Although a compromised epidermal permeability barrier can contribute to the development of contact dermatitis, whether subjects with hand eczema display abnormalities in baseline epidermal permeability barrier function in their uninvolved skin remains unknown. The aim of the present study was to assess epidermal permeability barrier function in subjects with and without hand eczema in clothing manufacturers. Upon approval by the institutional review board, volunteers were recruited from clothing manufacturers in Guangzhou City, China. An 11-item questionnaire was used to collect general data from the volunteers. The diagnoses of self-proclaimed hand eczema were further confirmed by a dermatologist. Epidermal biophysical properties, including transepidermal water loss (TEWL) rates, stratum corneum hydration and skin surface pH were measured on the flexural surface of the left forearm in all volunteers. Epidermal biophysical properties were compared among cohorts of subjects with active hand eczema, a prior history of hand eczema and without any history of hand eczema. A total of 650 questionnaires were collected from 462 females and 188 males, with a mean age of 36.7 ± 0.46 years (range 16–69 years; 95% CI 35.8–37.59). Thirty-five subjects (5.4%) currently had hand eczema, while 28 subjects (4.3%) reported a prior history of hand eczema that was inactive currently. The prevalence of hand eczema did not differ significantly between genders. Neither a prior personal nor a family history of allergies was associated with the prevalence of hand eczema, but certain occupations and frequent contact with disinfectants were independently associated with the prevalence of hand eczema. In the overall cohort, males displayed higher TEWL rates and stratum corneum hydration levels than did females. Both skin surface pH and TEWL rates differed significantly among normal controls and subjects with active hand eczema or a prior history of hand eczema (p < 0.05). In conclusion, the uninvolved skin site of subjects with hand eczema exhibits abnormalities in epidermal perme-ability barrier, supporting a pathogenic role of epidermal dysfunction in hand eczema. Whether subjects with hand eczema in other occupations also display altered epidermal function on uninvolved skin remains to be explored.

Defects in the epidermal permeability barrier can provoke cutaneous inflammation [1]. Conversely, improvements in the epidermal permeability barrier can prevent and alleviate some inflammatory dermatoses. Studies showed that improvements in epidermal permeability barrier with a topical lipid mixture markedly improved the severity scoring of atopic dermatitis in children [2]. Likewise, topical applications of a barrier repair emollient in combination with topical glucocorticoid cream reduced psoriasis area severity index scores by approximately 25% in comparison to glucocorticoid cream alone [3]. Moreover, recent studies demonstrated that improvements in epidermal permeability barrier function delayed the relapse of psoriasis [4]. Furthermore, expression levels of proinflammatory cytokines in normal-appearing aged murine skin could also be lowered simply by improvements in epidermal permeability barrier function [5]. Together, disparate types of evidence suggest a regulatory role for the epidermal permeability barrier in the development of cutaneous inflammation.

Hand eczema, a common dermatosis, belongs to the category of contact dermatitis and it is often associated with particular occupations. Studies suggest that a defective epidermal permeability barrier function could contribute to the development of contact dermatitis. First, mutation in filaggrin, a structural protein required for the epidermal permeability barrier, decreases thresholds for both irritant and allergic contact dermatitis in mice [6]. Likewise, filaggrin mutations are associated with an enhanced tendency to develop both irritant and allergic contact dermatitis in humans [7, 8]. Moreover, reductions in filaggrin content were found in lesional skin of hand eczema, supporting a possible role for the epidermal permeability barrier function in the pathogenesis of hand eczema [9]. Second, while deficiency in caspase 14 impairs the epidermal permeability barrier [10], the uninvolved skin of hand eczema subjects displays a lower expression of caspase 14 [11]. Third, deficiencies in late cornified envelope proteins, LCE3B and LCE3C, other structural proteins of the barrier, are associated with allergic contact dermatitis [12].

Collectively, these studies suggest a pathogenic role for defects in the epidermal permeability barrier in the development of hand eczema. However, there is still a lack of sufficient, direct evidence to support that a defective permeability barrier predisposes to the development of hand eczema. If the development of hand eczema is attributed to the defective epidermal permeability barrier, uninvolved skin sites should exhibit elevations in transepidermal water loss (TEWL) rates, an indicator of permeability status. Therefore, we compared here the epidermal permeability barrier function in a large cohort with or without hand eczema.

