Epidermal Nevus Syndrome Clinical Presentation
- Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD more...
Epidermal nevi are patches, plaques, or nodules that may be bilateral or distributed on most of the body. Usually, no symptoms of the nevi are present, with the exception of inflammatory linear verrucous epidermal nevus.
Inflammatory linear verrucous epidermal nevus is a linear, persistent, pruritic plaque, usually first noted on a limb in early childhood. The clinical history may reflect symptoms associated with underlying anomalies. Inflammatory linear verrucous epidermal nevus, unlike the other types of epidermal nevi, demonstrates erythema and sometimes pruritus.
Linear nevus comedonicus
Nevus comedonicus is evident clinically as confluent clusters of dilated follicular orifices plugged with keratin, giving the appearance of aggregated open comedones. These clusters are often arranged in a linear or zosteriform pattern, occasionally paralleling the lines of Voigt or the lines of Blaschko.
Although usually unilateral, bilateral occurrences have been noted. As with other epidermal nevi, the most common sites are the face, the trunk, and proximal extremities.
Nevus comedonicus may be associated with a number of other cutaneous and internal defects, such as skeletal anomalies (eg, scoliosis, fused vertebrae or hemivertebrae, spina bifida occulta, absent fifth finger), central nervous system defects (eg, seizures, changes noted on EEG, transverse myelitis), and ocular alterations (eg, cataracts).
Inflammatory linear verrucous epidermal nevus
Inflammatory linear verrucous epidermal nevus is a linear, persistent, pruritic plaque, usually first noted on a limb in early childhood. Inflammatory linear verrucous epidermal nevus is characterized by tiny, discrete, erythematous, slightly warty papules, which tend to coalesce in a linear formation.
Altman and Mehregan delineated 6 characteristic features: early age at onset, predominance in females (with a female-to-male ratio of 4:1), frequent involvement of the left leg, pruritus, marked refractoriness to therapy, and a distinctive psoriasiform and inflammatory histologic appearance.
The lesions may be observed at birth, but most appear during infancy and childhood. In the study by Altman and Mehregan, one half of patients were noted to have lesions by age 6 months with three quarters of the 25 patients developing lesions by age 5 years. Several patients were noted to develop lesions at an older age (eg, 1 patient developed a lesion at 49 y). The left side of the body, particularly on the left lower extremity, was more often involved.
Inflammatory linear verrucous epidermal nevus may occur with musculoskeletal abnormalities in a few children, prompting the classification of inflammatory linear verrucous epidermal nevus as part of epidermal nevus syndrome. One infant had inflammatory linear verrucous epidermal nevus with congenital dislocation of the ipsilateral hip and Fallot tetralogy of the heart. Another infant had congenital inflammatory linear verrucous epidermal nevus with congenital bony anomalies of the ipsilateral extremities. Nevus depigmentosus and inflammatory linear verrucous epidermal nevus may occur together, as may inflammatory linear verrucous epidermal nevus and melanodontia.
Linear sebaceous nevus (Jadassohn nevus phacomatosis)
In 84% of patients with linear sebaceous nevus, skin lesions are on the face, and in approximately 50%, lesions are on the scalp, the neck, and the forehead. In most patients, the lesions appear on 1 side of the body (nevus unius lateralis), as shown in the images below. Lesions on the scalp are devoid of hair.
Seizures are reported in 75% of patients with linear sebaceous nevus, mostly appearing in the first 6 months of life. The morphology of the seizures varies from infantile spasms or focal motor seizures to generalized tonic or tonic-clonic seizures. In some children, seizures are drug resistant and may result in progressive mental retardation, which is noted in approximately 70% of patients with Jadassohn nevus phacomatosis. Such regression of mental capacity is not observed in older children or adolescents.
Approximately 50% of patients demonstrate different neurologic deficits, including cranial nerve paresis (cranial nerves VI and VII), hemiparesis, or cortical blindness.
Linear sebaceous nevus syndrome is composed of multiple, well-demarcated linear, hairless plaques with evidence of neurologic or skeletal alterations, such as epilepsy or mental retardation. Skin lesions in linear sebaceous nevus syndrome are less obvious in infancy, and they are a smooth yellow-orange plaque. The nevus distribution pattern in this Schimmelpenning syndrome usually follows the lines of Blaschko. With age, these lesions become more visible, darker, verrucous, and hyperkeratotic. The last stage of development occurs in late adolescence or early adult life.
The verrucous nature of the lesions is further emphasized with cutaneous benign or malignant neoplasms noted in as many as 20-30% of patients. Trichoblastomas and syringocystadenoma papilliferum are the most likely benign neoplasms, whereas basal cell carcinoma, squamous cell carcinoma, and keratoacanthoma are the most common in the malignant category. Rarely, the squamous cell carcinoma may be of the spindle cell type. Trichoblastic carcinoma developing with a nevus sebaceus has been described along with seven secondary benign neoplasms.
