Keywords

1 Introduction

The chances of survival after a major burn injury have constantly increased over the past decades and further decreases in mortality rates seem to be out of reach [1]. Recent data shows that 96.8% of all patients treated in a US burn center survive [2]. However, many survivors suffer from disfiguring scarring, life-long physical disabilities, and adjustment difficulties. Focus has shifted more and more attempts to improve long-term outcomes with recent advances in discovering underlying mechanisms, treatment of scars, and early rehabilitation.

In addition to recent improvements in burn care, another important aspect is prevention of burn injuries, especially in high-risk groups and vulnerable populations such as young children and adolescents, disabled, or the elderly [3]. Given the fact that 73% of all burn injuries that require burn center treatment occur at home [2], education of the public and of specific groups could help decrease the overall number of burn victims, and decrease the number of patients with major disabilities that are unlikely to be reintegrated into society and economy due to devastating long-term sequelae.

This chapter focuses on the long-term outcomes after a severe burn injury. We emphasize one of the most relevant topics in burn rehabilitation: hypertrophic scarring, its treatment with laser therapy including practical guidance, and place them in context of the current literature.

2 Hypermetabolic Response and Long-Term Sequelae of Burn Injury on Organ Systems

2.1 Hypermetabolic Response to Burn Injury and Its Long-Term Effect on Muscle, Bone, and Glucose Metabolism

Severe burn injury leads to a pathophysiological response that affects almost every physiological system within the body. Hallmarks of that response are hypermetabolic stress (increased metabolic rate) with skeletal muscle catabolism (burn-induced muscle cachexia), and insulin resistance (stress-induced diabetes). This hypermetabolic state affects skeletal muscle-, bone-, glucose-, and lipid metabolism as well as the cardiovascular- and immune system and has been shown to persist for up to 3 years [4].

Muscle loss, strength, and cardiopulmonary capacity: After severe burn injury, skeletal muscle (depot of lean body mass) is the main endogenous source for amino acids that are required for production of acute phase proteins and wound healing. As a result, loss of lean body mass occurs after a major burn injury and aggressive nutritional support can only attenuate it partially [5]. This also has functional relevance since lean mass correlates directly with skeletal muscle function [6]. Muscle strength and cardiopulmonary exercise capacity are typically impaired in burned children and in adults compared to non-burned individuals for many years after the injury. Also pulmonary function has been shown to be reduced for up to 7 years after burn [7].

Bone: Severely burned children can be at an increased risk for fractures than their non-burned peers [8]. The exact mechanism that leads to reduced trabecular bone mass for at least 2 years after burn is not yet fully understood. However, resorptive cytokines, elevated endogenous glucocorticoid levels, oxidative stress, and immobilization seem to play an important role in mediating reduction of bone formation and bone resorption, with the result of bone net loss. It is also unclear if this leads to early osteoporosis later on [9].

Insulin resistance and glucose intolerance, and as a consequence hyperglycemia in the acute phase after burn contribute to poor wound healing, skin graft failure, and respiratory tract infections. In severely burned individuals, endogenous glucose production of the liver (central insulin resistance) is increased. At the same time, the ability to store glucose in skeletal muscle is reduced (peripheral insulin resistance). As a result, patients have abnormal high blood glucose levels that can last for up to 3 years after burn [10]. This exacerbates loss of lean body mass and patients might be at risk for developing diabetes.

Long-term effects of temporary hyperglycemia in burn patients are currently unknown; however, glucose levels are usually targeted to be in the range of 90–140 [11]. Treatment modalities for glucose level control are discussed in Sect. 3.1.

2.2 Cardiovascular Response

After a major burn injury, the reaction of the cardiovascular system is complex. The cardiac response to the altered sympathomimetic response of the beta-adrenergic system is problematic and leads to an imbalance of oxygen demand and supply [12]. Contractility is reduced directly after burn due to increased release of antidiuretic hormone (ADH) [13]. Circulating pro-inflammatory cytokines such as TNF-α are impacting intracellular calcium currents and thus account for inducing cardiomyocyte apoptosis and further decreasing myocardial contractility [14]. Furthermore, massive plasma losses after major burn are likely to lead to hypovolemia with hypoperfusion and subsequent central organ ischemia, including acute myocardial and renal ischemia [15]. Elevated pulmonary artery resistance caused by inhalation injury or pulmonary edema typically lead to right ventricular dysfunction [16]. Overall, these mechanisms lead to impaired relaxation, contractility, and reduced compliance of mainly the left ventricle [17, 18]. Compensation for the resulting reduced cardiac output occurs by increasing the heart rate, leading to increased demands of oxygen further leading to bilateral cardiac dysfunction [17, 19, 20].