This study was carried out in clothing manufacturer workers in Guangzhou City during the months of November and December. An 11-item questionnaire was used to collect general information of volunteers (online suppl. Table 1; for all online suppl. material, see www.karger.com/doi/10.1159/000506425). This questionnaire focused primarily on work-related questions. Subjects with self-proclaimed hand eczema were further examined by a dermatologist, who confirmed the diagnosis of hand eczema, according to its clinical features. No effort was made to distinguish between allergic and irritant contact dermatitis. Except for regular bathing and washing, no moisturizer lotion or cream was applied to measurement sites for at least 24 h prior to measurements. Epidermal biophysical properties, including TEWL rates and stratum corneum hydration were measured with GPskin Barrier® (GPower Inc., Seoul, South Korea) [13], while skin surface pH was measured with a portable skin pH meter (Hanna Instruments, Smithfield, RI, USA) on the flexor side of the left forearm. This study was approved by the institutional review board of the Dermatology Hospital of Southern Medical University (GDDHLS20180505). Informed consents were obtained from all subjects prior to the study.

Statistics

GraphPad Prism 5 software was used for all statistical analyses. The two-sided Fisher’s exact test or χ2 test was used when comparing qualitative variables. The Mann-Whitney test was used to determine the significance between groups, while one-way ANOVA was used to determine significances among more than two groups. Data are expressed as means ± SEM. p values are indicated in tables, the figure or figure legend.

Basic Characteristics of Subjects

A total of 650 questionnaires were obtained from 462 females and 188 males, with a mean age of 36.7 ± 0.46 years (range: 16–69 years; 95% CI: 35.8–37.59). Subjects with current hand eczema were 38.69 ± 1.90 years of age (median: 40; 95% CI: 34.83–42.54) while subjects with past hand eczema (not now) were 36.61 ± 2.17 years of age (median: 35; 95% CI: 32.16–41.06). A majority of these volunteers (73%) worked in the production line. Over 80% of subjects in these cohorts did neither routinely use detergents to wash their hands nor moisturizers after hand washing. Fifty-five (8%) subjects had a family history of allergy, while 29% of subjects had a personal history of allergy. Thirty-five subjects (5.4%) currently had hand eczema while 28 subjects (4.3%) only had a prior history of, but no current, hand eczema. Lifetime prevalence of hand eczema was 9.7% (63/650). Prevalence of hand eczema did not differ significantly between genders in this cohort although female dominance has been documented [3, 14]. Characteristics of these cohorts are summarized in Table 1.

Table 1.

Demographic characteristics of subjects

Demographic characteristics of subjects
Demographic characteristics of subjects

Occupation Dominates the Prevalence of Hand Eczema

Because routine occupational and/or household activities are often associated with the development of hand eczema, we first analyzed which of these activities are possible risk factors for hand eczema. The prevalence of hand eczema varied greatly with occupation (p < 0.0001, Table 2). Subjects working either at a production line or warehouse appeared to be at a higher risk for the development of hand eczema in comparison to other occupations (Table 2).

Table 2.

Possible risk factors of hand eczema

Possible risk factors of hand eczema
Possible risk factors of hand eczema

The prevalence of hand eczema varied greatly with exogenous substances or materials that hands frequently contacted (p = 0.0408). Among the substances and materials, disinfectants were most strongly associated with hand eczema (relative risk = 0.1727, p < 0.05; Table 2). Although wet work is considered as a major contributor to hand eczema [15], the prevalence of hand eczema did not differ significantly between wet and nonwet workers in this study. Likewise, the frequency of daily washing hands did not influence the development of hand eczema. Subjects with hand eczema washed their hands 7.9 ± 0.7 times per day (median: 7; 95% CI: 6.40225–9.42632) while subjects without hand eczema washed their hands 7.2 ± 0.2 times per day (median: 7; 95% CI: 6.85185–7.59789). Finally, the prevalence of hand eczema was comparable in subjects with or without a prior or family history of allergies (Table 2). Taken together, only occupation and materials that frequently contact hands appear to be risk factors for hand eczema in this occupational setting.

