Arch Dermatol Res (2008) 300:87–90

DOI 10.1007/s00403-007-0810-5

ORIGINAL PAPER

Prevalence and familial risk of ephelides in Han Chinese adolescents

Sen Yang · Sheng-Xin Xu · Feng-li Xiao · Wen-Hui Du · Jia-Hu Hao · Hong-Yan Wang · Dong-Qing Ye · Xue-Jun Zhang

Received: 3 April 2007 / Revised: 11 August 2007 / Accepted: 11 October 2007 / Published online: 30 October 2007© Springer-Verlag 2007

Abstract Ephelides are one of the most common lesionsof skin pigmentation mainly on sun-exposed skin.Although they are benign pigmented spots, ephelides causean increasing concern because of the wide-spreading cos-metic attention of society and possible association with skincancer. However, there have been few reports on the preva-lence of ephelides. The objective of this study was to esti-mate the prevalence of ephelides and the possible role ofgenetic factors in the pathogenesis of ephelides in the HanChinese adolescents. Assessment of the skin was conductedin college students of the Anhui Medical University inChina. Information on common skin conditions includingephelides were collected from 9697 Han Chinese collegestudents. A total of 1,841 ephelides cases and 582 normalcontrols were identiWed and they, along with their Wrst-degree relatives, provided information on ephelides condi-tions. The odds ratio was used to estimate the relative riskof ephelides between the Wrst-degree relatives of cases and

controls. The overall prevalence of ephelides was estimatedto be 19.0% in college students. Ephelides are more com-mon in female students (26.1%) than in males (12.1%;�2 = 06.7, P < 0.05). The mean ages of onset for males andfemales were 12.42 years (§4.61) and 12.88 years (§3.90;t = 2.11, P < 0.05), respectively. Positive family historywas observed in 932 of the 1,841(50.6%) patients. Theseverity of ephelides in females of light skin was found tobe signiWcantly higher than that in males with skin of simi-lar color (U = 3.904, P < 0.001). The risk of having epheli-des among Wrst-degree relatives of cases was signiWcantlyhigher than that for the relatives of normal controls (oddsratio 5.75, 95% conWdence interval (CI): 4.61–7.18,P < 0.001). Our study provided the Wrst information on theprevalence of ephelides in Chinese adolescents and sug-gests that familial factors are important in determining indi-vidual susceptibility to ephelides.

Keywords Ephelides · Prevalence · Case-control study

Introduction

Ephelides (or freckles) are the most common pigmentedlesions in sun-exposed skin. They are characterized by Xatred or light brown spots that appear during the sunnymonths and fade in the winter. Ephelides usually occur inchildhood and in young adults, and are more commonlyseen in the Caucasian population. Studies have shown thatthe prevalence of ephelides is diVerent across populations,varying from 16 to 47.8% [1, 2, 9].

Ephelides are benign pigmented spots, posing no healthrisk. Concern about ephelides arises when they are associ-ated with an increased risk of skin cancer [4, 5, 7]. More-over, ephelides have increasingly received attention from

S. Yang · S.-X. Xu · F.-l. Xiao · W.-H. Du · H.-Y. Wang · X.-J. Zhang (&)Institute of Dermatology and Department of Dermatology, The First Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, People’s Republic of Chinae-mail: ayzxj@vip.sina.com; ayzxj@mail.hf.ah.cn

S. Yang · S.-X. Xu · F.-l. Xiao · W.-H. Du · H.-Y. Wang · X.-J. ZhangKey Laboratory of Genome Research in Hefei, Hefei, Anhui Province, People’s Republic of China

S. Yang · J.-H. Hao · D.-Q. Ye (&)Department of Epidemiology, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, People’s Republic of Chinae-mail: cjdcp@mail.hf.ah.cn

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patients due to cosmetic concerns. Improved treatment mayhave reduced the occurrence and severity of ephelides, butit is still with a relatively high rate of recurrence [8].

The pathogenesis of ephelides has not yet been eluci-dated. Recent evidences have shown that genetic factorsmay play a role in the development of ephelides [3, 11]. Ithas been found that among identical twins, there was astriking similarity in the total number of ephelides. Such asimilarity was considerably less common in fraternal twins.Meanwhile, the variation in ephelides counts appears to bedue largely to heredity. To date, there have been few stud-ies of familial risk and prevalence on clinically conWrmedephelides, especially in Chinese or Asian populations.

In this study, we examined the prevalence and severityof ephelides in college students in central China. In addi-tion, we estimated the familial risk of ephelides among theWrst-degree relatives using a case-control design.

