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Nickel Allergy Is a Risk Factor for Endometriosis: An 11-Year Population-Based Nested Case-Control Study

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Background: A cross-sectional study has reported that nickel allergy is associated with endometriosis. However, causal studies of this association are limited. Objective: The objective of this study was to compare the prevalence of nickel allergy in women with and without endometriosis. Methods: We used a National Health Insurance Service (NHIS) sample cohort dataset that included approximately 1 million individuals from South Korea; the data were obtained between January 01, 2002, and December 31, 2013. We selected the endometriosis group according to diagnosis code (N80.X), surgery codes, and drug codes during the years 2009~2013. The controls were randomly matched to the endometriosis patients at a ratio of 4:1 by age and socioeconomic status. Patients with nickel allergy were defined in the cohort dataset as those with a simultaneous diagnosis code (L23.0) and patch test code during 2002~2008. Results: In total, 4,985 women were selected from the NHIS cohort database and divided into an endometriosis group (997 women) and a control group (3,988 women). The number of patients with nickel allergy in the endometriosis group was eight (0.8%), and that in the control group was thirteen (0.3%). After adjustment for age and socioeconomic status, the rate of nickel allergy in was higher in the endometriosis group than in the control group [odds ratio: 2.474; 95% confidence interval: 1.023~5.988; p = 0.044]. Conclusions: We found that nickel allergy is a risk factor for endometriosis.
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RESEARCH ARTICLE
Nickel Allergy Is a Risk Factor for
Endometriosis: An 11-Year Population-Based
Nested Case-Control Study
Jin-Sung Yuk
1,2
, Jong Seung Shin
3
, Ji-Yeon Shin
4
, Eunsuk Oh
5
, Hyunmee Kim
6
, Won
I. Park
1
*
1Department of Obstetrics and Gynecology, School of Medicine, Eulji University, Daejeon, South Korea,
2Department of Obstetrics and Gynecology, MizMedi Hospital, Seoul, South Korea, 3Department of
Obstetrics and Gynecology, Hyundai UVIS hospital, Incheon, South Korea, 4Department of Preventive
Medicine, School of Medicine, Eulji University, Daejeon, South Korea, 5Department of Internal Medicine,
MizMedi Hospital, Seoul, South Korea, 6Department of Family Medicine, MizMedi Hospital, Seoul, South
Korea
*pwi3110@eulji.ac.kr
Abstract
Background
A cross-sectional study has reported that nickel allergy is associated with endometriosis.
However, causal studies of this association are limited.
Objective
The objective of this study was to compare the prevalence of nickel allergy in women with
and without endometriosis.
Methods
We used a National Health Insurance Service (NHIS) sample cohort dataset that included
approximately 1 million individuals from South Korea; the data were obtained between Jan-
uary 01, 2002, and December 31, 2013. We selected the endometriosis group according to
diagnosis code (N80.X), surgery codes, and drug codes during the years 2009~2013. The
controls were randomly matched to the endometriosis patients at a ratio of 4:1 by age and
socioeconomic status. Patients with nickel allergy were defined in the cohort dataset as
those with a simultaneous diagnosis code (L23.0) and patch test code during 2002~2008.
Results
In total, 4,985 women were selected from the NHIS cohort database and divided into an
endometriosis group (997 women) and a control group (3,988 women). The number of
patients with nickel allergy in the endometriosis group was eight (0.8%), and that in the con-
trol group was thirteen (0.3%). After adjustment for age and socioeconomic status, the rate
of nickel allergy in was higher in the endometriosis group than in the control group [odds
ratio: 2.474; 95% confidence interval: 1.023~5.988; p = 0.044].
PLOS ONE | DOI:10.1371/journal.pone.0139388 October 6, 2015 1/8
OPEN ACCESS
Citation: Yuk J-S, Shin JS, Shin J-Y, Oh E, Kim H,
Park WI (2015) Nickel Allergy Is a Risk Factor for
Endometriosis: An 11-Year Population-Based Nested
Case-Control Study. PLoS ONE 10(10): e0139388.
doi:10.1371/journal.pone.0139388
Editor: Esaki Muthu Shankar, University of Malaya,
MALAYSIA
Received: June 27, 2015
Accepted: September 11, 2015
Published: October 6, 2015
Copyright: © 2015 Yuk et al. This is an open access
article distributed under the terms of the Creative
Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
Data Availability Statement: All relevant data were
obtained from the National Health Insurance Sharing
Service (NHISS) and are available upon request
through http://nhiss.nhis.or.kr/bd/ab/bdaba021eng.do.
Funding: The authors have no support or funding to
report.
Competing Interests: The authors have declared
that no competing interests exist.
Conclusions
We found that nickel allergy is a risk factor for endometriosis.
Introduction
Endometriosis is an estrogen-dependent disease that causes pelvic pain and subfertility in
610% of women [1]. Although debate continues regarding the cause of endometriosis, the
central theory involves the retrograde flow of endometrial cells into the pelvic cavity during
menstruation [1,2]. However, the main weakness of this theory is that only 610% of all
women have retrograde menstruation [1]; thus, some complementary theories are needed. One
hypothesis is that environmental substances such as dioxin, polychlorinated biphenyls and
organochlorine pesticides may cause endometriosis [3,4]. Another hypothesis is that changes
in the immune response might affect the survival of endometrial cells external to the endome-
trium [5,6].
Recently, using national claims data in South Korea, Yuk et al. demonstrated a high rate of
nickel allergy in women with endometriosis [7]. Because nickel allergy involves features of
environmental exposure and the immune response, there may be a relationship between nickel
allergy and the pathogenesis of endometriosis [8]. However, the study of Yuk et al. was not a
causal study but rather a correlational study. Thus, it is unclear which disease precedes the
other.
The aim of this nested case-control study was to evaluate the prevalence of nickel allergy in
women with and without endometriosis using national claims cohort data collected from 2002
to 2013. To the best of our knowledge, this is the first nested case-control study to assess the
causal relationship between nickel allergy and endometriosis.
Materials and Methods
Sample
We used a sample cohort dataset provided by the National Health Insurance Service (NHIS)
[9]. These data corresponded to approximately 1 million individuals selected randomly from
almost all South Koreans, totaling 45 million people, with national claims data for the period
from January 1, 2002, to December 31, 2013. The included variables were gender, 5-year age
group, socioeconomic status (with subjects divided into 10 categories based on income), diag-
nosis code, surgery code, drug prescription data (drug name, dosage, and date of prescription)
and billing code.