Uninvolved Skin Site of Subjects with Hand Eczema Displays Compromised Permeability Barrier Function

Previous studies have shown that a defective permeability barrier can enhance the percutaneous penetration of substances into the skin, predisposing to the development of contact dermatitis [16]. We next assessed the epidermal permeability barrier function in these subjects. In agreement with previous findings [17], males exhibited higher basal TEWL rates in comparison to females (Fig. 1a). Similarly, stratum corneum hydration levels in males were also significantly higher than those in females (Fig. 1a, p < 0.0001). Moreover, TEWL rates were significantly higher in subjects with current and a prior history of hand eczema altogether than in subjects without hand eczema (Fig. 1b, p < 0.01). Although skin surface pH did not differ significantly either between subjects with current and a prior history of hand eczema altogether, and subjects without hand eczema (Fig. 1b), subjects with active hand eczema displayed higher skin surface pH in comparison to subjects with either a prior history of hand eczema (q = 5.029, p < 0.01) or without a history of hand eczema (Fig. 1c, q = 6.09, p < 0.001). Stratum corneum hydration levels were 14% lower in subjects with active hand eczema than those without hand eczema (Fig. 1c, 27.46 ± 2.85 vs. 31.94 ± 0.52, p = 0.0635). Striking differences were found in TEWL rates among subjects without a history of hand eczema, with active or a prior history of hand eczema (Fig. 1c, F = 5.806, p = 0.0032). Furthermore, in subjects currently without active hand eczema but a prior history of hand eczema, their TEWL rates were 18% higher than in those without a history of hand eczema at all (10.42 ± 1.55 vs. 8.56 ± 0.24). Finally, subjects with and without a family history of hand eczema or allergy displayed comparable levels of TEWL, stratum corneum hydration and skin surface pH. These results demonstrate that subjects with hand eczema exhibit defects in epidermal permeability barrier and stratum corneum acidity on the involved skin site.

Fig. 1.

Comparison of epidermal function in subjects with and without hand eczema. a Comparison of epidermal function between males and females in this cohort. Because of nonnormality of the data, an unpaired t test (Mann-Whitney test) was used for comparisons between the two groups. b Comparison of epidermal function between subjects without hand eczema and subjects with either current or a prior history of eczema. Because of nonnormality of the data, an unpaired t test (Mann-Whitney test) was used for comparisons between the two groups. c Comparison of epidermal function among subjects without hand eczema, with current eczema or those with a history of eczema. Data are expressed as means ± SEM. A Kruskal-Wallis test was used to determine the significant differences among groups, and the differences between hand eczema and normal controls were determined using one-way ANOVA with post hoc Dunnett’s multiple comparison test. p values above the columns vary significantly between groups (a p < 0.05 and b p < 0.01) while p values in the columns are versus subjects without hand eczema (c p < 0.01 and d p < 0.001). n = 61 for hand eczema and n= 587 for subjects without hand eczema.

Fig. 1.

Comparison of epidermal function in subjects with and without hand eczema. a Comparison of epidermal function between males and females in this cohort. Because of nonnormality of the data, an unpaired t test (Mann-Whitney test) was used for comparisons between the two groups. b Comparison of epidermal function between subjects without hand eczema and subjects with either current or a prior history of eczema. Because of nonnormality of the data, an unpaired t test (Mann-Whitney test) was used for comparisons between the two groups. c Comparison of epidermal function among subjects without hand eczema, with current eczema or those with a history of eczema. Data are expressed as means ± SEM. A Kruskal-Wallis test was used to determine the significant differences among groups, and the differences between hand eczema and normal controls were determined using one-way ANOVA with post hoc Dunnett’s multiple comparison test. p values above the columns vary significantly between groups (a p < 0.05 and b p < 0.01) while p values in the columns are versus subjects without hand eczema (c p < 0.01 and d p < 0.001). n = 61 for hand eczema and n= 587 for subjects without hand eczema.

