ORIGINAL ARTICLE
The Influence of Different Solvents on Systemic Sclerosis
An Updated Meta-analysis of 14 Case-Control Studies
Jiu-Hua Zhao, MD,* Yu Duan, MD,† Yu-Jie Wang, MD,† Xiao-Lei Huang, MD,†
Guo-Jun Yang, MD,‡ and Jing Wang, PhD†
Background: Several studies have collected detailed data to examine
which specific solvents account for the association between solvents and
risk of systemic sclerosis (SSc). These studies generally reported elevated
risks associated with many of the specific solvents examined, such as tolu-
ene, xylene, and trichloroethylene. The previous meta-analysis was not
able to conduct separate analyses for specific solvent subtypes.
Objective: The aims of the new meta-analysis were to investigate a more
comprehensive estimate and to consider the effect of different solvents
on SSc.
Methods: We searched PubMed, Biosis Previews, China National
Knowledge Infrastructure, and Wanfang for all articles published before
July 2015. Fourteen case-control studies (1657 patients and 3838 controls)
were included. The quality of studies was scored according to the
Newcastle-Ottawa scale. The final odds ratios (ORs) and 95% confidence
intervals (CIs) were calculated by a fixed- or random-effects model accord-
ing to heterogeneity test. Publication bias was assessed using Begg test.
Results: The risk of SSc was significantly different among sex, age, and
exposure assessment methods. Separate analyses for specific solvent sub-
types indicated that SSc was associated with aromatic solvents (OR, 2.72;
95% CI, 1.21–6.09), trichloroethylene (OR, 2.07; 95% CI, 1.34–3.17), ha-
logenated solvents (OR, 1.49; 95% CI, 1.12–1.99), and ketones (OR, 4.20;
95% CI, 2.19–8.06).
Conclusions: Exposure to identified types solvents does seem to be a
risk factor for developing SSc. Needed efforts to decrease such exposures
are discussed.
Key Words: systemic sclerosis, solvents, epidemiology, meta-analysis
(J Clin Rheumatol 2016;22: 253–259)
S ystemic sclerosis (SSc), also known as scleroderma, is a mul-
tisystem, uncommon disease characterized by small vessel
vasculopathy, autoantibody production, and excessive collagen
deposition in the skin and internal organs.1,2 The prevalence of
SSc ranged from 7 per million to 489 per million. It has been re-
ported that the prevalence of SSc was higher in the United
States and Australia than in Japan and Europe.3 Besides that,
women are more commonly affected with a peak of incidence
From the *West Anhui Health Vocational College, Lu'an, Anhui; †Department
of Epidemiology and Biostatistics, School of Public Health, Anhui Medical
University; and ‡Department of Rheumatology and Immunology, Anhui
Medical University, Anhui Provincial Hospital, Hefei, China.
The authors declare no conflict of interest.
This work was partly supported by grants from the Academic Leader
Foundation of Anhui Medical University, the Natural Science Foundation
of Anhui Province in 2013 (code: 1308085MH169), the Key Project of the
Education Department of Anhui Province Natural Science Research (code:
KJ2012A165), and the Key Project of Teaching Research in Anhui
Province (code: 2012jyxm670).
Zhao and Duan contributed equally to this work and should be considered as
co–first authors.
Correspondence: Jing Wang, PhD, Department of Epidemiology and
Biostatistics, School of Public Health, Anhui Medical University, Meishan
Rd 81, Hefei, Anhui, 230032, China. E-mail: jwang2006@126.com.
