See

discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/251567480

Skin barrier impairment correlates with

cutaneous Staphylococcus aureus colonization
and sensitization to skin-associated microbial
antigens in adult patients with atopic
dermatiti...
Article in International journal of dermatology July 2013
DOI: 10.1111/ijd.12198 Source: PubMed

CITATIONS

READS

23

101

5 authors, including:
Ove Back

Artur Schmidtchen

Lund University

Lund University

77 PUBLICATIONS 1,688 CITATIONS

158 PUBLICATIONS 3,938 CITATIONS

SEE PROFILE

All in-text references underlined in blue are linked to publications on ResearchGate,

letting you access and read them immediately.

SEE PROFILE

Available from: Artur Schmidtchen

Retrieved on: 07 September 2016

Report

Skin barrier impairment correlates with cutaneous

Staphylococcus aureus colonization and sensitization
to skin-associated microbial antigens in adult patients
with atopic dermatitis
Camilla Ling Jinnest

al, MD, Emma Belfrage, MD, Ove B
ack, MD, PhD, Artur Schmidtchen,
MD, PhD, and Andreas Sonesson, MD, PhD

Division of Dermatology and Venereology,

Department of Clinical Sciences, Lund
University, Lund, Sweden
Correspondence
Andreas Sonesson, MD, PhD
Division of Dermatology and Venereology
Department of Clinical Sciences
Lund University, Biomedical centre B14
221 84 Lund, Sweden
E-mail: andreas.sonesson@med.lu.se
Conflicts of interest: None.
Funding: This work was supported by
grants from the Swedish Government
Funds for Clinical Research (ALF), the
Welander and Finsen Research
Foundations, Alfred Osterlund research
foundation, and the Eva and Oscar Ahrens
Research Foundation.

Abstract
Background Atopic dermatitis (AD) is a chronic inflammatory skin disease. The
pathogenesis of AD involves skin barrier defects and dysregulation of innate and adaptive
immunity. Some environmental factors such as stress, infections, and allergens are
associated with aggravation of AD. The aim of the study was to investigate the relationship
between skin barrier function, skin colonization of Staphylococcus aureus, and sensitization
to antigens of skin-associated microorganisms in adult patients with AD.
Methods Thirty adult patients with AD and 10 controls were recruited. Eczema severity
was assessed, and transepidermal water loss (TEWL) was measured. Bacterial samples
were taken from the skin using a swab technique for qualitative identification of S. aureus
and a contact agar disc method for quantitative assessment. Immunological analyses of
specific IgE to staphylococcal enterotoxins and yeasts as well as total serum IgE levels,
were performed.
Results TEWL was significantly higher among S. aureus-positive patients in comparison to
S. aureus-negative patients with AD (P < 0.05). TEWL increased with increasing bacterial
load (P = 0.018). In the group of patients sensitized to all three of the investigated skinassociated microorganisms (S. aureus, Malassezia, and Candida), an increased TEWL
was observed, in comparison to patients sensitized to none, or one or two (P = 0.026).
Conclusion In adult patients with AD, a disrupted skin barrier promotes skin colonization
by microbes, such as S. aureus. Heavy microbial colonization may facilitate skin
penetration of microbial antigens leading to subsequent IgE sensitization. These results
illustrate the importance of skin-associated microbial colonization and sensitization to
microbial-derived allergens in eczema pathogenesis.

Introduction
Atopic dermatitis (AD) is an inflammatory skin disease
with reported lifetime prevalence in adults of 210% and
1530% in children.1 In AD there is a high degree of heterogeneity of the clinical phenotype as well as in the
genetic background, which reflects the complexity of the
underlying mechanisms of the disease. AD is highly heritable involving genegene and geneenvironment interactions. Several candidate genes have been found, most of
them linked either to skin barrier function or the immune
system. The pathogenesis of AD involves skin barrier
defects, imbalance in adaptive immunity, and impairments of innate immunity.2 Some environmental factors
2013 The International Society of Dermatology

such as stress, infections, and allergens are associated

with aggravation of AD.1,3,4
Stratum corneum of the skin acts as an important barrier, protecting from physical stress, invading microbes,
and preventing water loss. The skin barrier function of
AD skin is disrupted, and increased transepidermal water
loss (TEWL) is correlated with increased AD severity in
both children and adults.57 The defective skin barrier
probably facilitates the effects of environmental trigger
factors.8 Moreover, Boralevi et al.9 reported an association between epidermal barrier impairment (high TEWL)
and sensitization to aeroallergens in infants. To a certain
degree, the skin barrier defect may involve mutations in
the filaggrin gene.10 Disturbed lipid composition and
International Journal of Dermatology 2014, 53, 2733

27

28

Report

Jinnest

a l et al.