Selection of subjects
We used the International Classification of Diseases (ICD) 10
th
edition to extract the endome-
triosis group and the control group. We selected the endometriosis group as follows. We
excluded patients with any endometriosis diagnosis code (N80.X) prior to 2009 from the endo-
metriosis group. We selected patients with an endometriosis diagnosis code (N80.X) assigned
between 2009 and 2013 from the NHIS sample cohort data collected during 20022013 (Fig 1).
Among these endometriosis patients, we selected patients who simultaneously had an endome-
triosis diagnosis code (N80.X) and one or more of the following surgery codes [R4122 (myo-
mectomy), R4160 (pelvic adhesiolysis), R4165 (fulguration), R4166 (foreign body removal),
R4170 (metroplasty of uterine anomaly), R4181 (Kustner operation), R4182 (manual
Nickel Allergy Is a Risk Factor for Endometriosis
PLOS ONE | DOI:10.1371/journal.pone.0139388 October 6, 2015 2/8
Nickel Allergy Is a Risk Factor for Endometriosis
PLOS ONE | DOI:10.1371/journal.pone.0139388 October 6, 2015 3/8
reduction), R4183 (total hysterectomy), R4331 (unilateral adnexectomy), R4332 (bilateral
adnexectomy), R4341 (ligation of fallopian tubes), R4342 (surgical fulguration of oviducts),
R4345 (laparotomy), R4421 (extirpation of benign adnexal tumor), R4430 (ovarian wedge
resection), R4435 (incision and drainage of ovarian cyst)]; patients with a simultaneous endo-
metriosis diagnosis code (N80.X) and gonadotropin-releasing hormone (GnRH) agonist code
[182602BIJ (leuprolide acetate), 182604BIJ (leuprolide acetate), 244902BIJ (triptorelin acetate),
167202BIJ (goserelin acetate), 167201BIJ (goserelin acetate), 198501CSI (nafarelin)]; and
patients with a simultaneous endometriosis diagnosis code (N80.X) and danazol code
(140301ACH, 140302ACH) to increase diagnostic accuracy. Among patients without any
endometriosis diagnosis code (N80.X) during 2002~2013, the controls were randomly matched
to the endometriosis patients at a ratio of 4:1 by 5-year age group and socioeconomic status
(Fig 1). Patients with nickel allergy were identified as those who simultaneously had a nickel
allergy diagnosis code (L23.0) and a test code [patch test (E7130), skin prick test (E7151,
EY853), intradermal test (E7152, EY854)] among the cohort dataset during 20022008.
Statistics
Data management and analysis were performed using the R statistical software (version 3.0.3;
Vienna, Austria). Significance was considered for p-values under 0.05. All of the statistical
analyses were performed using two-tailed tests. The chi-squared test or Fishers exact test was
applied to compare categorical differences between two groups. After adjustments for age,
socioeconomic status and sampling year, conditional logistic multivariate analysis was per-
formed to determine the effects of nickel allergy on endometriosis.
Ethics statement
For information protection, all of the patients received an anonymous identification code in
the sample data provided by the NHIS. The authors could not identify any patients in the sam-
ple data. Thus, we did not require the approval of the Institutional Review Board, in accordance
with the guidelines of the Institutional Review Board of MizMedi Hospital.
Results
A total of 4,985 women were selected from the NHIS cohort database, which included approxi-
mately 1 million individuals from 2002 to 2013. Among the 4,985 women, the endometriosis
group included 997 women. The control group included 3,988 women who were matched to
the endometriosis patients according to 5-year age group and socioeconomic status at a ratio of
4:1 (Fig 1 and Table 1). The mean age in both groups was 42.6±9.3 years in 2013. The number
of patients with nickel allergy in the endometriosis group was eight (0.8%), and the number of
patients with nickel allergy in the control group was thirteen (0.3%). After adjusting for 5-year
age group and socioeconomic status, the prevalence of nickel allergy was higher in the endome-
triosis group than in the control group [odds ratio (OR): 2.474; 95% confidence interval (CI):
1.0235.988; p = 0.044] (Table 2).
Fig 1. Flow chart representing the selection procedure based on the NHIS cohort data set from 20022013.
a
Surgery codes: R4122, R4160, R4165,
R4166, R4170, R4181, R4182, R4183, R4331, R4332, R4341, R4342, R4345, R4421, R4430, and R4435.
b
Gonadotropin-releasing hormone agonist
codes and danazol codes: 182602BIJ, 182604BIJ, 244902BIJ, 167202BIJ, 167201BIJ, 198501CSI, 140301ACH, and 140302ACH. Abbreviations: EMS,
Endometriosis; NHIS, National Health Insurance Service; GnRH, Gonadotropin-releasing hormone.
doi:10.1371/journal.pone.0139388.g001
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Discussion
Nickel is a silvery-white metal that is mainly used as an alloy with iron, copper, chromium, and
zinc, and it is used for plating, coins, batteries, jewelry, buttons, eyeglasses, zippers, valves, heat
exchangers, and promoters [10]. Nickel allergy has a prevalence that ranges from 1023%
among women [11,12], and it is one of the most common forms of allergic contact dermatitis,
which results in itching, redness, rash, dryness, swelling and blisters [13].
Our case-control study suggests that nickel allergy is a risk factor for endometriosis. To
date, there has been little quantitative analysis of the relationship between nickel allergy and
endometriosis. Recently, one study showed that nickel concentrations in the blood of patients
with endometriosis were higher than those in a control group [14]. More recently, Yuk et al.
reported a positive relationship between nickel allergy and endometriosis using a cross-sec-
tional population-based study [7]. However, no previous study has evaluated the causal link
between nickel allergy and endometriosis.
It is not yet clear why nickel allergy is a risk factor for endometriosis, although the studies
discussed below could provide clues on this topic. The occurrence of nickel allergy increases
Table 1. Characteristics of patients in the endometriosis group and the control group, 20022013.
