Ephelis (Freckle) and Lentigo

Freckles are small (c0.5 cm) brown macules that occur in profusion on the sun-exposed skin of the
face, neck, shoulders, and backs of the hands. They become prominent during the summer when exposed
to sunhght and subside, somehmes completely, during the winter when there is no exposure, Blonds and
red-heads with blue eyes and of Celtic origin (skln types I or 11) are especially susceptible. Ephelides
may be genet~cally determined and may recur in successwe genent~ons in similar locations and patterns
They usually appear around age 5. Ephel~s must be differentiated from lenhgo sinzptes. The lentigo is
a benlgn discrete hyperpigmented maculc appearing at any age and on any park or the body, ~ncludmg
the mucosa. Tbe intens~ty of the color is not dependent on sun exposure. The solar lentigo (frequently
misnamed "liver spot") appears at a later age, mostty in persons with long-term sun exposure, The backs
of the hands and face (especially the forehead) are favored sites. Histologically, the ephelis shows
increased production of melan~n pigment by a normal number of melanocytes. Otherwise, the epidermis
is normal, whereas the lentigo has elongated rete ridges that appear to be club shaped. Freckles and
lentigenes are best prevented by appropriate sun protect~on, Cryotherapy, top~cal tret~nom, and
adapalene are effective in the treatment of solar lentigenes.


The Epidemiology of Nevi and Signs of Skin Aging in the Adult General
Population: Results of the KORA-Survey 2000 Torsten Schafer
Jessica Merkl , Eckart Klemm , Heinz-Erich Wichmann, Johannes Ring and the KORA study group
Journal of Investigative Dermatology (2006) 126,14901496. doi:10.1038/sj.jid.5700269; published online 27 April 2006

Ephelides, lentigines solaris, and lentigines seniles
Ephelides were seen in 16% (CI 14.717.4%) of the study population, with women exhibiting ephelides
significantly more frequently than men. Men with ephelides, however, exhibited significantly more
freckles than women. Lentigines solaris were present in 62.4% (CI 60.664.2%) of the study population.
In this case, men were affected more frequently and with a higher number of lentigines than women.
Lentigines seniles were observed in one-third (33.2%, CI 31.534.9%) of the subjects. Here, women were
affected significantly more often and also exhibited a higher count of these lentigines.
Trends with age.Figure 1 shows the prevalence of elastosis, cutis rhomboidallis nuchae and Morbus
Favre Racouchot in 5 age groups. For all 3 entities a significant increasing trend could be observed on
different levels of frequency as expected. Similarly, here was a significant increasing trend of the
prevalence of lentigines solaris and lentigines seniles with age in women and men (Figure 2). As
expected, the increase of lentigines seniles is more pronounced later in life as compared to lentigines
solaris, but in the highest age group, both entities reach an almost equal prevalence. In contrast, ephelides
show a significant decreasing trend with age after 35 years.


A Gene for Freckles Maps to Chromosome 4q32q34
Xue-Jun Zhang, Ping-Ping He, Yan-Hua Liang, Sen Yang, Wen-Tao Yuan,wShi-Jie Xu, and Wei Huang
Institute of Dermatology & Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, China,
Chinese National Human Genome Center at Shanghai, Shanghai, China, Key Laboratory of Genome Research at
Anhui, Hefei, China
S. Yang J.-H. Hao D.-Q. Ye (&)
Department of Epidemiology, Anhui Medical University,
81 Meishan Road, Hefei, Anhui 230032,
Peoples Republic of China
e-mail: cjdcp@mail.hf.ah.cn