TEWL and S. aureus colonization in atopic eczema

increased endogenous enzymatic degradation are other

genetic factors contributing to barrier dysfunction.3 The
skin of patients with AD is susceptible to infection by
bacteria, fungi, and viruses.11 Secondary skin infections
are known to be associated with AD flares, and skin of
patients with AD is frequently colonized by S. aureus12
and, particularly in adults, Malassezia.11,13,14 Thus, the
presence of microbial proteases in highly colonized AD
lesions may be an additional factor facilitating disruption
of the skin barrier in AD.3,15 There are several reports
that have provided support for the role of S. aureus in
AD pathogenesis.16 Sampling on skin lesions of patients
with AD, using a contact agar method, showed the density of S. aureus colonization to be correlated to AD
severity.17 The majority of patients with AD have elevated serum levels of total IgE, and specific IgE antibodies
to skin-associated microbial allergens, as well as aeroallergens, are commonly found.4,18,19 IgE activates key
effector cells associated with allergic inflammation and
allergic diseases. Toxin producing S. aureus strains are
frequently found on AD skin. These toxins can act as superantigens that activate inflammatory cells in skin leading to an induction of proinflammatory cytokines and an
IgE-specific response. This contributes to and maintains
the inflammatory process of AD.20,21 Moreover, sensitization to antigens derived from Malassezia and Candida
seems to be common in patients with severe AD.18 However, the role of IgE in AD could be questioned as there
is lack of direct evidence of its causative role and by the
possibility that patients may fulfill the criteria of AD
without being sensitive to any allergen.19 Nevertheless,
there seems to be an association between allergic sensitization and impairments of the skin barrier.19 Skin barrier
defects in patients with AD, indicated by a high TEWL
level, are shown to be directly proportional to the systemic circulating total IgE levels.5 Apart from impairment
of the skin barrier, other factors contribute to predisposing of patients with AD to colonization and infection by
microorganisms. A T-helper (Th)2-induced expression of
adhesion molecules and impairment of the innate immune
response may contribute to the high density of S. aureus
in AD skin due to facilitated colonization and defective
bacterial clearance.21
It is plausible that a disrupted skin barrier promotes
skin colonization by microbes, such as S. aureus. Heavy
microbial colonization may facilitate skin penetration of
microbial antigens, such as antigens from S. aureus, Malassezia, and Candida, leading to a subsequent IgE sensitization and further impairment of the skin barrier.
Moreover, we have previously shown that sensitization to
skin-associated microbial allergens in adult patients with
AD is associated with severe AD.18 In this report, we
used TEWL as a marker of skin barrier function and
International Journal of Dermatology 2014, 53, 2733

explored whether TEWL correlated to skin colonization

by S. aureus and sensitization to microbial antigens in
adult patients with AD.
Materials and methods
Subjects

Adult (>18 years) patients with AD were recruited on visiting the Dermatology Clinic in Lund, Sweden. The diagnosis was verified by the UK refinement of the Hanifin
and Rajka diagnostic criteria for AD, referred to as the
Williams criteria.22,23 Patients undergoing topical treatment on the day of examination and patients on an ultraviolet treatment scheme were excluded from the study.
The control group consisted of 10 healthy individuals
without a history of AD.
All participants gave informed consent complying with
the Helsinki Declaration, and the study was performed
with the approval of the Regional Ethics Examination
Board of Lund.
Assessment of disease severity

The severity of AD was determined by the scoring of AD

(SCORAD) index classification, based on a consensus
report by the European Task Force on Atopic Dermatitis.24,25 Extent and intensity were assessed by the same
two physicians during the whole study.
Measurement of transepidermal water loss

