Int J Clin Exp Med 2016;9(9):17612-17619www.ijcem.com /ISSN:1940-5901/IJCEM0031322

Original ArticleCharacteristics of cosmetic dermatitis in China: a meta-analysis

Qinghai Zeng1*, Xiaoxin Wu2*, Li Lei1,3,4*, Shu Ding1, Jing Chen1, Jianyun Lu1, Fang Xia5, Jian Kang1, Yangfan Xiao6, Cuilian Li7, Liyang Kang1, Jianda Zhou8, Rong Xiao6, Jinhua Huang1

1Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, China; 2Department of Orthopaedics, Second Xiangya Hospital, Central South University, Changsha, China; 3Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; 4Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, China; 5Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, China; 6Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, China; 7Kunlun College of Qinghai University, Xining, China; 8Department of Plastic and Reconstructive Surgery, Third Xiangya Hospital, Central South University, Changsha, China. *Equal contributors.

Received April 27, 2016; Accepted August 5, 2016; Epub September 15, 2016; Published September 30, 2016

Abstract: Background: Cosmetic dermatitis (CD) refers to abnormal physiological changes in the skin or mucous membrane due to improper use of cosmetics. Objective: To analyze the characteristics ofCD in China in last 15 years. Methods: Using “cosmetic dermatitis”, “cosmetics-related diseases”, and “cosmetics adverse effects” as key words to search literatures published from 2000 to 2015. Open Meta software was used to process comprehensive analysis of data. Results: The most commonly type of CD was contact dermatitis (87.4%). In contact dermatitis pa-tients, allergic dermatitis accounted for 59.9%. Patch tests were positive in 54.4% cases. Highly allergic substances included: spices, preservatives, dyes, heavy metals, and excipients. 36.2% patients had previous histories of al-lergies. Poor-quality cosmetics related CD took up 14.2%. Conclusions: The main type of CD is contact dermatitis. Spices and preservatives are most commonly seen allergens in cosmetics. Customers with previous allergy histories are more prone to cosmetic dermatology.

Keywords: Cosmetic dermatitis, cosmetics, allergic substance, patch test

Introduction

Cosmetic dermatitis (CD) refers to abnormal physiological changes in the skin or mucous membrane due to improper use of cosmetics. Commonly seen manifestations include: skin redness, pimples, pigmentation, depigmenta-tion, and hair loss etc. [1, 2]. People choose cosmetics to protect their skins, beautify appearance, and to improve living quality; how-ever, CD is utterly counterproductive by affect-ing the appearance, leading to low self-esteem, causing depression, and undermining people’s social activities and quality of life [3, 4].

With the continuous improvement of living standards and the increasing pursuit of beauty, more and more people choose to use cosmet-ics in their daily lives [5], and the incidence of

CD has been increasing to be a common clinical disease. Majority of CD patients are 20-40 years old females. The most commonly seen CD is contact dermatitis. other types of skin lesions include abnormal pigmentation, acne-like lesions, photosensitive dermatitis, hairs damage and nail damage. Studies found spic-es, preservatives, and heavy metals, etc. [6-8] are common allergic ingredients in cosmetics.

CD has complex etiology, and can be results of interactions bettween internal factors (heredi-ty, diet, stress etc.) and external factors (cli-mate, chemicals, and pollution etc.) [9]. Com- plete mechanism of CD has not been clear yet, while most scholars believe that cosmetic con-tact dermatitis is an inflammatory reaction of the skin or mucous membrane when contact with exogenous cosmetic allergens. Cosmetics

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photosensitive dermatitis is a reaction due to the light-sensitive material in cosmetics exposed to ultraviolet light, becoming allergic substances. Cosmetic acne-like lesions are caused by sebum excretion disorder, during to pores blocking by cosmetics.

Recently, as China develops fast economically, the number of people using cosmetics increas-es year by year, so is the number of CD patients. At present, although there are some articles on CD, but no evidence-based medicine analysis was made. Therefore, we retrospectively ana-lyzed the reports focused on CD in China from 2000 to 2015, in terms of gender, clinical mani-festation, patch tests, allergens, poor quality cosmetics and allergy history.

Methods

Document retrieval

Using cosmetic dermatitis, cosmetic dermati-tis, cosmetics-related diseases, and cosmetics adverse effects as keywords to search in data bases as the Chinese National Knowledge Infrastructure (CNKI), Chinese Biology Medical Literature Database (CBM), VIP Database, and Wan Fang Med Online for all published litera-ture from January 2000 to April 2015, including dissertations, conference papers and so on.