Cardiac dysfunction is not only a problem during the acute phase, but persists at least for 2 years after burn [21]. A more recent study found that adolescents and young adults who were burned as children demonstrate cardiac abnormalities as long as 12 years after burn. In particular, they found myocardial fibrosis, systolic and diastolic dysfunction, and reduced exercise capacity compared to a non-burned control group. These findings indicate that burn injury leads to tissue remodeling in the heart [22]. Ongoing research aims in discovering underlying mechanisms.

2.3 Effects on the Pulmonary System

Inhalation injury contributes substantially to mortality in burn patients [23]. The pathophysiologic changes in the acute phase are well studied; however, only a few long-term studies exist. Furthermore, comparison of outcomes and measurements remains difficult because burn injury itself affects muscle mass and function, while scarring can lead to reduction of chest wall elasticity. Additionally, a consensual grading system for inhalation injury has not been developed [24].

Lung injury and subsequent long-term outcomes may be attributed to different mechanisms: inhalation injury and inhaled toxins, long-term mechanical ventilation, the systemic inflammatory response syndrome (SIRS), hypermetabolism, pneumonia, or sepsis [25].

For at least 6 months after smoke inhalation injury, airways are hyperactive and bronchospastic, causing patients to develop a productive cough. Elevated levels of inflammatory cytokines are typically found in serum, but elevated levels can also be seen in bronchioalveolar lavage [26]. Both, obstructive, and restrictive patterns, either alone or in combination, can occur after a burn injury, whereas it is more frequent in patients with concomitant inhalation injury [27]. Peak oxygen uptake (VO2 peak) and time to fatigue is reduced in severely burned patients when tested by an incremental exercise test 5 years after burn and compared to healthy controls [28]. Studies in severely burned children have shown that although they can reach the same endurance levels as their healthy peers, their effort is greater and their respiratory system is more challenged [29]. In summary, pulmonary function and aerobic capacity are impaired for several years after burn, both in adults and children. However, burned children with inhalation injury have comparable long-term quality of life outcomes as burned children without inhalation injury [30]. The effect of exercise programs on cardiopulmonary function are discussed elsewhere in this chapter.

2.4 Long-Term Effects of Kidney Dysfunction

Acute kidney injury (AKI) is strongly associated with high mortality, in particular if it develops in the early postburn phase [31]. Patients who need an increased number of operations, receive nephrotoxic drugs, receive a high cumulative fluid balance early on and develop sepsis are at an increased risk for kidney injury [32].

The overall prevalence of acute kidney injury is approximately 25% with a median mortality of 35%. Renal replacement therapy is required in about 1–3% of burn patients with acute kidney injury. Unfortunately, these patients have a mortality rate of up to 80%. Furthermore, AKI is associated with the need for mechanical ventilation and a longer intensive care unit stay [33, 34].

AKI is thought to be a complex problem that affects the whole body on a metabolic, endocrine, and overall organ function of all organs that can persist even after renal recovery. The mechanisms of the so-called organ crosstalk include elevated vascular permeability, changes in gene transcription, inflammatory cytokines, apoptosis, and cell recruitment [35, 36]. Preventing AKI therefore will not only reduce prevalence of chronic kidney dysfunction and its side effects but potentially has an effect on overall long-term outcomes.

2.5 Effects on the Liver

The liver is the major organ modulating the acute phase response via various pathways and thus affecting the inflammatory—and immune response, which has a great impact on recovery and mortality [37, 38].

Liver injury is correlated with the severity of the burn and is usually present to a variable extent in burn patients. Occurrence of liver and heart failure together is common and is associated with a longer hospital stay [39].

Fatty infiltration of the liver is a common finding in burn patients and is reversible [40]. Yet, in non-survivors fatty liver infiltration is associated with liver failure and sepsis, indicating an important role in the acute postburn phase [41].