TEWL was measured by using a closed chamber TEWL

meter, VapoMeter 300 (Delfin Technologies Ltd, Kuopio,
Finland). TEWL was measured on three different measuring points: left volar forearm, left dorsal forearm, and
abdomen (right to the umbilical). TEWL measurements
from the left volar arm were used in Figures 1 and 2. In
Figure 3, the relationship between IgE sensitization to
microbial antigen and TEWL, calculated as the average of
the measurements, was investigated. Before the measurements, the patient had to rest for 515 minutes. We aimed
for an ambient relative humidity of 1060% and an ambient temperature of 2022 C, according to the guidelines.26
Bacterial colonization

Bacterial samples were taken from the left volar forearm

or left antecubital fossa with a dry swab (Venturi Transystem, Copan, Italy) for qualitative identification of
S. aureus. The samples were conducted according to standard methods for identification of S. aureus and
performed at the Department of Clinical Microbiology
Laboratory at Sk

ane University Hospital in Lund,
Sweden. Additional bacterial samples were taken for
quantitative assessment using a contact agar disc method
2013 The International Society of Dermatology

Jinnest

a l et al.

Figure 1 Skin barrier function, expressed as TEWL level, is

measured in patients with AD with and without skin
colonization by S. aureus, as well as in healthy controls.
Patients with AD with skin colonization by S. aureus have a
significantly higher TEWL than patients with AD not
colonized or healthy controls. *P < 0.05. NS, not
significant; AD, atopic dermatitis; TEWL, transepidermal
water loss

TEWL and S. aureus colonization in atopic eczema

Report

Figure 3 Patients with AD sensitized to none, one, or two of

the skin-associated microorganisms compared to patients
with AD sensitized to all three of the investigated skinassociated microorganisms (P = 0.026). The skin barrier
function is expressed as TEWL level in patients with AD
sensitized to allergens derived from the skin-associated
microorganisms, S. aureus, Malassezia, and Candida. AD,
atopic dermatitis; TEWL, transepidermal water loss

Immunological analysis

Total serum IgE levels were measured. To investigate sensitization to the skin-associated microorganisms,
S. aureus, Malassezia, and Candida, serum-specific IgE
levels to S. aureus enterotoxin A (m80), enterotoxin
(SEB) (m81), TSST-1 (Rm226), as well as serum-specific
IgE levels to antigens derived from Malassezia (m227)
and Candida albicans (m5), were measured (ImmunoCAPTM system, Phadia AB, Uppsala, Sweden). Specific
IgE  0.35kU/l was considered positive.
Statistical analysis

Figure 2 Skin barrier function, among patients with AD, is

expressed as TEWL level in relation to the extent of
bacterial skin colonization, quantified by counting the
number of colony forming units (cfu). A significant
difference in the median values among the groups was
observed (P = 0.018). AD, atopic dermatitis; TEWL,
transepidermal water loss

(CADM), previously described,27 with modifications. The

sample was taken by pressing a TGSE agar food stamp
(Termometer.se Ltd, Gothenburg, Sweden) against the left
antecubital fossa for about five seconds and incubated at
room temperature for 4872 hours. The number of colony-forming units (cfu) was registered.
2013 The International Society of Dermatology

The WilcoxonMannWhitney rank sum test was used

for comparison between two different groups. A P value
of <0.05 was considered as a significant difference. For
comparison of several groups, KruskalWallis one-way
analysis of variance on ranks was used, and to define the
groups that differed, pairwise multiple comparison procedures (Dunns method) post-hoc test was used. The statistical software used was SigmaStat (Systat Software Inc.,
Point Richmond, CA, USA).
Results
Subjects

Thirty patients with AD and 10 controls were enrolled in

the study. S. aureus culture-positive patients with AD,
defined as patients with S. aureus isolated from the
International Journal of Dermatology 2014, 53, 2733

29

30

Report

Jinnest

a l et al.

