The role of bacterial skin infections in atopic dermatitis: expert statement and review from the International Eczema Council Skin Infection Group

Abstract

Patients with atopic dermatitis (AD) have an increased risk of bacterial skin infections, which cause significant morbidity and, if untreated, may become systemic. Staphylococcus aureus colonizes the skin of most patients with AD and is the most common organism to cause infections. Overt bacterial infection is easily recognized by the appearance of weeping lesions, honey-coloured crusts and pustules. However, the wide variability in clinical presentation of bacterial infection in AD and the inherent features of AD - cutaneous erythema and warmth, oozing associated with oedema, and regional lymphadenopathy - overlap with those of infection, making clinical diagnosis challenging. Furthermore, some features may be masked because of anatomical site- and skin-type-specific features, and the high frequency of S. aureus colonization in AD makes positive skin swab culture of suspected infection unreliable as a diagnostic tool. The host mechanisms and microbial virulence factors that underlie S. aureus colonization and infection in AD are incompletely understood. The aim of this article is to present the latest evidence from animal and human studies, including recent microbiome research, to define the clinical features of bacterial infections in AD, and to summarize our current understanding of the host and bacterial factors that influence microbial colonization and virulence.

Figure 1

Clinical features of bacterial skin infection in atopic dermatitis. Clinical features of S. aureus infection in atopic dermatitis lesions include (a) weeping, honey‐coloured crusts; (b) folliculitis; and (c) pustulation. (d) Beta‐haemolytic streptococcal infection may present with well‐defined bright red erythema.

Figure 2

Clinical features of eczema herpeticum. (a, b) Early eczema herpeticum lesions are superficial clusters of dome‐shaped vesicles and/or small, round, punched‐out erosions. (c, d) As the disease progresses, the lesions commonly become superficially infected with Staphylococcus aureus and may have the characteristic impetiginized scale.

Figure 3

Malassezia colonization in atopic dermatitis, which may drive inflammation in patients who have head and neck dermatitis.

Figure 4

Atopic dermatitis in different ethnic skin types. In dark‐skinned individuals perifollicular accentuation is often present in atopic dermatitis, and erythema appears violaceous.

Figure 5

Methicillin‐resistant Staphylococcus aureus infection in atopic dermatitis may cause recurrent flares that are resistant to standard treatment regimens.

Figure 6

Hypothetical damage–response framework for Staphylococcus aureus in atopic dermatitis (AD).82 Different host–S. aureus interactions result in different damage–response relationships. Curves A and B represent the damage–response relationships of S. aureus with two different hosts or those of a single host with two different S. aureus strains. The outcome for the host depends on the strength of the host response to S. aureus or the virulence of S. aureus. During intermediate host responses neither interaction (A or B) causes clinical evidence of infection, as the amount of damage incurred by the host is insufficient (1). However, in the setting of weak or strong responses both interactions cause an AD flare (2) and interaction B causes overtly infected AD (3). The position of the curve is determined by multiple host and S. aureus factors.

Figure 7

Possible mechanisms of Staphylococcus aureus colonization and virulence in atopic dermatitis (AD). Staphylococcus aureus colonization is increased in AD skin. This may be due to epidermal barrier dysfunction, reduced levels of antimicrobial peptides (AMPs), reduced microbial diversity or increased fibrinogen and fibronectin. Proteases produced by the host and S. aureus allow the bacteria to penetrate into the deeper layers of the skin. Staphylococcal enterotoxins (SEs) stimulate polyclonal T‐cell responses, SE‐specific IgE responses and interleukin (IL)‐31 expression. α‐Toxin can cause keratinocyte death and can activate keratinocyte IL‐1α and IL‐36α production to stimulate γδT cells, innate lymphoid cell (ILC)‐3‐mediated IL‐17 release and neutrophil (Neut) recruitment. δ‐Toxin causes mast cell (MC) degranulation. Staphylococcal protein A (SpA) activates proinflammatory pathways via tumour necrosis factor receptor 1 (TNFR1) on keratinocytes. Staphylococcus aureus lipoteichoic acid (LTA) and lipoproteins activate Toll‐like receptor (TLR)2 and TLR6 to produce thymic stromal lymphopoietin (TSLP), which activates dendritic cells (DC) and ILC‐2, leading to production of T helper cell (Th)2 cytokines.