Materials and methods

Study population and survey

A general survey was conducted in freshmen students inAnhui Medical University in central China from September2003–2006. Volunteers of Han Chinese were interviewedafter public invitation to enrolment during the time period.Skin assessment was conducted to collect information onskin conditions during the physical examinations afterschool enrolment. For skin assessment, each participantwas assessed by either of two teams, each consisting of adermatologist and a dermatology nurse. The number ofephelides presented on the exposed skin surface (includingthe head, neck and hands) of each individual was countedand recorded. The study was approved by the Medical Ethi-cal Committee (Anhui Medical University, Hefei, China)and written informed consent was obtained from all partici-pants before commencing the study.

Diagnostic criteria and study design

Ephelides were deWned as rather small (1–3 mm), pale, brownor red brown macular lesions with poorly deWned margins [2].Each participant was recorded as aVected or not aVectedbased on whether or not one has ephelides on exposed skinsurface. For the aVected people, counts of ephelides wereclassiWed into three groups: 1–20, 21–50 or more than 50counts. Age at onset was deWned as the age when the personWrst noticed the appearance of lesion or was remarked by his/her family members or friends on the appearance of ephelides.

In order to examine the familial risk for ephelides, infor-mation on ephelides among the relatives of case and controlcohorts was collected. All diagnosed cases served as the

case group, and 585 normal controls were randomlyselected from those who were determined to be withoutephelides on the whole integument. Each selected partici-pant in the case–control cohort was asked to contact theirWrst-degree relatives via telephone to see if anyone of themhad had ephelides, and the information on ephelides of theWrst-degree relatives was recorded and brought back to theproject coordinator. The clinical pictures of ephelides, solarlentigines (or senile lentigines) and melanocytic nevi wereshown to the participants in order to help them distinguishephelides from other common freckle-like lesions. If therewas any doubt, the relative was contacted and an examina-tion was carried out by an experienced dermatologist.

Skin pigmentation was assessed at the inner side of theupper arm close to the axilla to minimize the variabilityinduced by previous tanning. The visual determination ofskin pigmentation was supported and standardized by high-quality color reference photographs of skin. Skin color wasclassiWed as “dark”, “medium”, or “light” complexion.

Since the skin assessment was conducted by two derma-tologists, the consistency in the assessment results of thetwo teams was examined. To assess the inter-observer vari-ability, a total of 90 consecutive participants were exam-ined independently by both dermatologists. KappacoeYcient was used to measure the inter-observer consis-tency. We also conducted quality check on the report of theWrst-degree relatives. Samples of 160 Wrst-degree relativesrandomly selected from cases and controls, respectively,were examined by an experienced dermatologist.

Statistical analysis

Data collected from the participants were entered into a com-puter and veriWed on a relational database developed on Epi-Data 3.1 (the EpiData Association, Denmark) where a seriesof checking was incorporated to detect data inconsistencies.All statistical analyses were conducted using SPSS 10.0, andthe prevalence was estimated for the study population. TheStudent’s t test was used to compare the diVerence in meanage at onset, based on gender. Chi-squared trend test was usedto examine the diVerence in severity among diVerent skincomplexions. Mann–Whitney U test was employed to com-pare the severity of ephelides between males and females,while controlling for skin color. Odds ratio (OR) was used toestimate the familial risk of ephelides among Wrst-degree rela-tives of ephelides and controls. DiVerences were consideredstatistically signiWcant if P < 0.05 in two-tailed tests.

Results

The participants included 9,697 Han Chinese students,excluding 1,356 students who declined to participate and

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Arch Dermatol Res (2008) 300:87–90 89

52 invalids. Among these participants, males and femalesaccounted for 50.7% (4915) and 49.3% (4782), respec-tively. The age of participants ranged from 15 to 21 years,with a mean age of 17.6 years (§1.6). The consistency ofthe skin evaluation between the two assessment teams wasvery high for both skin color classiWcation and counts ofephelides. The kappa coeYcients, which measure the con-sistency of inter-rates, were 0.78 and 0.88, respectively.Consistency of the assessment of ephelides conditionsamong Wrst-degree relatives of cases and controls was92.5% and 89.4%, respectively.

Table 1 presents the prevalence of ephelides, based ongender. Out of the 9,697 participants, 1,841 were assessedas having ephelides. The overall prevalence of facial ephe-lides was 19.0%. Ephelides was more common in females(26.1%) than in males (12.1%; �2 = 306.7,P = 0.000 < 0.05). The mean ages of onset for males andfemales were 12.42 (§4.61) and 12.88 (§3.90) years(t = 2.11, P = 0.035 < 0.05), respectively. Positive familyhistory was observed in 932 cases, which account for50.6% of 1,841 patients. This is signiWcantly higher thanthat observed in the control group, which is 74 (13.8%)among 535 controls (�2 = 229.9, P = 0.000 < 0.05).