TEWL and S. aureus colonization in atopic eczema

forearm, showed significantly higher SCORAD values in

comparison to patients with AD not colonized with
S. aureus (P = 0.002). Table 1 summarizes the characteristics of the subjects.
Staphylococcus aureus colonization and transepidermal
water loss

Staphylococcus aureus culture-positive patients with AD

showed significantly higher TEWL levels in comparison
to patients with AD not colonized with S. aureus (Fig. 1)
(P < 0.05). Moreover, a marked correspondence between
the extent of bacterial skin colonization, quantified by
counting the number of cfu isolated from the forearm,
and TEWL was found (Fig. 2) (P = 0.018). CADM displayed more than 100 cfu in patients with S. aureus culture-positive swabs. The remaining S. aureus swab
culture-negative patients showed few or no cfu when
assessed by CADM or were not assessed by quantitative
analysis at all. No S. aureus was isolated from the
controls.
Sensitization to skin-associated microorganisms
and transepidermal water loss

When comparing patients with AD sensitized to all of the

three
investigated
skin-associated
microorganisms
(S. aureus, Candida, and Malassezia), we found an
increased TEWL, SCORAD, and total IgE, in comparison
to patients sensitized to none, one, or two of the studied
skin-associated
microorganisms
(Fig. 3,
Table 2),
(P = 0.026, 0.008 and <0.001, respectively). The patients
with AD in both groups were frequently sensitized to

antigens from the yeasts Candida and/or Malassezia

(Table 2). Interestingly, sensitization to S. aureus enterotoxin A occurred among all patients with AD in the
group sensitized to all three of the investigated skin-associated microorganisms (Table 2). When the patients
instead were subdivided into groups depending on how
many (none to five) of the microbial antigens they displayed sensitization to, the results showed high TEWL
levels, high total serum IgE levels, as well as high SCORAD values in the subgroup with registered sensitization
to multiple (five) microbial antigens (Table 3).
Discussion

The results showed that TEWL is significantly higher in

a Swedish cohort of adult patients with AD colonized
by S. aureus than in non-colonized patients and correlates with the extent of colonization. To the best of our
knowledge, this has not been studied before. However,
higher TEWL levels in association with skin colonization
of S. aureus have been observed among subjects with
normal skin.28 Moreover, the relationship between
S. aureus genotype and skin barrier function has been
investigated, but no significant correlations were
found.29 In a recent study, S. aureus was isolated from
the antecubital area, popliteal fossa, and anterior nares
in 39 patients with AD. The relationship of TEWL and
the number of colonization sites was investigated and
shown to be correlated but was not statistically signinificant.30
Interestingly, only patients that were positive for
S. aureus showed a significant bacterial load (more than

Table 1 Characteristics of the patients with AD and controls

Women, n (%)
Men, n (%)
Median age in years (range)
Total IgE level > 200 kU/l, n (%)
Mean level total IgE, kU/l
Median level total IgE, kU/l (range)
IgE sensitizationa to Candida, n (%)
IgE sensitizationa to Malassezia, n (%)
IgE sensitizationa to S. aureus toxins, n (%)
Left volar forearm, TEWL g/m2/h median, (range)
SCORAD median (range)
Mild AD (SCORAD < 25), n (%)
Moderate AD (SCORAD 2550), n (%)
Severe AD (SCORAD > 50), n (%)

S. aureus culture
positive patients
with AD (n = 10)

S. aureus culture
negative patients
with AD (n = 20)

Controls (n = 10)

4 (40%)
6 (60%)
32.5 (1973)
8 (80%)
3715
1554 (16.813910)
8 (80%)
8 (80%)
5 (50%)
19.2 (9.447.6)*
53 (3684)**
0 (0%)
4 (40%)
6 (60%)

17 (85%)
3 (15%)
32.5 (1969)
12 (60%)
889
256 (14.94151)
12 (60%)
10 (50%)
5 (25%)
9.3 (1.819.7)1
33 (1554)*
6 (30%)
12 (60%)
2 (10%)

7 (70%)
3 (30%)
41 (2256)
0 (0%)
28
18 (494)
0 (0%)
0 (0%)
1 (10%)
9.1 (3.111.8)
NA
NA
NA
NA

AD, atopic dermatitis; NA, not applicable; SCORAD, scoring AD; TEWL, transepidermal water loss.
*P < 0.05 and **P = 0.002 between S. aureus culture-positive and culture-negative patients with AD.
a
Serum-specific IgE  0.35 kU/l.
International Journal of Dermatology 2014, 53, 2733

2013 The International Society of Dermatology

Jinnest

a l et al.

