Skin Failure: Concept Review and Proposed Model : Advances in Skin & Wound Care

Skin Failure: Concept Review and Proposed Model : Advances in Skin & Wound Care

Skin failure is increasingly recognized as a clinical syndrome. Like all other organs, skin can fail; however, experts continue to grapple with definitions, causative factors, and identifying manifestations. There are currently a number of overlapping clinical entities that have not been well defined by rigorous research criteria nor recognized by all providers and regulatory bodies across the healthcare continuum. Establishing skin failure as an entity by defining contributing factors similar to other organ systems will enable providers to recognize and address it effectively in practice and assist regulators by recognizing and incorporating these pathophysiologic factors into quality measurement criteria. There is a pressing need to define skin failure as a clinical syndrome and understand its pathophysiology because of its implications for both clinical care and healthcare policy.

For over 3 decades, clinicians have sought clarity on skin failure, offering various hypotheses and nomenclatures regarding its genesis and existence. The purpose of this article is to establish a scientific basis for skin failure by identifying pathophysiologic factors that lead to consequences at the cellular level resulting in disruption of the cutaneous barrier and underlying tissues. The model in the Figure details the synergy of these factors including acute and chronic conditions and how they act to alter dermal physiology leading to barrier disruption and skin failure. The model does not include wounds related to acute trauma such as lacerations or skin tears, wounds related to malignancy, or factors that impact healing discussed elsewhere. Rather, the goal of this article is to propose a conceptual framework for future discussions and research as well as a path to a clear, unifying classification system that takes into consideration terminologies and diagnoses that fall within the skin failure spectrum.

It should be noted that current definitions of skin failure assume visible changes and/or disruption of the dermal barrier. However, the physiologic processes that lead to skin failure take place before visible disruption appears and may involve tissues below the skin, including connective tissue and muscle, which are subject to the same stressors.

A definition for skin failure was initially proposed by Irvine in 1991: “Skin failure could be defined as a loss of normal temperature control with inability to maintain the core temperature, failure to prevent percutaneous loss of fluid, electrolytes and protein with resulting imbalance and failure of the mechanical barrier to penetration by foreign materials.” He proposed that skin failure is equivalent to the failure of other organs and included etiologies such as thermal burns and dermatologic conditions such as erythroderma, toxic epidermal necrolysis, and Stevens-Johnson syndrome, but did not mention pressure injuries (PIs) as a manifestation of skin failure.

The next contribution to the definition of skin failure was offered by Langemo and Brown in 2006: “…an event in which the skin and underlying tissue die due to hypoperfusion that occurs concurrent with severe dysfunction or failure of other organ systems.” They postulated the existence of acute skin failure occurring with critical illness, chronic skin failure concurrent with chronic disease states, and end-stage skin failure occurring at the end of life, with hypoperfusion as the primary cause. Langemo and Brown’s definition was expanded by Levine, who stated, “Skin failure is the state in which tissue tolerance is so compromised that cells can no longer survive in zones of physiological impairment that includes hypoxia, local mechanical stresses, impaired delivery of nutrients, and buildup of toxic metabolic byproducts.” He further acknowledged that skin failure could be acute or chronic, and chronic skin failure is characterized by disruptions in skin integrity that fail to heal or regenerate in a normal sequential manner to regain structure and function. Delmore et al furthered the acute skin care definition through their research. Like Langemo and Brown, Delmore and Cox stated that acute skin failure is a complex phenomenon distinct from a PI. They postulated that the main etiology is attributable to failure of the skin and/or supporting structures from diseases and conditions during critical illness.

The dermatology literature offers a different set of criteria whereby acute skin failure is a life-threatening situation with single-organ genesis requiring immediate treatment. These diagnoses share a series of events that result in involvement of the entire body with consequences that include hemodynamic changes, impaired thermoregulatory control, and metabolic complications.

Several authors have proposed a variety of terminologies and clinical syndromes that fall within the spectrum of skin failure. These include the Kennedy terminal ulcer, Trombley Brennan terminal tissue injury, Skin Failure at Life’s End, and unavoidable PI. In a review of terminal ulcer terminology, Levine pointed out these terms’ intrinsic weaknesses that include conflating separate concepts of diagnosis and prognosis, the wide spectrum of definitions of the end-of-life period, and the lack of accuracy in predicting death. Adding to the confusion, the term acute skin failure, which commonly occurs in critical care situations, is often used interchangeably with the more general term skin failure.