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 1076-1608
DOI: 10.1097/RHU.0000000000000354
JCR: Journal of Clinical Rheumatology • Volume 22, Number 5, August 2016
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
between 45 and 64 years of age.4 Although the pathogenesis of
SSc remains unclear, environmental factors are known to play
important roles in disease development. Currently, environ-
mental factors including exposure to silica, solvents, epoxy
resin, hand-transmitted vibration, and some nonoccupational
agents that have been implicated as possible risk factors for SSc.5
The impact of occupational exposure to organic solvents on
the development of SSc has attracted broad attention. Over the
years, a series of case reports and several epidemiological studies
reported the relationship between solvents or solvent categories or
specific jobs and SSc. The meta-analysis published in 2001, in-
cluding 7 case-control studies and a cohort study, obtained a sig-
nificantly increased relative risk for SSc (relative risk, 2.9; 95%
confidence interval [CI], 1.6–5.3) in subjects exposed to sol-
vents.6 In 2007, Kettaneh et al7 conducted a new meta-analysis
to further access features associated with the magnitude of SSc
risk. The article that combined results of 11 case-control studies
and took selection bias into account confirmed the hypothesis of
a link between SSc and occupational exposure to solvents. They
also reported a difference in the magnitude of SSc risk associated
with solvent exposure in men (odds ratio [OR], 3.0; 95% CI,
1.9–4.6) and women (OR, 1.8; 95% CI, 1.5–2.1). Besides that,
systematic review and meta-analysis were performed to assess
the association between organic solvents and autoimmune dis-
eases in 2012.8 The authors concluded that exposure to organic
solvents was a risk factor for developing autoimmune diseases.
They also described the possible pathogenic mechanism of sol-
vents in the development of SSc. For species differences, the
chemical structure and toxicity effect of solvents are also different.
For example, trichloroethylene (TCE) could inhibit cellular apo-
ptosis of naive CD4+ and CD8+ T-cells subset; epidermal necrosis,
degeneration, and hyperplasia may be caused by exposure to white
spirit.9,10 However, the 3 meta-analyses were not able to conduct
separate analyses for specific solvent subtypes on SSc risk be-
cause of a limited number of studies for each solvent category.
Furthermore, the methods of exposure assessment could have ef-
fects on the results, but they did not describe and discuss the var-
iable definition of exposure to solvents among included studies.
Therefore, an updated meta-analysis, including 3 additional
relevant studies and 1 latest study when compared with the 2007
meta-analysis, was performed to investigate a more comprehen-
sive estimate. In this article, the effects of different solvents on
SSc (including impact of sex, age, and assessment methods)
were considered.
METHODS
Literature Search Strategy
The search was performed using the databases PubMed,
Biosis Previews, China National Knowledge Infrastructure, and
Wanfang (Chinese large network database) and took into account
articles published before July 2015. Subject terms (“scleroderma,
systemic,” “solvents”) and key words (“systemic sclerosis,”
“scleroderma,” “solvents”) were used to retrieve relevant articles.
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Zhao et al JCR: Journal of Clinical Rheumatology • Volume 22, Number 5, August 2016
Articles cited in the references of these articles were also evaluated
for inclusion if they could be found through the online searches.
Articles in languages other than English were selected if the infor-
mation could be obtained from other published articles.
Inclusion and Exclusion Criteria
For inclusion in the meta-analysis, articles should meet the
following criteria: (1) the study was a case-control; (2) SSc was
defined by the 1980 revision of the American College of Rheuma-
tology SSc criteria or the consultant's criteria; (3) there was an ex-
posure to certain solvent; and (4) the study contained enough data
to calculate OR value. Studies were excluded from the analysis if the
study did not definitely list certain solvent as an exposure category or
included the same data that were published in another study.
Apart from these criteria, for included studies for the analy-
ses according to demographic characteristics and assessment
methods, articles should report explicitly the following infor-
mation: (1) the geographical origin of subjects, (2) the number
of different sexes in cases and controls, and (3) the ways of data
collection. For the subgroup analyses according to solvent catego-
ries, which kind of solvents subjects were exposed to and the
number of exposed individuals should be reported clearly in the
included studies.
Data Extraction
The studies were carefully reviewed, and all the data were
extracted according to the inclusion and exclusion criteria by 2 in-
dependent reviewers. If they failed to reach an agreement, the
results would be assessed by a third investigator. We coded data
about country, year, author, sex, characteristics of subjects, and ex-
posure assessment.