Inclusion criteria

All included documents match the following conditions: 1) subjects of study were Chinese patients diagnosed withCD; 2) published in

independently. Basic information extracted as follows: first author, year of publication, the total number of cases, the number of male and female, the number of cases of certain disease subtype, patch test results, the number of cases of poor-quality products caused aller-gies, and allergy history. When collected results did not match, a third party assisted auditing.

Statistical analysis

Open Meta software was used to analyze all included studies, to calculate the results of pooled estimates, 95% confidence interval (CI), and P values. Also, bias analysis and sensitivity analysis were included. Heterogeneity among studies was examined by the inconsistency index (I2) test. If the heterogeneity between studies was small (I2<50%), the fixed-effect model was used to calculate the statistical val-ues, otherwise a random effects model was used.

Results

Literature search results

A total of 1925 literatures were found, and a final of 51 papers were included. Inclusion pro-cess is shown in Figure 1. The general informa-tion of included literatures is listed in Table 1.

Meta-analysis results

Male and female incidence ratio: Gender infor-mation was reported in 45 studies (a total of 13216 patients). Male patients accounted for

Figure 1. Literature inclusion flow chart.

2000-2015; 3) subtype analy-sis (including gender, cosmet-ic dermatology classification, patch test analysis, allergens, poor-quality product or aller-gies, etc.) data are complete; 4) most-recently published lit-erature was chosen if there were repeated publication. All documents were carefully reviewed by two independent investigators, according to the inclusion criteria.

Data extraction

After eliminating duplicate documents, two investigators collected and evaluated data

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8.3% [95% CI (0.053 to 0.074), P<0.001], while female patients accounted for 91.7% [95% CI (0.903 to 0.930), P<0.001] (Forest plots were not presented).

CD sub-type analysis: In 25 stud-ies, a total of 10571 patients were reported in CD subtypes. We excluded three studies by sensi-tivity analysis, and a total of 5401 patients were included in the rest 22 studies. Analysis results showed that contact dermati- tis account CD for 87.4% of DC, abnormal pigmentation 4.7%, acne-like lesions 3.1%, photosen-sitive dermatitis 1.0%, hair dam-age 0.8%, nail damage 0.8%, oth-ers 0.1% (Figure 2) (Forest plots were not presented).

Sub-types of contact dermatolo-gy: In 14 studies, a total of 1597 patients were reported in con- tact dermatology sub-types. Ana- lysis showed: Irritant dermatitis accounted for 40.1% [95% CI (0.298 to 0.504), P<0.001]. Allergicdermatitis accounted for 59.9% [95% CI (0.496 to 0.702), P<0.001] (Forest plots were not presented).

Positive rate of patch test for sus-picious cosmetic: In 25 studies, a total of 5745 patients were report-ed to have brought suspicious cosmetics for patch test. Results showed patch tests positive rate was 54.4% [95% CI (0.471 to 0.618), P<0.001] (Figure 3).

Allergens analysis: In 6 studies, standard series of antigen kits were used to test patients’ aller-gens. Results showed that highly allergic substances included: spi- ces, aromatic mixture, p-phenyl-enediamine, thimerosal, nikel sul-fate, formaldehyde, cobalt chlo-ride, imidazolidinyl urea, and para-bens etc. (Table 2).