The distinction between skin failure and PI remains controversial. In 2010, experts at a consensus conference hosted by the National Pressure Ulcer Advisory Panel defined unavoidable PI as occurring even though providers have evaluated the individual’s clinical condition and risk factors and implemented interventions that are consistent with individual needs, goals, and recognized standards of practice. Adding further complexity, the CMS adopted the concept of unavoidable PI and terminal ulcers in their regulations governing skilled nursing facilities, although there are no similar guidelines in acute care environments. This disparity is perplexing because human disease follows the same pathologic and physiologic principles across the healthcare continuum. In addition, PIs are a commonly designated quality indicator. A determination of quality deficit brings adverse consequences including dissatisfied patients, regulatory citations, and risk management issues, all of which may not be warranted if the quality indicator is faulty or inadequately defined or, in this case, inconsistently applied.

When determining the presence of skin failure, the clinician’s focus should be on the primary etiology of a wound, whether it occurred from pressure forces or a combination of pathophysiologic factors leading to skin failure. Proper prevention strategies should always be applied based on a patient’s risk factors, and wounds occurring from inadequate prevention should not be labeled as skin failure or acute skin failure. When all possible strategies have been applied and a wound still evolves, the next step is to determine the primary etiology.

Before identifying and discussing the risk factors and physiologic consequences of skin failure, a brief review of dermal anatomy and physiology is necessary to provide context. The skin is the largest and arguably the most complex organ, and to this point, its multiple functions are summarized in Table 1 (not all of which pertain to the proposed model of skin failure).

The discussion on skin failure concentrates primarily on physical, chemical, immunologic, and microbiome barrier functions, all of which intertwine to protect the organism. The physical barrier is composed of various anatomic levels of skin that include the system of tight junctions between cells in the stratum corneum and the complex vascular structures that supply oxygen and nutrients and remove waste. The immune barrier is composed of resident cells that sense microbial danger signals, initiate immune response, and trigger inflammation. The chemical barrier is composed of sebum, which contains triglycerides and cholesterols, as well as an acidic surface pH, all of which maintain natural moisturization. The microbiome barrier is a microbial community including commensal bacteria and fungi that control potential pathogens. Underlying illnesses and concomitant physiologic aberrancies weaken barrier function and can result in skin failure.

Despite its size and complexity, and in contrast with other organ systems, there are currently no reliable biomarkers to measure skin failure. In contrast, congestive heart failure can be measured by ejection fraction, presence of left ventricular hypertrophy, and elevated central venous pressure. Renal failure can be measured with blood urea nitrogen, creatine, and glomerular filtration rate. Biliary failure can be measured with ammonia level, international normalized ratio, and bilirubinemia. The absence of biomarkers should not prevent clinicians from diagnosing skin failure if clinical criteria are defined and recognized. There is thus an urgent need to recognize the existence of skin failure, define clinical criteria, and identify biomarkers.

Some argue that the diagnosis of skin failure is not possible when manifestations are limited to specific portions of the organ (ie, in dermatologic conditions such as Stevens-Johnson syndrome or toxic epidermal necrolysis). A corollary of this argument is the assumption that skin failure and PIs are separate entities. These arguments do not hold up when taking into consideration regional variations in skin anatomy and physiology and how these variations alter the response to regional stressors, particularly in the setting of advanced age and/or comorbid conditions. There are striking regional anatomic variations in epidermal thickness, pigmentation, amount of pilosebaceous units and eccrine glands, concentration of melanocytes, presence of smooth muscle, structure of dermal papillae, thickness of fat layer, presence of nerve endings, density of capillaries and other vascular structures, and others. These regional variations are genetically programmed in positional codes that arise during embryonic development and manifest in a level of anatomic and physiologic complexity beyond what is represented diagrammatically in cross sections of skin commonly found in textbooks. Regional differences are also impacted by aging and disease, increasing the propensity to develop local areas of skin failure. In addition, certain drugs and other therapeutics such as radiation therapy can alter and impair anatomy and physiology of skin, as well as disease processes that affect macrovasculature and microvasculature.