Quality Assessment
We used the modified version of the Newcastle-Ottawa scale
to access the quality of included studies (http://www.ohri.ca/programs/
clinical_epidemiology/oxford.htm). In case-control studies, this scale
rates high-quality choices by stars for the selection of case and
controls, comparability of cases and controls, and ascertainment
of exposure. The selection item is rated over a maximal number
of 4 stars, for adequacy of case definition, representativeness
of the cases, selection of controls, and definition of controls. The
comparability item is rated over a maximal number of 2 stars,
1 for the most important factor for comparability and 1 for any
additional factor. We selected matching by age and sex as the most
important factor and matching by smoking and/or residency area
as the other important factors. The exposure item is rated over
a maximal number of 3 stars, 1 for ascertainment of exposure,
1 for same method of ascertainment for cases and controls, and
1 if there was the same nonresponse rate in cases and controls.
A score of lower than 5 stars indicates that the quality of the
study is not very high.
Statistical Analyses
To assess heterogeneity among the selected studies, we used
the Cochran Q and I 2 statistics. A significant Q statistic (P < 0.10)
showed heterogeneity across studies. The I 2 test was expressed as
a ratio ranging from 0% to 100%, thus showing that the proportion
of observed dispersion was real rather than spurious. I 2 values of
25%, 50%, and 75% were qualitatively classified as low, moder-
ate, and high, respectively. First, the pooled OR and its 95% CI
were combined by the Mantel-Haenszel random-effect model if
the studies indicated heterogeneity. Then, by fixed-effects model
under the condition of the heterogeneity, statistic did not reach a
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significant level. Publication bias was observed by visual inspec-
tion of funnel plot. When there is a publication bias, the funnel
plot should be asymmetric. Funnel plot asymmetry was assessed
by Begg test. All the statistical analyses were conducted using
STATA version 11 (StataCorp LP, College Station, TX).
RESULTS
Study Selection
As shown in the Figure, a total of 111 published articles were
included in the initial literature searching. After screening for rel-
evancy and excluding review articles, meta-analysis, and case reports,
34 original studies were identified for retrieval. Then, 14 repetitive ar-
ticles were eliminated. Overall, 20 studies were downloaded for more
detailed evaluation. Then, we excluded 1 cohort study11 and 1 cross-
sectional study.12 The other 3 publications13–15 only with an English
abstract were also eliminated. From the abstracts, we know that
the Italian case-control study13 observed significant association
between patients with SSc and occupational exposure to solvents;
the Danish study15 found that 13 patients (46%) with SSc had
been subject to organic solvents. However, we could not get the
full text or enough information. Finally, a total of 14 reports were
reserved in the following meta-analysis.
Study Description
The 14 eligible reports16–29 published between 1989 and
2014 included 1657 cases and 3838 controls. The characteristics
of the eligible studies were presented in Table 1. Of the 14 studies,
916–18,22,24,26–29 were conducted in Europe (Hungary, England,
Italy, France, and Germany), 419,20,23,25 were performed in North
America (Canada and United States), and 121 was from Japan. All
the articles were epidemiological studies using a case-control design.
The English study17 published in 1992 focused on males, whereas
the Hungarian study24 published in 2002 and the American study25
published in 2003 concentrated on females. Sex ratio was ex-
tremely variable among other studies but was similar in each study
between cases and controls.
Main Results of Meta-Analysis
The summary of the meta-analysis for the association of sol-
vents with SSc is shown in Tables 2 and 3. In total, 14 studies involv-
ing 1657 cases and 3838 controls were included. The combined
estimator of ORs using random-effects model on the 14 studies
was 2.07 (95% CI, 1.55–2.78), which indicated that exposure to
solvents was associated with SSc. Significant heterogeneity
existed among the studies (I 2 = 51.7%, P < 0.10).
