Effects of coal tar treatment on natural moisturizing factors
in atopic dermatitis patients

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disorder
with a wide spectrum of clinical presentations and combinations of symptoms. It
affects up to 20 percent of children and 2-10 percent of adults and often
predates the development of allergic airway diseases like rhinitis and asthma

Skin barrier dysfunction, which can be inherited or acquired, is a major
hallmark of AD, allowing for enhanced allergen and microbial penetration across
the skin.
A defective skin barrier in AD exists even in nonlesional skin and is
characterized by increased transepidermal water loss (TEWL) as well as enhanced
percutaneous penetration of chemicals.3

The discovery that mutations in the gene encoding the stratum corneum (SC)
structural protein filaggrin (FLG) are a remarkably strong risk factor for AD,
underscores the importance of the skin barrier in AD. Among patients with
moderate-to-severe AD, up to 57 percent carry 1 or more FLG-null mutations, and
the population attributable risk fraction has been estimated at between 4.2
percent and 15.1 percent.4,5 Filaggrin is a major structural protein in the SC,
crucial for the structural and biophysical integrity of the skin. Proteolysis
of Filaggrin results in small peptides known as natural moisturizing factor
(NMF). 6. These NMF keep water from evaporating from the skin and thus low
levels of NMF result in a dry and easily cracked skin and unsurprisingly a
filaggrin null mutation genotype is associated with a change in NMF-profile in
the SC

Topical use of coal tar is believed to be the oldest known therapy for AD. Its
molecular-working mechanism however, is still under investigation. In vitro
coal tar has shown to activate the aryl hydrocarbon receptor (AHR), resulting
in enhanced epidermal differentiation, increasing the levels of Filaggrin and
inhibiting the IL-4/STAT6 signalling pathway [5].This should, in principle,
strengthen the skin barrier. In vivo this has not yet been shown.

The current standard treatment of AD is the application of topical
corticosteroids and immunosuppressive ointments to counter the immunological
reaction and thus control flares. However, prolonged use of
immunosuppressivants treatment can induce side-effects on long-term, stressing
the need to develop new treatment applications. The use of coal tar therapy has
declined over the past decennia in favour of topical immunosuppressivants due
the unfavourable dark colour and unpleasant odour of coaltar. Although tar is
known to be carcinogenic, we know from large and long-term follow-up studies
that no carcinogenic effect can be shown in the topical use of coal tar

Therapeutic intervention in AD should be aimed at both restoring skin barrier
function and reducing inflammation in the entire integument in general and in
AD lesions in particular, as impaired skin barrier function is present in
lesion as well as clinically uninvolved skin.[7] Corticosteroids have been the
mainstay of treatment for AD, in the acute as well as the chronic phase of the
disease. In short-term however, corticosteroids may have a negative impact on
skin barrier function leading to e.g. decreased production and secretion of
epidermal lamellar bodies and decreased SC cohesion and integrity.[8] Similar
observations have been encountered with the usage of calcineurin inhibitors,
such as pimecrolimus and tacrolimus[9]. Therefore other substances such as coal
tar should be investigated for their skin barrier restoration properties.

To objectify skin barrier repair characteristics of coal tar in atopic
dermatitis patients, by quantifying changes in NMF, lipid levels, TEWL,
SCORAD-score and cytokine levels

This is a single-center, randomized, intra-individual comparison (right/left)
intervention study

The risks taken with participating are low. Large and long-term follow-up
studies show that no carcinogenic effect can be related to topical use of coal
tar. All measurements done are non-invasive and not painfull therefore the
burden of participation is low.