EMS group Control group Total p-value
Number of patients 997 3,988 4,985
2009
a
183
2010
a
198
2011
a
198
2012
a
201
2013
a
217
Mean age group
b
8.5±1.8 8.5±1.9 8.5±1.8 1
Mean age (years)
c
42.6±9.2 42.6±9.3 42.6±9.3
Mean group socioeconomic status
d
6.0±2.9 6.0±2.9 6.0±2.9 1
Nickel allergy 0.052
e
Present 8 (0.8%) 13 (0.3%) 21
Not present 989 (99.2%) 3975 (99.7%) 4964
a
First diagnosis of EMS was made in the year noted.
b
Mean age groups per 5 years in 2013. 1; 04 years, 2; 59 years,......., 17; 8084 years, 18; 85 years+.
c
The mean age was calculated from the mean age groups per 5 years.
d
Mean socioeconomic status groups in 2013. 1; upper 09%, 2; upper 1014%,......., 9; upper 9094%, 10; upper 95%+.
e
Fishers exact test
Data are presented as numbers or means ±standard deviations
doi:10.1371/journal.pone.0139388.t001
Table 2. Multivariate logistic regression analysis of endometriosis and nickel allergy.
Adjustment Crude OR Adjusted OR
a
OR (95% CI) p-value OR (95% CI) p-value
Age group per 5 years 1.001 (0.963~1.038) 1 1.001 (0.964~1.039) 0.977
Socioeconomic status group (decile) 1.000 (0.976~1.024) 1 1.000 (0.976~1.024) 0.977
Nickel allergy 2.473 (1.022~5.984) 0.045 2.474 (1.023~5.988) 0.044
a
Covariates: Age group per 5 years, socioeconomic status group (decile), nickel allergy.
CI, Condence interval; OR, Odds ratio
doi:10.1371/journal.pone.0139388.t002
Nickel Allergy Is a Risk Factor for Endometriosis
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with exposure to nickel. As an example, one study has reported that women, who are frequently
exposed to nickel accessories, show a higher prevalence of nickel allergy than men, who are not
[8]. In addition, there is a higher prevalence of nickel allergy among hairdressers, who fre-
quently use nickel alloy scissors, and retail clerks, who handle coins more frequently than the
general population [8]. Because frequent exposure to nickel occurs throughout daily life, nickel
allergy has been associated with high nickel levels in the blood [15,16]. Thus, a high blood con-
centration of nickel in patients with nickel allergy might cause endometriosis.
If this relationship is true, what characteristics of nickel might cause endometriosis?
Although we do not know the exact reason, the estrogenic characteristics of nickel might affect
endometriosis [17,18]. Specifically, nickel can bind the metal-binding sites on the estrogen
receptor (ER) in vitro [19], and nickel has also been shown to stimulate ERαexpression and
activity in breast cancer cells [20]. Furthermore, nickel concentrations in blood, urine, hair,
and breast tumor tissues have been positively correlated with breast tumors [18]. Several such
lines of evidence suggest that nickel has estrogenic characteristics. Similarly, certain chemicals
have estrogen-like characteristics [21,22], and estrogens have an important effect on endome-
triosis [1]. In conclusion, nickel allergy is associated with high nickel blood levels, and these
high nickel levels might affect the development of endometriosis due to the estrogenic effects
of nickel.
As discussed earlier, endometriosis and nickel allergy may share a common pathogenesis
[8]. The underlying mechanism of nickel allergy is delayed cell-mediated hypersensitivity [23].
Similarly, endometriosis is related to an increased T-helper 1 response, which plays a key role
in cell-mediated hypersensitivity [24].In addition, certain autoimmune diseases, such as auto-
immune thyroiditis, involve increased lymphocyte reactivity to nickel [25].Nickel allergy pre-
dominantly affects women [11]. These findings indicate that nickel may exhibit autoimmune
characteristics. Given the autoimmune characteristics of endometriosis, endometriosis and
nickel allergy may share common features [26]. However, the some characteristics of the
immune response in each disease are different; nickel allergy is an immunologic cell-mediated
response involving a hapten (a low-molecular-weight compound) [27], whereas endometriosis
has not been associated with any trigger chemicals, such as haptens, to date. Additionally,
endometriosis is not related to other allergic diseases such as allergic rhinitis, atopic dermatitis
or even other forms of contact dermatitis, with the exception of nickel allergy, according to a
cross-sectional population-based study [7]. It thus remains unclear whether immune dysregu-
lation caused by nickel exposure is a causal mechanism in the development of endometriosis.
Our results should be interpreted with caution. Because the prevalence of women in whom
nickel allergy preceded endometriosis was only 0.8%, the influence of nickel allergy in the path-
ogenesis of endometriosis may be of low clinical importance. However, most cases of nickel
allergy are diagnosed clinically based on history and physical examination findings [28]. In
contrast, in our study, we restricted our cohort of patients with nickel allergy to women who
had undergone patch testing to increase the accuracy of the diagnosis. Therefore, the number
of patients with nickel allergy might be underestimated in our study. In support of this possibil-
ity, the prevalence of nickel allergy was only 0.3% in the control group. Considering that the
prevalence of nickel allergy ranges from 1023% in the general population, the true prevalence
of nickel allergy in our study might be much higher than 0.3% [11,12]. Therefore, although it is
impossible to assert that nickel allergy affects all patients with endometriosis, nickel allergy
might be one of several causes influencing the development of endometriosis.
This study also had several limitations. First, there was a lack of patient data regarding the
histological findings and staging of endometriosis. To complement this point, only endometri-
osis patients who had undergone surgery or received a GnRH agonist or a danazol injection
were included in our study. Despite these efforts, there may be some limitation to the analysis
Nickel Allergy Is a Risk Factor for Endometriosis
PLOS ONE | DOI:10.1371/journal.pone.0139388 October 6, 2015 6/8
of endometriosis, especially regarding stage. Second, there is a possibility that patients were
miscoded with respect to their diagnosis, examination, surgery or administered drugs. How-
ever, because the possibility of miscoding was similar in the endometriosis group and the con-
trol group, the influence of this possibility may be limited. Third, our data did not include the
stage of endometriosis, obstetric history or occupation. Thus, we could not adjust for those var-
iables in our logistic regression analysis.
In conclusion, we found that nickel allergy is a risk factor for endometriosis. Further study
with greater focus on the irritant features or immune response to nickel is suggested.
Author Contributions
Conceived and designed the experiments: JSY JSS. Analyzed the data: JYS. Wrote the paper:
EO HK WIP.
