Topical tacrolimus in atopic dermatitis: Effects of ... - Helda - Helsinki.fi

increased adhesion to the eczematous skin via fibronectin and fibrinogen (Cho et al.
2001). The bacteria also produce superantigens (S. enterotoxin A, S. enterotoxin B,
toxic shock syndrome toxin-1) which are important effectors in AD (Bunikowski et al.
2003). They cause S. aureus-specific IgE production that correlates with disease
severity (Leung et al. 1993). Superantigens also cause nonspecific IgE production,
activate T cells, B cells, and macrophages, and stimulate their proliferation (Ou et al.
2004). Lately, they have been found to induce chemokines such as CCL1 and CCL18,
which bind to CLA-positive T cells in peripheral blood, thus possibly playing a role in
T cell homing to the skin (Pivarcsi et al. 2004, Gombert et al. 2005). The superantigens
seem to reduce the immunosuppressive activity of certain immunosuppressive
regulatory T cells, which may, in turn, increase the inflammatory T cell activation (Ou
et al. 2004). They are also known to induce corticosteroid resistance complicating the
treatment of atopic diseases (Gould et al. 2007).
HSV infections can lead to the acute disseminated viral infection eczema
herpeticatum, which often requires hospitalization (Novak & Bieber 2005). Smaller,
local lesions with or without typical blisters are another typical form of the infection.
HSV superinfection is a risk factor for acute and severe exacerbations of AD (Bork &
Brauninger 1986). In AD patients, immunosuppressive treatment (corticosteroids,
calcineurin inhibitors) is a potential trigger of HSV infections (Novak & Bieber 2005).
�-defensins have shown some antiviral activity against HSV (Ong et al. 2002). Other
mechanisms favoring HSV overgrowth in AD include predisposition to Th2 type
responses and impaired recruitment of plasmocytoid dendritic cells to the skin, which
leads to reduced amounts of antiviral type 1 IFN-� and IFN-� (Wollenberg et al. 2003,
Novak & Bieber 2005).
Malassezia yeast species colonize the skin of 90% of AD patients compared with
35% of healthy controls, especially the sebaceous areas face, scalp, and upper body.
Species associated with AD include Malassezia globosa, sympodialis, restricta, and
furfur. (Scheynius et al. 2003) Their role in AD exacerbations has been controversial
despite the fact that specific IgE antibodies to Malassezia species can be found in AD
patients but not in healthy controls (Roll et al. 2004, Baker 2006).
Allergic vs. nonallergic atopic dermatitis
About 70 to 80% of patients with AD are considered to have classical, i.e. IgEassociated
or allergic, AD because they show elevated s-IgE levels or positive skin
prick test results for aeroallergens or food allergens, whereas the remaining 20 to 30%
never show this kind of IgE- mediated sensitization and are considered to have non-IgEassociated
or nonallergic AD (Wütrich 1978). IgE-mediated sensitization may not yet
be evident in infants or young children but it develops with increasing age. After a
thorough or repeated allergologic work-up, some nonallergic AD patients may be
reclassified as having allergic AD (Novak & Bieber 2003). It is unclear whether the
allergic and nonallergic atopic diseases are truly separate diseases or represent different
degrees of severity of the same disease. The nonallergic type is usually clinically milder
17