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

Specific issues related to treatment of atopic
dermatitis
Effects of treatment on skin barrier function
Topical corticosteroids are known to induce stratum corneum thinning. They cause
upregulation of endogenous proteases that cause degradation of corneodesmosomes
forming junctions between corneocytes. These changes, leading to clinically measurable
increase in TEWL, can already be detected already after short (3-7 days) treatment
periods as well as after longer-term treatment (Cork et al. 2006). Treatment of AD skin
with tacrolimus ointment reduces TEWL to normal or almost normal levels, which
suggests that tacrolimus could have a normalizing effect on skin barrier function
(Granlund et al. 2001, Pournaras et al. 2002).
Skin atrophy and collagen synthesis of the skin
A well known problem related to topical corticosteroid treatment is skin atrophy.
Naturally thin skin areas such as the face, neck, eyelids, and scrotum are especially
sensitive for the atrophogenic effect. Skin atrophy is caused by suppression of
connective tissue, especially collagen synthesis in the dermal fibroblasts. Long-term
treatment or repeated treatment periods lead to clinically visible skin changes: redness,
telangiectasies, striae, bruising, and thinning (Smith et al. 1976). At laboratory level,
however, findings suggesting suppressed collagen synthesis can be seen even after short
treatment periods. Methods suitable for assessing skin atrophy noninvasively include
skin ultrasound for measuring skin thickness, and collection of dermal suction blister
fluid (SBF) from which procollagen propeptides can be measured (Kiistala 1968).
Collection and analysis of suction blister fluid reflects skin collagen synthesis
specifically and is unaffected by synthesis from other organs unlike the corresponding
markers detected in serum (Oikarinen et al. 1992). In ultrasound, atrophy can be masked
by inflammation and edema, as seen in atopic dermatitis, which can result in increased
skin thickness despite decreased collagen synthesis (Reitamo et al. 1998). Other factors
such as age, sex, time of day, and hormonal phase in women may also have an effect on
skin thickness (Eisenbeiss et al. 1998 and 2001, Gniadecka et al. 1994, Seidenari et al.
1994, Haapasaari et al. 1996).
Collagen synthesis of the skin
Collagens are the most abundant protein of human connective tissue and can be found
in organs and structures requiring tensile strength. Collagen fibers make up 70 to 80%
of the dry weight of the skin and tendons, 50 to 60% of cartilage, and about 90% of the
organic tissue of mineralized bone, and occur also in the walls of the great arteries and
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