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Clinical Evidence: Internal Factors

Key points Less than 50% of patients affected with atopic dermatitis have a genetic mutation of the skin barrier protein, filaggrin. Thus additional contributing factors, barrier defects, and beyond could account for disease triggering of the other 50% of patients with atopic dermatitis but without filaggrin mutation. Patients affected with ichthyosis vulgaris and genetic defect of skin barrier protein filaggrin do not all develop atopic dermatitis.…

Epigenetics

Key points There are three major types of epigenetic modifications: DNA methylation, microRNAs, and posttranslational histone modifications. DNA methylation and microRNAs alter the expression of atopic dermatitis-associated genes identified in multiple genomewide association studies. Epigenetic alterations also impact epidermal barrier function and immune activity, two critical components that contribute to the immunopathogenesis of atopic dermatitis. Epigenetic modifications provide a potential mechanism by which environmental factors associated…

Neurosensory Mechanisms

Key points Both itch and pain are very frequent symptoms in patients with atopic dermatitis, with a prevalence of more than 50%. Patients with atopic dermatitis show neuronal sensitization to both itch and pain. Itch neuronal sensitization is associated with alloknesis (phenomena in which normal or nonpruritic stimuli are perceived as itchy) and hyperknesis (excessive itch perception to pruritic stimuli). Pain neuronal sensitization is associated with…

Skin-Gut-Lung Epithelial Permeability

Key points The atopic march is a phenomenon characterized by progressive development of atopic dermatitis, food allergy, allergic rhinitis, and later asthma. The mechanism by which atopic dermatitis advances toward gastrointestinal or airway disease remains to be fully elucidated, but current evidence points to multiorgan epithelial breakdown contributing to pathogenesis. Initial disruption in the skin epidermal barrier permits allergen sensitization and colonization by pathogens. Allergen sensitization…

Cellular Factors

Key points Atopic dermatitis (AD) is a complex disease with various types of leukocytes involved in its pathology. Multiple subsets of CD4 + helper T cells, which are sensitized, activated, and differentiated by antigen presenting cells (i.e., Langerhans cells and dendritic cells) in damaged skin and Staphylococcus aureus infection, lead to acute and chronic inflammation in AD. Mast cells, granulocytes (basophils and eosinophils), and group 2…

Humoral Factors

Key points Allergen-specific B cells are differentiated into plasma cells producing immunoglobulin E (IgE) antibodies. Through binding to the receptors (FcεRI and FcεRII), IgE induces cytokine and chemokine production from immune cells. Intrinsic atopic dermatitis is T-cell mediated, involving Th2 cytokines that cause skin inflammation and pruritus. Extrinsic atopic dermatitis is IgE mediated, involving allergen-specific IgE, including autoreactive IgE. Cytokines and chemokines that play a key…

Microvasculature

Key points Cutaneous microcirculation, a type of microvasculature situated just below the epidermis, is composed of major components of blood vessels (arterioles and venules) and lymphatic vessels. The cutaneous blood vessels are organized into a superficial plexus near the dermal-epidermal junction and a lower plexus near the dermal-subcutaneous junction. Cutaneous arteriole delivers oxygen and nutrients to the skin. It is also the conduit from which the…

Keratinocytes

Key points Epidermis is the outermost layer of skin surface that forms the first line of defense against invaders from the environment. Keratinocyte is the epidermis’s principle cell type responsible for generating and maintaining the integrity of the epidermis. Besides being the structural foundation of the epidermis, keratinocytes also possess functions capable of interacting with their environment immunologically. Keratinocytes are capable of expressing neurologic factors that…

Clinical Evidence: External Factors

Key points The fact that up to 50% of atopic dermatitis (AD) patients have loss-of-function genetic mutations of skin barrier protein filaggrin points to a cutaneous weakness that allows external factors to trigger skin inflammation in AD. Various studies documented that between 30% and 100% of patients with AD have pathogenic Staphylococcus aureus colonization on their skin, and this colonization worsens skin inflammation. Powerful evidences point…

Oxidative Stress, Environmental Factors, and Pollutants

Key points The worldwide prevalence of atopic dermatitis (AD) has risen over recent decades, paralleling industrial and urban growth. Airborne pollutants induce oxidative damage at the skin interface with the outside world, setting in motion a cycle of inflammation, skin barrier disruption, and repeated irritant entry in AD. Common forms of environmental pollution found to affect the skin barrier and AD include cigarette smoke, particulate matter,…

Nutrition

Key points Maternal supplementation of omega-3 polyunsaturated fatty acids may reduce risk of atopic dermatitis (AD). Fish intake during early childhood may decrease the risk of developing AD. Early oral introduction of potentially allergenic foods in combination with improved skin barrier function may decrease the risk of developing food allergies in patients with AD. Food allergy is common in patients with AD but usually does not…

Immunogens

Key points Patients with atopic dermatitis are more susceptible to developing irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). ICD can present with phenotypic subtypes such as asteatotic ICD, airborne ICD, acneiform ICD, chronic ICD, and acute ICD with characteristic body sites involved, predominant morphologic features, time courses, and irritant sources. ACD is a type IV delayed hypersensitivity reaction and is preceded by prior sensitization…

Skin and Gut Microbiome

Key points The human microbiome consists of a wide variety of microorganisms that assist in key physiologic processes. The majority of microbial diversity is found on the skin and in the gut; and microbial composition is influenced by multiple host factors. Disruption in microbiome homeostasis is termed dysbiosis and is associated with disease states such as atopic dermatitis. Flares of atopic dermatitis are associated with changes…

Skin Barrier

Key points The four layers of the epidermis—stratum corneum, stratum granulosum, stratum spinosum, and stratum basale—are composed of keratinocytes, which undergo differentiation and mature as they become more superficial until they are terminally differentiated at the stratum corneum. The dermis provides structure, houses epidermally derived appendages, and provides vascular supply to the skin. There are many factors that may contribute to the development of atopic dermatitis,…

Epidemiology

Key points Atopic dermatitis is one of the most common inflammatory diseases of the skin, with both genetic and environmental etiologies. The prevalence of atopic dermatitis is increasing globally due to changes in climate, microbes, urbanization, among other factors. Atopic dermatitis can have broad effects on mental health, quality of life, development, and psychosocial function, which can affect patients and their families. The financial burden of…

Atopy of the Skin

Key points Atopy of the skin is manifested as atopic dermatitis (atopic eczema). Histologically, the atopy of the skin is characterized by epidermal and dermal infiltration predominantly by lymphocytic cells as well as eosinophils and mast cells. In some patients, the granular cell layer is diminished because of the absence of filaggrin protein. The skin surface of patients affected by skin atopy is commonly characterized by…

Atopy Redefined

Key points Although the original term atopy provides a general framework of understanding about allergic clinical conditions, this big umbrella now includes a group of patients who have heterogeneous clinical and laboratory-defined characteristics. Similarly, atopic dermatitis , the skin atopy, characterizes a group of patients with heterogeneous clinical and laboratory-based findings. Since the immune milieu in children is a dynamic system, atopic dermatitis manifested in childhood…

Historic Perspective

Key points From the historic perspective, atopic dermatitis has gone through several evolutionary periods of understanding and development. From ancient times to the 18th century, medical communities started to recognize a type of itchy skin disease. Although the term eczema had been used, no unified concept had been developed and no understanding of its underlying pathophysiology was established. The 19th century witnessed the rapid development of…