Liver dysfunction is present immediately after burn, it typically peaks 2 weeks after burn and persists for 4–12 weeks. Mortality is also higher in patients who develop liver dysfunction than in those without [42]. In a study by Jeschke et al. [40], liver weight and size were massively elevated for up to 12 months postburn and hepatic protein synthesis was affected for up to 9 months. In particular, patients had reduced serum levels of albumin, pre-albumin and transferrin, and elevated acute phase protein levels. Serum AST and ALT levels, markers of hepatocyte damage, remained significantly elevated for up to 4 weeks after burn and returned to normal levels afterwards.

It is known that hepatocytes undergo both, necrosis and apoptosis. The mechanisms however have not been fully discovered yet. Hypoperfusion or ischemia-reperfusion and circulatory pro-inflammatory cytokines are considered leading to apoptosis and enzyme release. Hepatomegaly in burn patients is caused by two mechanisms: intrahepatic steatosis and edema. Fluid overload lasts for only about 1 week after resuscitation. Hence, over-resuscitation seems not to be the cause for edema formation [40, 43].

The liver also plays a central role in glucose metabolism postburn, as it releases more glucose than the body is able to utilize (central insulin resistance), as discussed above.

2.6 Mental Health and Pain

2.6.1 Acute- and Post-traumatic Stress Disorder

Preexisting psychiatric disorders are very common in burn patients and increase the risk for sustaining a burn either directly by leading to self-inflicting burns and suicide attempts, or indirectly increasing the risk (e.g., impulse control disorder, personality disorders, substance abuse including smoking, major depression). Those patients also have an increased risk to develop psychiatric problems after the burn [44]. The two most common psychiatric problems after a burn are Acute Stress Disorder (ASD) and Post-Traumatic Stress Disorder (PTSD). Both have many criteria in common, with the most important difference being time of occurrence. The cutoff point is 1 month after burn. Adults more frequently develop PTSD than children, with a prevalence ranging between 3% and 35% at 2 years postburn. That number decreases to 7–25% 3 years postburn [45] and is 2–19% in children [46, 47].

Patients that develop PTSD after a trauma are highly likely to develop psychological comorbidities such as anxiety, depression, substance abuse, and in particular suicidal behavior in adults [48, 49]. Especially children can develop issues in regard to mood and sleep as well as conduct, attention, and learning problems [50]. In addition, burn survivors in particular suffer frequently from adjustment difficulties and disturbed body image due to hypertrophic scars and disfigurement. Patients typically experience flashbacks or nightmares of the trauma, apart from various symptoms that can overlap with other psychiatric disorders [51]. Good relationships and social surroundings, participation in leisure activities as well as positive expectations of the future are helpful in preventing PTSD [45]. Tools for assessment of PTSD can be found at https://www.ptsd.va.gov/professional/assessment/all_measures.asp.

Support groups are an important way to help burned individuals recover and often accompany them for life. They offer a variety of support for all age groups, and especially provide mental support. More detailed information can be found at the websites of The Phoenix Society and Burn Model Systems at https://www.phoenix-society.org and https://msktc.org/burn.

2.6.2 Pain

Burn patients often experience pain that can potentially be limiting and disabling. In fact, it is their number one complaint. An increase in the severity of pain and/or localizations correlate with depression and anxiety. But more interestingly, if symptoms of anxiety or depression are present, patients experience more severe pain [52]. Adequate pain control not only reduces pathophysiological stress responses with reduced production of cortisol and catecholamines, it also reduces the likelihood for the development of post-traumatic pain symptoms [53, 54]. Furthermore, reduced or abnormal sensibility does not only occur in the burned or grafted areas, but also in non-burned regions of the same patients. Thus, changes in the central nervous system are suggested [55].

2.6.3 Post-traumatic Growth

In modern trauma therapy, the focus is not only on reducing adverse effects, but also on supporting psychologic development from the traumatic event. Post-traumatic growth (PTG) is the “positive psychological change that results from a struggle through a life-altering experience” and in adult trauma survivors consists of “greater appreciation of life, improved interpersonal relationships, greater personal strength, recognition of new possibilities in one’s life course, and spiritual or religious growth [56, 57].” To gain PTG, the trauma needs to be strong enough to significantly affect the patient’s world view, but must not be so detrimental that the patient cannot recover. Notably, it is possible that PTG and distress are present at the same time, and studies have shown that distress is necessary initially for growth to happen later in the recovery phase [58]. Several factors have been identified as predictors for PTG; however, ultimately problem-focused coping and cognitive processing can be actively therapeutically addressed [59].