Freckles, or ephelides are numerous pigmented spots of the skin commonly occurring in the Caucasian
population (Bastiaens et al, 1999). They are mainly confined to the face, even arms and back. Freckles
first appear at about 5 y as light-brown pigmented macules on light-exposed skin. They increase in
number, size, and depth of pigmentation during the summer months, and are smaller, lighter, and fewer in
number in the winter. Histologically, the freckles show increased production of melanin pigment by a
normal number of melanocytes. Freckles commonly stop spreading before adolescence and last for life,
but could sometimes be subtle in adulthood. They are transmitted as an autosomal dominant pattern
(Brues, 1950). Several pigmented skin disorders such as dyschromatosis symmetrica
hereditaria (Online Mendelian Inheritance in Man (OMIM) 127400), xeroderma pigmentosum (OMIM
278700), and cutaneous malignant melanoma (OMIM 155600) are associated with freckles; however,
freckles mainly occur as an independent trait, and most cases with freckles have no other abnormalities.
Freckles are cosmetically disfiguring and treatment may be requested on cosmetic grounds. This disorder
is also very common in the Chinese population. There are approximately 3000 Chinese individuals that
have ever sought treatment for freckling (Ma, 1998; Wang and Li, 1998; Liang and Luo, 1999; Chen et al,
2000). In Caucasians, freckling is most frequent in individuals with red hair and fair skin (Aziziet al,
1988; Bastiaenset al, 1999). Based on the close relationship between red hair, fair skin, and freckles,
Bastiaenset al(2001) performed an association study with the melanocorin-1-receptor (MC1R) gene,
freckles, and solar lentigines, and found that the MC1R gene variants could play an important part in the
development of freckles and solar lentigines, but most of the freckling subjects who attended the study are
affected with melanoma or nonmelanoma skin cancer. As an independent trait, freckles have not been
mapped to any chromosome region and even recorded into the OMIM up to now. To localize the gene
responsible for freckles, we performed a genome-wide scan and first mapped the freckle gene to
chromosome 4q32q34.
Freckles are characterized by pigmented macules (13 mm) on the face, even on the neck, shoulders, and
backs of the hands (Wilson and Kligman, 1982). They are genetically determined and may recur in
successive generations in similar locations and patterns. Some cases with pigmented diseases such as
dyschromatosis symmetrica hereditaria, xeroderma pigmentosum, and cutaneous malignant melanoma
also show freckle features and the genes for these disorders have been mapped and even cloned. Recently,
dyschromatosis symmetrica hereditaria loci have been localized to chromosomes 1q11q21 and 6q24.2
q25.2 by Zhanget al(2003) and Xing et al(2003), respectively, but we failed to confirm the linkage to
these two regions using this freckle family.



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 lesions of skin pigmentation mainly on sun-exposed skin.
Although they are benign pigmented spots, ephelides cause an increasing concern becauseof the wide-
spreading cosmetic attention of society and possible association with skin cancer. However, there have
been few reports on the prevalence of ephelides. The objective of this study was to estimate the
prevalence of ephelides and the possible role of genetic factors in the pathogenesis of ephelides in the
Han Chinese adolescents. Assessment of the skin was conducted in college students of the Anhui Medical
University in China. Information on common skin conditions including ephelides were collected from
9697 Han Chinese college students. A total of 1,841 ephelides cases and 582 normal controls were
identiWed and they, along with their Wrstdegree relatives, provided information on ephelides conditions.
The odds ratio was used to estimate the relative risk of ephelides between the Wrst-degree relatives of
cases and controls. The overall prevalence of ephelides was estimated to be 19.0% in college students.
Ephelides are more common in female students (26.1%) than in males (12.1%;2 = 06.7, P< 0.05). The
mean ages of onset for males and females were 12.42 years (4.61) and 12.88 years (3.90;t= 2.11, P<
0.05), respectively. Positive family history was observed in 932 of the 1,841(50.6%) patients. The
severity of ephelides in females of light skin was found to be signiWcantly higher than that in males with
skin of similar color (U= 3.904, P< 0.001). The risk of having ephelides among Wrst-degree relatives of
cases was signiWcantly higher than that for the relatives of normal controls (odds ratio 5.75, 95%
conWdence interval (CI): 4.617.18, P< 0.001). Our study provided the Wrst information on
theprevalence of ephelides in Chinese adolescents and suggests that familial factors are important in
determining individual susceptibility to ephelides.