Epidermal nevus and epidermal nevus syndrome
- Teresa S Wright, MD, FAAD, FAAP
Teresa S Wright, MD, FAAD, FAAP
- Associate Professor, Dermatology and Pediatrics
- University of Tennessee Health Science Center
- Division Chief, Pediatric Dermatology
- LeBonheur Children's Hospital
Epidermal nevi are benign, hamartomatous growths of the skin that are present at birth or develop in early childhood. They may be composed of a variety of epidermal cells and structures, including keratinocytes, sebaceous glands, hair follicles, apocrine and eccrine glands, and smooth muscle cells, and are thought to represent a form of cutaneous mosaicism [1,2]. Lesions with prominent adnexal components (eg, sebaceous, follicular, and/or apocrine) are sometimes referred to as "organoid," while lesions with primarily epidermal differentiation are known as "non-organoid" or "keratinocytic" nevi.
Keratinocytic epidermal nevi, also called linear epidermal nevi or linear verrucous epidermal nevi, are the most common form. They present as linear or whorled, skin-colored to brown plaques that tend to follow linear patterns on the skin known as "lines of Blaschko" (figure 1 and picture 1A-C).
This topic will review the pathogenesis, clinical presentation, and management of linear epidermal nevus. Nevus sebaceous is discussed separately. (See "Nevus sebaceus and nevus sebaceus syndrome".)
Epidermal nevi occur in approximately 1 to 3 per 1000 live births; males and females tend to be equally affected . Most epidermal nevi occur sporadically as an isolated finding, but they also may occur in association with a variety of developmental abnormalities. Familial cases have been reported [3,4].
Epidermal nevi originate from pluripotential germinative cells in the basal layer of the embryonic epidermis. They are thought to represent forms of mosaicism, resulting from postzygotic mutations (or other genetic alteration) in embryonic cells destined to populate a particular area of the epidermis. Theoretically, mutations occurring very early in embryonic development give rise to more extensive epidermal nevi and may potentially affect additional organ systems .
- Sugarman JL. Epidermal nevus syndromes. Semin Cutan Med Surg 2007; 26:221.
- Brandling-Bennett HA, Morel KD. Epidermal nevi. Pediatr Clin North Am 2010; 57:1177.
- Fearfield LA, Bunker CB. Familial naevus sebaceous of Jadassohn. Br J Dermatol 1998; 139:1119.
- Happle R, König A. Familial naevus sebaceus may be explained by paradominant transmission. Br J Dermatol 1999; 141:377.
- Hafner C, Toll A, Real FX. HRAS mutation mosaicism causing urothelial cancer and epidermal nevus. N Engl J Med 2011; 365:1940.
- Hafner C, López-Knowles E, Luis NM, et al. Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern. Proc Natl Acad Sci U S A 2007; 104:13450.
- Hafner C, van Oers JM, Vogt T, et al. Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi. J Clin Invest 2006; 116:2201.
- Hafner C, Toll A, Gantner S, et al. Keratinocytic epidermal nevi are associated with mosaic RAS mutations. J Med Genet 2012; 49:249.
- Paller AS, Syder AJ, Chan YM, et al. Genetic and clinical mosaicism in a type of epidermal nevus. N Engl J Med 1994; 331:1408.
- Tsubota A, Akiyama M, Sakai K, et al. Keratin 1 gene mutation detected in epidermal nevus with epidermolytic hyperkeratosis. J Invest Dermatol 2007; 127:1371.
- Akhyani M, Kiavash K, Kamyab K. Bullous ichthyosiform erythroderma in a child born to a parent with systematized linear epidermolytic hyperkeratosis. Int J Dermatol 2009; 48:215.
- Chassaing N, Kanitakis J, Sportich S, et al. Generalized epidermolytic hyperkeratosis in two unrelated children from parents with localized linear form, and prenatal diagnosis. J Invest Dermatol 2006; 126:2715.
- Kono M, Suga Y, Akashi T, et al. A Child with Epidermolytic Ichthyosis from a Parent with Epidermolytic Nevus: Risk Evaluation of Transmission from Mosaic to Germline. J Invest Dermatol 2017; 137:2024.
- Su WP. Histopathologic varieties of epidermal nevus. A study of 160 cases. Am J Dermatopathol 1982; 4:161.
- Ersoy-Evans S, Sahin S, Mancini AJ, et al. The acanthosis nigricans form of epidermal nevus. J Am Acad Dermatol 2006; 55:696.
- Dupre A, Christol B. Inflammatory linear verrucose epidermal nevus. A pathologic study. Arch Dermatol 1977; 113:767.
- Tesi D, Ficarra G. Oral linear epidermal nevus: a review of the literature and report of two new cases. Head Neck Pathol 2010; 4:139.
- Hafner C, Klein A, Landthaler M, Vogt T. Clonality of basal cell carcinoma arising in an epidermal nevus. New insights provided by molecular analysis. Dermatology 2009; 218:278.
- De D, Kanwar AJ, Radotra BD. Basal cell carcinoma developing in verrucous epidermal nevus. Indian J Dermatol Venereol Leprol 2007; 73:127.