TEWL and S. aureus colonization in atopic eczema

Report

Table 2 Characteristics of the patients with AD sensitized to none, one or two, and patients with AD sensitized to all three of
the investigated skin-associated microorganisms; S. aureus, Candida and Malassezia

Number of patients with AD (female/male)

Age, median (range)
Total IgE kU/l, median (range)
SCORAD, median (range)
TEWL g/m2/h, median (range)
IgE sensitizationa to SEA, n (%)
IgE sensitizationa to SEB, n (%)
IgE sensitizationa to TSST-1, n (%)
IgE sensitizationa to Candida, n (%)
IgE sensitizationa to Malassezia, n (%)

Patients with AD sensitized

to none, one or two of the
skin associated microorganisms

Patients with AD sensitized

to all three of the skin-associated
microorganisms

22
32.5
228.5
36
10.7
1
1
2
14
11

8 (5/3)
35 (1954)
3711 (136413910)
51 (3985)
19.0 (8.480.9)
8 (100%)
5 (63%)
4 (50%)
8 (100%)
8 (100%)

(16/6)
(1973)
(14.94151)
(1555)
(2.632)
(5%)
(5%)
(9%)
(64%)
(50%)

P value

<0.001
0.008
0.026

AD, atopic dermatitis; SCORAD, scoring AD; SEA, S. aureus enterotoxin A; SEB, S. aureus enterotoxin B; TEWL, transepidermal water loss; TSST-1, staphylococcal toxic shock syndrome toxin-1.
a
Serum-specific IgE  0.35 kU/l.

Table 3 Characteristics of patients with AD displaying sensitization to none, one or several (two to five) of the investigated
skin-associated microbial antigens. IgE sensitization (  0.35 kU/l) to the antigens of S. aureus enterotoxin A (SEA) and B
(SEB), staphylococcal toxic shock syndrome toxin-1 (TSST-1), Candida albicans and Malassezia, were assessed
IgE sensitizationa;
number of skin-associated
microbial antigens
Number of patients with AD
(female/male)
Age, median (range)
Total IgE kU/l, median (range)
SCORAD, median (range)
TEWL g/m2/h, median (range)

1
6 (3/3)

30
72.5
34
13.4

(2069)
(14.9121)
(1654)
(2.632)

2
5 (5/0)

25
31.8
35
10.5

(1940)
(21.2644)
(1544)
(4.712.3)

3
10 (7/3)

32.5 (2173)
360 (1634151)
41 (2055)
10.8 (6.526.2)

4
3 (2/1)

30
2196
45
13

(2246)
(13643102)
(3948)
(8.430.1)

5
2 (2/0)

36 (2943)
1880 (14822278)
37 (3143)
11.5 (914)

4 (2/2)
43.5 (1954)
7485 (432013910)
75 (5585)
22.6 (17.980.9)

Serum-specific IgE  0.35 kU/l.

100 cfu) in the quantitative analysis. This indicates that

the CADM may be a reliable and simple method for bedside estimation of colonization in patients with AD. Furthermore, our results indicate that the bacterial load (the
number of cfu) correlates with an increase in TEWL and
demonstrates that CADM may serve as an indirect marker of an impaired skin barrier in patients with AD
(Fig. 2). In the present study, the number of S. aureus
culture-positive patients as well as the bacterial load
(total cfu) was relatively low. It should be noted, however, that the majority of the sampling was conducted in
patients exhibiting mild or moderate AD activity, and
hence uninvolved skin sites with less abundant colonization.
Considering microbial colonization and AD pathogenesis, S. aureus V8 protease has been shown to impair the
epidermal barrier, and may degrade the antimicrobial
2013 The International Society of Dermatology

peptide LL-37 as well as thymic stromal lymphopoietin,

an important cytokine involved in allergic and atopic diseases.15,31 Ceramide, a component in the lipid matrix that
is part of the skin barrier and serves as a major water holding molecule in the stratum corneum, is degraded by ceramidase from S. aureus.20,32 By such mechanisms, S. aureus
might contribute to ceramide deficiency as well as impairment of the epidermal barrier in AD skin.20 The barrier
defects may facilitate sensitization and lead to further
inflammation and persistence of the T-helper 2-dependent
immune response observed in AD.15 Moreover, cell wall
components of S. aureus may trigger the production of
chemokines leading to increased infiltration of inflammatory cells.11 Cytokines produced by T-helper 2 cells suppress both the expression of filaggrin and antimicrobial
peptides, contributing to further skin barrier defects and
enhanced bacterial colonization.3 The present findings are
International Journal of Dermatology 2014, 53, 2733

