Are You Confident of the Diagnosis?
What you should be alert for in the history
The freckle is a small pigmented lesion that is distinctly associated with sun exposure. The patient may report worsening with sun exposure and lightening with sun avoidance. An autosomal dominant inheritance is likely, so that patients can be questioned about familial involvement. Freckles are a strong risk indicator for melanoma and nonmelanoma skin cancers; patients should be questioned about new or changing moles and non-healing lesions.
Characteristic findings on physical examination
On physical examination, lesions are well demarcated, round or irregularly shaped macules of light or dark brown color (
Freckles do not involve mucous membranes. They are most common in individuals with type I and II skin, and blonde or red hair. Axillary or inguinal freckling (Crowe’s sign) should prompt a complete skin examination and review of systems to rule out neurofibromatosis.
Biopsy, although rarely necessary, shows keratinocytes with increased melanin content, likely secondary to enlarged melanosomes in the basal layer. There is no increase in the number of melanocytes.
The freckle must be distinguished from lentigines, nevi, and melanoma. (
Solar Lentigo - for comparison.
Seborrheic keratosis, for comparison.
Who is at Risk for Developing this Disease?
Risk factors include fair skin, red or blonde hair, and sun exposure.
What is the Cause of the Disease?
Freckles are caused by sun- induced melanogenesis. The melanocytes are larger, more highly branched, and transport fully melanized melanosomes to keratinocytes.
Evidence suggests that a variation in the melanocortin-1-receptor gene is necessary for ephelides development.
Systemic Implications and Complications
Freckles do not have any systemic significance , but can be a cosmetic concern. They also indicate a risk factor for the development of melanoma, and nonmelanoma skin cancers.
Treatment options are summarized in
Treatment options for ephilides
|Medical Treatment||Surgical Treatment||Physical Modalities|
|Topical retinoids (tretinoin 0.025%- 0.1% cream nightly )||Lasers (Q switched Alexandrite and Nd:Yag)||Intense pulsed Light|
|Bleaching agents (hydroquinone- 2% or 4% twice daily )||Cryotherapy|
|Superficial chemical peels|
Optimal Therapeutic Approach for this Disease
Sun protection should be stressed as a preventative measure for all patients. It will both help to lighten lesions and is important because these patients are at a higher risk for skin cancer. A sunscreen with both ultraviolet (UV) A and UVB protection should be reapplied every 2 to 3 hours when in sunlight, as well as sun avoidance or seeking shade between the hours of 10 AM and 4 PM. Sun-protective clothing such as wide-brimmed hats and sun shirts can also be recommended.
Topical treatments with retinoids or bleaching agents.
Tretinoin strength can be started at lower doses of 0.025% and increased to 0.1% as the patient tolerates the agent. Hydroquinone 2% over the counter or 4% prescription twice a day may be used for up to six months.
Although costly, laser treatments have been shown to be very efficacious in the treatment of freckles. Both Q-switched NdYag and Q-switched Alexandrite lasers are appropriate for the destruction of melanin containing cells in the epidermis. The Q switched Alexandrite laser is associated with less post-inflammatory hyperpigmentation. The Nd:Yag is has the best efficacy and tolerability at the double frequency 532nm setting with short pulses (10ns).
Intense pulsed light
Intense pulsed light can be used for freckle treatment and has minimal postinflammatory hyperpigmentation, but demonstrates less efficacy than the Q-switched alexandrite and the short pulsed NdYag.
Cryotherapy may be used due it is availability, however there is a risk of pigment alteration and scarring. Superficial chemical peels such as alpha and beta hydroxy acids, Jessner’s, modified Jessner’s, resorcinol and tricholoracetic acid peels (10-15%) are all used for removal of stratum corneum and therefore can even out pigmentation discolorations.
Explain the association of ephildes with sun exposure and educate the patient about sun protection. Emphasize that they are at an increased risk for melanoma and nonmelanoma skin cancers. Encourage the patient to monitor themselves for new or changing moles, and nonhealing lesions. If ephilides are extensive, the patient has a family history of melanoma, or has concomitant dysplastic nevus syndrome, consider monitoring with yearly skin examinations.
