin, a damage similar to chronic skin burn, which in turn can bleed spontaneously.

Progression of Keloids Over Time

Keloid is often an active biological process. Over time, keloids grow and become larger, and even merge with the nearby keloids. This aspect of keloid biology has not been adequately studied. Clearly, from observation alone, we can conclude that certain growth activating pathways remain active over time and result in progression and enlargement of keloids. Formation of keloids is often triggered by an injury to skin. Such an injury can clearly result in induction of pathological pathways that ultimately form keloid tissue. These pathways are either shut down at some point in future, resulting in a growth arrest of the keloid, or the pathways remain autonomously active and are not shut down, thereby causing growth and progression of keloid. The two images below clearly show progression of the chest keloids in this particular patient. The images were taken are approximately one year apart.
The blue arrow above points to the area where two adjacent keloids have now merged. Much research in needed to better understand the biology of this understudied disorder. I encourage each and every keloid patient to participate in a keloid study, so that we can better understand this disorder, and hopefully one day, find a cure for it. Please follow the links on this website to the keloid research program and participate in as many studies as you can.

Hypertrophic Scars

Among all of human organs and tissues, skin is the one that is most vulnerable to injuries. Skin however, has an amazing ability to heal itself. When injuries are superficial and do not penetrate to deep structures of the skin, the healing is usually complete without leaving any marks. However, when the skin is cut deeply, the healing process will always leave a scar behind.

How the skin heals itself is a very complex process. Imagine a tear in the fabric of your shirt. Repairing the tear of your shirt is possible, yet the fabric will never look perfect again. Same stands true for skin. When there is a deep cut and tearing of the skin, skin will repair and seal itself, yet the healed skin will never look perfect again. Under normal circumstances, the healed skin will be flat and free of any bumps, yet with a visible scar.

Under certain conditions, like skin burn, the scar tissue will have excess growth of fibrous tissue, which results in a bumpy or uneven skin surface. Some burn scars can be very thick and even grow out of control to cause Keloids.

On the other hand, some individuals are prone to develop heavy scars, even after a minor injury to their skin. Often, these heavy scars remain limited to the area of skin injury. The term “Keloid” is use to describe heavy scaring that extends beyond the area of injury. Below is a video recording of a treatment of a 2 weeks old scar in a patient who had developed #keloids before. This scar, within two weeks, already looked like it was transforming to a keloid. In this case, Dr. Tirgan injected the length of the scar with steroids, to prevent occurrence of a new keloid. At a follow up visit a few weeks later, the scar appeared completely flat and without any evidence of keloid formation.
Revisions of scars is a tedious and time consuming process. This requires patience and persistence and trial of different modalities to achieve improvement in the appearance of the scar.

Treatment of hyperthrophic scars depends on the location, size and thickness. Some scars just need cryotherapy, others need to be injected with steroids, or be removed with dermabrasion or dermal surgery.

Pathology of Keloid

When we look at keloids under microscope, we notice that the top levels of skin, what is known as epidermis, is relatively normal and deep parts of the skin, where the keloid tissue resides, is mostly made of excessive amounts of tightly packed collagen fibers randomly oriented in irregular sheets.
Collagen is produced by specialized cells, known as fibroblasts. Collagen is a group of naturally occurring proteins that is abundant in human body and other animals and mammals. Collagen makes up about 25% to 35% of the whole-body protein content. It is made of three separate long chains of amino acids and forms a helix, which put side by side, form very thin fibers, known as collagen fibrils.
Collagen, in the form of elongated fibrils, is mostly found in fibrous tissues such as tendon, ligament and skin, and is also abundant in cornea, cartilage, bone, blood vessels, the gut, and intervertebral disc.

Collagen is found in many parts of human body. So far, 28 types of collagen have been identified and described. The five most common types are: Collagen I; which is mostly found in skin, tendon, vascular ligature, organs, bone (main component of the organic part of bone). Over 90% of the collagen in the body is of type one.

Collagen II is mostly found in cartilage. It is the main component of cartilage tissue. Collagen III is known as reticulate collagen and is commonly found alongside type I collagen. Collagen IV is elemental to the structure of basement membranes which is found is most tissues in the body. Collagen V is mostly found in cell surfaces, hair and placenta.

The Collagen in keloid tissue is mostly Collagen I and III.

Tattoos and Keloids

Keloid disorder is a genetic condition of the skin, whereby a triggering event such as a wound or cut, can result in formation of keloids. I am often asked to comment on the safely of tattooing procedure in individuals who have already been diagnosed with a keloid. As can be seen below, the injury of tattooing process can indeed lead to keloid formation. Treatment of this type of keloid is extremely difficult. All those who have been diagnosed with keloid, should avoid tattooing or piercing procedures.