In the subgroup analyses by sex, we found that the relative
risk was higher in men (OR, 5.28; 95% CI, 3.46–8.05) than in
women (OR, 1.62; 95% CI, 1.34–1.96). In terms of region, the
pooled OR of American studies was 1.68 (95% CI, 0.98–2.86),
with significant heterogeneity (I 2 = 81.2%, P = 0.005). For the
European studies, the pooled OR was 2.25 (95% CI, 1.75–2.89),
with nonsignificant heterogeneity (I 2 = 28.6%, P = 0.181). For sub-
jects for which the duration of solvent exposure was 3 months
or longer and/or where an exposure to solvents was analyzed
using the score for the employment period, the pooled OR was
2.40 (95% CI, 1.48–4.03); for self-reported subjects, the pooled
OR was 2.01 (95% CI, 0.78–5.23).
In addition, logistic regression was conducted among differ-
ent groups. The results showed that there were significant differ-
ences in sex, region, and assessment methods.
Stratified analyses about exposure categories revealed that
aromatic solvents (OR, 2.72; 95% CI, 1.21–6.09), TCE (OR, 2.07;
© 2016 Wolters Kluwer Health, Inc. All rights reserved.
JCR: Journal of Clinical Rheumatology • Volume 22, Number 5, August 2016
FIGURE. Selection process for study inclusion in this meta-analysis.
95% CI, 1.34–3.17), halogenated solvents (OR, 1.49; 95% CI,
1.12–1.99), and ketones (OR, 4.20; 95% CI, 2.19–8.06) had sig-
nificant association with SSc. However, among other kinds of sol-
vents, the association was absent.
Publication Bias
Begg test was performed to assess the publication bias of the
studies. The results did not reveal any statistical evidence of pub-
lication bias (Tables 2 and 3).
DISCUSSION
As reported by a previous meta-analysis,7 the results of the
article indicated that the risk of SSc was associated with exposure
to solvents. However, publication bias may have been present be-
cause of the possible failure of investigators to submit negative re-
sults or failure of journals to publish negative studies. Our analysis
did not suggest a publication bias. However, there was significant
heterogeneity among the 14 studies. This was to be expected be-
cause of the overall nature of the population studied (such as sex
and age) and because the design specifications (such as the type
of controls and matching factors) were so variable among the stud-
ies. Importantly, the poor estimation of the exposures should also
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Solvents and Systemic Sclerosis
be noticed. In some studies, exposure to solvents was described to
be possible or probable. It is possible that some workers did not
have a clear recognition about the chemical agents to which they
had been exposed. Although the data of working conditions were
usually collected through the participants' self-report, only half of
the studies invited relevant experts to conduct exposure assessment.
In contrast, there were several studies that defined and investigated
the exposure duration using semiquantitative estimates of exposure.
The study also confirmed that the relative risk was higher in
men than in women. This may be because the frequency and inten-
sity of solvents to which men were exposed were stronger than
those of women or because men have greater susceptibility to sol-
vent exposure. Besides that, ethnic and racial differences were
considered to influence the occurrence of SSc, and the putative
role of geographical factors came from data suggesting that the
SSc phenotype might differ among subjects from different ethnic
backgrounds.4 The association between solvents and SSc was sig-
nificant among European subjects but meaningless among the
American population, maybe because of variations in both addi-
tive and nonadditive genetic factors and because the environmen-
tal variances are specific to the investigated population.
To our knowledge, this is the first report of association be-
tween specific solvent subtypes and SSc risk. However, the precise
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Zhao et al JCR: Journal of Clinical Rheumatology • Volume 22, Number 5, August 2016

TABLE 1. Characteristics of the Studies Examined in the Meta-analysis

Quality Score
Exposure
Study Controls Sex of Cases No. Cases ACR Criteria Assessment S C E
16
Czirják et al, CC Female/male 1 No Organic solvents; occupational *** *
1989, Hungary exposure to benzene, isopropyl
alcohol, ethyl acetate in the
life history, self-reported.