2.7 Long-Term Effects on the Skin: Hypertrophic Scarring

2.7.1 Pathophysiology of the Hypertrophic Burn Scar

Hypertrophic scarring (HTS) is currently one of the most challenging problems after burn injury, if not the most challenging. With a prevalence of approximately 70% [60], it is a massive burden to burn patients and affects them physically, functionally, and psychologically and is therefore the most important issue for reintegration into society.

Hypertrophic scars and keloids are the result of aberrant wound healing, with greatly enhanced fibroblast activity and deposition of collagen. HTS consist of thin collagen fibers that are typically organized in nodules with presence of α-smooth muscle actin (α-SMA), whereas in keloids collagen fibers are thickened and hyalinized [61]. Due to their different pathophysiologic mechanism, keloids grow over a long period of time and can occur without an obvious trigger. They grow beyond the border of the original wound and exhibit a high recurrence rate after surgical excision. HTS on the other hand develop within a few weeks after the skin injury, remain within the borders of the wound, tend to regress to a certain extent over time, and have typically low recurrence rates [62].

In this chapter, we focus on the current understanding of pathophysiology, development, characteristics, and current treatment options of the most relevant scar type developing after burn injury: the hypertrophic scar.

2.7.2 Key Aspects of Hypertrophic Scar Development

The deeper the burn wound, the longer it takes to heal [63]. As a result, deep burn wounds that take longer than 3 weeks to heal are significantly associated with higher risk for developing HTS [64, 65].

The composition and architecture of the extracellular matrix (ECM) is drastically changed, fibroblasts and keratinocytes display increased profibrotic properties and profibrotic cytokines are upregulated and expressed for a prolonged period of time. Collagen production and collagen degradation, both are impaired. In normal wound healing, immature type III collagen is gradually replaced by mature type I collagen, and collagen bundles are organized parallel to the skin surface. In HTS however, type III collagen is proportionally increased and the bundles are highly disorganized [66]. Elastin, important for skin elasticity, is not present in HTS for several years after burn [67].

Nodules, consisting of highly unorganized, immature collagen, small vasculature and large amounts of mucopolysaccharide are seen histologically. These pathognomonic nodules are sharply delineated from surrounding scar tissue, which are mostly composed of similar materials but demonstrate features of more mature scars (i.e., parallel orientation of collagen fibrils) [67].

2.7.3 Proteoglycans and Glycoproteins

Another feature of HTS is elevated turgor and volume due to elevated glycosaminoglycan levels that lead to a hyperhydrated state. Decorin, a small leucine-rich proteoglycan (SLRP), responsible for collagen fibril organization, is significantly downregulated in HTS. It also controls profibrotic cytokines (TGF-β, PDGF) and several growth factors (epidermal growth factor EGF, insulin-like growth factor 1 IGF-1) by antagonistically binding and downregulation, what is disturbed in HTS [68].

2.7.4 Cellular Mechanism Involved in HTS

Deep dermal fibroblasts also play a role in HTS development. They are larger and exhibit the following features compared to superficial fibroblasts: increased collagen and decreased collagenase and decorin production, with increased production of inflammatory cytokines, namely transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF) [69]. It is still unclear whether superficial fibroblasts are simply destroyed by injury and therefore cannot initiate the wound remodeling process or if cytokine stimulation leads to selective proliferation of deep dermal fibroblasts [70].

Myofibroblasts are responsible for wound contraction in the normal wound healing process. In HTS, they express large amounts of alpha α-smooth actin—similar to smooth muscle cells—and are the main factor responsible for the extensive contractions after burn injury [71]. Mechanical stress increases myofibroblast activity, prevents apoptosis of myofibroblasts [72], and leads to excessive accumulation of extracellular matrix. Yet, in burn patients HTS paradoxically occur also in areas minimally exposed to mechanical stress.

Hyperproliferative keratin phenotypes produced by activated keratinocytes have been identified in HTS tissue. These activated keratinocytes suggest disturbances at an epidermal-mesenchymal level [73] and may have negative impact on re-epithelialization.

2.7.5 Cytokines

Several cytokines play an important role in HTS development. TGF-β, for example, is a strong proliferative cytokine that interacts with many other cytokines and is highly upregulated in the serum and in wounds of burn patients. It plays an essential role in many wound healing processes. Of notice, one isoform, namely TGF- β3, has antifibrotic properties and plays a role in the remodeling phase, which could be a potential therapeutic target [74].

