Atopic Dermatitis: Pathophysiology

Abstract

The pathophysiology of atopic dermatitis is complex and multifactorial, involving elements of barrier dysfunction, alterations in cell mediated immune responses, IgE mediated hypersensitivity, and environmental factors. Loss of function mutations in filaggrin have been implicated in severe atopic dermatitis due to a potential increase in trans-epidermal water loss, pH alterations, and dehydration. Other genetic changes have also been identified which may alter the skin's barrier function, resulting in an atopic dermatitis phenotype. The imbalance of Th2 to Th1 cytokines observed in atopic dermatitis can create alterations in the cell mediated immune responses and can promote IgE mediated hypersensitivity, both of which appear to play a role in the development of atopic dermatitis. One must additionally take into consideration the role of the environment on the causation of atopic dermatitis and the impact of chemicals such as airborne formaldehyde, harsh detergents, fragrances, and preservatives. Use of harsh alkaline detergents in skin care products may also unfavorably alter the skin's pH causing downstream changes in enzyme activity and triggering inflammation. Environmental pollutants can trigger responses from both the innate and adaptive immune pathways. This chapter will discuss the multifaceted etiology of atopic dermatitis which will help us to elucidate potential therapeutic targets. We will also review existing treatment options and their interaction with the complex inflammatory and molecular triggers of atopic dermatitis.

A Review of the Anti-Inflammatory Effects of Rosmarinic Acid on Inflammatory Diseases

“…The clinical features of the disease are the exacerbation and relief of eczema skin, accompanied by inflammation, itching and flaking, desquamation, dry skin and susceptibility to skin bacteria, and mold infections (Cabanillas et al, 2017). The pathophysiology of AD is intricate and multifactorial, including barrier dysfunction, cell-mediated immune response changes, IgE-mediated hypersensitivity, and environmental factors (David Boothe et al, 2017). Currently, a lot of researchers are energetically trying to develop therapeutic drugs with great anti-inflammatory effects and few side reactions.…”

Nicotinamide for photoprotection and skin cancer chemoprevention: A review of efficacy and safety

“…Oral NAM reduces transepidermal water loss (TEWL) by ~6%‐7% as early as 3 months after commencement of doses of 1 g daily, and topical 2% NAM applied twice daily over 4‐8 weeks provides a more effective moisturiser as measured by a reduction in TEWL, when compared with white petroleum alone ( P < 0.05) . Hence, NAM seems to enhance skin barrier function, which may contribute to its efficacy in rosacea and acne, and may make it an adjunctive treatment for dermatitis, as these skin conditions demonstrate increased transepidermal water loss within the stratum corneum, when compared to healthy skin …”

Therapeutic effects of shikonin on skin lesions in mouse models of allergic dermatitis and wound

“…Furthermore, on DNA microarray analysis shikonin inhibited the expression of inflammatory molecules, notably cytokines (TNF‐α, IL‐1β and IL‐4), chemokines (macrophage inflammatory protein (MIP)‐1β and monocyte chemotactic protein (MCP)‐2), and inflammatory modulators (nuclear factor of activated T‐cells, cytoplasmic 3 (NFATC3) and prostaglandin‐endoperoxide synthase 2 (PTGS2)) in lipopolysaccharide‐stimulated human monocytic THP‐1 cells . Of these, IL‐4 is a key T‐helper (Th) type 2 cytokine critical for Th2 cell differentiation, IgE production and eosinophil recruitment, and plays pivotal roles in the development of AD . These reports suggest that shikonin improves the clinical severity of allergic dermatitis through inhibiting the expression of these inflammatory molecules around inflammatory sites.…”