- Ceylan C, Ozdemir F, Oztürk G, Akalin T. A case of basal cell carcinoma arising in epidermal nevus. Int J Dermatol 2002; 41:926.
- Masood Q, Narayan D. Squamous cell carcinoma in a linear epidermal nevus. J Plast Reconstr Aesthet Surg 2009; 62:693.
- Turk BG, Ertam I, Urkmez A, et al. Development of squamous cell carcinoma on an inflammatory linear verrucous epidermal nevus in the genital area. Cutis 2012; 89:273.
- Toya M, Endo Y, Fujisawa A, et al. A metastasizing squamous cell carcinoma arising in a solitary epidermal nevus. Case Rep Dermatol Med 2012; 2012:109632.
- Happle R. The group of epidermal nevus syndromes Part I. Well defined phenotypes. J Am Acad Dermatol 2010; 63:1.
- König A, Happle R, Bornholdt D, et al. Mutations in the NSDHL gene, encoding a 3beta-hydroxysteroid dehydrogenase, cause CHILD syndrome. Am J Med Genet 2000; 90:339.
- García-Vargas A, Hafner C, Pérez-Rodríguez AG, et al. An epidermal nevus syndrome with cerebral involvement caused by a mosaic FGFR3 mutation. Am J Med Genet A 2008; 146A:2275.
- Moreira AI, Ferreira G, Santos M, et al. Epidermal nevus syndrome associated with hypophosphatemic rickets. Dermatol Online J 2010; 16:14.
- Narazaki R, Ihara K, Namba N, et al. Linear nevus sebaceous syndrome with hypophosphatemic rickets with elevated FGF-23. Pediatr Nephrol 2012; 27:861.
- Sethi SK, Hari P, Bagga A. Elevated FGF-23 and parathormone in linear nevus sebaceous syndrome with resistant rickets. Pediatr Nephrol 2010; 25:1577.
- Heike CL, Cunningham ML, Steiner RD, et al. Skeletal changes in epidermal nevus syndrome: does focal bone disease harbor clues concerning pathogenesis? Am J Med Genet A 2005; 139A:67.
- Peramiquel L, Baselga E, Dalmau J, et al. Lichen striatus: clinical and epidemiological review of 23 cases. Eur J Pediatr 2006; 165:267.
- Hauber K, Rose C, Bröcker EB, Hamm H. Lichen striatus: clinical features and follow-up in 12 patients. Eur J Dermatol 2000; 10:536.
- Saraswat A, Sandhu K, Shukla R, Handa S. Unilateral linear psoriasis with palmoplantar, nail, and scalp involvement. Pediatr Dermatol 2004; 21:70.
- Akelma AZ, Cizmeci MN, Kanburoglu MK, Mete E. A diagnostic dilemma: inflammatory linear verrucous epidermal nevus versus linear psoriasis. J Pediatr 2013; 162:879.
- Chien P Jr, Rosenman K, Cheung W, et al. Linear psoriasis. Dermatol Online J 2009; 15:4.
- Happle R. Linear psoriasis and ILVEN: is lumping or splitting appropriate? Dermatology 2006; 212:101.
- Lee BJ, Mancini AJ, Renucci J, et al. Full-thickness surgical excision for the treatment of inflammatory linear verrucous epidermal nevus. Ann Plast Surg 2001; 47:285.
- Park JH, Hwang ES, Kim SN, Kye YC. Er:YAG laser treatment of verrucous epidermal nevi. Dermatol Surg 2004; 30:378.
- Thual N, Chevallier JM, Vuillamie M, et al. [CO2 laser therapy of verrucous epidermal nevus]. Ann Dermatol Venereol 2006; 133:131.
- Paradela S, Del Pozo J, Fernández-Jorge B, et al. Epidermal nevi treated by carbon dioxide laser vaporization: a series of 25 patients. J Dermatolog Treat 2007; 18:169.
- Toyozawa S, Yamamoto Y, Kaminaka C, et al. Successful treatment with trichloroacetic acid peeling for inflammatory linear verrucous epidermal nevus. J Dermatol 2010; 37:384.
- Panagiotopoulos A, Chasapi V, Nikolaou V, et al. Assessment of cryotherapy for the treatment of verrucous epidermal naevi. Acta Derm Venereol 2009; 89:292.
- Kim JJ, Chang MW, Shwayder T. Topical tretinoin and 5-fluorouracil in the treatment of linear verrucous epidermal nevus. J Am Acad Dermatol 2000; 43:129.
- Koh MJ, Lee JS, Chong WS. Systematized epidermal nevus with epidermolytic hyperkeratosis improving with topical calcipotriol/betametasone dipropionate combination ointment. Pediatr Dermatol 2013; 30:370.
- Herman AR, Scott RA. Systematized epidermal nevus treated with isotretinoin. J Drugs Dermatol 2002; 1:195.
- CLINICAL PRESENTATION
- Linear verrucous epidermal nevus
- Inflammatory linear verrucous epidermal nevus
- Clinical course and complications
- EPIDERMAL NEVUS SYNDROME
- Additional evaluation
- DIFFERENTIAL DIAGNOSIS
- GENETIC COUNSELING
- SUMMARY AND RECOMMENDATIONS