Unusual Clinical Scenarios to Consider in Patient Management
Patients with xeroderma pigmentosum have extensive photo damage, including numerous ephilides at a very young age. Patients usually see the first symptoms between 6 months of age and 3 years. Vesicles, bullae, and sunburns after minimal UV exposure as well as photophobia and conjunctivitis are noted. In addition to freckling, lentigines, a mottled appearance, keratoses, atrophy and telangectasias are seen in sun exposed areas.
Neurofibromatosis type I demonstrates axillary or inguinal freckling in 20-50% of patients between 3 and 5 years of age. Coupled with multiple (greater than 6) cafe au lait macules of greater than 0.5 cm in children, or 1.5 cm in adolescents and adults, allows a definite diagnosis of Type I neurofibromatosis.
Hydroquinone use, typically those compounded at greater than 4%, can cause exogenous ochronosis.
What is the Evidence?
Hurwitz, S. Cinical Pediatric Dermatology. WB Saunders. 2006. pp. 284-90.(A review of disorders of hyperpigmentation including freckles and neurofibromatosis, as well as xeroderma pigmentosum.)
Barnhill, RL, Rabinovitz, H, Bolognia, J, Jorizzo, J, Rapini, R. "Benign melanocytic neoplams". Dermatology. Mosby, Elsevier. 2008. pp. 1723-6.(Review of ephilides epidemiology, pathogenesis, clinical and pathological features, as well as treatments.)
Bastiaens, M, Hurrne, J, Gruis, N, Bergman, W, Westerndopr, R, Vermeer, B, Bavinck, J. "The melanocortin-1-receptor gene is the major freckle gene". Hum Mol Genet. vol. 10. 2001. pp. 1701-8.(This study of the melanocortin-1 receptor gene that plays a role in human pigmentation genetics showed that MC1R gene variants were associated with fair skin, red hair, and melanoma and nonmelanoma skin cancers. Carriers of one or two MC1R gene variants had a 3- to 11-fold increased risk of developing ephelides, and a 1.5 to 2 times risk of developing severe solar lentigines. Nearly all individuals with ephelides were carriers of at least one MC1R gene variant, thus implying that MC1R gene variants are necessary for freckle development.)
Azizi, E, Lusky, M, Kushelevsky, A, Schewach-Millet, M. "Skin type, hair color, and freckles are predictors of decreased minimal erythema ultraviolet radiation dose". J Am Acad Dermatol. vol. 19. 1998. pp. 32-8.(This article proves that there is decreased sun sensitivity with increasing skin type number. It demonstrated that skin types I and II , red or blonde hair, and freckles predict a decreased minimal erythema ultraviolet radiation dose.)
Wang, C, Sue, Y, Yang, C, Chen, C. "A comparison of Q-switched alexandrite laser and intense pulsed light for the treatment of freckles and lentigines in Asian persons: A randomized, physical -blinded, split-face comparative trial". J Am Acad of Dermatol. vol. 54. 2006. pp. 804-10.(Illustratesthat although there is a higher rate of postinflammatory pigmentaryalterations after treating freckles with the Q-switched alexandritelaser, the results are significantly better than treatment with intensepulsed light.)
Vejjabhinanta, V, Elsaie, M, Patel, S, Patel, A, Caperton, C, Nouri, K. "Comparison of short-pulsed and long-pulsed 532nm lasers in the removal of freckles". Lasers Med Sci. vol. 25. 2010. pp. 9-1-6.(This article verifed that at the same energy settings, the short pulse 532nm laser is superior to the long pulsed 532nm laser for freckle treatment. This treatment has minimal side effects for patients of skin type I-IV and is a very tolerable treatment.)
Baumann, L. Cosmetic dermatology. McGraw Hill. 2009. pp. 148-60.(An overview of chemical peels including their contents, depth, and targeted results.)
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