Close modal

While hand eczema is a common dermatosis in the USA and Europe, information about the prevalence of hand eczema in China is limited. We show here that the lifetime prevalence of hand eczema was 9.7%, while point prevalence was 5.4% in this cohort, which both were lower than that reported in European populations [14]. Although no efforts were made to differentiate allergic from irritant contact dermatitis, hand eczema in this cohort likely was, at least to a large extent, irritant contact dermatitis because (1) the majority of occupational hand eczemas are irritant rather than allergic contact dermatitis [15, 18] and (2) the prevalence of hand eczema was comparable in subjects with and without a history of allergies.

Regarding risk factors, many factors can contribute to the development of hand eczema. Occupational wet work and frequent hand washing have been considered as major contributors to hand eczema at least in the health care industry [18, 19]. However, the present study did not reveal any link between hand eczema and either wet work or frequent hand washing. The discrepant results between the present study and others could be due to the relatively small sample size in the present study, where there were only 13 wet workers. Regarding a possible link between atopic dermatitis and hand eczema, it is inconclusive. While subjects with atopic dermatitis display a higher prevalence of hand eczema compared to those without atopic dermatitis [20], the rates of allergic contact dermatitis on the hands were comparable between atopic and nonatopic subjects [21]. Moreover, it is no surprise that no subjects with atopic dermatitis were present in this cohort, possibly because of the low overall prevalence of adult atopic dermatitis (<%1) in China [22]. The link between topical use of disinfectant and hand eczema is also uncertain. While previous studies showed no association of disinfectants with hand eczema, the present study demonstrated that over 28% (2/7) of subjects with hand eczema frequently contacted disinfectants, but our sample size was too small to draw any conclusions. That occupation markedly influenced the prevalence of hand eczema is consistent with prior observations [19]. In this cohort, subjects working in production lines and warehouses exhibited the highest risk for hand eczema, possibly because they repeatedly contact the same or similar substance(s) daily. In such cases, occasional contact with substances at low concentration may not be harmful, but repeated contact could eventually provoke hand eczema. Finally, other studies have shown that single nucleotide polymorphisms of inflammation-related genes are associated with hand eczema [23]. Whether such genes were altered in these subjects is unknown.

A pathogenic role for a defective epidermal permeability barrier in hand eczema has long been proposed, because (1) expression levels of barrier-related proteins, including filaggrin and caspase 14, decline in the lesional skin of hand eczema [9, 11], (2) TEWL rates increase in lesional skin and adjacent nonlesional skin [11], (3) topical barrier repair strategies delay the relapses of and/or improve hand eczema [24, 25] and (4) skin disorders, such as atopic dermatitis, with a defective permeability barrier are risk factors of hand eczema [26]. However, direct evidence to support the role of epidermal permeability dysfunction in hand eczema is far less sufficient. In most, if not in all studies, measurements of TEWL rates were performed on lesional or their adjacent sites. Here, we showed that TEWL rates also elevated in the uninvolved skin sites of subjects with hand eczema, but the underlying mechanisms are unclear. Although filaggrin mutations, a presumed cause of barrier dysfunction, are associated with hand eczema, particularly irritant contact dermatitis [27, 28], the following evidence does not support a role of filaggrin mutations in the elevated TEWL rates in the present cohort: (a) not all hand eczema has been associated with filaggrin mutations, while environmental factors largely account for the development of hand eczema [29, 30]; (b) humans with and without filaggrin mutation display comparable basal barrier function [31, 32]; and (c) in mice with filaggrin mutations, elevations in TEWL rates were observed only in aged, but not young mice [6], while our subjects were under 40 years of age. Therefore, filaggrin mutations likely did not contribute to the increased TEWL rates in this cohort. Nonetheless, doubtlessly elevated TEWL rates play a significant role in the pathogenesis of hand eczema. A number of previous studies have shown that disruption of the epidermal permeability barrier not only induces production and release of proinflammatory cytokines [1, 33], but also stimulates T-cell proliferation [32], leading to reductions in thresholds of response to external stimuli [34]. Whereas hand eczema belongs to the category of contact dermatitis, results of the present study support the notion that pre-existing dysfunction of the epidermal permeability barrier predisposes to the development of hand eczema. Although the skin surface pH in subjects with hand eczema was significantly higher than that in subjects without hand eczema, it still falls within a normal range. Thus, the marginal elevation in skin surface pH likely did not contribute to the development of hand eczema.