2.7.6 Summary

Despite many theories to explain the mechanism of hypertrophic scar formation, it is still poorly understood and subject to extensive ongoing research.

3 Therapeutic Approaches of Long-Term Burn Sequelae

3.1 Pharmaceutical Treatment Options and Investigational Drugs

Recombinant growth hormone (rhGH) has been shown to lead to faster burn wound closure and donor site healing in children and adult burn victims [75]. At our center (Shriners Hospitals for Children and UTMB, Galveston), Branski and colleagues demonstrated numerous beneficial long-term effects (for up to 2 years) after a yearlong rhGH administration in severely burned children. Hypermetabolism was attenuated, lean body mass increased, body fat decreased, and cardiac output had decreased [76].

When administered acutely in critically ill adults, it led to increased morbidity and mortality [77]. Therefore, patients should be monitored closely for possible side effects, in particular hyperglycemia and hypercalcemia. Another disadvantage is the need for daily subcutaneous injections. The effects of long-term growth hormone administration (for 9 months after burn) on cardiac function, muscle strength, cardiopulmonary exercise function, after burn scarring, and overall safety in adult burn survivors are currently under investigation.

Oxandrolone, an orally administered anabolic steroid with a better side effect profile than rhGH, has been shown to attenuate hypermetabolism and lead to an increase in lean body mass, muscle strength, and growth in height in severely burned children, when administered for 1-year postburn [78], with even greater increases in bone density when administered for 2 years [79]. In adult burn victims, long-term data is lacking; however, beneficial effects have been documented for the early rehabilitative phase [80]. Although no liver failure has been reported, transaminases need to be monitored closely due to risk of abnormal liver function.

The non-selective β-adrenergic antagonist propranolol effectively and safely attenuates the hypermetabolic response and reduces heart rate and resting energy expenditure after burn [81, 82]. It has been shown that it not only blunts acute skeletal muscle loss [83], but more recently it also helps regain muscle mass in the early rehabilitation phase when administered for 1 year after burn [81].

The combination of oxandrolone and propranolol administered for 1 year after burn injury was shown to be safe and seems to have positive effects on hypertrophic scars and physical and psychological outcomes in children. Improvements could be shown 2 years after burn and therefore is suggested to be considered a treatment option in severely burned children [84].

Several therapies have been investigated to treat bone loss: Early intravenous administration of the bisphosphonate pamidronate successfully prevented loss of total body and spine bone mineral content (BMC) in the short term compared to placebo as well as 2 years postburn where BMC was still increased in the spine but no difference in whole body BMC was seen. Oxandrolone, given for 1 or 2 years has the potential to improve BMC as well as accelerate growth in height in burned children [79, 85]. Vitamin D substitution has not been shown to improve loss of BMC postburn to date, however improved serum Vitamin D levels in adults and reduced fracture incidence in children were seen [86, 87].

Several strategies exist for attaining glucose control to improve insulin sensitivity and to reduce skeletal muscle catabolism. With insulin therapy, glucose control can usually be maintained, however puts the patient at risk for hypoglycemia, and therefore has to be monitored closely [88].

An alternative treatment option is the oral biguanide metformin, with low risk for hypoglycemia [89]. Fenofibrate, a drug of the fibrate class, was shown to attenuate insulin resistance. However, data is too sparse yet to recommend it as standard treatment [88].

3.2 Physical Exercise Therapy

Positive effects on muscle strength, lean body mass, and peak cardiovascular exercise capacity during the rehabilitative phase after major burn injury in children [90, 91] and adults [92] have been shown after different exercise protocols. These effects seem to be even stronger if in addition if the growth hormone oxandrolone (0.1 mg/kg/day) is administered for 1-year postburn [93]. Also the combination of exercise with the non-selective β-adrenergic blocker propranolol (4–8 mg/kg/day, depending on resting-heart rate) appears to have beneficial effects on cardiovascular exercise capacity (VO2 peak) in burned children [94]. More recently, the combination of the two drugs has been shown to add positively to exercise training to gain muscle strength and improve protein turnover during the early rehabilitative phase [95]. 12 weeks of a combined aerobic and resistance exercise training program was shown to be beneficial in severely burned children with improvements in peak oxygen uptake (VO2 peak) and pulmonary function [96].

