Patients with AD are often colonized with Staphylococcus aureus and are more susceptible to bacterial skin infections than the general population[11–13] (Table 1). Among allergic disorders, the increased risk of infection is AD specific; no association with impetigo has been observed for asthma or allergic rhinitis. Despite the frequency of antibiotic use to treat these infections, methicillin-resistant S aureus appears to be no more common (and perhaps even less common) among patients with AD than the general population.[14–17] However, data from a large national database found the prevalence of serious infections including cutaneous, respiratory, multi-organ, and systemic infections to be higher in hospitalized adults with AD than in those without AD.
Patients with AD are also more susceptible to certain viral skin infections (Table 1). Although there is no apparent increased risk for common herpes simplex infection, patients with AD have a greater risk of developing eczema herpeticum (a potentially life-threatening, disseminated herpes simplex virus infection),[19–22] especially patients with more severe AD, a history of cutaneous S. aureus infection,[19,20] a history of food allergy or asthma,[19–21] or with early-onset AD.[20,22] Patients with AD and coxsackie infection, especially coxsackie A6, may develop "eczema coxsackium," with extensive cutaneous involvement that can resemble that of eczema herpeticum. Whether patients with AD have increased susceptibility to molluscum contagiosum infection remains controversial,[11,24–26] but molluscum dermatitis and more severe courses of molluscum contagiosum infection (including accentuation of AD lesional sites) occur more commonly.[11,27–29] Susceptibility to human papillomavirus-related cervical cancer and chickenpox[31,32] also appears to be greater in patients with AD. In addition, patients with AD are at increased risk for extra-cutaneous infections, including those of the respiratory,[12,13,31–37] gastrointestinal,[13,31,38] and urinary tracts (Table 1); this risk increases as the number of allergic diseases increases.
The increased susceptibility to bacterial and disseminated viral skin infections observed in AD is thought to be owing, at least in part, to epidermal barrier defects. However, because patients with psoriasis, which is associated with a similar degree of epidermal barrier dysfunction (based on transepidermal water loss),[39,40] do not demonstrate a similar propensity for skin infection, other factors likely contribute. This difference in susceptibility may be a reflection of the nature of skin inflammation in AD vs. psoriasis, i.e., increased type 2 helper T cell (Th2; also called type 2) cytokines (interleukin-4 and interleukin-13) and a decreased Th1/Th2 ratio in AD, but not in psoriasis.[41–43] Furthermore, the risk of infection/S. aureus colonization correlates with markers of systemic Th2 predominance.[19,22,32,44–49] Th2-mediated inflammation is thought to suppress inducible antimicrobial peptide expression and/or secretion (including β-defensins and cathelicidin) in symptomatic/lesional and asymptomatic skin of patients with AD relative to that seen in patients with psoriasis and healthy controls.[41,50–52] However, antimicrobial peptide expression in healthy control skin in young children is much greater than in healthy control adult skin, and cutaneous antimicrobial responses in early AD (within the first 6 months in children under 5 years of age) are not reduced relative to age-matched controls, suggesting the need for further investigation.
Th2 cytokine expression also reduces the expression of the constitutive antimicrobial peptide dermcidin in sweat. Among subgroups of patients with AD, dermcidin and cathelicidin expression is lower for those with a history of bacterial superinfection and/or eczema herpeticum, demonstrating a potential causal link between Th2 inflammation and susceptibility to infection. The risk for eczema herpeticum in patients with AD may be the result of distinct genetic abnormalities, as filaggrin mutations that confer risk of AD also confer greater risk for eczema herpeticum. In addition, patients with eczema herpeticum appear to have unique abnormalities in interferon-γ response and genetic variants in interferon regulatory factor 2 have been reported to be associated with eczema herpeticum.
Th2-mediated alterations in antimicrobial peptide expression have also been implicated in the microbiome shifts observed with flares,[58–60] including a reduction in commensal organisms that may produce anti-S. aureus factors. Topical application of non-pathogenic organisms that produce anti-S. aureus factors is being considered as potential therapy. Th2 inflammation also increases fibronectin and/or fibrinogen expression on the skin surface, leading to greater attachment of S. aureus in AD than in patients with psoriasis or healthy controls. Scratching may also contribute by exposing laminin and fibronectin on the skin surface, while loss-of-function filaggrin mutations contribute via reduced amounts of filaggrin breakdown products, which have been shown to inhibit S. aureus colonization.Staphylococcus aureus-derived staphylococcal enterotoxin can also trigger skin inflammation directly, perpetuating inflammation and further increasing susceptibility to infection. Shared risk factors such as low vitamin D levels,[66,67] or exposure to cigarette smoke and other air pollutants,[68,69] may also contribute to the increase in susceptibility to infection observed in AD.
Am J Clin Dermatol. 2018;19(6):821-838. © 2018 Adis Springer International Publishing AG