Prior studies have demonstrated the importance of measuring epidermal permeability barrier function in evaluating the status and therapeutic efficacy of certain dermatoses. In both adults and children with atopic dermatitis, TEWL rates positively correlate with disease severity [35-37]. Moreover, measurement of TEWL rates is a reliable approach to evaluate the therapeutic efficacy of the treatments for both atopic dermatitis and psoriasis [2, 3, 38]. In addition, infants with higher TEWL rates during the first week of life predict a higher risk of atopic dermatitis later in the life independently of filaggrin mutations [39]. Likewise, TEWL rates predict the relapse of psoriasis, i.e., psoriasis relapses sooner in subjects with higher TEWL rates [4]. We showed here that uninvolved skin sites of subjects with hand eczema displayed higher TEWL rates, suggesting that TEWL rates could possibly serve as a proxy in predicting the risk of developing hand eczema, a notion which requires further studies. Notably, the TEWL rates were 2 g/m2/h higher in males than in females in this cohort. However, we did not observe the difference in the prevalence of hand eczema between males and females, probably because males and females commonly have different occupations, which can influence the development of eczema. However, whether the gender differences in TEWL rates can contribute to the different prevalences of hand eczema between males and females remains to be determined, ideally in a large cohort that both males and females have the same or similar occupation.

In conclusion, the uninvolved skin sites of patients with hand eczema exhibit defects in epidermal permeability barrier function, which could contribute to the development of hand eczema. Conversely, improvements in the epidermal permeability barrier could prevent and/or treat hand eczema.

Limitations

There are several limitations in the present study, including (a) data using questionnaires to obtain parti-cipants’ history of skin disorders may not be accurate, (b) whether and how much prior and/or current skin disorders contribute to the development of hand eczema remains to be determined and (c) because of the low prevalence of hand eczema, studies in large cohorts are required to confirm the results of the present study.

This work was reviewed and approved by the Institutional Review Board of Dermatology Hospital (Approval No. GDDHLS-20180505).

All authors declare no conflicts of interest.

This work was supported in part by the China National Natural Science Foundation (NSFC 81903188, LY), with resources from the Research Service, Department of Veterans Affairs Medical Center, San Francisco, CA, USA.

Wang X., Ye L., Lai Q., Wen S., Long Z. and Qiu X. performed experiments. Man M.-Q. and Yang B. designed experiments. Man M.-Q. analyzed and interpreted data, and wrote the draft. Elias P.M. and Yang B. interpreted data and critically reviewed the paper.

