Staphylococcus aureus plays an important role in the pathogenesis and course of atopic dermatitis. Compared to the normal pediatric population, atopic patients are especially susceptible to colonization and recurrent infections of S aureus.
Staphylococcus aureus plays an important role in the pathogenesis and course of atopic dermatitis. Compared to the normal pediatric population, atopic patients are especially susceptible to colonization and recurrent infections of S aureus. This article summarizes the role S aureus plays in atopic dermatitis. Additionally, we review the approaches of decolonization in the context of “containment” strategies, given that true decolonization of this virulent bacteria remains challenging.
S aureus causes the majority of bacterial skin infections, including some historically caused by streptococcal species. Bacterial skin infections can be classified as primary or secondary and as an initial episode or a recurrence. Primary infections manifest in normal, intact skin. Examples include impetigo, cellulitis, folliculitis, or furunculosis. Secondary infections manifest in conditions with an impaired skin barrier. Common examples include atopic dermatitis, bites, burns, and wounds. In atopic dermatitis, S aureus colonization is common and secondary S aureus infections are a major concern (Figures 1, 2). Patients with atopic dermatitis are at risk for secondary infections due to impaired physical barrier function, colonization with pathogenic bacteria, and alterations to the skin microbiome.1
An additional risk for infection relates to deficiencies in the antimicrobial defenses of the skin. The skin serves 2 important barrier roles as a permeability barrier and an antimicrobial barrier.2-4 The stratum corneum provides a physical barrier to microbes, and the epidermis acts as a chemical defense shield. Healthy skin constitutively produces antimicrobial peptides, including lysozyme, RNase 7, calprotectin, and dermcidin. During infection, keratinocytes produce inducible antimicrobial peptides, including human beta-defensin-2, human beta-defensin-3 (hBD-3), and cathelicidin.5 The inducible antimicrobial peptide hBD-3 specifically defends against S aureus and is deficient in patients with atopic dermatitis. Atopic patients also have deficient levels of cathelicidin, implicating deficient hBD-3 and cathelicidin for the propensity for these patients to develop S aureus infections.5,6
Patients with atopic dermatitis have increased rates of colonization with pathogenic bacteria. S aureus colonization in patients with atopic dermatitis is high, ranging from 46% to 80%, compared with approximately 10% of nonatopic patients.7,8 Patients with more severe atopic dermatitis are more likely to be colonized as are older versus younger pediatric patients.9 Depending on the study, colonization with methicillin-resistant S aureus (MRSA) ranges from 13% to 31% of patients with atopic dermatitis.7,10 Of skin and soft tissue infections caused by S aureus, MRSA is responsible for 44% in nonatopic patients but only 14% in atopic dermatitis patients.8 When looking at disease severity, however, more severely affected patients are more likely to have MRSA infections.10
Bacterial colonization may be considered in the context of the skin microbiome. The term “microbiome,” coined by the American microbiologist Joshua Lederberg, refers to the entire collection of microbes that reside in and on the human skin. The skin microbiome consists of bacteria, archaea (a distinct class of nonbacterial microorganisms), fungi, viruses, and mites. The human body contains over 10 times more microbial cells than human cells, and the body-microbiome interaction is of increasing interest.11
The skin microbiome plays a part in health and disease. A diverse milieu of microorganisms colonizes the skin, comprised of beneficial, harmless, and potentially harmful organisms. Colonization is driven by the ecology of various skin surfaces, topographic location, host factors, and environmental factors. The cutaneous immune system, both innate and adaptive, modulates the skin microbiota, and the microbiota, in turn, educates the immune system.12
In atopic dermatitis, the microbiome may help us understand the disease and treatment. The microbiomes of patients with and without atopic dermatitis were evaluated in an important National Institutes of Health study.1 The skin’s microbial diversity decreased in areas affected by atopic dermatitis, the antecubital, and popliteal creases. The change in the microbiome’s diversity was influenced by topical atopic dermatitis treatments such as corticosteroids, calcineurin inhibitors, and antibiotics, causing the return of diversity prior to clinical improvement. Patients with disease flares who had not recently used any topical therapy had a higher proportion of S aureus composing their microbiome compared with the baseline, postflare, and controls. The influence of S aureus on the pathogenesis of atopic dermatitis is suggested as well as the positive effect of atopic dermatitis therapies on the microbiome.1
Staphylococcal infections can present differently in patients with atopic dermatitis. The patient may have an infection that is clinically similar to a patient with nonatopic skin, such as impetigo, cellulitis, folliculitis, and furuncles. In these instances, diagnosis and treatment are relatively straightforward. Another presentation seen in patients with atopic dermatitis is refractory atopic dermatitis related to S aureus infection. Infection should be considered in patients with flaring atopic disease that is resistant to normal therapy, and obtaining a bacterial culture of involved skin before starting antibiotics is helpful. In addition to containment of S aureus, clinically infected atopic dermatitis patients should be treated with oral antibiotics based on culture and sensitivities.13 Practitioners should continue to treat infected atopic dermatitis with topical corticosteroids or calcineurin inhibitors to help correct the primary process of inflammation and defective skin barrier.