Note the images below:
Epidermal nevus syndrome has been described in association with a complex ocular choristoma. Further experience may show whether this linkage is significant.
Linear epidermal nevus may be bilateral or distributed on most of the body. The lesions appear as asymptomatic patches or plaques, with the head and the neck, as well as the trunk, being the most common sites.
The lesions may have a somewhat verrucous appearance. They lack erythema, and they are not pruritic.
An epidermal nevus may be associated with oral involvement and cleft palate.
Epidermal nevus syndrome has been described with a combination of widespread eccrine proliferation, multiple facial and oral poxlike lesions, gingival synechiae, blepharophimosis, body asymmetry, and mental retardation. This complex phenotype fits the genetic mosaicism theory.
The basis of the cause may be the activation of an autosomal dominant lethal mutation that survives by mosaicism. These cells might survive only by being adjacent to normal ones Inflammatory linear verrucous epidermal nevus has been described in a mother and daughter.
Happle R. Gustav Schimmelpenning and the syndrome bearing his name. Dermatology. 2004. 209(2):84-7. [Medline].
Mall V, Heinen F, Uhl M, Wellens E, Korinthenberg R. CNS lipoma in patients with epidermal nevus syndrome. Neuropediatrics. 2000 Aug. 31(4):175-9. [Medline].
Altman J, Mehregan AH. Inflammatory linear verrucose epidermal nevus. Arch Dermatol. 1971 Oct. 104(4):385-9. [Medline].
Vidaurri-de la Cruz H, Tamayo-Sanchez L, Duran-McKinster C, de la Luz Orozco-Covarrubias M, Ruiz-Maldonado R. Epidermal nevus syndromes: clinical findings in 35 patients. Pediatr Dermatol. 2004 Jul-Aug. 21(4):432-9. [Medline].
Chantorn R, Shwayder T. Phacomatosis pigmentokeratotica: a further case without extracutaneous anomalies and review of the condition. Pediatr Dermatol. 2011 Nov-Dec. 28(6):715-9. [Medline].
Groesser L, Herschberger E, Sagrera A, Shwayder T, Flux K, Ehmann L, et al. Phacomatosis Pigmentokeratotica Is Caused by a Postzygotic HRAS Mutation in a Multipotent Progenitor Cell. J Invest Dermatol. 2013 Jan 21. [Medline].
Happle R. Linear Cowden nevus: a new distinct epidermal nevus. Eur J Dermatol. 2007 Mar-Apr. 17(2):133-6. [Medline].
Bakhach M, Abbas O, Kibbi AG, Kurban M, Jundi MA. Nevoid hypertrichosis, diffuse lipoatrophy and epidermal nevus: a new syndrome?. Int J Dermatol. 2013 Mar 3. [Medline].
Igawa S, Honma M, Minami-Hori M, Tsuchida E, Iizuka H, Ishida-Yamamoto A. Novel postzygotic KRAS mutation in a Japanese case of epidermal nevus syndrome presenting with two distinct clinical features, keratinocytic epidermal nevi and sebaceous nevi. J Dermatol. 2016 Jan. 43 (1):103-4. [Medline].
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 Dec 1. 139A(2):67-77. [Medline].
Garcia-Vargas A, Hafner C, Perez-Rodriguez AG, et al. An epidermal nevus syndrome with cerebral involvement caused by a mosaic FGFR3 mutation. Am J Med Genet A. 2008 Sep 1. 146A(17):2275-9. [Medline].
Ousager LB, Bygum A, Hafner C. Identification of a novel S249C FGFR3 mutation in a keratinocytic epidermal nevus syndrome. Br J Dermatol. 2012 Jan 9. [Medline].
Farschtschi S, Mautner VF, Hollants S, Hagel C, Spaepen M, Schulte C, et al. Keratinocytic epidermal nevus syndrome with Schwann cell proliferation, lipomatous tumour and mosaic KRAS mutation. BMC Med Genet. 2015 Feb 10. 16(1):6. [Medline]. [Full Text].
Rijntjes-Jacobs EG, Lopriore E, Steggerda SJ, Kant SG, Walther FJ. Discordance for Schimmelpenning-Feuerstein-Mims syndrome in monochorionic twins supports the concept of a postzygotic mutation. Am J Med Genet A. 2010 Nov. 152A(11):2816-9. [Medline].
Rogers M, McCrossin I, Commens C. Epidermal nevi and the epidermal nevus syndrome. A review of 131 cases. J Am Acad Dermatol. 1989 Mar. 20(3):476-88. [Medline].
Ball EA, Hussain M, Moss AL. Squamous cell carcinoma and basal cell carcinoma arising in a naevus sebaceous of Jadassohn: case report and literature review. Clin Exp Dermatol. 2005 May. 30(3):259-60. [Medline].