Allergy history analysis: In 4 stud-ies, 874 patients’ allergy histories

Table 1. General information of included studies

Studies Year TotalCase

SexCD3 CCD4 Patch test

I7 H8

M1 F2 W5 S6

10 Wei 2000 52 8 4411 Tang 2001 153 39 114 D12 Zhang 2001 120 26 94 D13 Jin 2002 65 13 52 D D D D14 Wan 2002 108 12 96 D D D15 Tang 2002 104 12 9216 Xu 2003 989 119 870 D D17 Yuan 2003 78 6 72 D18 Zhang 2004 106 11 95 D D D19 Liu 2004 39 3 36 D20 Shi 2004 1168 99 106921 Zhang 2004 76 9 67 D D D22 Deng 2004 227 - - D23 Fang 2004 565 - - D D24 Lai 2005 565 34 531 D D D25 Liu 2005 157 32 125 D D26 Xie 2005 383 41 342 D D D27 Yang 2006 68 6 6228 Zhang 2006 177 11 166 D D D29 Qu 2006 128 16 112 D D D D30 Chen 2006 112 20 92 D31 Gao 2007 64 5 5932 Zhang 2007 116 14 102 D D D D33 Ren 2007 32 5 2734 Lu 2007 59 0 59 D D D D35 Fang 2007 1053 57 996 D36 Qian 2008 41 16 2537 Zhao 2008 50 0 5038 Shi 2008 56 7 49 D D D D39 Yin 2008 306 13 293 D D D D40 Chen 2008 327 5 322 D D41 Yang 2008 226 - - D42 Zhang 2008 1156 - - D43 Wang 2009 68 0 6844 Xie 2009 200 12 188 D D D45 Wang 2009 173 24 149 D D46 Xie 2009 240 13 227 D D D47 Xu 2010 84 3 81 D D D48 Feng 2010 88 16 72 D D D49 Yang 2011 890 7 883 D D D50 Sun 2011 110 2 108 D D D D51 Yang 2011 926 12 914 D D D52 Huang 2011 3128 181 294753 Chou 2011 58 4 54 D54 Luo 2011 72 5 67 D D55 Chen 2012 18 3 1556 Zhao 2012 116 2 114 D D57 Chen 2012 256 30 22658 Lan 2013 123 8 115 D59 Hou 2013 123 - - D60 Zhong 2014 26 5 211: Male; 2: Female; 3: Classification of diseases; 4: Classification of contact dermatitis; 5: With questionable cosmetics; 6: Standard kits; 7: Irregular prod-ucts; 8: History of allergies; D: Precise data.

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were reported. Analysis results showed that 36.2% patients had an allergy history [95% CI (0.330 to 0.393), P=0.338] (Figure 4).

Poor-quality products

In 19 studies, 645 of 5942 patients were reported to use poor-quality cosmetics, accounting for 14.2% [95% CI (0.110 to 0.174), P<0.001] (Figure 5).

Publication bias analysis: Open Meta software was used to draw funnel plots for assessing the possibility of publication bias. For summary estimate of female incidence ratio, cosmetic dermatology subtypes, contact dermatitis subtypes, suspicious cosmet-ics patch test positive rate, poor-quality cosmetics and allergy histories, no significant publication biases were found duing to symmetrical plots. However, funnel plots of male incidence ratio, CD subtypes, and poor-quality cosmetics ratio were not symmetrical, indicating possible publication bias. (funnel plots are not pre-sented for there are too many of them).

Sensitivity analysis: Open Me- ta software was applied to do sensitivity analysis for all included studies in each indi-cator. No individual study was found having excessive influ-ence on the pooled effect. (data not presented).

Discussion

As economy improves, people are using more and more cos-metics to pursue beauty; how-ever, these cosmetics may be harmful if people are exposed

Figure 2. Sub-types of cosmetic dermatology: contact dermatology 87.4% [I2=88%, 95% CI (0.848 to 0.899), P<0.001], pigmentation changes 4.7% [I2=85%, 95% CI (0.034 to 0.060), P<0.001], acne-like lesions 3.1% [I2=67%, 95% CI (0.023 to 0.040), P<0.001], photosensitive dermatitis 1.0% [I2=62%, 95% CI (0.006 to 0.014), P<0.001], hair damage 0.8% [I2=68%, 95% CI (0.004 to 0.011), P<0.001], nail damage 0.1% [I2=13%, 95% CI (0.000 to 0.002), P=0.292], else 0.1% [I2=0%, 95% CI (0.000 to 0.002), P=0.874].

Figure 3. Positive rate of patch test for suspicious cosmetic. Forests plots showed that positive rate of patch test was 54.4% [I2=97%, 95% CI (0.471 to 0.618), P<0.001], therefore the random effects model was used as the pooling method.