References
1. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012; 98:
511519. doi: 10.1016/j.fertnstert.2012.06.029 PMID: 22819144
2. Sampson J. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the
peritoneal cavity. Am J Obstet Gynecol. 1927; 14: 9394.
3. Bruner-Tran KL, Yeaman GR, Crispens MA, Igarashi TM, Osteen KG. Dioxin may promote inflamma-
tion-related development of endometriosis. Fertil Steril. 2008; 89: 12871298. doi: 10.1016/j.fertnstert.
2008.02.102 PMID: 18394613
4. Upson K, De Roos AJ, Thompson ML, Sathyanarayana S, Scholes D, Barr DB, et al. Organochlorine
pesticides and risk of endometriosis: findings from a population-based case-control study. Environ
Health Perspect. 2013; 121: 13191324. doi: 10.1289/ehp.1306648 PMID: 24192044
5. Matarese G, De Placido G, Nikas Y, Alviggi C. Pathogenesis of endometriosis: natural immunity dys-
function or autoimmune disease? Trends Mol Med. 2003; 9: 223228. PMID: 12763528
6. Rier SE. Environmental immune disruption: a comorbidity factor for reproduction? Fertil Steril. 2008;
89: e103108. doi: 10.1016/j.fertnstert.2007.12.040 PMID: 18308048
7. Yuk J-S, Kim YJ, Yi K-W, Tak K, Hur J-Y, Shin J-H. High rate of nickel allergy in women with endometri-
osis: A 3-year population-based study. J Obstet Gynaecol Res. 2015
8. Thyssen JP, Milting K, BregnhøjA,Søsted H, Duus Johansen J, Menné T. Nickel allergy in patch-
tested female hairdressers and assessment of nickel release from hairdressersscissors and crochet
hooks. Contact Dermatitis. 2009; 61: 281286. doi: 10.1111/j.1600-0536.2009.01624.x PMID:
19878243
9. National Health Insurance Data Sharing Service (NHISS) [Internet]. [cited 17 Apr 2015]. Available:
http://nhiss.nhis.or.kr/bd/ab/bdaba000eng.do;jsessionid = thbGlRHMum10cMHqTOBhKUWdA1k0vr
3zoarVeFFl5wtug7WK66Gz267GcW0no7GC.primrose2_servlet_engine1
10. ATSDRToxicological Profile: Nickel. In: ATSDR [Internet]. 2015 [cited 1 Jun 2015]. Available: http://
www.atsdr.cdc.gov/toxprofiles/tp.asp?id=245&tid=44
11. Cheng T-Y, Tseng Y-H, Sun C-C, Chu C-Y. Contact sensitization to metals in Taiwan. Contact Dermati-
tis. 2008; 59: 353360. doi: 10.1111/j.1600-0536.2008.01468.x PMID: 19076886
12. Thyssen JP, Johansen JD, Carlsen BC, Menné T. Prevalence of nickel and cobalt allergy among
female patients with dermatitis before and after Danish government regulation: a 23-year retrospective
study. J Am Acad Dermatol. 2009; 61: 799805. doi: 10.1016/j.jaad.2009.03.030 PMID: 19632002
13. Darlenski R, Kazandjieva J, Pramatarov K. The many faces of nickel allergy. Int J Dermatol. 2012; 51:
523530. doi: 10.1111/j.1365-4632.2011.05233.x PMID: 22515577
14. Silva N, Senanayake H, Waduge V. Elevated levels of whole blood nickel in a group of Sri Lankan
women with endometriosis: a case control study. BMC Res Notes. 2013; 6: 13. doi: 10.1186/1756-
0500-6-13 PMID: 23317102
15. Gammelgaard B, Veien NK. Nickel in nails, hair and plasma from nickel-hypersensitive women. Acta
Derm Venereol. 1990; 70: 417420. PMID: 1980976
16. Boscolo P, Di Gioacchino M, Conti P, Barbacane RC, Andreassi M, Di Giacomo F, et al. Expression of
lymphocyte subpopulations, cytokine serum levels and blood and urine trace elements in nickel sensi-
tised women. Life Sci. 1998; 63: 14171422. PMID: 9952287
Nickel Allergy Is a Risk Factor for Endometriosis
PLOS ONE | DOI:10.1371/journal.pone.0139388 October 6, 2015 7/8
17. Darbre PD. Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to
the oestrogenic burden of the human breast. J Appl Toxicol JAT. 2006; 26: 191197. doi: 10.1002/jat.
1135 PMID: 16489580
18. Aquino NB, Sevigny MB, Sabangan J, Louie MC. The role of cadmium and nickel in estrogen receptor
signaling and breast cancer: metalloestrogens or not? J Environ Sci Health Part C Environ Carcinog
Ecotoxicol Rev. 2012; 30: 189224. doi: 10.1080/10590501.2012.705159
19. Medici N, Minucci S, Nigro V, Abbondanza C, Armetta I, Molinari AM, et al. Metal binding sites of the
estradiol receptor from calf uterus and their possible role in the regulation of receptor function. Biochem-
istry (Mosc). 1989; 28: 212219.
20. Martin MB, Reiter R, Pham T, Avellanet YR, Camara J, Lahm M, et al. Estrogen-like activity of metals in
MCF7 breast cancer cells. Endocrinology. 2003; 144: 24252436. PMID: 12746304
21. Defrère S, Lousse JC, González-Ramos R, Colette S, Donnez J, Van Langendonckt A. Potential
involvement of iron in the pathogenesis of peritoneal endometriosis. Mol Hum Reprod. 2008; 14: 377
385. doi: 10.1093/molehr/gan033 PMID: 18508952
22. Heilier JF, Donnez J, Verougstraete V, Donnez O, Grandjean F, Haufroid V, et al. Cadmium, lead and
endometriosis. Int Arch Occup Environ Health. 2006; 80: 149153. doi: 10.1007/s00420-006-0114-7
PMID: 16688463
23. Becker D. Allergic contact dermatitis. J Dtsch Dermatol Ges J Ger Soc Dermatol JDDG. 2013; 11: 607
619; quiz 620621. doi: 10.1111/ddg.12143
24. Podgaec S, Dias Junior JA, Chapron C, Oliveira RM de, Baracat EC, Abrão MS. Th1 and Th2 ummune
responses related to pelvic endometriosis. Rev Assoc Médica Bras 1992. 2010; 56: 9298.