The sacrococcygeal and heel areas are unique in their circulation and structure compared with the rest of the body, rendering them more prone to skin failure in the presence of multiple synergistic comorbidities and chronic conditions. The sacrococcygeal junction, buttocks, and ischium differ in circulation and tissue composition. Of these areas, the sacrococcygeal area is more easily compromised than the buttocks and ischium. Circulation and elastic fibers allow tissue recovery after deformation and sacral skin has adequate capillary density but less elastic fibers. This imbalance can delay tissue recovery, and when significant comorbidities are present that decrease tissue oxygenation and perfusion, the response and recovery time will be delayed. The heel area suffers the same fate and is equally vulnerable to ischemic damage. The posterior calcaneus is a large bone with relatively little skin and subcutaneous tissue that receives its blood supplies from collateral circulation.

The body has been described as a three-dimensional jigsaw puzzle supplied by source arteries responsible for perfusion of skin and underlying structures, with composite units termed angiosomes. When a disease process such as atherosclerosis impairs a specific artery’s flow, the areas of skin perfused by that artery will be more prone to failure than others. When additional comorbidities such as microvascular disease are superimposed, the susceptibility of these areas to hypoperfusion is further increased. Other sources of tissue deformation, particularly in the context of multiple physiologic aberrancies, will accelerate the process of local skin failure.

There are several pathophysiologic factors that lend credence to the theory that skin failure and acute skin failure are the result of multiple acute and chronic/comorbid conditions. These include hypoperfusion, hypoxia, inflammation, vascular permeability, and edema. Skin failure may include levels of tissue adjacent to and/or below the skin that share similar dependence on oxygen, nutrients, and intact structural anatomy. Accordingly, skin failure can be conceptualized as a local or widely distributed phenomenon.

Hypoperfusion is simply decreased blood flow to an organ. Hypoperfusion has multiple causes, including decreased cardiac output, decreased oxygen-carrying capacity of the blood, and vasculature obstruction. In hypotension or low cardiac output states, the ability to perfuse tissues and organs becomes compromised. Diseases such as valvular disorders, congestive heart failure, cardiac tamponade, shock, and large volume blood loss will reduce cardiac output, decreasing the ability to maintain BP. Failure of the cardiovascular system to perfuse tissue leads to dysfunction in cellular metabolism and impairment in both oxygen and glucose use. Respiratory failure can result in hypoperfusion when pulmonary function is compromised. Anemia is a state of reduced oxygen-carrying capacity of the blood that contributes to impaired tissue perfusion. Hypoperfusion can influence tissue oxygen levels and thus is associated with hypoxia.

Hypoxia is present when insufficient oxygen leads to failure of homeostasis. When oxygen delivery is impaired, a detrimental physiologic cascade occurs at the cellular level that includes membrane instability, cellular edema, and intracellular acidosis caused by the switch to anaerobic metabolism, including release of hypoxia-inducible factor. Impaired oxygen use forces cells to switch from aerobic metabolism to anaerobic metabolism, resulting in a deficit of adenosine triphosphate production and cellular edema. Anaerobic metabolism affects pH by producing lactate leading to metabolic acidosis. As blood pH decreases, reduced oxygen-carrying capacity in the blood ensues. In severe low output states such as shock, blood is shunted from the peripheral circulation to improve oxygenation and perfusion to the central vital organs, which in turn compromises perfusion to skin including at-risk anatomic areas such as the heels. Moreover, impaired tissue perfusion impedes the skin’s tolerance for pressure by forcing capillaries to close at lower interface pressures.

Both macrovascular and microvascular diseases contribute to hypoperfusion; hypertension, hyperlipidemia, and diabetes mellitus are important risk factors. Diabetes mellitus, particularly when poorly controlled, results in a spectrum of vascular disease that includes reduced vasodilatation, and microvascular and macrovascular impairment, resulting in local hypoxia and poor tissue perfusion. The relationship of hypoxia and inflammation has been linked to many conditions including certain cancers, infection, and acute pulmonary conditions.

