Ear keloid in an Afro-American patient
In this chapter we aim to show evidence that stress can affect wound healing producing unaesthetic scars, such as keloids, and suggest possible solutions.
Importance of Scars
Impact of Inadequate Skin Scars
Inadequate scars can lead to loss of function, restriction of growth, restriction of movement (particularly because of contractures over joints), poor aesthetics, and adverse psychological effects.
Increase in Surgical Procedures
The USA population is becoming older. It is estimated that people aged 65 and over will almost double its population of 2012 in 2050 . Consequently, there is an increased chance that people may require an operative procedure in some point of life and therefore may be susceptible to development of scars.
The numbers of plastic surgeries are also increasing due a change in the mentality and awareness about the benefits of this type of surgery. There are also many new products and devices available. Non-invasive or minimally invasive procedures can also cause scars .
Any surgery, even endoscopic surgeries in which very small incisions are made, will always produce a scar. These scars can be a small yet permanent reminder of the disease that was treated by surgery or they can become a problem itself.
The goal of the surgeon, especially if the surgery is performed in the face and/or for cosmetic purpose, is to achieve a non-visible scar (or at least minimally visible scar). Many patients do not want other people to know they went through a surgery, especially if it was a plastic surgery. A bad scar can be a major problem for these patients.
In order to obtain a pleasant scar, the surgeon must be aware of the factors that should either be avoided or performed during surgical procedures, as well as the patient’s habits and characteristics. For example, the habit of smoking is known to interfere with all scarring stages. This habit should ideally be discontinued before any surgery, especially before certain cosmetic surgeries, such as facelifts that can produce visible scars . On the other hand, patients’ ethnical background or skin types (precisely IV or V) may impact negatively on the scar , but this cannot be changed. The surgeon’s obligation is to recognize and when possible, change the factors that can impact in the scar healing.
Recent studies have been shown the impact of an interesting modifying factor in the healing process: the stress.
Stress can be modified or managed with innumerous anxiety-decreasing techniques, such as exercising, relaxation techniques, and medications, which goes beyond the scope of this chapter. It is recommended that elective surgeries should be avoided during stressful periods, such as school testing period.
The process of wound healing can be divided into three main processes: inflammation, proliferation, and remodeling.
Inflammation starts when disruptions of capillary blood vessels start the induction of the hemostatic cascade. The leaked intra- vascular contents form fibrin clots. Platelets degranulation releases enzymes and cytokines that recruit cells such as fibroblasts.
The second stage in wound healing is proliferation, which begins around day 4 or 5 with the migration of fibroblasts into the wound matrix. The fibroblasts synthetize extracellular matrix (ECM), which paves the way for migration of various cells that collaborate in the wound healing process.
Wound contraction usually begins around day 10 to 12. Myofibroblasts, which contain actin filaments, help to initiate wound contraction.
By 2–4 weeks, the fibroblasts replace the fibrin with a more robust matrix of collagen fibers. In the mature wound, the initial elastic fiber network is no longer observed and explains the firmness and absence of elasticity of scars.
The third and last stage in wound healing is the remodeling phase, which usually begins 3 weeks after tissue injury. Microscopic findings of this stage include decreases in fibroblast count, occlusion of blood vessels, and hardening of collagen fibers (transformation from collagen type III to type I).
Continuous collagen production and degradation has an effect of remodeling the mature wound matrix for approximately 6 months post injury. At this point, production and degradation balances each other, and no significant change in collagen amount is observed. The remodeling phase is the most responsible for intra and interpersonal variations in scar qualities. A wound can become an unsightly scar during this period.
There are different types of stress. Stress can be chronic, acute, sequenced, distant, actual or perceived.
Actual stress involves things that have a direct effect on the subject, which includes environmental stress (air, water and noise pollution), harming behaviors (smoking, drinking, diets, lack of sleep) and even psychological stress (issues related to relationships, job, financial, and others). On the other hand, perceived stress are the feelings or thoughts that an individual has about how much stress they are under at a given point in time or over a given time period. It is result of the interaction between the individual and his or her environment, and this assessment is influenced by traits such as personality, coping resources, and social support .
In addition, the question is: Would there be a difference in the healing process and therefore formation of unaesthetic scars or keloids if the person were experiencing actual stress or perceived stress? To correctly answer this question is important to keep in mind that actual and perceived stress are not directly proportional. Sometimes, people with high perceived stress have low actual stress levels. But perceived stress raises cortisol levels just as the actual stress does.
Burns et al.  evaluated the immune response to a vaccine, and found that high perceived stress, but not life events stress (actual stress), was associated with low antibody titers (low immunity) .
In addition to directly modulating physiological responses to skin damage, stress can also indirectly influence wound repair by promoting the adoption of health-damaging behaviors. Individuals who experience greater levels of stress are more likely to increase their alcohol and tobacco use, decrease their participation in physical activity, experience sleep disturbances, and make poorer diet choices, compared to individuals reporting less distress. These negative health behavior practices can then compound the detrimental impact of stress on physiological healing processes .
The Patophisiology of the Stress on Scars
The skin is actually considered part of the Neuro-Immune-Endocrine System, establishing a bidirectional communication: from periphery (skin) to central (central nervous system) and vice-versa (Table 7.1).
Hormones and signals produced by the skin relating the skin to the Neuro-Endorine-Immune system
CRH (corticotropin-releasing hormone)
Keratinocytes, melanocytes, pilosebaceous units
ACTH (adrenocorticotropic hormone) and α-MSH (α-melanocyte stimulating hormone)
Keratiinocytes, melanocytes, pilosebaceous units, fibroblasts, endothelial cells
Keratinocytes, pilosebaceous units
Cytokines and growth factors
IL-1 (inteleukin 1)
Keratinocytes, melanocytes, fibroblasts, endothelial cells
Keratinocytes, fibroblasts, pilosebaceous units, endothelial cells
TNF-α (Tumor necrosis factor-α)
There are two important axis: (1) the skin has an equivalent to the Hypothalamus-pituitary-adrenal (HPA) axis, which coordinates stress responses with the central HPA axis. The activity of the HPA axis is governed by the production of Corticotrophin releasing hormone (CRH) by the Hypothalamus, which on your turn activate the secretion of Adrenocorticotropic hormone (ACTH) by the Pituitary gland. The ACTH stimulates the secretion of steroids by the Adrenal cortex. (2) Since the skin is highly innervated with sensory nerves derived from the dorsal root ganglion, it forms a direct path between skin and the adrenal glands, the(Sympathetic-Adrenal-Medullary axis). This system mediates the main adaptive response to systemic stress, either external or internal. In the skin, it protects against stressors such as the UV radiation and pathogens.
Skin reactions to stress can range from itching and pain (which are well known as psychodermatosis, induced by neurotrophins and neuropeptides) sweating (that can cause alteration of skin conductance and impedance, which alters patterns of migration of cells to injured areas), and affected barrier function by alteration of permeability homeostasis and can facilitate infection (induced by increased levels of glucocorticoids which inhibit epidermal lipid synthesis). All these factors can alter the process of wound healing [1, 7, 13, 20].
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Stress X Scars: Human Studies
Many studies show that psychological stress can affect the skin, for example in diseases such as psoriasis, atopic dermatitis and urticaria. Studies performed in animal models showed that psychological stress induced by insomnia, over-crowding, and noise affect the wound healing process [1, 5]. A few prospective studies were conducted in humans to evaluate the effect of the stress in the wound healing (Table 7.2).
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