Lentigo and Freckles (Ephelides)
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- Ephelides, commonly known as freckles, are one of the most frequently identified pigmented lesions seen on skin recognized by the general public.
- These tend to occur in light-skinned individuals with red or blonde hair and are often in sun-exposed areas such as the face, upper trunk, and the posterior aspect of the arms and hands.
- Ephelides are benign skin lesions that are usually round in shape, light to dark brown in color, and are just a few millimeters in diameter.
- Early in life, they can increase in number and distribution, but they often decrease in number as a person reaches adulthood.
- They are thought to be directly influenced by exposure to sunlight, and thus, less ultraviolet (UV) exposure such as during winter months will result in lightening of the freckles.
- Lentigo (plural lentigines) is a discrete hyperpigmented macule that is mostly benign. Two main types of lentigines are simple lentigo and solar lentigo. The color of lentigines does not change in response to sunlight.
- Solar lentigines, often referred to as sun spots, liver spots, age spots, or actinic lentigines, are well circumscribed, round to irregularly shaped macules with varying colors ranging from light brown to black. These occur in response to chronic photodamage and are therefore most commonly seen in the elderly. They may, however, present in young adults in areas where patients often have a lot of sun exposure, similar to ephelides. Solar lentigines are mainly seen in people with lighter skin.
- A simple lentigo or lentigo simplex is a dark brown macule (darker than ephelides) that can rarely be seen at birth or more often can present during childhood or puberty. They can occur in all races, on any part of the body, and are not induced by sun exposure. Simple lentigines have a more generalized and sparse distribution than ephelides, with the potential to occur anywhere on the body. Of these three pigmented macules, this is the only one that can appear on mucosal surfaces.
The incidence of ephelides, solar lentigines, and simple lentigines is currently unknown, with limited information on these benign entities reported in the literature.
- Some sources estimate that in the United States, solar lentigines may be detected in up to 90% of Caucasians >60 years.
- In general, ephelides and lentigines are very common, particularly in patients with lighter skin types.
Etiology and Pathophysiology
- Ephelides occur as a result of increased melanin content inside of keratinocytes, mainly seen in the basal cell layer. The number of melanocytes is normal.
- Freckles are known to darken as well as increase in number with repetitive sun exposure due to the UV light stimulating melanogenesis and an increase in the transfer of melanosomes from melanocytes to keratinocytes.
- Similarly, solar lentigines occur when repeated UV radiation stimulates increased melanin synthesis. These lesions display hyperpigmentation predominantly involving the basal cell layer of the skin and elongation of the epidermal rete ridges. Melanocyte hyperplasia can also be seen along with other signs of chronic actinic damage such as solar elastosis in the dermis.
- Simple lentigines are the result of increased melanocytes in the stratum basale layer of the skin and sometimes increased melanin content in the upper layers of the epidermis and stratum corneum. They can occur anywhere on the skin and also involve the lips, inside the mouth, and genitalia. Unlike ephelides or solar lentigines, they are not thought to be influenced by sun exposure.
- An autosomal dominant pattern of inheritance has been suggested in the literature for ephelides given that freckles can be seen in multiple generations within a family (1).
- Solar lentigines are thought to be more acquired, and along with simple lentigines, the genetic associations related to these diagnoses are not clearly defined in the literature. Multiple lentigines can occur without associated conditions and is known as generalized lentigines or lentigines profusa. Of note, however, the appearance of multiple lentigines may be related to specific genetic syndromes (mentioned below).
- Young patients with fair skin are at an increased risk for developing ephelides on sun-exposed areas.
- Patients with fair skin are at an increased risk of developing solar lentigines later in life on areas that are chronically sun exposed.
- The general risk factors for lentigo simplex remain unknown.
The best way to prevent ephelides and solar lentigines is sun avoidance. Complete sun avoidance is not feasible, and so, realistic recommendations include using a broad-spectrum sunscreen daily with proper reapplication, seeking shade, and wearing sun-protective clothing to reduce the likelihood of developing ephelides and solar lentigines.
Commonly Associated Conditions
- Numerous ephelides and solar lentigines are often observed in fair-skinned, sun-sensitive patients with red hair containing specific genetic polymorphisms in the melanocortin 1 receptor (MC1R) gene. The MC1R gene encodes for the receptor of the melanocyte-stimulating hormone on the surface of melanocytes. The binding of melanocyte-stimulating hormone to MC1R promotes the production of the dark pigment eumelanin, which helps to protect against UV light (2).
- Numerous simple lentigines may be observed in several genetic conditions including Carney complex (LAMB/NAME syndromes), LEOPARD syndrome, Laugier-Hunziker syndrome, Bandler syndrome, xeroderma pigmentosum, and Peutz-Jeghers syndrome.