25. Hybenova M, Hrda P, Procházková J, Stejskal V, Sterzl I. The role of environmental factors in autoim-
mune thyroiditis. Neuro Endocrinol Lett. 2010; 31: 283289. PMID: 20588228
26. Sundqvist J, Falconer H, Seddighzadeh M, Vodolazkaia A, Fassbender A, Kyama C, et al. Endometri-
osis and autoimmune disease: association of susceptibility to moderate/severe endometriosis with
CCL21 and HLA-DRB1. Fertil Steril. 2011; 95: 437440. doi: 10.1016/j.fertnstert.2010.07.1060 PMID:
20797713
27. Peiser M, Tralau T, Heidler J, Api AM, Arts JHE, Basketter DA, et al. Allergic contact dermatitis: epide-
miology, molecular mechanisms, in vitro methods and regulatory aspects. Current knowledge assem-
bled at an international workshop at BfR, Germany. Cell Mol Life Sci CMLS. 2012; 69: 763781. doi:
10.1007/s00018-011-0846-8 PMID: 21997384
28. Usatine RP, Riojas M. Diagnosis and management of contact dermatitis. Am Fam Physician. 2010; 82:
249255. PMID: 20672788
Nickel Allergy Is a Risk Factor for Endometriosis
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... Другими факторами риска развития аллергии у девушек-подростков является высокий уровень эстрогенов и повышенная проницаемость кожи, которая развивается при снижении уровня железа, что наблюдается при установлении менструального цикла. При обследовании взрослых женщин было выявлено, что аллергия на никель является фактором риска развития эндометриоза, однако объяснение данному факту пока не найдено [12]. ...
Article
The article provides basic information about nickel-associated allergic contact dermatitis (NACD). Nickel is a common metal that is commonly used in alloys for jewelry, accessories and household items. Contact with this metal often leads to the development of allergic contact dermatitis in sensitized individuals. The prevalence of NACD among the population is high: up to 19% among adults and about 10% among children and adolescents. It is noted that in female’s sensitization to nickel is observed several times more often than in males. On the risk of developing an allergic reaction to nickel, the integrity of the skin barrier, the frequency of contacts with nickel-containing household items, the presence of piercings, high humidity and hyperhidrosis are of decisive importance. Nickel ions entering the body through the alimentary route are capable of both sensitizing the body and forming tolerance to it. The pathogenesis of NACD is based on the classic delayed-type hypersensitivity reaction. The main clinical forms of this allergic dermatosis, as well as the characteristic features of the course of the disease are presented. The features of the course of NACD in patients with atopic dermatitis (AD) are analyzed in detail. The presented data clearly demonstrate that contact allergy to nickel can not only maintain, but also significantly aggravate the course of AD. The main criteria for the differential diagnosis between simple contact and allergic contact dermatitis are shown schematically. The need for early identification and termination of contact with nickel-containing household items is noted as the initial stage of NACD treatment. The main treatment for NACD is local therapy with topical glucocorticosteroids.
... Risk factors for endometriosis include low parity, short breastfeeding duration, short menstrual cycles, early menarche, late menopause, alcohol, low body mass index, and nickel allergy [1,9,10]. The most accepted theory of endometriosis pathogenesis is the retrograde menstruation theory [1,9], which indicates that endometriosis occurs when menstrual blood flows through the fallopian tubes into the abdominal cavity [1,9]. ...
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Background: This retrospective cohort study aimed to determine whether there is a difference in reoperation rates between patients who used dienogest (DNG) and patients who did not use DNG. Methods: Using Health Insurance Review and Assessment Service (HIRA) data generated between 1 January 2010 and 30 June 2018, we identified women with an endometriosis diagnosis code who used GnRH agonists after gynecological surgery. Among them, women prescribed DNG were selected as the DNG group, and those who did not receive DNG were selected as the control group. A survival analysis of the reoperation between the two groups was performed. Results: DNG and control groups were extracted from 9735 people each. The reoperation rates were 0.4% and 0.6% in the DNG and control groups, respectively, without adjusting. In the Cox proportional risk analysis, DNG use increased the reoperation rate {hazard ratio (HR), 1.599; 95% confidence interval (CI), 1.005-2.545}. The site of endometriosis and the number of GnRH agonist injections were not associated with reoperation (HR, 1.008; 95% CI, 0.739-1.374; HR, 1.062; 95% CI, 0.690-1.635). In the subgroup survival analysis, according to the period between the last GnRH agonist injection and the first DNG dose, DNG did not increase the reoperation rates up to 9 months (~3 months: HR, 0.968; 95% CI, 0.551-1.699; 4~6 months: HR, 1.094; 95% CI, 0.58-2.063; 7~9 months: HR, 2.419; 95% CI, 0.735-7.962), but DNG increased the reoperation rate from 10 months onwards (10~12 months: HR, 3.826; 95% CI, 1.164-12.579 and ~13 months: HR, 8.436; 95% CI, 4.722-15.072). Conclusions: Women who used DNG had a higher endometriosis reoperation rate than women who did not use DNG. However, the initiation of DNG treatment within nine months after the last GnRH agonist injection did not affect the endometriosis reoperation rate.
... 23 The variegated symptomatological expression of a systemic allergy to Ni creates problems of differential diagnosis with other pathological conditions, which mimic symptoms or are often associated with Ni allergy. [24][25][26][27][28][29][30] In 2017, a study explored the associations between SNAS and Irritable Bowel Syndrome (IBS) underlining that IBS gastrointestinal disorders are similar to those caused by the ingestion of Ni-containing foods in SNAS patients (nausea, heartburn, bloating, abdominal pain, diarrhea, constipation). 31 Furthermore, growing evidence 32 suggests that IBS patients have reduced intestinal barrier function associated with a mild degree of inflammation of the mucosa. ...