1.
Elias
PM
,
Wood
LC
,
Feingold
KR
.
Epidermal pathogenesis of inflammatory dermatoses
.
Am J Contact Dermat
.
1999
Sep
;
10
(
3
):
119
26
.
[PubMed]
1046-199X
2.
Chamlin
SL
,
Kao
J
,
Frieden
IJ
,
Sheu
MY
,
Fowler
AJ
,
Fluhr
JW
, et al
Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: changes in barrier function provide a sensitive indicator of disease activity
.
J Am Acad Dermatol
.
2002
Aug
;
47
(
2
):
198
208
.
[PubMed]
0190-9622
3.
Liu
M
,
Li
X
,
Chen
XY
,
Xue
F
,
Zheng
J
.
Topical application of a linoleic acid-ceramide containing moisturizer exhibit therapeutic and preventive benefits for psoriasis vulgaris: a randomized controlled trial
.
Dermatol Ther (Heidelb)
.
2015
Nov-Dec
;
28
(
6
):
373
82
.
[PubMed]
2193-8210
4.
Man
MQ
,
Ye
L
,
Hu
L
,
Jeong
S
,
Elias
PM
,
Lv
C
.
Improvements in epidermal function prevent relapse of psoriasis: a self-controlled study
.
Clin Exp Dermatol
.
2019
Aug
;
44
(
6
):
654
7
.
[PubMed]
0307-6938
5.
Hu
L
,
Mauro
TM
,
Dang
E
,
Man
G
,
Zhang
J
,
Lee
D
, et al
Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines
.
J Invest Dermatol
.
2017
Jun
;
137
(
6
):
1277
85
.
[PubMed]
0022-202X
6.
Scharschmidt
TC
,
Man
MQ
,
Hatano
Y
,
Crumrine
D
,
Gunathilake
R
,
Sundberg
JP
,et al
Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens. J Allergy Clin Immunol.
2009
;124:496-506, 506.e1-6.
7.
de Jongh
CM
,
Khrenova
L
,
Verberk
MM
,
Calkoen
F
,
van Dijk
FJ
,
Voss
H
, et al
Loss-of-function polymorphisms in the filaggrin gene are associated with an increased susceptibility to chronic irritant contact dermatitis: a case-control study
.
Br J Dermatol
.
2008
Sep
;
159
(
3
):
621
7
.
[PubMed]
0007-0963
8.
Molin
S
,
Vollmer
S
,
Weiss
EH
,
Ruzicka
T
,
Prinz
JC
.
Filaggrin mutations may confer susceptibility to chronic hand eczema characterized by combined allergic and irritant contact dermatitis
.
Br J Dermatol
.
2009
Oct
;
161
(
4
):
801
7
.
[PubMed]
0007-0963
9.
Molin
S
,
Merl
J
,
Dietrich
KA
,
Regauer
M
,
Flaig
M
,
Letulé
V
, et al
The hand eczema proteome: imbalance of epidermal barrier proteins
.
Br J Dermatol
.
2015
Apr
;
172
(
4
):
994
1001
.
[PubMed]
0007-0963
10.
Denecker
G
,
Hoste
E
,
Gilbert
B
,
Hochepied
T
,
Ovaere
P
,
Lippens
S
, et al
Caspase-14 protects against epidermal UVB photodamage and water loss
.
Nat Cell Biol
.
2007
Jun
;
9
(
6
):
666
74
.
[PubMed]
1465-7392
11.
Wang
B
,
Liu
LL
,
Zhao
ZT
,
Tu
P
.
Impaired Skin Barrier Function and Downregulated Expression of Caspase-14 in Moderate to Severe Chronic Hand Eczema
.
Dermatology
.
2018
;
234
(
5-6
):
180
5
.
[PubMed]
1018-8665
12.
Molin
S
,
Vollmer
S
,
Weiss
EH
,
Weisenseel
P
,
Ruzicka
T
,
Prinz
JC
.
Deletion of the late cornified envelope genes LCE3B and LCE3C may promote chronic hand eczema with allergic contact dermatitis
.
J Investig Allergol Clin Immunol
.
2011
;
21
(
6
):
472
9
.
[PubMed]
1018-9068
13.
Ye
L
,
Wang
Z
,
Li
Z
,
Lv
C
,
Man
MQ
.
Validation of GPSkin Barrier® for assessing epidermal permeability barrier function and stratum corneum hydration in humans
.
Skin Res Technol
.
2019
Jan
;
25
(
1
):
25
9
.
[PubMed]
0909-752X
14.
Behroozy
A
,