The focus of this article is S aureus, but other skin infections should be considered on the differential of eroded, crusted, resistant atopic dermatitis including herpes simplex virus, coxsackie virus, and group A streptococcus. Herpes simplex virus (eczema herpeticum) should be considered if the patient has monomorphous, round, punched-out, grouped lesions that quickly spread in areas of atopic dermatitis. These patients are typically more ill appearing. Coxsackie virus can also cause widespread vesicles and erosions, but usually involve the more classic locations of the hands, feet, mouth, and buttocks. Group A streptococcus can cause a serious secondary infection with a more ill-appearing child. Impetiginized eczema may be coinfected with both group A streptococcus and S Aureus, which influences antibiotic choices.14 For an ill-appearing child with atopic dermatitis and for whom there is concern for infection, a dermatologist should be consulted for assistance with management and hospital admission can be considered. Typical S aureus infections with or without atopic dermatitis flares can be managed on an outpatient basis.
For recurrent primary and secondary infections with S aureus, especially MRSA, attempts at decolonization of the skin and improved hygiene are recommended. The approach to decolonization of a patient with recurrent S aureus infections includes treatment with intranasal mupirocin in isolation or in combination with either chlorhexidine or dilute bleach baths (Table 1).15 If a dilute bleach bath solution is included in decolonization, the needed measurements for either a bathtub or a 1-gallon container can be found in Table 2.15
Given that true decolonization of S aureus is challenging to achieve, we have begun to adopt the concept of containment strategies. Patients should be instructed to cover draining lesions, bathe and wash hands regularly, and not to share personal items such as razors and towels. Disinfection of high-traffic objects (eg, door knobs, counters, bath tubs, toilet seats) in the home is another hygiene measure that can be accomplished with any number of antiseptics found in cleaning products.15 Commonly used antiseptics are alcohol, hydrogen peroxide, chlorhexidine, triclosan, iodophors, benzoyl peroxide, and sodium hypochlorite (bleach) (Table 3).16,17 Topical antiseptics are available in various strengths and can work against S aureus and other organisms. Practitioners should be aware, however, of the possibility of S aureus resistance to chlorhexidine and triclosan.
For patients with atopic dermatitis, S aureus plays an important role in disease pathogenesis and severity as well as causing secondary infections. Patients with a history of secondarily infected atopic dermatitis improve when treated with intranasal mupirocin and dilute bleach baths.18 In a study of patients with atopic dermatitis and secondary bacterial infection, patients were randomized to either intranasal mupirocin ointment treatment with dilute bleach baths or placebo for 3 months following treatment of the acute infection. Mean Eczema Area and Severity Index (EASI) scores decreased, but only for body sites submerged in the dilute bleach bath, correlating the dilute bleach application with improved atopic dermatitis.
Even clinically noninfected atopic patients may benefit from such treatment.19,20 Investigators studied patients with moderate-to-severe atopic dermatitis who were colonized, but not infected, with S aureus. Patients used a commercial sodium hypochlorite body wash with surfactants (CLn BodyWash; Top MD Skin Care Inc, Dallas, Texas), approximately the concentration of a dilute bleach bath, 3 times a week for 3 months. This resulted in improved Investigator Global Assessment (IGA) scores and reduced body surface area (BSA) affected.20 A recent study of 40 pediatric patients with moderate-to-severe atopic dermatitis examined the role of the same dilute sodium hypochlorite wash on dermatitis severity. After 2 weeks of daily use, patients had improved atopic dermatitis on multiple measures: EASI score, IGA score, pruritus visual analog scale, BSA involvement, and quality-of-life indices. The improvement was maintained for 6 weeks of sodium hypochlorite wash use.21 These studies further support that containment of S aureus improves atopic dermatitis and that the new sodium hypochlorite body wash is a simple alternative to bleach baths.20,21
Topical agents to contain S aureus were evaluated in a study comparing controls with intranasal mupirocin, intranasal mupirocin plus chlorhexidine, and intranasal mupirocin plus dilute bleach baths. Study subjects with recurrent skin and soft-tissue infections were recruited if they were colonized with S aureus, based on cultures from the nose and skin folds. Following treatment, S aureus eradication rates were 48% for controls; 56% for intranasal mupirocin alone; 54% for intranasal mupirocin plus chlorhexidine; and 71% for intranasal mupirocin plus dilute bleach baths. All groups received hygiene education. Despite this, up to 36% of participants had recurrent skin and soft-tissue infections at follow-up.22
It is important to note that it is not recommended to treat atopic dermatitis with topically applied antibiotics.13
S aureus infections play an important role in the pathogenesis and course of atopic dermatitis. Patients with atopic dermatitis have impaired physical and chemical skin barriers that make them susceptible to infection. Growing evidence also points to the role of the skin microbiome in the disease process. In cases of refractory atopic dermatitis, the clinician should investigate for the possibility of S aureus infection, including both methicillin-sensitive and methicillin-resistant strains. Atopic patients with clinically active infections typically require treatment with oral antibiotics. Approaches to true decolonization are challenging, and perhaps containment is a more realistic goal. Atopic patients benefit from various containment strategies that aim to decrease S aureus colonization. Along with improved hygiene measures, these strategies include a combination of intranasal mupirocin, dilute bleach baths, or similar sodium hypochlorite-formulated washes.
