Chapter 3. Importance of Infection
Patients with atopic dermatitis have increased problems secondary to the following types of microbes:
Staphylococcus aureus is the major pathogen in atopic dermatitis. It is found on the skin of most patients (up to 90%!) with atopic dermatitis. In contrast, less than 5% of normal subjects have S. aureus on their skin. Honey-colored crusting, extensive serous weeping, folliculitis, and pyoderma indicate bacterial infection usually secondary to S. aureus in patients with atopic dermatitis (PICTURE A). These patients can have a sudden exacerbation of their skin disease and respond rapidly to antibiotic therapy. In patients who do not respond well to antibiotics, drug-resistant S. aureus should be suspected and the organism should be cultured and tested for antibiotic sensitivities.
The strategy by which S. aureus enhances skin inflammation in AD is by secreting toxins such as superantigens which stimulate marked activation of T cells and antigen-presenting cells in the skin. Interestingly, AD patients colonized with S. aureus often make IgE antibodies directed against staphylococcal superantigens suggesting that these toxins can act as allergens which persistently stimulate allergic reactions in atopic skin. Indeed, the presence of IgE antibodies to superantigens have been found to correlate with atopic dermatitis skin disease severity. In addition to acting as an allergen, superantigens have also been found to induce corticosteroid resistance of T cells suggesting that several mechanisms exist by which superantigens increase AD severity. Interestingly, antibiotics are highly effective at shutting down the production of superantigens. These studies may explain the clinical observation in poorly-controlled atopic dermatitis, superinfected with S. aureus, that combined treatment with anti-staphylococcal antibiotics and topical corticosteroids is much more effective than use of topical corticosteroids alone to control severity of skin inflammation.
The increased binding of S. aureus to atopic skin has been found to be secondary to underlying allergic skin inflammation. This is supported by the clinical observation that treatment with topical corticosteroids or calcineurin inhibitors reduces S. aureus counts on atopic skin. Scratching likely enhances S. aureus binding by disturbing the skin barrier and exposing extracellular matrix molecules in the skin that acts as adhesins for S. aureus, e.g. fibronectin and collagens. In studies of S. aureus binding to skin lesions, bacterial binding was significantly greater at skin sites with allergic inflammation. This was localized to interleukin-4 induced expression of fibronectin. Compounding the problem, atopic dermatitis skin has also been found to be deficient in antimicrobial peptides needed for host defense against bacteria, fungi and viruses. Thus, S. aureus not only binds avidly to atopic dermatitis, as compared to normal, skin but once the S. aureus attaches to the skin of atopic dermatitis patients an inadequate skin host defense allows bacteria to grow and predispose patients to microbial infection.
These laboratory observations have important clinical implications for management of patients with atopic dermatitis who are prone to S. aureus infection. In patients with an acute exacerbation of atopic dermatitis due to S. aureus infection, antistaphylococcal antibiotics are certainly helpful in regaining control of the skin disease. Topical mupirocin or fusidic acid offers some utility in the treatment of localized impetiginized lesions. In patients with extensive superinfection with sensitive S. aureus strains, a course of systemic antibiotics such as erythromycin and the newer macrolide antibiotics (azithromycin and clarithromycin) is usually beneficial. However, for macrolide-resistant S. aureus, a penicillinase-resistant penicillin (dicloxacillin, oxacillin, or cloxacillin) or first-generation cephalosporins are preferred.
Due to the increased risk of bacterial antibiotic resistance accompanying frequent use of antibiotics, it is important to combine antimicrobial therapy with effective anti-inflammatory therapy. As already discussed, the excoriated inflamed skin of AD predisposes to S. aureus colonization. Therefore use of antibiotic therapy must be carried out with good skin hydration to restore skin barrier function and topical steroids or calcineurin inhibitors to reduce overall skin inflammation and S. aureus colonization. In patients with superantigen-induced steroid resistance, the topical calcineurin inhibitors may have an advantage in controlling underlying skin inflammation. In selected patients, phototherapy may be useful in reducing bacterial load and gaining control of skin inflammation.
Individuals with atopic dermatitis have an increased propensity toward severe skin viral infections especially with Herpes simplex which can result in eczema herpeticum, also known as Kaposi's varicelliform eruption. After an incubation period of 5 to 12 days, multiple, itchy, vesiculopustular lesions erupt in a disseminated pattern; vesicular lesions are umbilicated, tend to crop and often become hemorrhagic and crusted. The presence of punched-out erosions (PICTURE B), vesicles, and/or infected skin lesions that fail to respond to oral antibiotics should initiate a search for herpes simplex. Antiviral treatment for cutaneous herpes simplex infections is of critical importance in the patient with widespread AD since life-threatening dissemination has been reported.
Mollusca contagiosa, a poxvirus infection, and warts can also be significant clinical problems in individuals with atopic dermatitis. The viral manifestations of atopic dermatitis has recently attracted much worldwide attention because smallpox vaccination of these patients or even exposure to vaccinated individuals may cause a severe widespread skin rash called eczema vaccinatum, similar in appearance to eczema herpeticum. The mechanisms underlying this propensity for viral infections in patients with atopic dermatitis likely relate to defects in innate and adaptive immune responses.
Patients with atopic dermatitis have an increased prevalence of fungal infections compared to non-atopic controls. In particular, there has been interest in the role of Malassezia furfur (Pityrosporum ovale), a lipophilic yeast commonly present in the seborrheic areas of the skin such as the scalp, face, and neck. M. furfur is cultured with the same frequency from patients with atopic dermatitis and normal age-matched controls, suggesting that colonization with this yeast is not more common on atopic dermatitis skin. However, patients with atopic dermatitis have a much higher prevalence of IgE antibodies against M. furfur, as compared to non-atopic controls. M. furfur is most frequently found in patients with head and neck dermatitis. The potential clinical importance of M. furfur as well as other dermatophyte infections is further supported by reports that the severity of skin disease in patients with atopic dermatitis with IgE to M furfur or overt dermatophyte infections improves following treatment with anti-fungal agents. Thus sensitivity to M. furfur should be considered in any patient with poorly controlled atopic dermatitis or primarily head and neck dermatitis. Although sensitivity to other fungi including Candida albicans has been implicated in atopic dermatitis, the data supporting their role in atopic dermatitis is unproven.