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

early childhood, and is accompanied by asthma and rhinitis later at preschool or school
age or in early adulthood. The development of these atopic diseases with age is often
called “the atopic march” (Spergel & Paller 2003). Risk factors for allergic asthma
include positive family history for asthma and atopic diseases, allergic sensitization,
allergic rhinitis, and AD, especially severe AD (Arruda et al. 2005, Corren 2007).
According to several studies on the epidemiology of the atopic diseases, 40 to 50% of
AD patients will develop asthma and approximately the same precentage allergic
rhinitis (Spergel 2005, Corren 2007). Co-morbid AD and allergic rhinitis further
increase asthma risk (Arruda et al. 2005). In patients with severe AD, occurrence of
asthma may be over 60%. (Spergel 2005, Gustafsson et al. 2000). In one study, only
16% of AD patients developed neither asthma nor allergic rhinitis (Spergel 2005).
Several studies suggest a connection between the skin and airways and that
epicutaneous antigen exposure may promote systemic allergic responses. Epicutaneous
exposure to peanut via barrier-disrupted skin has led to specific IgE-production and Th2
type immune responses (Lack et al. 2003, Strid et al. 2005). A mouse model showed
that epicutaneous sensitization to ovalbumin may be the first step leading to bronchial
hyper-responsiveness (Spergel et al. 1998). Similarly, in mice, epicutaneous latex
exposure can induce lung inflammation and airway hyper-responsiveness (Lehto et al.
2005), and epicutaneous Aspergillus fumigatus exposure may result in systemic Th2
immunity predisposing to allergic nasal responses (Akei et al. 2006).
Several reviews have concluded that skin barrier dysfunction correlates directly
with both the AD severity and the probability of progression through atopic march to
asthma; such dysfunction thus may be the initiating factor in the “atopic march”
(Spergel & Paller 2003, Beck & Leung 2000). The fact that many genes related to AD
are expressed in the epidermis or mucosa suggests that epithelial surfaces may initiate
the atopic disease process (Cookson 2004). The actual mechanism behind the sequential
development of atopic diseases may be in the AD-related systemic T cell trafficking
from the skin to distant lymph nodes where Th2 type cytokines direct naive T cells to
develop into Th2 type cells. These cells will then migrate to other tissues such as the
bronchial and nasal mucosa where they start the atopic inflammatory process (Spergel
& Paller 2003).
Atopic blepharoconjunctivitis
Allergic conjunctivitis is often associated with allergic rhinitis, whereas atopic
blepharoconjunctivitis—or atopic keratoconjunctivitis—affecting also the eyelids and
possibly the cornea is a chronic ocular manifestation of AD (Foster et al. 1991). It
usually develops in middle-age, and most of the patients have AD in other skin areas,
usually the face and neck (Foster et al. 1991). The histopathology of atopic
blepharoconjunctivitis shares features of both acute allergic conjunctivitis, and chronic
atopic inflammation. Eosinophils, mast cells, neutrophils, and lymphocytes, especially
activated T cells, are present in conjunctival cytology (Bielory 2002). The primary
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