Keegel
TG
.
Wet-work Exposure: A Main Risk Factor for Occupational Hand Dermatitis
.
Saf Health Work
.
2014
Dec
;
5
(
4
):
175
80
.
[PubMed]
2093-7911
15.
Johannisson
A
,
Pontén
A
,
Svensson
Å
.
Prevalence, incidence and predictive factors for hand eczema in young adults - a follow-up study
.
BMC Dermatol
.
2013
Oct
;
13
(
1
):
14
.
[PubMed]
1471-5945
16.
Darlenski
R
,
Kazandjieva
J
,
Tsankov
N
,
Fluhr
JW
.
Acute irritant threshold correlates with barrier function, skin hydration and contact hypersensitivity in atopic dermatitis and rosacea
.
Exp Dermatol
.
2013
Nov
;
22
(
11
):
752
3
.
[PubMed]
0906-6705
17.
Mehta
HH
,
Nikam
VV
,
Jaiswal
CR
,
Mehta
HB
.
A cross-sectional study of variations in the biophysical parameters of skin among healthy volunteers
.
Indian J Dermatol Venereol Leprol
.
2018
Jul-Aug
;
84
(
4
):
521
.
[PubMed]
0378-6323
18.
Mekonnen
TH
,
Yenealem
DG
,
Tolosa
BM
.
Self-report occupational-related contact dermatitis: prevalence and risk factors among healthcare workers in Gondar town, Northwest Ethiopia, 2018-a cross-sectional study
.
Environ Health Prev Med
.
2019
Feb
;
24
(
1
):
11
.
[PubMed]
1342-078X
19.
Hamnerius
N
,
Svedman
C
,
Bergendorff
O
,
Björk
J
,
Bruze
M
,
Pontén
A
.
Wet work exposure and hand eczema among healthcare workers: a cross-sectional study
.
Br J Dermatol
.
2018
Feb
;
178
(
2
):
452
61
.
[PubMed]
0007-0963
20.
Coenraads
PJ
.
Hand eczema
.
N Engl J Med
.
2012
Nov
;
367
(
19
):
1829
37
.
[PubMed]
0028-4793
21.
Coenraads
PJ
,
Diepgen
TL
.
Risk for hand eczema in employees with past or present atopic dermatitis
.
Int Arch Occup Environ Health
.
1998
Feb
;
71
(
1
):
7
13
.
[PubMed]
0340-0131
22.
Nutten
S
.
Atopic dermatitis: global epidemiology and risk factors
.
Ann Nutr Metab
.
2015
;
66
Suppl 1
:
8
16
.
[PubMed]
0250-6807
23.
Yucesoy
B
,
Talzhanov
Y
,
Michael Barmada
M
,
Johnson
VJ
,
Kashon
ML
,
Baron
E
, et al
Association of MHC region SNPs with irritant susceptibility in healthcare workers
.
J Immunotoxicol
.
2016
Sep
;
13
(
5
):
738
44
.
[PubMed]
1547-691X
24.
Lodén
M
,
Wirén
K
,
Smerud
K
,
Meland
N
,
Hønnås
H
,
Mørk
G
, et al
Treatment with a barrier-strengthening moisturizer prevents relapse of hand-eczema. An open, randomized, prospective, parallel group study
.
Acta Derm Venereol
.
2010
Nov
;
90
(
6
):
602
6
.
[PubMed]
0001-5555
25.
Jordan
L
.
Efficacy of a Hand Regimen in Skin Barrier Protection in Individuals With Occupational Irritant Contact Dermatitis
.
J Drugs Dermatol
.
2016
Nov
;
15
(
11
):
s81
5
.
[PubMed]
1545-9616
26.
Ruff
SM
,
Engebretsen
KA
,
Zachariae
C
,
Johansen
JD
,
Silverberg
JI
,
Egeberg
A
, et al
The association between atopic dermatitis and hand eczema: a systematic review and meta-analysis
.
Br J Dermatol
.
2018
Apr
;
178
(
4
):
879
88
.
[PubMed]
0007-0963
27.
Handa
S
,
Khullar
G
,
Pal
A
,
Kamboj
P
,
De
D
.
Filaggrin gene mutations in hand eczema patients in the Indian subcontinent: A prospective case-control study
.
Contact Dermat
.
2019
Jun
;
80
(
6
):
359
64
.
[PubMed]
0105-1873
28.
Landeck
L
,
Visser
M
,
Kezic
S
,
John
SM
.
Genotype-phenotype associations in filaggrin loss-of-function mutation carriers