At our institution (Shriners Hospitals for Children and UTMB, Galveston), exercise protocols are in place as standard of care to help burn victims restore lean body mass, muscle function and to improve cardiopulmonary capacity. Future research should focus on objectively measurable exercise parameters to develop adequate exercise programs also for adult burn survivors since there is great inconsistency between burn centers and lack of awareness of the importance of such programs, as the survey of Diego and colleagues has shown [97]. It should be pointed out that no study has shown that beneficial effects of exercise training last beyond the rehabilitative phase. Nonetheless, as with the non-burn population, it is essential that physical exercise becomes an integral part in a burn survivor’s life to be beneficial long term.

3.3 Scar Therapy

Apart from the stigma and unpleasant aesthetic appearance that accompanies hypertrophic burn scars, burn survivors suffer from severe pruritus, neuropathic pain, and contractures that often limit range of motion [98, 99]. The most important scar treatment is their prevention. Early excision, the avoidance of skin grafts—if possible, according to burn depth—and early pressure garment therapy are key. If a scar has formed despite preventive therapy, the most effective and important therapy is reconstructive surgery. This is discussed in detail elsewhere in this book.

A holistic approach is usually applied to prevent and treat hypertrophic scars, ranging from traditional conservative therapies, such as compression garments, silicone sheets or gels, physical therapy, intralesional injection of corticosteroids, or 5-fluorouracil. Effectiveness of these extensively used conservative methods has been proven empirically and are widely acknowledged legitimately as standard of care; however, to date little scientific evidence exists supporting their use due to the fact it is difficult to conduct adequately powered randomized clinical trials. Side effects can occur [62, 100,101,102], however in general they are quickly reversible once the treatment is stopped.

Pressure garments are in use for the prevention and treatment of HTS for over half a century and are still considered as standard basic treatment. They are worn for almost 24 h a day for at least 6 months after burn. The pressure achieved ranges between 15 and 40 mmHg [103, 104]. A recent animal study suggests starting pressure therapy immediately after skin graft take might be beneficial [105]. Even though in many cases it is difficult to attain sufficient pressure to the affected area and due to comfort issues, lack of compliance can occur, pressure garments are still to date considered standard treatment for burn scars.

Silicone sheets are usually worn for at least 12 h/day for several months, beginning therapy 2 weeks after wound healing. The mechanisms of action of silicone gel sheeting are occlusion and therefore increased skin hydration and electrical charge changes possibly due to the silicone molecule. To prevent maceration, sheets have to be removed intermittently to let the skin dry [101]. Side effects such as rash, pruritus, contact dermatitis, and dry skin can occur [106]. The combination of both, pressure garments and silicone sheets, exhibits increased efficiency over one treatment alone [102].

The combination of intralesional injections with Triamcinolone (TAC) and Fluorouracil (5-FU) is the most effective regimen. It is more effective over each single treatment alone and has also less side effects, like skin atrophy or telangiectasia. As standard regimen 0.1 mL 40 mg/mL concentrated TAC mixed with 0.9 mL 50 mg/mL concentrated 5-FU is recommended. Scars should be treated weekly for at least 8 weeks. The dose administered should not exceed 2 mL in total per session or 0.5 mg/cm2 [102].

Medical needling is indicated for large burn scar plates that cannot be treated with excision and flaps. A roller with 1–3-mm-long needles is typically rolled in vertical, horizontal, and diagonal directions over the scarred area. The small needles penetrate the papillary and reticular dermis causing mechanical micro injuries without thermal injury or necrosis as compared to other scar resurfacing methods. This induces new collagen and elastin formation and results in thinning of dermis, thickening of the epidermis, increase in non-inflammatory cytokines, and improvement of scar texture with a very low risk for hypo-/hyperpigmentation and scarring. The procedure can be performed under local- or short systemic anesthesia. Currently, there are fully automated devices on the market which are adjustable in speed and penetration depth; however, the principle remains the same. Noninvasive medical needling is also used for intralesional delivery of topical drugs, or can be used in combination with radiofrequency [107, 108]. Figure 1 shows pre- and post-interventional results.

Fig. 1
figure 1

Medical needling results. Left: Hypertrophic scar area localized on the right cheek and neck, preoperatively. Right: Result 3 months after medical needling. The scar texture has significantly improved without changes in pigmentation

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Autologous fat grafting for reconstructive or aesthetic purposes became popular over the recent years. Basic science studies have shown that regeneration of all three layers of the skin is possible with autologous adipose-derived stem cells [109]. This seems to be of great benefit in particular for the treatment of burn wounds. Studies in burn patients have shown that it supports restructuring of collagen, improvement of pigment disorders and overall scar texture. Even though level of evidence is low and more clinical studies are required [110], autologous fat grafting is a promising therapeutic option for the treatment of burn scars, especially in combination with other therapies.