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Nickel (Ni), the main responsible for allergic contact dermatitis worldwide, is also involved in systemic condition called “Systemic Nickel Sulfate Allergy Syndrome (SNAS).” Likewise, IgE-mediated reactivity to Lipid Transfer Protein (LTP) represents the main cause of primary food allergy in adults of Mediterranean countries. We evaluated the prevalence of SNAS in LTP allergic patients and investigated patients’ clinical features with double sensitization (LTP and Ni). A retrospective, single-center, observational study was conducted performing a complete allergological work-up including: (1) skin prick tests; (2) serum specific IgE for plant food allergens and rPru p3 (LTP); (3) patch test with 5% Ni sulfate in petrolatum. We enrolled 140 LTP allergic patients of which 36 patients (25.7% of sample) showed additional positivity to Ni patch test. Patients with double sensitization were more frequently females and reported fewer cutaneous symptoms. Higher values of sIgE for peach, apple, peanut, walnut, grain, corn, and garlic were found in LTP allergic patients, while higher values for hazelnut in the other subgroup. The prevalence of SNAS in the LTP allergic population is clinically relevant. Moreover, the clinical and immunological profiles of patients with double sensitization were different from patients monosensitized to LTP.
... For instance, Andrioli et al. (2015) suggested that individuals suffering from the SNAS as an immune-mediated disease had an increased risk for thyroid autoimmunity. Yuk et al. (2015) reported that nickel allergy may be a risk factor for endometriosis. Aslan et al. (2017) showed that the majority of foods that increase gastroesophageal reflux symptoms contain nickel. ...
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The European Commission asked EFSA to update its previous Opinion on nickel in food and drinking water, taking into account new occurrence data, the updated benchmark dose (BMD) Guidance and newly available scientific information. More than 47,000 analytical results on the occurrence of nickel were used for calculating chronic and acute dietary exposure. An increased incidence of postimplantation loss in rats was identified as the critical effect for the risk characterisation of chronic oral exposure and a BMDL10 of 1.3 mg Ni/kg body weight (bw) per day was selected as the reference point for the establishment of a tolerable daily intake (TDI) of 13 lg/kg bw. Eczematous flare-up reactions in the skin elicited in nickel-sensitised humans, a condition known as systemic contact dermatitis, was identified as the critical effect for the risk characterisation of acute oral exposure. A BMDL could not be derived, and therefore, the lowest-observed-adverse-effect-level of 4.3 lg Ni/kg bw was selected as the reference point. The margin of exposure (MOE) approach was applied and an MOE of 30 or higher was considered as being indicative of a low health concern. The mean lower bound (LB)/upper bound (UB) chronic dietary exposure was below or at the level of the TDI. The 95th percentile LB/UB chronic dietary exposure was below the TDI in adolescents and in all adult age groups, but generally exceeded the TDI in toddlers and in other children, as well as in infants in some surveys. This may raise a health concern in these young age groups. The MOE values for the mean UB acute dietary exposure and for the 95th percentile UB raises a health concern for nickel-sensitised individuals. The MOE values for an acute scenario regarding consumption of a glass of water on an empty stomach do not raise a health concern.
... Gastrointestinal symptoms in endometriosis may also be related to IBS or IBS-like disorders [45]. Recent studies showed a higher prevalence of Ni skin allergy in women with endometriosis, as well as a possible Ni involvement in its etiopathogenesis [20,46,47]. On these bases, it is possible to hypothesize that an IBS-like disorder, such as Ni ACM, may be the cause or contributing factor of gastrointestinal symptoms in women with endometriosis. ...
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Alimentary nickel (Ni) may result in allergic contact mucositis (ACM), whose prevalence is >30% and may present with IBS-like and extra-intestinal symptoms. These symptoms are also frequent in endometriosis, and Ni allergic contact dermatitis has already been observed in endometriosis. Therefore, intestinal and extra-intestinal symptoms in endometriosis may depend on a Ni ACM, and a low-Ni diet could improve symptoms. We studied the prevalence of Ni ACM in endometriosis and focused on the effects of a low-Ni diet on gastrointestinal, extra-intestinal, and gynecological symptoms. We recruited 84 women with endometriosis, symptomatic for gastrointestinal disorders. Thirty-one out of 84 patients completed the study. They underwent Ni oral mucosa patch test (omPT), questionnaire for intestinal/extra-intestinal/gynecological symptoms, and a low-Ni diet. Clinical evaluation was performed at baseline (T0) and after three months (T1). Twenty-eight out 31 (90.3%) patients showed Ni omPT positive results, with Ni ACM diagnosis, whereas three out of 31 (9.7%) patients showed negative Ni omPT. After three months of low-Ni diet, all gastrointestinal, extra-intestinal and gynecological symptoms showed a statistically significant reduction. Ni ACM has a high prevalence in endometriosis and a low-Ni diet may be recommended in this condition to reduce gastrointestinal, extra-intestinal and gynecological symptoms.
... [6][7][8][9][10]. Currently, pain medication, hormonal treatment, and surgery are the major therapeutic methods for endometriosis. ...
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Purpose: Endometriosis is one of the most common, difficult, and complicated gynecological disorders. Vascular cell adhesion molecule 1 (VCAM-1) has been reported to be aberrantly expressed in patients with endometriosis. However, the exact role and mechanism of VCAM-1 in endometriosis remains unclear. Methods: The expression of transforming growth factor beta 1 (TGF-β1) and VCAM-1 was determined by quantitative real-time polymerase chain reaction and western blotting. Human endometriotic cells were cultured and their responsiveness to TGF-β1 was evaluated by Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, and transwell migration and invasion assays. Results: The levels of TGF-β1 and VCAM-1 mRNA were upregulated in the endometriotic tissues. Knockdown of TGF-β1 in endometriotic cyst stromal cells caused a marked inhibition of cell proliferation, migration, and invasion. Treatment of endometriotic cyst stromal cells with TGF-β1 resulted in an obvious promotion of cell proliferation, migration, and invasion, and strikingly increased the protein expression of VCAM-1. Silencing of Smad3 abated TGF-β1-stimulated VCAM-1 expression. Furthermore, the promoting effects of TGF-β1 on the proliferation, migration, and invasion of endometriotic cyst stromal cells were blocked by silencing of VCAM-1. Conclusion: Knockdown of VCAM-1 impedes TGF-β1-mediated proliferation, migration, and invasion of endometrial cells, thereby indicating that VCAM-1 may serve as a therapeutic target for endometriosis.