31

32

Report

TEWL and S. aureus colonization in atopic eczema

thus compatible with the hypothesis that an impaired epidermal barrier, in combination with S. aureus colonization, enables a continuous penetration of skin-associated
microbial allergens, which finally result in increased sensitization to microbial allergens and high IgE levels. Such a
continuous stimulation of the immune response will lead
to a vicious circle that further disrupts skin barrier
function.3,11 Interestingly, restoration of the skin barrier is
followed by both a reduction of inflammation and
improvement of the antimicrobial defense in AD skin.33
In conclusion, skin barrier defect is undoubtedly an
important factor in the pathogenesis of AD. However,
aberrations in immune defense, mutations in AD candidate genes as well as microbial colonization, most notably
S. aureus, are probably involved in the pathogenic vicious
loop in AD.34 The clinical manifestations of this are an
inflamed skin and intense pruritus. Moreover, the
impaired skin barrier facilitates penetration of allergens
and irritants that may result in sensitization and retaining
of the activated inflammatory cells in the skin, which perpetuate the eczema. In the treatment of AD, it is therefore
fundamental to protect and heal the skin barrier as well as
consider aberrations in the immune system. Thus, the
results presented herein further illustrate the importance
of skin-associated microbial colonization and sensitization
to microbial-derived allergens in the pathogenesis of AD.
Acknowledgments
Associate Professor Ola Bergendorff is greatly acknowledged for providing the VapoMeter used in this study for
TEWL measurements.
References
1 Bieber T. Atopic dermatitis. Ann Dermatol 2010; 22:
125137.
2 Bieber T. Atopic dermatitis 2.0: from the clinical
phenotype to the molecular taxonomy and stratified
medicine. Allergy 2012; 67: 14751482.
3 Elias PM, Steinhoff M. Outside-to-inside (and now back
to outside) pathogenic mechanisms in atopic dermatitis.
J Invest Dermatol 2008; 128: 10671070.
4 Avgerinou G, Goules AV, Stavropoulos PG, et al. Atopic
dermatitis: new immunologic aspects. Int J Dermatol
2008; 47: 219224.
5 Addor FA, Takaoka R, Rivitti EA, et al. Atopic
dermatitis: correlation between non-damaged skin barrier
function and disease activity. Int J Dermatol 2012; 51:
672676.
6 Gupta J, Grube E, Ericksen MB, et al. Intrinsically
defective skin barrier function in children with atopic
dermatitis correlates with disease severity. J Allergy Clin
Immunol 2008; 121: 725730e2.

International Journal of Dermatology 2014, 53, 2733

Jinnest

a l et al.