Laser therapy has become widely accepted as a major modality for the treatment of burn scars, especially with growing evidence of its effectiveness over the recent years [100, 111]. Attenuating the scar both aesthetically and functionally and to reduce pain and itching are the ultimate goals. Laser therapy can be used alone or in adjunct prior to surgery to soften the scar and improve outcomes.

3.3.1 Laser Types

Different types of lasers target a specific chemical entity known as a chromophore. Laser energy of a specific wavelength is absorbed by the three main chromophores melanin, hemoglobin, intra- and extracellular water. Penetration depth is dependent upon the amount of energy used [112].

Mechanistically, it has to be distinguished between ablative/non-ablative and fractional/non-fractional lasers. Non-ablative lasers use lower temperatures around 50–70 °C, which lead to coagulation of proteins and collagens, respectively. Whereas ablative lasers use temperatures greater than 100 °C, which cause tissue vaporization, surrounded by a thermal coagulation zone [113].

Fractional ablative laser therapy was developed to overcome side effects related to non-fractional ablative lasers and was first introduced in 2004 by Manstein and Anderson, who termed it fractional photothermolysis [114]. Fractional lasers split the laser beam into many microbeams, leading to hundreds to thousands of small micro injuries, called microthermal treatment zones (MTZ). Ultra-fast pulsed laser beams produce tissue ablation while significantly reducing heat deposition, and therefore causing less collateral damage. The spared surrounding tissue allows for a rapid wound healing response (re-epithelialization after 1-day post treatment), neocollagenesis, and tissue remodeling [115, 116].

Although a huge variety of different lasers have been studied for the treatment of hypertrophic burn scars, ablative fractionate lasers (AFLs) and pulsed dye laser therapy (PDL) seem to be the most beneficial.

The most frequently used laser for the treatment of hypertrophic burn scars are the ablative fractional CO2 lasers and erbium:YAG (er:YAG). At our institution (Shriners Hospitals for Children and UTMB, Galveston), we use the fractional CO2 laser, which we have extensive experience with. The CO2 laser targets water in abnormal collagen up to 4 min below the surface. Figure 2 shows results of CO2 laser therapy.

Fig. 2
figure 2

CO2 laser treatment. 11-Year-old male with hypertrophic scars with hypo- and hyperpigmented areas 2 years postburn. Left to right: Pre OP, 1 day post OP, 6 days post OP, 3 months post OP

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3.3.2 Laser Effects and Side Effects

The main effects that can be accomplished with CO2 laser are a reduction of scar thickness, increased scar elasticity, improvement in surface texture and firmness, improvement in scar pigmentation (hyper- and hypopigmentation), dermal restructuring—reduction of TGF-β1 expression, increase of collagen Type I and III, thickening of epidermis, and last but not least a reduction of pain and pruritus [113, 117, 118].

Improvements in scar appearance have been shown to occur after only one single treatment [119], however usually several sessions with breaks of approximately 4 weeks to 3 months in between are required to attain a good result and can be combined with other treatment modalities like triamcinolone injections [120, 121].

Histologically, laser treatment leads to decrease in collagen bundle thickness and density in the upper dermis, and newly formed dermal papilla [122, 123]. Recent studies identified molecular effects on keratinocytes and fibroblasts [124].

Side effects/complications range from discrete to moderate erythema or edema (what usually resolves in 7–10 days), hyper- or hypopigmentation, post-inflammatory hyperpigmentation (PIH), pruritus or imprints from the laser-grid. Blistering is more common after PDL, whereas CO2 lasers cause more often postprocedural pain, which can usually be treated sufficiently with non-opioid analgesics. Darker skin types are more likely to develop hypopigmentation or blistering. Overall, adverse events are rare and it can be considered a safe procedure if applied correctly [125, 126].

3.3.3 Laser Therapy: Practical Guidance

Treatment should not begin no less than 6 months after wound healing is complete and the scar has matured; however, expert’s opinions vary widely. Successful results have also been accomplished with older burn scars of up to 7–23 years postburn [122, 127].