The inflammatory response can be acute or chronic and serves as a protective mechanism to destroy pathogens, trigger adaptive immunity, and initiate healing. Although inflammation is protective, it can damage living tissue by adversely affecting the vascular endothelium, increasing permeability, and impairing function of the dermal barrier and underlying tissue. In turn, this causes edema and structural compromise and decreases nutrient delivery and waste product removal, elevating the risk for skin failure.

Inflammation is activated by injury in vascularized tissue by conditions including infection, ischemia, and physical and chemical injuries. Acute inflammation induces a rapid onset of changes to microcirculation that includes hemostasis, vasodilation, increased vascular permeability causing fluid leakage into the interstitial space, and white blood cell adhesion. Chronic inflammation can occur as a result of an unsuccessful acute inflammatory response, or as a distinct clinical process with insidious onset, prolonged course, and slow resolution. Most chronic illnesses including diabetes manifest a component of inflammation. Both hyperglycemia and aging are associated with increased levels of inflammation that cause accelerated damage to tissue.

Increased vascular permeability as a result of endothelial dysfunction occurs with an array of comorbidities resulting in leakage of fluid into the interstitial space. Capillary walls consist of a single layer of flattened endothelial cells that constitute a dynamic barrier between the blood and surrounding tissue. Other components include the basement membrane, extracellular matrix, and endothelial glycocalyx (a mesh-like matrix that prevents proteins from passing into the interstitium). Regulation of vascular permeability is dependent on interaction of intrinsic and extrinsic factors and inflammatory mediators. Both inflammation and hypoalbuminemia cause increased vascular permeability.

Vascular permeability is influenced by BP and molecular regulators such as growth factors and inflammatory mediators. Physiologic insults such as burns and sepsis derange the microvascular barrier. Several disease states causing vascular hyperpermeability include infections, diabetes mellitus, immune disorders, and cancer, as well as age-dependent alterations in basement membrane thickness. The presence of these preexisting conditions sets the stage for accelerated vascular hyperpermeability with a predisposition for skin failure because of structural compromise, impaired oxygen and nutrient transport, and inability to remove waste.

Edema represents structural compromise in an abnormal accumulation of fluid either within cells or in the interstitial space, thereby increasing the diffusion distance for delivery of oxygen and other nutrients and limiting waste removal. There are two types of edema: intracellular and interstitial. Intracellular edema is primarily a consequence of ischemia, whereas interstitial edema is caused by increased hydrostatic pressure, decreased colloid osmotic pressure, and impaired lymphatic drainage. Both contribute to the development of PIs and deep tissue injury.

Edema and its extreme form anasarca have multiple causes, including decreased plasma oncotic pressure from hypoalbuminemia, increased plasma volume, increased vascular permeability, and lymphatic obstruction, as well as illnesses including liver disease, congestive heart failure, renal disease, malignancies, and others. Medications that worsen edema include estrogens, antihypertensives, thiazolidinediones, corticosteroids, calcium-channel blockers, and nonsteroidal anti-inflammatory drugs.

Hypoalbuminemia is a common cause of edema from loss of oncotic pressure and has many contributing factors, including malnutrition, nephrotic syndrome, liver failure, chronic renal or hepatic disease, protein-losing enteropathies, and inflammatory states. Serum albumin level can drop precipitously in the setting of inflammation and is therefore a negative acute-phase reactant. Whatever the cause, edema distorts tissue architecture, impedes nutrient delivery and waste removal, and increases susceptibility to skin failure.

In summary, an array of underlying pathophysiologic factors can lead to skin failure synergistically. For example, patients with acute pulmonary conditions can experience simultaneous inflammation, hypoxia, hypoperfusion, and edema. Moreover, inflammation results in increased vascular permeability, which manifests as edema. Skin failure is therefore a complex phenomenon reflective of multiple preexisting conditions and cellular interactions.

A number of acute and chronic conditions produce physiologic effects that promote or facilitate disruption of the cutaneous barrier and underlying tissues. This section provides examples illustrating how these effects lead to skin failure. The authors acknowledge that there are complex multifactorial conditions that may not fall into a single physiologic classification leading to skin failure, including changes with age and the dying process.