Silman and Jones,17 CC Male 56 No Organic solvents; job histories *** ** *
1992, England were assessed, blind to the
case or control status, by an
occupational hygienist using
standard occupational directories.
Bovenzi et al,18 HC Female/male 21 Yes Aromatic solvent; exposure *** * **
1995, Italy duration ≥ 6 mo, assessed
by 2 occupational physicians
who were blinded about the
case-referent condition.
Goldman,19 CD Female/male 33 Yes Organic solvents, PCE, TCA, ** *
1996, United States petroleum, fluorocarbon solvent;
occupational or environmental
exposure, self-reported.
Nietert et al,20 HC Female/male 178 Yes Solvents, PCE, TCA, benzene, * **
1998, United States CCl4; exposure duration ≥ 1 y,
assessed by job exposure matrix.
Mori et al,21 HC Female/male 57 Yes Petroleum; occupational exposure *** * *
1998, Japan in the life history, self-reported.
Diot et al,22 HC Female/male 80 Yes Organic solvents; assessed by a ** ** **
2002, France committee of experts, the exposure
score for each employment period
was expressed as probability
 intensity  frequency  duration.
Thompson and Pope,23 HC Female/male 91 Yes Aromatic solvent, halogenated solvent, ** * *
2002, Canada hydrocarbons; exposure at the
workplace or at home,
self-reported.
Czirjak and Kumanovics,24 HC Female 63 Yes Solvents; occupational ** ** **
2002, Hungary exposure in the life history,
self-reported.
Garabrant et al,25 CC Female 660 Yes Hydrocarbons, chlorinated solvents; **** ** **
2003, United States exposure duration ≥ 3 months,
assessed by an expert who
was blinded about the
case-referent condition.
Bovenzi et al,26 HC Female/male 55 Yes Solvents; exposure duration ≥ 6 mo, *** ** *
2004, Italy assessed by an expert who was
blinded about the case-referent
condition.
Maître et al,27 CC Female/male 93 Yes Solvents; assessed by a **** ** ***
2004, France group of experts according
to the potential level of
exposure to toxins on a 3-level scale:
zero or low, moderate, and high.
Kütting et al,28 CD Female/male 109 NA Solvents; occupational or ** *
2006, Germany environmental exposure,
self-reported.
Marie et al,29 CC Female/male 100 Yes Organic solvents; exposure duration ≥ 3 mo, **** ** **
2014, France assessed by a committee of experts,
the exposure score for each employment
period was expressed as probability
 intensity  frequency  duration.
*Evaluation of the quality of studies, a score of lower than five stars (*****) indicated that the quality of study is not very high.
ACR, American College of Rheumatology; C, comparability; CC, community controls; CD, patients with other connective tissue diseases; E, exposure;
HC, hospital controls; PCE, perchloroethylene; S, selection; TCA, trichloroethane.