Laser selection is based on the following criteria: dyschromia (i.e., erythema, hypo- or hyperpigmentation), type of scar (hypertrophic, flat, atrophic), location (i.e., face, neck, trunk), and patient characteristics (i.e., skin type and comorbidities) [128].

We have found that the CO2 laser is the most effective tool in almost all patients because it penetrates deep into tissues, necessary to treat thick hypertrophic scars. There are numerous commercially available fractional CO2 laser units. At our institution (Shriners Hospitals for Children and UTMB, Galveston), we use the Lumenis Ultrapulse device (Lumenis, Santa Clara, CA) with various settings (ActiveFX®, DeepFX®, or SCAAR FX™). We tend to use the SCAAR FX setting for thick, hypertrophic scars, and the Deep FX setting for atrophic, papery scars. The ActiveFX is used to assist in surface changes and to treat hyperpigmentation. For immature hypertrophic burn scars, we use vascular laser settings. The underlying principle is to coagulate micro blood vessels, by targeting the chromophores hemoglobin and oxyhemoglobin, and thus eliminating the vascular supply to the scar. It also addresses localized pruritus, which can be a serious problem, especially in burned children. Historically, pulsed dye laser (PDL) has been used effectively for the treatment of burn scars [129]; however, it is slow and the endpoint required to see as indicator for an effective treatment is a purpuric response. At our institution, we use the Lumenis-M22 platform with different modules. One advantage of the 590 nm filter is that it has the benefits of the PDL but is faster and does not generate a purpuric response. For targeting any telangiectasia within the scar, we use the Nd:YAG handpiece. We often use the vascular laser and the CO2 laser in the same session, with the vascular laser being used first as otherwise the effect of any vascular laser to a bleeding wound would be negligible. Figure 3 shows results of vascular laser treatment. Figure 4 summarizes frequently used laser settings.

Fig. 3
figure 3

Vascular laser treatment. 3-Year-old male with erythematous scars after a scald burn on both hands and forearms. Left: 7 months postburn, before treatment. Right: 16 months postburn, after two treatments with M22 laser. Additionally, the patient has been in compression garments since his wounds were closed

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Fig. 4
figure 4

Common laser/IPL Settings. SCAAR synergistic coagulation and ablation for advanced resurfacing, PDL, pulsed dye laser, Nd:YAG neodym YAG laser, IPL intense pulsed light

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Pre- and aftercare: Perioperative antibiotic prophylaxis is indicated in patients with a history of infection or colonization with multi-resistant organisms. Patients with a history of herpes simplex virus undergoing ablative fractional laser treatment on the face should receive acyclovir for prophylaxis. Both are usually not necessary for non-ablative laser therapy. For patients who are likely to develop PIH, we advocate the use of Azelaic acid (15%) for its tyrosine kinase inhibitory action and have seen great results in most of our patients. Others use hydroquinone prior to laser therapy. For the actual treatment of PHI, a combination of a steroid, hydroquinone, and tretinoin can be used.

Directly after the procedure, we cool the wounds with ice packs. Lasered areas should be left open to air and kept elevated until swelling subsides. We recommend to wash treated areas twice daily with antimicrobial skin cleanser and application of hydrophilic ointment several times a day to prevent dryness and crustiness, until areas are fully epithelialized. By then, compression garments can be worn again. If pruritus occurs, hydrocortisone cream (1%) is applied locally. Sun should be avoided and at least SPF30 sunscreen lotion should be applied daily for a year when exposed after wounds have healed to support preventing PIH.

3.3.4 Conclusion

Despite its clear benefits, laser is certainly not a panacea for all burn scars. Surgical release and rearrangement of tissue is still a mainstay. However, laser therapy is definitively an essential part of any burn reconstruction program and has now become part of the standard of care. Scar management with the ablative fractional CO2 laser is most effective in facial scars, large scar plates of the trunk, and less severe scar bands over joint surfaces, and has replaced conventional surgery in many instances.

4 Summary

Burn injury is not limited to the acute phase. On the contrary, with prolonged hypermetabolism and hypercatabolism as drivers, almost every organ system is affected. Many pharmaceutical options exist, some of them seem to be beneficial for several postburn problems at once, like muscle wasting and scarring. For the most visible organ, the skin, laser therapy has huge potential. However, well-timed surgery and proper surgical techniques are key. In order to achieve the overall goal of reintegration into everyday life, society, work place, school, etc., an individual multidisciplinary treatment plan needs to be developed and constantly adapted for each patient.