.
Contact Dermat
.
2013
Mar
;
68
(
3
):
149
55
.
[PubMed]
0105-1873
29.
Lerbaek
A
,
Bisgaard
H
,
Agner
T
,
Ohm Kyvik
K
,
Palmer
CN
,
Menné
T
.
Filaggrin null alleles are not associated with hand eczema or contact allergy
.
Br J Dermatol
.
2007
Dec
;
157
(
6
):
1199
204
.
[PubMed]
0007-0963
30.
Lerbaek
A
,
Kyvik
KO
,
Mortensen
J
,
Bryld
LE
,
Menné
T
,
Agner
T
.
Heritability of hand eczema is not explained by comorbidity with atopic dermatitis
.
J Invest Dermatol
.
2007
Jul
;
127
(
7
):
1632
40
.
[PubMed]
0022-202X
31.
Angelova-Fischer
I
,
Mannheimer
AC
,
Hinder
A
,
Ruether
A
,
Franke
A
,
Neubert
RH
, et al
Distinct barrier integrity phenotypes in filaggrin-related atopic eczema following sequential tape stripping and lipid profiling
.
Exp Dermatol
.
2011
Apr
;
20
(
4
):
351
6
.
[PubMed]
0906-6705
32.
Jungersted
JM
,
Scheer
H
,
Mempel
M
,
Baurecht
H
,
Cifuentes
L
,
Høgh
JK
, et al
Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema
.
Allergy
.
2010
Jul
;
65
(
7
):
911
8
.
[PubMed]
0105-4538
33.
Wood
LC
,
Elias
PM
,
Calhoun
C
,
Tsai
JC
,
Grunfeld
C
,
Feingold
KR
.
Barrier disruption stimulates interleukin-1 alpha expression and release from a pre-formed pool in murine epidermis
.
J Invest Dermatol
.
1996
Mar
;
106
(
3
):
397
403
.
[PubMed]
0022-202X
34.
Nishijima
T
,
Tokura
Y
,
Imokawa
G
,
Seo
N
,
Furukawa
F
,
Takigawa
M
.
Altered permeability and disordered cutaneous immunoregulatory function in mice with acute barrier disruption
.
J Invest Dermatol
.
1997
Aug
;
109
(
2
):
175
82
.
[PubMed]
0022-202X
35.
Gupta
J
,
Grube
E
,
Ericksen
MB
,
Stevenson
MD
,
Lucky
AW
,
Sheth
AP
, et al
Intrinsically defective skin barrier function in children with atopic dermatitis correlates with disease severity
.
J Allergy Clin Immunol
.
2008
Mar
;
121
(
3
):
725
730.e2
.
[PubMed]
0091-6749
36.
Kim
DW
,
Park
JY
,
Na
GY
,
Lee
SJ
,
Lee
WJ
.
Correlation of clinical features and skin barrier function in adolescent and adult patients with atopic dermatitis
.
Int J Dermatol
.
2006
Jun
;
45
(
6
):
698
701
.
[PubMed]
0011-9059
37.
Sugarman
JL
,
Fluhr
JW
,
Fowler
AJ
,
Bruckner
T
,
Diepgen
TL
,
Williams
ML
.
The objective severity assessment of atopic dermatitis score: an objective measure using permeability barrier function and stratum corneum hydration with computer-assisted estimates for extent of disease
.
Arch Dermatol
.
2003
Nov
;
139
(
11
):
1417
22
.
[PubMed]
0003-987X
38.
Darlenski
R
,
Hristakieva
E
,
Aydin
U
,
Gancheva
D
,
Gancheva
T
,
Zheleva
A
, et al
Epidermal barrier and oxidative stress parameters improve during in 311 nm narrow band UVB phototherapy of plaque type psoriasis
.
J Dermatol Sci
.
2018
Jul
;
91
(
1
):
28
34
.
[PubMed]
0923-1811
39.
Horimukai
K
,
Morita
K
,
Narita
M
,
Kondo
M
,
Kabashima
S
,
Inoue
E
, et al
Transepidermal water loss measurement during infancy can predict the subsequent development of atopic dermatitis regardless of filaggrin mutations
.
Allergol Int
.
2016
Jan
;
65
(
1
):
103
8
.
[PubMed]
1323-8930

Xiaohua Wang and Li Ye contributed equally to this work.

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