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JCR: Journal of Clinical Rheumatology • Volume 22, Number 5, August 2016 Solvents and Systemic Sclerosis

TABLE 2. Exposure to Solvents and the Risk of SSc in the Whole Sample and Subgroups

(Sub)sample Studies, n Cases, n (%a) Controls, n (%a) OR (95% CI) P for OR I 2 (%) P for Q statistic P for bias
Overall (solvents) 14 1581 (22.1) 3838 (14.9) 2.07 (1.55–2.78) 0.000 51.7 0.013 0.125
Male 10 249 (45.0) 372 (24.0) 5.28 (3.46–8.05) 0.000 15.0 0.305 0.074
Female 9 1206 (16.7) 3104 (12.5) 1.62 (1.34–1.96) 0.000 45.1 0.608 0.593
European 9 638 (24.5) 1142 (15.2) 2.25 (1.75–2.89) 0.000 28.6 0.181 0.074
United States 3 822 (19.8) 2552 (14.1) 1.68 (0.98–2.86) 0.056 81.2 0.005 0.296
Exposure duration ≥ 3 6 873 (21.5) 2757 (13.5) 2.40 (1.48–4.03) 0.000 60.5 0.027 0.133
mo and/or analyzed
by using the score for
employment period
Self-reported 6 387 (28.9) 612 (13.7) 2.01 (0.78–5.23) 0.151 81.0 0.000 1.000
a
Proportion of subjects exposed to solvents

mechanisms responsible for the development of environmentally
induced SSc remain unclear. It has been hypothesized that solvents
could penetrate through the skin and/or airways, initiate the auto-
immune humoral and cell-mediated responses, and stimulate the
production of fibrogenic proteins and growth factors that are gen-
erated in SSc.8 According to several animal experiments, which
examined autoimmune response in relation to TCE exposures
by different routes of exposure and dose ranges, short exposure
might accelerate the development of autoimmune response,30–32
and longer exposure might induce inflammatory hepatic infiltrate,
diffuse alopecia, skin inflammation, and ulceration.9,33 In a popu-
lation exposed to domestic contamination of water with TCE,
high levels of CD4+ and CD8+ T lymphocytes in peripheral blood
were found, suggesting that this agent may alter normal immunity
by modification of autoantigens.34 In addition, Palbykin et al35
found that low doses of TCE exposure induced DNA hypermethy-
lation in the Serca2 promoter region in cardiac myoblast cells and
rat embryonic cardiac tissue. Aromatic solvents are generally vol-
atile, flammable, and toxic. They can enter the body by vapor in-
halation and then are carried by the blood stream throughout the
body. They can even dissolve the protective skin lipids and pene-
trate the skin as well as gloves and shoes made of rubber. The ner-
vous system, the respiratory system, the gastrointestinal system,
the liver, and the skin can be affected by repeated contact, and this
phenomenon might cause both localized (hand and feet) and mul-
tisystem involvement of scleroderma.18 However, benzene, tolu-
ene, and xylene, which are contained in this type of solvents,
did not have significant associations with the risk of SSc in our
meta-analysis. For ketones, studies related to SSc were scarce; de-
spite that, combined results were meaningful. All of these need
further and deeper research.
It should also be noted that solvent exposure could influence
the clinical characteristics of triggered SSc. To explore the rela-
tionship between occupational risk factors and severity markers
of SSc, Magnant et 36 conducted a study among 105 French pa-
tients. Results showed that there were significant or close-
to-significant associations between toxic exposure and diffuse
SSc (dSSc), pulmonary involvement, and anticentromere nega-
tive. The associations between dSSc and the categories exposure
to white spirit and aromatic solvents were also close to significant.

TABLE 3. Exposure to Certain Solvents and the Risk of SSc in the Subgroups

(Sub)sample Studies, n Cases, n (%a) Controls, n (%a) OR (95% CI) P for OR I2 (%) P for Q statistic P for bias
Aromatic solvent
Aromatic solvent 518,22,23,27,29 359 (10.9) 795 (4.7) 2.72 (1.21–6.09) 0.000 56.5 0.056 0.462
Benzene 320,23,25 866 (2.9) 2445 (1.6) 1.02 (0.59–1.75) 0.951 0.0 0.630 0.147
Toluene 422,23,25,29 868 (2.2) 2705 (1.2) 1.41 (0.78–2.54) 0.251 34.7 0.204 0.320
Xylene 325,27,29 814 (2.0) 2662 (1.2) 1.35 (0.72–2.52) 0.350 0.0 0.866 0.480
Halogenated solvent
TCE 520,22,23,25,29 1029 (4.7) 2884 (1.5) 2.07 (1.34–3.17) 0.001 47.0 0.109 0.776
PCE 319,23,25 714 (1.3) 2479 (0.9) 2.03 (0.44–9.27) 0.363 66.4 0.051 0.606
TCA 419,20,23,25 887 (2.3) 2664 (1.1) 1.37 (0.76–2.48) 0.293 42.7 0.155 0.665
Other halogenated 520,22,25,27,29 1158 (6.9) 3129 (4.7) 1.49 (1.12–1.99) 0.003 33.7 0.197 1.000
solvents
Hydrocarbons
White spirit 422,23,25,29 873 (11.3) 2707 (6.9) 2.22 (0.65–7.63) 0.204 92.1 0.000 0.652
Other hydrocarbons 419,21,23,25 803 (6.0) 2583 (3.3) 1.13 (0.74–1.73) 0.560 45.3 0.140 0.228
(petroleum, gasoline,
or turpentine)
Ketones 222,29 180 (13.3) 460 (3.9) 4.20 (2.19–8.06) 0.000 15.0 0.278 —
a
Proportion of subjects exposed to solvents.
