Immunology and Treatment of Atopic Dermatitis
Jonathan M. Spergel
Abstract
Atopic dermatitis (AD) is a chronic inflammatory disease hypothesized to be the product of complex interactions among the host's environment, susceptibility genes, skin barrier dysfunction, and immune system dysregulation. The objective of this article is to describe the pathobiology and treatment of AD, with particular focus on the role of immune system dysregulation and therapies designed to target this. Literature review indicates that there are immunologic differences between the lesional and non-lesional skin of atopic individuals, and that the non-lesional skin of atopic individuals presents an immunologic profile distinct from that of the skin of healthy individuals. Thus, immune system dysregulation is postulated to be a key contributing factor to the complex etiology of AD.
Atopic dermatitis (AD) is a chronic inflammatory disease hypothesized to be the product of complex interactions among the host's environment, susceptibility genes, skin barrier dysfunction, and immune system dysregulation. The objective of this article is to describe the pathobiology and treatment of AD, with particular focus on the role of immune system dysregulation and therapies designed to target this. Literature review indicates that there are immunologic differences between the lesional and non-lesional skin of atopic individuals, and that the non-lesional skin of atopic individuals presents an immunologic profile distinct from that of the skin of healthy individuals. Thus, immune system dysregulation is postulated to be a key contributing factor to the complex etiology of AD.
Immunomodulatory agents such as topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs), which address the underlying immunopathology of AD, are the foundation for the pharmacologic treatment of flares. TCSs and TCIs both target the inflammatory response responsible for an AD flare but via two distinct mechanisms of action. Whereas TCSs have a more widespread impact on the immune system, the action of TCIs is targeted to the calcineurin pathway and inhibition of T-cell activation. Together, TCSs and TCIs represent the backbone of a long-term treatment strategy for AD.
1. Overview of Atopic Dermatitis (AD)
Atopic dermatitis (AD), a chronic, highly pruritic, inflammatory skin disease affecting more than 1020% of children and 13% of adults, is a heterogeneous disease characterized by a clinical course that alternates between flares (exacerbation of disease) and periods of remission. The physical, psychological, and economic burdens that AD places upon patients and their families can be substantial. Specifically, AD has been shown to impair daily activities (school performance, participation in sports, and other social activities) and cause sleep disruption and social embarrassment in children. Similarly, adults with AD report that the disease causes them great embarrassment and adversely affects their daily activities and family life. Parents of children with AD experience high stress levels, sleep disturbance, and financial burdens associated with physician visits, child care, and medications not covered by insurance. Annually, the cost of AD to the US healthcare system is estimated to be between $US0.9 and $US3.8 billion.
Several studies have linked the incidence and severity of AD during childhood with subsequent development of food allergies, asthma, and allergic rhinitis. Collectively, these three disorders are referred to as the 'atopic march,' and therapies that modify the severity of AD in childhood may delay this progression from AD to other atopic disorders. Current approaches to long-term management of AD involve a combination of non-pharmacologic and pharmacologic approaches
aimed at reducing the severity and frequency of flares. Non-pharmacologic measures include trigger avoidance and proper skin care with agents that alleviate xerosis and pruritus (e.g. ointments, emollients, hydrogels), whereas immunomodulatory treatments are designed to have a direct impact on the disease by targeting local immune dysregulation. This article reviews what is known currently about the pathobiology underlying AD, briefly outlines non-pharmacologic approaches to symptom management, and discusses how different immunomodulatory treatments may modify the disease course.
1. Overview of Atopic Dermatitis (AD)
Atopic dermatitis (AD), a chronic, highly pruritic, inflammatory skin disease affecting more than 1020% of children and 13% of adults, is a heterogeneous disease characterized by a clinical course that alternates between flares (exacerbation of disease) and periods of remission. The physical, psychological, and economic burdens that AD places upon patients and their families can be substantial. Specifically, AD has been shown to impair daily activities (school performance, participation in sports, and other social activities) and cause sleep disruption and social embarrassment in children. Similarly, adults with AD report that the disease causes them great embarrassment and adversely affects their daily activities and family life. Parents of children with AD experience high stress levels, sleep disturbance, and financial burdens associated with physician visits, child care, and medications not covered by insurance. Annually, the cost of AD to the US healthcare system is estimated to be between $US0.9 and $US3.8 billion.
Several studies have linked the incidence and severity of AD during childhood with subsequent development of food allergies, asthma, and allergic rhinitis. Collectively, these three disorders are referred to as the 'atopic march,' and therapies that modify the severity of AD in childhood may delay this progression from AD to other atopic disorders. Current approaches to long-term management of AD involve a combination of non-pharmacologic and pharmacologic approaches
aimed at reducing the severity and frequency of flares. Non-pharmacologic measures include trigger avoidance and proper skin care with agents that alleviate xerosis and pruritus (e.g. ointments, emollients, hydrogels), whereas immunomodulatory treatments are designed to have a direct impact on the disease by targeting local immune dysregulation. This article reviews what is known currently about the pathobiology underlying AD, briefly outlines non-pharmacologic approaches to symptom management, and discusses how different immunomodulatory treatments may modify the disease course.
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