7 Kim DW, Park JY, Na GY, et al. Correlation of clinical

features and skin barrier function in adolescent and adult
patients with atopic dermatitis. Int J Dermatol 2006; 45:
698701.
8 Taieb A, Hanifin J, Cooper K, et al. Proceedings of the
4th Georg Rajka International Symposium on Atopic
Dermatitis, Arcachon, France, September 1517, 2005.
J Allergy Clin Immunol 2006; 117: 378390.
9 Boralevi F, Hubiche T, Leaute-Labreze C, et al.
Epicutaneous aeroallergen sensitization in atopic
dermatitis infants determining the role of epidermal
barrier impairment. Allergy 2008; 63: 205210.
10 Irvine AD, McLean WH. Breaking the (un)sound barrier:
filaggrin is a major gene for atopic dermatitis. J Invest
Dermatol 2006; 126: 12001202.
11 Biedermann T. Dissecting the role of infections in atopic
dermatitis. Acta Derm Venereol 2006; 86: 99109.
12 Brook I, Frazier EH, Yeager JK. Microbiology of infected
atopic dermatitis. Int J Dermatol 1996; 35: 791793.
13 Katsarou A, Armenaka M. Atopic dermatitis in older
patients: particular points. J Eur Acad Dermatol
Venereol 2011; 25: 1218.
14 B
ack O, Bartosik J. Systemic ketoconazole for yeast
allergic patients with atopic dermatitis. J Eur Acad
Dermatol Venereol 2001; 15: 3438.
15 Hirasawa Y, Takai T, Nakamura T, et al.
Staphylococcus aureus extracellular protease causes
epidermal barrier dysfunction. J Invest Dermatol 2010;
130: 614617.
16 Ong PY, Leung DY. The infectious aspects of atopic
dermatitis. Immunol Allergy Clin North Am 2010; 30:
309321.
17 Williams RE, Gibson AG, Aitchison TC, et al.
Assessment of a contact-plate sampling technique and
subsequent quantitative bacterial studies in atopic
dermatitis. Br J Dermatol 1990; 123: 493501.
18 Sonesson A, Bartosik J, Christiansen J, et al. Sensitization
to skin-associated microorganisms in adult patients with
atopic dermatitis is of importance for disease severity.
Acta Derm Venereol Epub 2012; 92. doi: 10.2340/
00015555-1465.
19 Liu FT, Goodarzi H, Chen HY. IgE, mast cells, and
eosinophils in atopic dermatitis. Clin Rev Allergy
Immunol 2011; 41: 298310.
20 Maintz L, Novak N. Modifications of the innate immune
system in atopic dermatitis. J Innate Immun 2011; 3:
131141.
21 Baker BS. The role of microorganisms in atopic
dermatitis. Clin Exp Immunol 2006; 144: 19.
22 Brenninkmeijer EE, Schram ME, Leeflang MM, et al.
Diagnostic criteria for atopic dermatitis: a systematic
review. Br J Dermatol 2008; 158: 754765.
23 Williams HC, Burney PG, Hay RJ, et al. The U.K.
Working Partys Diagnostic Criteria for Atopic
Dermatitis. I. Derivation of a minimum set of
discriminators for atopic dermatitis. Br J Dermatol 1994;
131: 383396.

2013 The International Society of Dermatology

Jinnest

a l et al.

24 Severity scoring of atopic dermatitis: the SCORAD index.

Consensus report of the European task force on atopic
dermatitis. Dermatology 1993; 186: 2331.
25 Schmitt J, Langan S, Williams HC. What are the best
outcome measurements for atopic eczema? A systematic
review J Allergy Clin Immunol 2007; 120: 13891398.
26 Pinnagoda J, Tupker RA, Agner T, et al. Guidelines for
transepidermal water loss (TEWL) measurement. A
report from the standardization group of the European
society of contact Dermatitis. Contact Dermatitis 1990;
22: 164178.
27 Akiyama H, Hamada T, Huh WK, et al. Confocal laser
scanning microscopic observation of glycocalyx
production by Staphylococcus aureus in skin lesions
of bullous impetigo, atopic dermatitis and
pemphigus foliaceus. Br J Dermatol 2003;
148: 526532.
28 Shin K, Lee TR, Lee E, et al. Staphylococcus aureus in
relation to physical, physiological and subjective
conditions of apparently normal human skin. J Dermatol
Sci 2011; 63: 201203.
29 Kim DW, Park JY, Park KD, et al. Are there
predominant strains and toxins of Staphylococcus aureus

2013 The International Society of Dermatology

TEWL and S. aureus colonization in atopic eczema

30

31

32

33

34

Report

in atopic dermatitis patients? Genotypic characterization

and toxin determination of S. aureus isolated in
adolescent and adult patients with atopic dermatitis J
Dermatol 2009; 36: 7581.
Na SY, Roh JY, Kim JM, et al. Analysis of colonization
and genotyping of the exotoxins of Staphylococcus
aureus in patients with atopic dermatitis. Ann Dermatol
2012; 24: 413419.
Sonesson A, Kasetty G, Olin AI, et al. Thymic stromal
lymphopoietin exerts antimicrobial activities. Exp
Dermatol 2011; 20: 10041010.
Ohnishi Y, Okino N, Ito M, et al. Ceramidase activity in
bacterial skin flora as a possible cause of ceramide
deficiency in atopic dermatitis. Clin Diagn Lab Immunol
1999; 6: 101104.
Park KY, Kim DH, Jeong MS, et al. Changes of
antimicrobial peptides and transepidermal water loss
after topical application of tacrolimus and ceramidedominant emollient in patients with atopic dermatitis.
J Korean Med Sci 2010; 25: 766771.
Boguniewicz M, Leung DY. Atopic dermatitis: a disease
of altered skin barrier and immune dysregulation.
Immunol Rev 2011; 242: 233246.

International Journal of Dermatology 2014, 53, 2733

33