Multiple organ dysfunction syndrome (MODS) is the progressive dysfunction of two or more organs as a result of a massive inflammatory response caused by a severe illness or injury, which can result from an infectious process such as septic shock or noninfectious conditions such as massive trauma. A major feature of MODS is maldistribution of blood flow, endothelial disruption, and hypermetabolic state with inadequate oxygen delivery to the tissues. An imbalance in the demand for oxygen and widespread hypoxia to body tissues and organs results in cellular acidosis, impaired cellular function, and increased risk for skin failure. Many of these characteristics are shared by systemic inflammatory response syndrome and severe sepsis, both of which manifest systemic inflammation and increased capillary permeability. As discussed by Langemo and Brown, skin as an organ is subject to failure. Therefore, as the largest organ of the body, acute skin failure should be considered in the spectrum of MODS.

Skin injuries with MODS have been reported by several investigators. Recent investigations examining acute skin failure in critically ill patients found failure of two organs (lung and liver) to be significantly associated with the development of acute skin failure. In a follow-up study, Delmore et al found respiratory and renal failure predictive of acute skin failure.

Protein-calorie malnutrition (PCM) impacts the skin’s barrier function and protective mechanisms and plays a key role in both frailty and sarcopenia. Malnutrition results from inadequate intake of protein, calories, and micronutrients, as well as hypermetabolism or negative nitrogen balance from disease-associated inflammation and other mechanisms. This becomes a vicious cycle as inflammation potentiates PCM from anorexia and decreased food intake with elevation of resting energy expenditure and increased muscle catabolism. Any condition that results in inflammatory, hypermetabolic, and/or hypercatabolic states will increase the risk for malnutrition and impair the body’s response to nutrition interventions.

Along with accompanying micronutrient deficiencies, negative nitrogen balance, and other imbalances, PCM creates a state whereby the skin cannot respond adequately to physiologic stressors. Therefore, PCM promotes skin failure by attacking all levels of the cutaneous barrier via hypoalbuminemia, edema, vascular leakage, immune compromise, hypoperfusion, and so on, impairing the skin’s ability to respond appropriately to challenges and increasing vulnerability to skin failure.

The immune system is an integral component of the dermal barrier for both infection prevention and structural maintenance. There are multiple components of the dermal immune system including biomolecules and pH regulation, cell-mediated and humoral immunity, and maintenance of the microbiome. When tissue becomes vulnerable, stressed, damaged, or invaded by pathogenic microorganisms, the immune system steps in to prevent further damage and initiate the process of healing.

Protective biomolecules include antimicrobial peptides and lipids that participate in skin defense by disrupting bacterial membranes. The pH of human skin is slightly acidic, rendering it inhospitable for pathogens and promoting a commensal and protective microbiome. An array of cellular and humoral constituents protects and promotes tissue function and acts as sentinels by actively sampling environmental antigens. Cellular elements, which are only a partial component of the skin’s immune system, are presented in Table 2.

Because of its inherent complexity, immune system compromise can occur via multiple mechanisms and in concert with other physiologic stressors can lead to skin failure. Causes can include infectious diseases such as HIV, autoimmune diseases, pharmacologic factors such as steroids, immunomodulators, cancer chemotherapies, and changes with age. Diabetes mellitus is a disease commonly associated with altered immune response resulting from glycosylation of immunoglobulins and leukocyte dysfunction leading to lower resistance to infection, which further accelerates skin breakdown and impairs healing. Immunocompromise via multiple mechanisms therefore impacts integrity of the cutaneous barrier, creating susceptibility to skin failure.

There are acute and chronic conditions that may not fall into a single physiologic classification leading to skin failure, including changes with age and the dying process, but that have a common denominator in increasing the vulnerability of skin. For example, a central discussion in geriatrics is differentiating between changes with age and changes associated with specific diseases.Homeostenosis is an older term that references the increased vulnerability to disease that occurs with aging because of decreased physiologic reserve. This concept has subsequently been subsumed into the evolving concept of frailty, which is addressed below. Changes with age are both intrinsic and extrinsic and cause both structural and physiologic compromise that increases the vulnerability of skin (Table 3). The cumulative result is decreased homeostasis and increased risk for damage, which can begin the process of skin failure.

