Keloids & Hypertrophic Scars
Discussion - Hypertrophic and Keloidal Scarring
Question: What is the present state of the research on Hypertrophic Scars (HS) and Keloids (K).
Answer:The etiology of Hypertrophic scars (HS) and keloids (K) has remained a mystery to researchers and clinicians alike. More often than not research offering proposed origins and causes of these scars turn out to be only effects of even deeper causes. In light of this continuing unraveling the etiology of (HS) and (K) appears to be centered in the dysfunctional skin barrier covering them. It seems ironic, but the evidence is conclusive that the disorder of scars is usually characterized as an over-proliferation of the dermis are producing measurements like resurfaced skin or open blister wounds (1). The research suggest that a functionally compromised skin barrier covering these scars sends a perpetual signal leading to the over proliferation of scar tissue (2). The concept of this etiology almost represents a paradigm shift because it reverses the more traditional healing models centered deeper in the dynamics of the dermis.(2) The stratum corneum study produced objective measurements exhibiting (HS) and (K) having four times the Trans-epidermal water loss (TEWL), as well as four times the stratum corneum turn over rate and electric conductivity when compared to normal skin and atrophic scars (1). Not only is there growing evidence showing (HS) and (K) can be more correctly viewed as unhealed lesions with a compromised barrier driving a hyper-proliferation of scar tissue but other early wound healing symptoms seem present such as redness, itching, and swelling. Also coming into the (HS) and (K) research mix is the isolation of certain lipids as signal transducers to turn on and off certain healing cascades and the dynamics of fibroblast, macro- microphage and scavenger cell morphology.
Question: Why is the skin barrier of (HS) and (K) compromised?
Answer: The top layer of skin or the barrier called the stratum corneum can be likened to a brick wall made of corneocytes (protein bricks) held together by lamellar bodies (lipid mortor) The normal repair of the stratum corneum occurs through the release of cholesterol (3 parts), ceramide (1 part) and free fatty acids (1 part) from the lamellar bodies to the barrier. Evidently in (HS) and (K) the delivery of cholesterol is not reaching
Question: What about traditional therapies such as surgical excision, inter-lesional steroid injections or radiation therapy?
Answer: These traditional therapies are mostly invasive and inconsistent and more successful when noninvasive alternative adjuncts are used. Surgical excision leads to reoccurance 90% of the time. When silicone sheeting is used as a prophalatic after incision there is 90% non-occurance rate. Interlesion steroid injections are thought to work by destroying fibroblast cells that produce collegen. We have found in a clinical setting that more consistent results can be achieved non-invasively through the use of a cerami de cream which acts as a signal transducer inhibiting protein kinase C. In short we are starting to believe nutritional therapy in wound care may prove be more effective than tranditional invasive therapies. Research is centering around catobolization and delivery of these nutrients in the proper timing.
Question: Can you categorize predisposition (HS) and (K) ?
Answer: These over-proliferating scarring disorders can develop from traumatic injuries, severe bums, and surgical procedures. Certain surgical procedures such as breast reduction, or horizontal cesarean sections are very prone. These scars may also develop spontaneously from minor injuries such as acne, ear piercing and even mosquito bites. HS and K are unique to humans and have up to eight times the incidence in darker skin populations such as Asian, African and Hispanic skin types (2% vs.16%) as well as having higher occurrence in tropical regions. Patients family history of scarring disorders is also a strong indication. HS and K also predominate in certain anatomical locations mainly the sternum, stomach, back, jaw, neck, and ears. Very rarely are these scars found in the palms of the hand or soles of the feet. Accutane has been recognized to raise the chances of (K) and (HS). Also, traditionally where we rarely saw patients over forty years old forming these scars there has been a noticeable rise in patients in their sixties and seventies taking the anti-coagulant Coumadin forming (HS) and (K) after heart surgery.
Question: Can you summarize what is involved in the resolution of these scars?
Answer: The best resolution of these scarring disorders is a preventative approach. If you are in a category of predisposition ReJuveness should be applied immediately after the wound is dry or if there is a persistent red mark one month after regular healing time. In established (HS) and (K) the lack of consistent therapies has generated frustration for both clinicians and Researchers in the field have found difficultly in interpreting data and isolating an etiology in the midst of complex dynamic of cellular and physiological events. These scars are resolved by the three step synchronistic process consisting of: I) repair of the skin barrier covering them 2) the elimination of sebum and scar tissue comprising them 3) the apoptosis of fibroblast that are over producing scar tissue. Explain the malfunctioning skin barrier covering HS and K. The stratum corneum or top layer of skin can be likened to a brick wall made of corneocytes (protein bricks) held together by lamellar bodies (lipid morter). The normal repair of the skin barrier occurs through the release of cholesterol, ceramide and free fatty acids by lamellar bodies to the barrier. One signal that initiates the release of lamellar bodies leading to barrier repair is the decrease of calcium gradient. Calcium is more concentrated on the outside layers of skin or the stratum corneum. The calcium gradient is also higher in hypertrophic scars (4) The regulation of the calcium gradient is also essential to the balance of collegen production and destruction ( ) An extra-cellular environment high in calcium will stretch fibroblast promoting collagen proliferation. Conversely a low concentration of calcium typically found at the latter stages of wound healing rounds fibroblast producing collagenase the enzyme which digest and eliminate collagen and scar tissue.(1 0) .
Where does the calcium come from?
The calcium gradient is raised in the early wound through a released by platelets brought in by circulation and eliminated through TEWL. In the micro-vascular occluded HS and K calcium is released from their intercellular stores by inositol triphosphate (IP3) a secondary messenger in the inositude cascade. In what particular way does calcium promote collagen production?
Calcium activates protein Kinase C causing the fibroblast to hyper-proliferate collagen.
How is the collagen production stopped?
Cerami de inhibits protein kinase C and promotes apoptosis of fibroblast ceasing scar tissue production. In K and HS the lamellar bodies are evidently are not being replenished with cholesterol needed to rebuild the compromised skin barrier. Cerami de is apparently absent nor to serve as signal transduction in the inhibitation of proitien kinase C and the apoptosis of fibroblast. The absence of functioning ceramide and cholesterol in HS and K seems to be caused by a malfunction in their catobolization from ox LDL (oxidized low density lipoproteins) The LDL lipid clusters are oxidized by the high amount of free radicals initially at the wound sites but are also oxidized by interferon being brought into the wound site by circulation. Macrophage catabolism of ox LDL occurs only with the proper function of scavenger proteins CD36 and SR-BI (5). The etiology of keloid scarring; anti CD36 anti-body. CD-36 the means by which cholesterol is moved from the basal layer to normalize the stratum corneum. keep up eliminating the excess scar tissue. This process creates excess nitric acid promoting more free radical production, oxidizing low density lipoproteins which when taken up into macrophages where it is reported to metabolizes arachidonic acid. It seems that the high levels archidonic acid found in keloids is inhibiting the influx of CD36 ( ) The catobolization and movement of fatty acid complexes is accomplished by scavenger glyco-protein SR-BI or CD36, which is essential to repair the stratum corneum ( ). CD36 is also essential as well as catobolizing ceramide from cholesterol essential for the apoptosis ? of fibroblast. The elimination of collagen is done by the bacteria collagenase also produced by rounded fibroblast in a calcium free environment. The central interest in the current research on the mechanism of action of silicone sheeting revolves around the scavenger receptor protein called CD36 or SR-BI because of its multi role as a cataboliser and transporter of essential fats, lipids, cholesterol and cerami de in repair of the compromised stratum corneum common to (HS) and (K) as well as the signal transduction of ceramide on protein kinase C.