1. Kong HH. Skin microbiome: genomics-based insights into the diversity and role of skin microbes. Trends Mol Med. 2011;17(6):320–328.
2. Feingold KR. The outer frontier: the importance of lipid metabolism in the skin. J Lipid Res. 2009;50(Suppl):S417-S422.
3. Elias PM, Schmuth M. Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Curr Allergy Asthma Rep. 2009;9(4):265-272.
4. Borkowski AW, Gallo RL. The coordinated response of the physical and antimicrobial peptide barriers of the skin. J Invest Dermatol. 2011;131(2):285-287.
5. Schröder JM. Antimicrobial peptides in healthy skin and atopic dermatitis. Allergol Int. 2011;60(1):17-24.
6. Leyden JJ, Marples RR, Kligman AM. Staphylococcus aureus in the lesions of atopic dermatitis. Br J Dermatol. 1974;90(5):525-530.
7. Tang CS, Wang CC, Huang CF, et al. Antimicrobial susceptibility of Staphylococcus aureus in children with atopic dermatitis. Pediatr Int. 2011;53(3):363-367.
8. Matiz C, Tom WL, Eichenfield LF, et al. Children with atopic dermatitis appear less likely to be infected with community acquired methicillin-resistant Staphylococcus aureus: the San Diego experience. Pediatr Dermatol. 2010;28(1):6-11.
9. Balma-Mena A, Lara-Corrales I, Zeller J, et al. Colonization with community-acquired methicillin-resistant Staphylococcus aureus in children with atopic dermatitis: a cross-sectional study. Int J Dermatol. 2011;50(6):682-688.
10. Suh L, Coffin S, Leckerman KH, et al. Methicillin-resistant Staphylococcus aureus colonization in children with atopic dermatitis. Pediatr Dermatol. 2008;25(5):528-534.
11. NIH HMP Working Group; Peterson J, Garges S, Giovanni M, et al. The NIH Human Microbiome Project. Genome Res. 2009;19(12):2317-2323.
12. Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2011;9(4):244-253.
13. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116-132.
14. Hersh AL, Weintrub PS, Cabana MD. Antibiotic selection for purulent skin and soft-tissue infections in ambulatory care: a decision-analytic approach. Acad Pediatr. 2009;9(3):179-184.
15. Liu C, Bayer A, Cosgrove SE, et al; Infectious Diseases Society of America. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18-e55.
16. Noguchi N, Hase M, Kitta M, et al. Antiseptic susceptibility and distribution of antiseptic-resistance genes in methicillin-resistant Staphylococcus aureus. FEMS Microbiol Lett. 1999;172(2):247-253.
17. Seaman PF, Ochs D, Day MJ. Small-colony variants: a novel mechanism for triclosan resistance in methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 2007;59(1):43-50.
18. Huang JT, Abrams M, Tlougan B, et al. Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity. Pediatrics. 2009;123(5):e808-e814.
19. Bath-Hextall FJ, Birnie AJ, Ravenscroft JC, Williams HC. Interventions to reduce Staphylococcus aureus in the management of atopic eczema: an updated Cochrane review. Br J Dermatol. 2010;163(1):12-26.
20. Ryan C, Shaw RE, Cockerell CJ, et al. Novel sodium hypochlorite cleanser shows clinical response and excellent acceptability in the treatment of atopic dermatitis. Pediatr Dermatol. 2013;30(3):308-315.
21. Bohaty B, Hebert A, Paller A, et al. A novel new sodium hypochlorite formulated wash as an adjunctive approach to the management of pediatric subjects with moderate to severe atopic dermatitis colonized with Staphylococcus aureus. J Am Acad Dermatol. 2014;70(5 Suppl 1):AB60.
22. Fritz SA, Camins BC, Eisenstein KA, et al. Effectiveness of measures to eradicate Staphylococcus aureus carriage in patients with community-associated skin and soft-tissue infections: a randomized trial. Infect Control Hosp Epidemiol. 2011;32(9):872-880.
Dr Osier is a clinical research fellow at University of California, San Diego, and Rady Children’s Hospital San Diego, Division of Pediatric and Adolescent Dermatology.
Dr Matiz is a clinical assistant professor at University of California, San Diego, and Rady Children’s Hospital San Diego, Division of Pediatric and Adolescent Dermatology.
Dr Ghali is a clinical assistant professor at University of Texas Southwestern and Baylor Medical Center, Department of Dermatology, Dallas, TX.
Dr Eichenfield is a clinical professor at University of California, San Diego, and Rady Children’s Hospital San Diego, Division of Pediatric and Adolescent Dermatology.
None of the authors have anything to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.