Frailty and sarcopenia are conditions associated with aging that share components of malnutrition, functional decline, and increased mortality risk. Frailty is characterized by decreased functional reserve and ability to respond to physiologic stressors, resulting in greater vulnerability and increased risk for adverse outcomes. It is postulated that frailty represents a final common pathway that manifests in cognitive and functional decline, disability, falls, failure to thrive, PIs, institutionalization, prolonged hospital stay, readmissions, and death. Sarcopenia is associated with a progressive and generalized loss of skeletal muscle mass and function, and many authorities consider sarcopenia a cause of frailty. Components of sarcopenia include increased inflammatory cytokines, reduced food intake, decreased blood flow to muscle, and age-related decline in anabolic hormones such as growth hormone. Because of their multifactorial impact on function and nutrition, both frailty and sarcopenia should be considered risk factors for skin failure.

The barrier function of skin requires intact cellular structures and anatomic connections between cells. A number of forces promote or facilitate disruption of the cutaneous barrier and underlying tissues. This section provides examples of structural impairment, illustrating how each promotes cell death and impairs the protective function of skin leading to skin failure. This discussion regarding structural impairment does not include acute trauma such as surgical wounds, lacerations, and skin tears.

Cells are networked in systems that have the capability to adapt and respond to their internal and external environment. The effective barrier function of skin is dependent on this intact structure. This adaptability includes the cell cytoskeleton continuously reacting to maintain the cell’s shape and morphology and support normal cell functions. The cytoskeleton allows for the mechanical stability required to withstand extracellular forces that can cause shear stress and deformation. The cytoskeleton can become dysfunctional with external forces causing tissue distortion, leading to cell deformation and loss of integrity, thereby generating a cascade of destruction that leads to apoptosis. Tissue deformation as caused by pressure and shear is an important component of PI genesis. Given the well-described impact of external deformation and cytoskeletal dysfunction, the authors include PI as a factor that impairs structural integrity and increases vulnerability to skin failure.

Moisture creates threats to the skin’s barrier function that include maceration from prolonged exposure to various sources of moisture or the failure to maintain proper microclimate. However, moisture alone is not enough to cause skin damage, but rather the chemical content of the moisture and presence of pathogenic microorganisms contribute to impaired skin integrity. The disturbance caused by excessive moisture, the chemical composition of the causative agent, and alteration of the acid mantle with changes in pH interferes with the ability to suppress bacteria and maintain normal tensile strength. Therefore, in the context of skin failure, and similar to external forces of pressure/shear and other comorbidities, moisture can synergistically potentiate failure of the skin’s protective barrier function.

Several pharmaceuticals increase susceptibility to skin failure through a variety of mechanisms including alteration of skin anatomy, decrease in blood perfusion, and impaired immune function. Corticosteroids, also known as glucocorticoids, are anti-inflammatory drugs that have the immediate effect of suppressing the immune system. Prolonged systemic or topical administration can lead to irreversible atrophy of the skin. In addition to immune suppression, systemic corticosteroids cause glucose intolerance and edema, both of which can increase vulnerability of skin.

Vasopressors are pharmacologic agents often prescribed in the setting of hypotension refractory to fluid resuscitation. Vasopressors shunt blood from the skin and peripheral circulation to central vessels by increasing peripheral vascular resistance and elevate mean arterial pressure in shock states. Because of their potent vasoconstrictive action, vasopressor agents contribute to the high incidence of PIs reported in critical care. The risk may be compounded by administration of more than one pressor agent, refractory hypotension, and prolonged mechanical ventilation. Vasopressors’ contribution to acute skin failure is suspected, but currently, this lacks empirical evidence, and further study is warranted.

Chemotherapeutic agents target rapidly dividing cancer cells at different points in the cell cycle, resulting in impaired tumor growth, but adverse events affecting skin are well known. Mechanisms of action vary widely from direct cellular toxicity to altering cutaneous vasculature. As a result of these effects on various cells and tissues, chemotherapeutic agents in conjunction with the debility of advanced cancer and other comorbidities can increase risk for skin failure.