Table 2 shows the severity of ephelides based on genderand skin color. Overall, most (57.5%) exhibited fewer than20 ephelides. There was no signiWcant diVerence in epheli-des severity between diVerent skin colors of the same gen-der, and no signiWcant trend of the severity in males(�2 = 7.499, P = 0.112.) or females (�2 = 1.498, P = 0.221).Mann–Whitney U test showed that the severity of ephelidesin females with fair skin was signiWcantly higher than in

males with similar color of skin (U = 3.904, P < 0.001). AsigniWcant diVerence in the severity of ephelides betweenmales and females was also observed in the medium-com-plexioned group (U = 2.307, P = 0.021 < 0.05).

Familial risk of ephelides

Table 3 summarizes the family history of ephelides amongthe Wrst-degree relatives of the case and control groups. Outof the 4,313 Wrst-degree relatives of the case group, 1,284had ephelides, indicating a prevalence of 29.8%. In con-trast, only 98 of the 1,428 Wrst-degree relatives of the con-trol group had ephelides, the proportion being 6.9%. Thisshows that there is a strong association of family historywith ephelides (OR = 5.75, 95% conWdence interval (CI):4.61–7.18, P < 0.001).

Discussion

To our knowledge, this is the Wrst epidemiological studythat estimates the prevalence of ephelides in Chinese ado-lescents and evaluates the role of the genetic component inthe pathogenesis of ephelides. The estimated prevalence ofephelides among Chinese college students is 19%, which isrelatively lower than those reported in previous studies onother populations. Among Chinese adolescents, ephelidesare more common in females than in males, but the meanage of onset is signiWcantly lower in males than in females.The severity of ephelides in females of light or mediumskin is signiWcantly higher than in males with the same

Table 1 Prevalence of ephelides among male and female college stu-dents

Males (%) Females (%) Total (%)

AVected 595 (12.1) 1,246 (26.1) 1,841 (19.0)

Not aVected 4,320 (87.9) 3,536 (73.9) 7,856 (81.0)

Total 4,915 4,782 9,697

Table 2 Severity of ephelides based on skin color and gender in Chinese adolescents

Skin color Males Females Ub P-value

Number of ephelides Number of ephelides

<20 »20 »50 <20 »20 »50

Light 98 29 5 244 141 50 3.904 0.000

Medium 219 123 24 355 200 92 2.307 0.021

Dark 57 31 9 86 53 25 1.237 0.216

�2 trenda 7.499 1.498

P-value 0.112 0.221

a Chi-squared trend test among diVerent types of skin color based on sexb Mann–Whitney U test, the diVerence in severiry between diVerent sexes with control for skin color

Table 3 Family history of ephelides in the Wrst-degree relatives ofcases and controls

History of ephelides

First-degree relatives of cases

First-degree relatives of controls

Total

Positive 1,284 98 1,382

Negative 3,029 1,330 4,359

Total 4,313 1,428 5,741

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skin. Half of the cases have a positive family history, andthe prevalence in the Wrst-degree relatives of the case groupis signiWcantly higher than in the control group. The oddsratio is 5.75, which suggests a strong family risk for epheli-des.

There are limited studies on the prevalence of ephelidesto date. The estimated prevalence of ephelides from ourstudy (19%) is slightly higher than the recently reportedprevalence of 16% in German adults (mean age 49 years,50% women) [9], but is much lower than the prevalence of47.8% in the Dutch population reported by Bastiaens MT[2]. Our study shows that ephelides are more prevalent infemales with fair skin than in males, which is consistentwith some previous studies [2, 4, 10]. Our study indicatedthat the Wrst-degree relatives of the cases are more likely tohave ephelides than those of the control group, suggestingthat the genetic components may aVect the development ofephelides. This is also consistent with the Wndings fromprevious twin and family studies [3, 11].

Although ephelides pose no health risk, it may aVect thefacial aesthetics of those severely aVected and may interferewith the normal development of psycho intelligence. Thestrong association between ephelides and melanoma, as amajor risk marker [5, 6], suggests that the identiWcation ofthe causes of ephelides may help in understanding thecauses of melanoma and the appropriate ways to prevent it.We also intended to look at the relation between the severityof ephelides and skin cancer. But none of the 5,741 Wrst-degree relatives concerned reported to have a history of mel-anoma. So, we failed to establish any relationship betweenseverity of ephelides and development of melanoma.

Our study suggests that familial factors are important indetermining individual susceptibility to ephelides. Geneticmake-up may determine the increase of activity of epheli-des in early childhood or adolescence under induction ofsome environmental factors. It is worthy to note that famil-ial risk may indicate some other shared family environ-ment. Due to the limitation in data collection, we wereunable to adjust for those shared family environment orindividual characteristics. Our Wndings need to be con-Wrmed by studies of other ethnic groups, and the relativeroles of environmental and genetic factors need to be fur-ther elucidated.

Acknowledgments We are most grateful to the ephelides family forparticipating in this study. The authors thank Dr. Fengyu Zhang andJianjun Liu for their helpful comments. Dr. Hailin Wang assisted onthe days of examination at the school. This work was supported bygrants from the Chinese High Tech Program (863) (2002BA711A10).

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