Bacterial and Viral Infections in Atopic Dermatitis: a Comprehensive Review

Abstract

Atopic dermatitis (AD) is the most common allergic skin disease in the general population. It is a chronic inflammatory skin disease complicated by recurrent bacterial and viral infections that, when left untreated, can lead to significant complications. The current article will review immunologic and molecular mechanisms underlying the propensity of AD patients to microbial infections. These infections include Staphylococcus aureus (S. aureus) skin infections, eczema herpeticum, eczema vaccinatum, and eczema coxsackium. Previous studies have shown that skin barrier defects, a decrease in antimicrobial peptides, increased skin pH, or Th2 cytokines such as IL-4 and IL-13 are potential contributing factors for the increased risk of skin infections in AD. In addition, bacterial virulence such as methicillin-resistant S. aureus (MRSA) produces significantly higher number of superantigens that increase their potential in causing infection and more severe cutaneous inflammation in AD patients. More recent studies suggest that skin microbiome including Staphylococcus epidermidis or other coagulase-negative staphylococci may play an important role in controlling S. aureus skin infections in AD. Other studies also suggest that genetic variants in the innate immune response may predispose AD patients to increased risk of viral skin infections. These genetic variants include thymic stromal lymphopoietin (TSLP), type I interferon (α, ß, ω), type II interferon (γ), and molecular pathways that lead to the production of interferons (interferon regulatory factor 2). A common staphylococcal toxin, α-toxin, may also play a role in enhancing herpes simplex virus skin infections in AD. Further understanding of these disease processes may have important clinical implications for the prevention and treatment of skin infections in this common skin disease.

Staphylococcus aureus Epicutaneous Exposure Drives Skin Inflammation via IL-36-Mediated T Cell Responses

“…S. aureus colonization and impetiginization of the skin contribute to the exacerbation of skin inflammation in diseases such as AD, which has previously been attributed to the activity of S. aureus toxins and superantigens (Ong and Leung, 2016; Spaulding et al, 2013). In addition, studies in humans and mice have suggested that IL-1 family members ( i.e.…”

“…Although the precise etiology is not clear, AD is associated with a barrier defect in the skin, a dermal infiltration of T helper 2 (Th2) cells and a systemic Th2 cytokine response with elevated serum IgE and eosinophilia (Weidinger and Novak, 2016). S. aureus is linked to AD disease severity and flares (Kong et al, 2012) that have been attributed to S. aureus secreted toxins and superantigens (Ong and Leung, 2016; Spaulding et al, 2013). However, the immune signaling pathways that are activated during S. aureus epicutaneous exposure that contribute to skin inflammation are unclear.…”

Staphylococcal Biofilms in Atopic Dermatitis

“…Filaggrin (encoded by the gene FLG ) is a structural protein that is crucial to the formation of an intact normal skin barrier; it condenses keratin fibers from the cytoskeleton into tight clusters [25] and is crucial to maintaining the physical strength of the stratum corneum. Mature filaggrin is the result of proteolytic processing of the profilaggrin precursor, which also results in the release of peptides that are essential for skin homeostasis, e.g., natural moisturizing factor (NMF), and for maintenance of an acidic pH [26]. …”

“…Interestingly, the CoNS strains that expressed AMPs were found to frequently colonize normal skin but were rarely detected on AD lesional skin [103••]. Furthermore, AD skin also exhibits decreased levels of keratinocyte-secreted AMPs [26, 104], which is correlated with increased S. aureus colonization [103••]. Recently, it was shown that the human AMP LL-37 when combined with antimicrobial peptides produced by the commensal Staphylococcus hominis can inhibit S. aureus survival more effectively than human or bacterial AMPs individually.…”

“…TSLP secretion results in a strong itch response [112] that can exacerbate excoriation of the skin. Furthermore, TSLP induces dermal dendritic cell activation and recruitment of Th2 cells that secrete IL-4 and IL-13, which have a suppressive effect on AMPs [26], further limiting protection from pathogens. It was also recently shown that extracts of S. aureus biofilms inhibited the terminal differentiation of keratinocytes [113•].…”