Immunomodulators and immunosuppressants are a class of drugs that revolutionized the treatment of inflammatory and autoimmune diseases and assist in the survival of transplanted organs. Mechanisms of action vary, but they share selective inhibition of various aspects of the immune system. Immunosuppressive agents have adverse effects on wound healing and increase the risk for infection. Because the immune system is a major component of the cutaneous barrier, immune compromise could increase the risk for skin failure in conjunction with other conditions. For both chemotherapeutics and immunosuppressants, it is the compounded effects of both the condition and the treatment that predisposes the skin to fail.

Skin disruption in persons who are dying was recognized in the 19th century when Charcot described the decubitus ominosus. The dying process is associated with alterations in skin integrity, and a variety of terminologies have been offered to describe terminal ulceration. In today’s healthcare environment, incorporation of this terminology is problematic particularly because there is no common consensus as to the end-of-life period. Medical technology offers powerful interventions to prolong or delay the dying process, rendering these terms inappropriate except in patients who are recognized by both clinicians and family as actively dying.

Research on skin changes associated with the dying process is sparse; however, commonly recognized physiologic changes include hypotension and decreased oxygen saturation. In an effort to define skin failure within this context, the proposed model connects a common denominator of physiologic principles to this clinical syndrome, which is recognized across the healthcare continuum. The model therefore considers disruption of skin integrity related to the dying process as a component of the spectrum of skin failure.

The dermatologic literature offers several disorders postulated to cause skin failure. These include graft-versus-host disease, Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythroderma (exfoliative dermatitis) that are accompanied by hemodynamic changes, impaired thermoregulatory control, and metabolic complications. Because of their single organ genesis as proposed by the dermatologic discipline, they appear as a separate pathway in the proposed model.

Other conditions such as radiation dermatitis can compromise the intrinsic structure of skin and underlying tissues, rendering it prone to failure when subjected to internal and external stressors. The long-term histopathologic effects of radiation therapy can remain for months or years, depending on dose and volume. Although these effects typically involve the epidermal and dermal layers, subcutaneous or other structures can be affected, creating an increased vulnerability to skin failure.

Scar tissue contains attenuated vasculature and densely packed collagen that maintains only 80% of the strength of normal tissue. In addition, many closed PIs might have ongoing activity in the proliferative and remodeling phases of wound healing, resulting in intrinsic structural weakness. Insofar as this represents structural compromise, scar tissue is a potential starting point for skin failure.

Skin is the largest organ of the body and arguably the most complex. Just as there is no single function of skin, there is no single cause of skin failure. From a clinical standpoint, the term skin failure likely applies not only to skin but also to the levels of tissue adjacent and underneath. Clarification of the pathophysiology of skin failure has important implications for clinical care, quality measurement, and healthcare policy. In reviewing contributors to skin failure, several common pathophysiologic mechanisms emerge that can be considered a pathway toward this clinical phenomenon. This article proposes a model that relies on physiologic principles common to other organ systems that apply to patients across the healthcare continuum. It is likely that future research will reveal additional physiologic mechanisms that are equally if not more important to consider in this model, such as mitochondrial dysfunction.

When assessing a wound, the clinician must carefully evaluate the patient to determine the risk factors that exist and critically determine the most probable etiology. Documentation should include a full patient assessment that includes risk factors and underlying illnesses. The term acute skin failure could be considered when causative factors are associated with acute critical illness. It should be cautioned that these terms should not be applied to wounds attributable to inadequate or inconsistent prevention strategies. Proper prevention should always be applied based on a patient’s risk factors. When all possible strategies have been applied, including timely interventions and care plan revision, and a wound still evolves, the next step is to determine the primary etiology.

The proposed model for skin failure brings together a variety of elements that include risk factors, pathophysiologic contributors, and overlapping entities that include terminal ulceration. Given the controversies on etiology and classification discussed herein, researchers, clinicians, and those in the regulatory arena require a clear path to further study skin failure and acute skin failure phenomena, develop algorithms and biologic markers to further elucidate diagnosis, and supply a rationale for uniform and consistent terminology. The authors urge caution regarding assignment of an International Classification of Diseases code for skin failure or related components on the skin failure spectrum such as terminal ulceration until further data-driven evidence is obtained and interdisciplinary consensus is reached. A common understanding of skin failure could reveal new pathways for prevention, early intervention, and treatment.

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