PCE, perchloroethylene; TCA: trichloroethane.

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Zhao et al JCR: Journal of Clinical Rheumatology • Volume 22, Number 5, August 2016
In another latest French study, authors found that patients exposed
to solvents were more frequently developing dSSc, digital ulcers,
interstitial lung disease, myocardial dysfunction, and cancer. In
addition, these patients were more frequently anti–Scl 70 positive
and anticentromere negative.37 These results tend to support the
hypothesis that toxic agents may amplify the cellular response
rather than the humoral response, acting as fibrogenic stimuli in the
sites where they are deposited (mainly skin or lungs), by increasing
the release of IL-1, IL-6, tumor necrosis factor α, and transforming
growth factor ß, and eventually induce diffuse cutaneous sclerosis
and pulmonary involvement through double penetration.
There are some limitations of this meta-analysis. First, the in-
cluded case-control studies may have the following defects: the in-
formation about exposure was primarily based on interviews and
may be subject to recall bias; verifying the information on expo-
sure can be difficult or even impossible. Second, most of the stud-
ies included a small number of subjects because of the rarity of the
disease, which resulted in a wide CI. Third, we were unable to es-
tablish a dose-response relationship to support causality because
of inadequate information on the duration of exposure. Only 3
studies16,17,19 provided data on the length of exposure, and 4 stud-
ies20,22,27,29 offered the level of exposure. These data were power-
less to construct a combined dose-response curve. Fourth, the
majority of reports included in the meta-analysis had been pub-
lished 10 or more years ago; this may influence the implications
of the article. Lastly, there are several publications13–15 only with
an English abstract, of which we cannot get full text or sufficient
information; this may lead to an underreporting.
In conclusion, solvents, aromatic solvents, TCE, halogenated
solvent, and ketones had significant associations with SSc, and
these associations may be affected by sex, race, and assessment
methods. Specific prevention for occupational groups who are
easily exposed to toxic factors seems to be more important in
the absence of effective treatments of SSc. So, to decrease the ex-
posure of organic solvents, it is necessary in the following areas to
take measures. (1) For the government and its relevant depart-
ments, strengthen occupational health inspection and organize
various trainings regularly for owners and workers to improve
their work-related knowledge and behavior.
(2) For enterprises that are producing or using organic sol-
vents, strengthen the construction of safeguards in the workplace,
such as ventilation detoxification, isolation, and closeness; warn-
ing marks and warning explanations should be set up at eye-
catching places. They should also strengthen the occupational
health examination before mount guard, exclude susceptible pop-
ulation and occupational contraindications, improve the automatic
production level of the company, and develop safer alternatives.
(3) For exposed workers, strengthen personal protection, receive
regular health checks, take exercise, and eat sensibly. (4) For re-
search institutions, strengthen basic research, elucidate the patho-
genesis of disease, explore biological indicators of occupational
exposure and early effective index, and make occupational chem-
ical exposure risk prediction model, to provide reference for set-
ting up safety evaluation methods.
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