... Â CF n ) 1/n where CF is contamination factor and n is number of metals considered; Igeo ¼ log 2 (C n /1.5 B n ), where C n and B n represent concentrations of metal(s) in the sample and the background sample, respectively, and factor of 1.5 is used to incorporate changes in the background that occur naturally and to address the inherent lithogenic changes in metal concentrations (Muller 1969 Table ST3). Cr appears to be contributed by Ni-Cr electroplating, stainless-steel and other alloys industries in BIA (Yuk et al. 2015). Chromiun is too contributed by chrome pigment production and Tanneries Govil 2005, 2008) but these industries do not make their presence in BIA. ...
Article
To understand distribution, toxicity, and health risk assessment of Cu, Ni, Cr, Pb, Zn, Fe, and Mn, 33 surface dust samples were collected during June 2015 from Bhiwadi Industrial Area (BIA) in north India. Average metal concentrations exceeded their corresponding values in upper continental crust depending upon metal(s) and sampling site(s). Industrial emissions resulted in high contamination factors and high pollution load index for metals. The BIA falls under least to moderately for Mn, unpolluted to heavily and extremely for Ni and Cu, Pb, and Zn and moderately to extremely polluted region for Cr. Inter-metal correlations and PCA indicated common and mixed sources for metals such Ni–Cr electroplating and alloys, battery recycling, stainless-steel, electrical wires, galvanizing, vehicular emissions, and wear and tear of vehicle parts. Non-carcinogenic health risk due to metals in surface dust was high in children compared to adults and major pathways were ingestion followed by dermal and inhalation. Surface dust in BIA falls under hazardous category as metals leached in toxicity characteristics leaching procedure and waste extraction test exceeded their prescribed regulatory limits. Leaching of metals can cause contamination of surface water, groundwater, and soils in surrounding areas, and can pose risk to human health and ecology.
... Gastrointestinal symptoms in endometriosis may also be related to IBS or IBS-like disorders [45]. Recent studies showed a higher prevalence of Ni skin allergy in women with endometriosis, as well as a possible Ni involvement in its etiopathogenesis [20,46,47]. On these bases, it is possible to hypothesize that an IBS-like disorder, such as Ni ACM, may be the cause or contributing factor of gastrointestinal symptoms in women with endometriosis. ...
... Furthermore, the participants of this study may include patients with dysmenorrhea symptoms such as pelvic pain and excessive menstruation, and infertility. There are some reports that endometriosis is related to infertility, pain, socioeconomic condition, stress, nickel allergy, vitamin D intake [39][40][41][42], and these potential confounding factors cannot be excluded completely with only the variabilities that we adjusted. However, owing to the small sample size of this study, it was difficult to adjust for all of these factors. ...
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Background Endometriosis is a known cause of infertility. Differences in immune tolerance caused by regulatory T cells (Tregs) and transforming growth factor-β (TGF-β) are thought to be involved in the pathology of endometriosis. Evidence has indicated that Tregs can be separated into three functionally and phenotypically distinct subpopulations and that activated TGF-β is released from latency-associated peptide (LAP) on the surfaces of specific cells. The aim of this study was to examine differences in Treg subpopulations and LAP in the peripheral blood (PB) and peritoneal fluid (PF) of patients with and without endometriosis. MethodsPB and PF were collected from 28 women with laparoscopically and histopathologically diagnosed endometriosis and 20 disease-free women who were subjected to laparoscopic surgery. Three subpopulations of CD4+ T lymphocytes (CD45RA+FoxP3low resting Tregs, CD45RA−FoxP3high effector Tregs, and CD45RA−FoxP3low non-Tregs) and CD11b+ mononuclear cells expressing LAP were analyzed by flow cytometry using specific monoclonal antibodies. ResultsProportions of suppressive Tregs (resting and effector Tregs) were significantly higher in the PF samples of patients with endometriosis than in those of control women (P = 0.02 and P < 0.01, respectively) but did not differ between the PB samples of patients and controls. The percentage of CD11b+LAP+ macrophages was significantly lower in PF samples of patients with endometriosis than in those of controls (P < 0.01) but was not altered in the PB samples. Conclusion Proportions of suppressive Tregs and LAP+ macrophages are altered locally in the PF of endometriosis patients.
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Nickel-resistant bacteria have been isolated so far only in contaminated soils and wastewaters polluted with different industrial sources. The aim of our study was to determine if nickel-resistant bacteria could also be isolated from human samples. In this brief communication, we describe how we were able to isolate human bacterial strains that grew without oxygen and in the presence of high concentration of nickel. The identification was made by phenotypic and genetic techniques. The bacterial sequences have been deposited in the NCBI database repository. Our finding shows that there are several different heavy metal tolerant bacteria in humans that should be considered for further studies.
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Endometriosis is considered an estrogen-dependent disease. Persistent environmental chemicals that exhibit hormonal properties, such as organochlorine pesticides (OCPs), may affect endometriosis risk. We investigated endometriosis risk in relation to environmental exposure to OCPs. We conducted the current analyses using data from the Women's Risk of Endometriosis (WREN) study, a population-based case-control study of endometriosis conducted among 18-49 year old female enrollees of a large healthcare system in western Washington State. OCP concentrations were measured in sera from surgically confirmed endometriosis cases (n=248) first diagnosed between 1996 and 2001 and population-based controls (n=538). We estimated odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, adjusting for age, reference date year, serum lipids, education, race/ethnicity, smoking, and alcohol intake. Our data suggested increased endometriosis risk associated with serum concentrations of β-hexachlorocyclohexane (HCH) (third vs. lowest quartile: OR 1.7; 95% CI: 1.0, 2.8; highest vs. lowest quartile OR 1.3; 95% CI: 0.8, 2.4) and mirex (highest vs. lowest category: OR 1.5; 95% CI: 1.0, 2.2). The association between serum β-HCH concentrations and endometriosis was stronger in analyses restricting cases to those with ovarian endometriosis (third vs. lowest quartile: OR 2.5; 95% CI: 1.5, 5.2; highest vs. lowest quartile: OR 2.5; 95% CI: 1.1, 5.3). In our case-control study of women enrolled in a large healthcare system in the U.S. Pacific Northwest, serum concentrations of β-HCH and mirex were positively associated with endometriosis. Extensive past use of environmentally persistent OCPs in the United States or present use in other countries may impact the health of reproductive-age women.