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to them long-termly and improperly, and result-ing in CD [62].

important evidence of CD. In this study, suspi-cious cosmetic patch test positive rate was

Table 2. Standard Series antigen kit patch test resultsStudies Standards High allergens13 Jin (2002) Peking University First Hospital Perfumery1, Imidazolidinyl urea2, Parabens2

16 Xu (2003) Nanjing Corning Medical Development Corporation Aromatic mixture1, Cobalt chloride4, Nickel sulfate4

25 Liu (2005) Beijing Medical University Aromatic mixture1, P-phenylenediamine3, Formaldehyde2

45 Wang (2009) Beijing Yuan Kang Medical Corporation Thimerosal2, Nickel sulfate4, Aromatic mixture1

49 Feng (2010) Affiliated Hospital of Nanjing Medical University Aromatic mixture1, P-phenylenediamine3, Formaldehyde2

59 Lan (2013) Ruimin cosmetics kit C-1000 Span-835, Kathon CG2, AMO alcohol5

1, perfumery; 2, antiseptic; 3, hair dye; 4, heavy metal; 5, vehicle/emulsifier/surfactant.

Figure 4. Allergy history analysis: Forest plots showed 36.2% patients had allergy histories [I2=11%, 95% CI (0.330 to 0.393), P=0.338], therefore the fix effects model was used as the pooling method.

Figure 5. Poor-quality products caused CD ratio: forest plots showed that poor-quality products caused CD accounted for 14.2% of all allergenic cos-metics [I2=96%, 95% CI (0.110 to 0.174), P<0.001]. The random effect mod-el was used.

In this study, female patients of CD took up 91.7%, while male patients took up 8.3%. Although most CD patients are females in China, still there are a certain amount of male patients. Therefore, his-tory of cosmetics use should not be ignored for male patients in dermatological clinics.

The subtype proportion of CD differs in different areas. This study showed that the major types of CD were contact der-matitis in China, followed by abnormal pigmentation, acne-like lesions, photosensitive dermatitis, hair damage and nail damage. Alani JI reported, in the United States, the most commonly seen CD were also contact dermatitis, but fol-lowed by hair damage and nail damage [61]. Different habits of using cosmetics, environ-ment, and economic situation may be the reasons for region-al differences. Furthermore, we found that 59.9% of con-tact dermatitis patients are allergic dermatitis. So when treating these patients, phy- sicians should adequately assess the subtypes in order to provide more suitable treat- ment.

Suspicious cosmetic patch test is supposed to be an

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55.1%. Low positive rate may be caused by: ① cosmetic sellers were reluctant to provide cos-metics; ② patients were reluctant to go to hos-pitals repeatedly; ③ after patients got refund or compensation, they refused to take more tests [60]. It is not hard to diagnose cosmetic contact dermatitis, but when CDs present as photosensitive dermatitis, acne-like lesions, skin pigmentation abnormalities and other clin-ical manifestations, diagnosis of CD can be tricky. Delayed diagnosis and treatment may result in further progress of disease. Suspicious cosmetic patch test can provide effective refer-ence for the diagnosis of such diseases.

Positive result of patch test can help diagnose CD, and further cosmetic standard series anti-gen patch test may help to find cosmetics spe-cific allergens, so as to further prevent/treat such disease. In this study, there were six dif-ferent Antigen kit used to detect allergens, and we summarized the most commonly seen aller-gens (Table 2). Results showed that in China, the most common allergens were spices and preservatives, possibly because the wide use of spices and preservatives in Chinese cosmet-ics [63, 64].

Allergic constitution of patients may increase the risk of CD. There were four studies reported histories of CD patients. Meta-analysis found that 36.2% of CD patients had a history of aller-gy for drug, food and/or alcohol. These results suggest that patients with allergy histories should be more careful for selecting and using cosmetics.

In addition, we found that poor-quality cosmet-ics (Labeling without health permits, manufac-turer name and address, or valid identification) took up 12.8% of all CD. These cosmetics may contain excessive heavy metals, unknown sub-stances, or even toxic substances, which make them more likely to cause CD than high-quality cosmetics do.

Publication bias analysis results showed that female incidence ratio, contact dermatitis sub-types, suspicious cosmetic patch test positive rate, and sensitizing drug analysis had no sig-nificant publication bias; male incidence ratio, CD subtypes and poor-quality cosmetics ratio analysis had certain publication bias. For- tunately, sensitivity analysis found these bias-es had no significant effect on the final com-

bined effect, so the results are basically reli-able and stable.

Acknowledgements

Thanks to the authors who made detailed data available for this meta-analysis and our col-leagues for their hard work.

Disclosure of conflict of interest

None.

Address correspondence to: Dr. Jinhua Huang, Department of Dermatology, Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan, China. Tel: +86 13974863959; Fax: +86 731 88618576; E-mail: huangjinhua60@ 163.com

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