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Background Endometriosis is characterized by the persistence of endometrial tissue in ectopic sites outside the uterine cavity. Presence of nickel, cadmium and lead in ectopic endometrial tissue has been reported previously. While any association between blood levels of nickel and endometriosis is yet to be described in literature, conflicting reports are available with regards to cadmium and lead levels in blood and urine. Findings In fifty patients with endometriosis and fifty age-matched controls confirmed by laparoscopy or laparotomy, whole blood samples were collected and digested using supra pure 65% HNO3. Whole blood levels of nickel and lead were measured using Total Reflection X-ray Fluorescence (TXRF) while cadmium levels were evaluated using graphite furnace atomic absorption spectroscopy (GFASS). Women with endometriosis had significantly higher (P=0.016) geometric mean (95% CI) whole blood nickel levels [2.6(1.9-3.3) μg/L] as compared to women without endometriosis [0.8 (0.7-0.9) μg/L]. Whole blood levels of cadmium and lead were similar between the two groups. Conclusions Although women with endometriosis in this study population had higher levels of nickel in whole blood compared to controls, whether nickel could be considered as an aetiological factor in endometriosis remains inconclusive in view of the smaller sample that was evaluated.
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During the past half-century, incidences of breast cancer have increased globally. Various factors-genetic and environmental-have been implicated in the initiation and progression of this disease. One potential environmental risk factor that has not received a lot of attention is the exposure to heavy metals. While several mechanisms have been put forth describing how high concentrations of heavy metals play a role in carcinogenesis, it is unclear whether chronic, low-level exposure to certain heavy metals (i.e., cadmium and nickel) can directly result in the development and progression of cancer. Cadmium and nickel have been hypothesized to play a role in breast cancer development by acting as metalloestrogens-metals that bind to estrogen receptors and mimic the actions of estrogen. Since the lifetime exposure to estrogen is a well-established risk factor for breast cancer, anything that mimics its activity will likely contribute to the etiology of the disease. However, heavy metals, depending on their concentration, are capable of binding to a variety of proteins and may exert their toxicities by disrupting multiple cellular functions, complicating the analysis of whether heavy metal-induced carcinogenesis is mediated by the estrogen receptor. The purpose of this review is to discuss the various epidemiological, in vivo, and in vitro studies that show a link between the heavy metals, cadmium and nickel, and breast cancer development. We will particularly focus on the studies that test whether these two metals act as metalloestrogens in order to assess the strength of the data supporting this hypothesis.
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Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German 'Federal Institute for Risk Assessment' hosted an 'International Workshop on Contact Dermatitis'. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15-20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed.
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AimThe aim of this study was to evaluate the prevalence rates of nickel allergy, contact dermatitis, drug allergy, allergic rhinitis and atopic dermatitis among women with and without endometriosis.Material and Methods Data were obtained from the National Patient Sample of the Republic of Korea, which was provided by the Korean Health Insurance Review and Assessment Service. We evaluated women aged 20–40 years who visited a health care institution from 2009–2011. We estimated the prevalence of allergic diseases among women with and without endometriosis.ResultsWe extracted a sample of 1 843 447 women from the total patient sample of approximately 3 million. We identified 7259 women with endometriosis and 535 818 women without endometriosis. After adjusting for age and data year, the women with endometriosis had higher rates of nickel allergy (odds ratio = 1.175; 95% confidence interval, 1.011–1.366; P = 0.04). Additionally, after adjusting for age, data year and other allergic diseases, the women with endometriosis had higher rates of nickel allergy (odds ratio = 1.167; 95% confidence interval, 1.004–1.357; P = 0.04). After adjusting for other covariates, we found that other allergic disorders, such as allergic rhinitis, atopic dermatitis and contact dermatitis, were not associated with endometriosis.Conclusion Women with endometriosis had higher rates of nickel allergy. Further research is required to clarify the relation between nickel allergy and endometriosis.
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The article below summarizes a roundtable discussion of a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Maayan-Metzger A, Schushan-Eisen I, Todris L, et al. Maternal hypotension during elective cesarean section and short-term neonatal outcome. Am J Obstet Gynecol 2010;202:56.e1-5. The full discussion appears at www.AJOG.org, pages e12-e14.
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Allergic contact dermatitis is a frequent inflammatory skin disease. The suspected diagnosis is based on clinical symptoms, a plausible contact to allergens and a suitable history of dermatitis. Differential diagnoses should be considered only after careful exclusion of any causal contact sensitization. Hence, careful diagnosis by patch testing is of great importance. Modifications of the standardized test procedure are the strip patch test and the repeated open application test. The interpretation of the SLS (sodium lauryl sulfate) patch test as well as testing with the patients' own products and working materials are potential sources of error. Accurate patch test reading is affected in particular by the experience and individual factors of the examiner. Therefore, a high degree of standardization and continuous quality control is necessary and may be supported by use of an online patch test reading course made available by the German Contact Dermatitis Research Group. A critical relevance assessment of allergic patch test reactions helps to avoid relapses and the consideration of differential diagnoses. Any allergic test reaction should be documented in an allergy ID card including the INCI name, if appropriate. The diagnostics of allergic contact dermatitis is endangered by a seriously reduced financing of patch testing by the German statutory health insurances. Restrictive regulations by the German Drug Law block the approval of new contact allergens for routine patch testing. Beside the consistent avoidance of allergen contact, temporary use of systemic and topical corticosteroids is the therapy of first choice.
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Originally described over three hundred years ago, endometriosis is classically defined by the presence of endometrial glands and stroma in extrauterine locations. Endometriosis is an inflammatory, estrogen-dependent condition associated with pelvic pain and infertility. This work reviews the disease process from theories regarding origin to the molecular basis for disease sequelae. A thorough understanding of the histopathogenesis and pathophysiology of endometriosis is essential to the development of novel diagnostic and treatment approaches for this debilitating condition.
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Hypersensitivity reactions to nickel are one of the most common in the modern world. Nickel allergy prevalence is constantly growing in many countries and represents a major health and socioeconomic issue. Herein the current understanding on nickel allergy is summarized with a practical approach to the dermatologist, allergist, and general practitioner. The personal experience with some practical clinical cases of nickel dermatitis is shared. A special emphasis is put on the possible strategies for treatment and prevention of the disease.
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This study investigates the association of rheumatoid arthritis-associated single nucleotide polymorphisms in endometriosis. We found an association of CCL21 (rs2812378) and HLA-DRB1 (rs660895) with moderate to severe endometriosis.