Wu ZW, Shi WM, Sun Y, Li XJ, Song J. Cutaneous spindle cell squamous cell carcinoma in nevus sebaceous. Int J Dermatol. 2010 Dec. 49(12):1429-31. [Medline].
Liu Y, Valdebran M, Chen J, Elbendary A, Wu F, Xu M. Nevus Sebaceous of Jadassohn With Eight Secondary Tumors of Follicular, Sebaceous, and Sweat Gland Differentiation. Am J Dermatopathol. 2016 Apr 19. [Medline].
Miyagawa Y, Nakazawa M, Kudoh T. Epidermal nevus syndrome associated with anterior scleral staphyloma and ectopic bone and cartilaginous intraocular tissue. Jpn J Ophthalmol. 2010 Jan. 54(1):15-8. [Medline].
Menni S, Boccardi D, Gualandri L. Keratinocytic epidermal nevus with oral involvement and cleft palate. G Ital Dermatol Venereol. 2008 Oct. 143(5):347-9. [Medline].
Castori M, Annessi G, Castiglia D, et al. Systematized organoid epidermal nevus with eccrine differentiation, multiple facial and oral congenital scars, gingival synechiae, and blepharophimosis: a novel epidermal nevus syndrome. Am J Med Genet A. 2010 Jan. 152A(1):25-31. [Medline].
Happle R. Epidermal nevus syndromes. Semin Dermatol. 1995 Jun. 14(2):111-21. [Medline].
Mahto M, Ashworth J, Vickers DM. A case of linear epidermal naevus presenting as genital warts--a cautionary tale. Int J STD AIDS. 2005 Mar. 16(3):267-9. [Medline].
Wiedemeyer K, Hartschuh W. Trichoblastomas with Merkel cell proliferation in nevi sebacei in Schimmelpenning-Feuerstein-Mims syndrome - Histological differentiation between trichoblastomas and basal cell carcinomas. J Dtsch Dermatol Ges. 2009 Feb 2. [Medline].
Idriss MH, Elston DM. Secondary neoplasms associated with nevus sebaceus of Jadassohn: a study of 707 cases. J Am Acad Dermatol. 2014 Feb. 70(2):332-7. [Medline].
Pernet C, Munoz J, Bessis D. [PENS (papular epidermal nevus with "skyline" basal cell layer)]. Ann Dermatol Venereol. 2015 Jan. 142(1):41-5. [Medline].
Jaqueti G, Requena L, Sanchez Yus E. Trichoblastoma is the most common neoplasm developed in nevus sebaceus of Jadassohn: a clinicopathologic study of a series of 155 cases. Am J Dermatopathol. 2000 Apr. 22(2):108-18. [Medline].
Micali G, Nasca MR, Musumeci ML. Effect of topical calcipotriol on inflammatory linear verrucous epidermal nevus. Pediatr Dermatol. 1995 Dec. 12(4):386-7. [Medline].
Zvulunov A, Grunwald MH, Halvy S. Topical calcipotriol for treatment of inflammatory linear verrucous epidermal nevus. Arch Dermatol. 1997 May. 133(5):567-8. [Medline].
Davison SP, Khachemoune A, Yu D, Kauffman LC. Nevus sebaceus of Jadassohn revisited with reconstruction options. Int J Dermatol. 2005 Feb. 44(2):145-50. [Medline].
Winston KR, Kang J, Laoprasert P, Kleinschmidt-DeMasters BK. Hemispherectomy in a premature neonate with linear sebaceous nevus syndrome. Pediatr Neurosurg. 2008. 44(2):159-64. [Medline].
Kiedrowicz M, Kacalak-Rzepka A, Królicki A, Maleszka R, Bielecka-Grzela S. Therapeutic effects of CO2 laser therapy of linear nevus sebaceous in the course of the Schimmelpenning-Feuerstein-Mims syndrome. Postepy Dermatol Alergol. 2013 Oct. 30(5):320-3. [Medline]. [Full Text].
Shahgholi E, Mollaian M, Haghshenas Z, Honarmand M. Congenital rhabdomyosarcoma, central precocious puberty, hemihypertrophy and hypophosphatemic rickets associated with epidermal nevus syndrome. J Pediatr Endocrinol Metab. 2011. 24(11-12):1063-6. [Medline].
Hato N, Tsujimura M, Takagi T, Okada M, Gyo K, Tohyama M, et al. Infantile inflammatory pseudotumor of the facial nerve as a complication of epidermal nevus syndrome with cholesteatoma. Auris Nasus Larynx. 2013 Feb 19. [Medline].
Lefkowitz A, Schwartz RA, Lambert WC. Nevus comedonicus. Dermatology. 1999. 199(3):204-7. [Medline].
Miteva LG, Dourmishev AL, Schwartz RA. Inflammatory linear verrucous epidermal nevus. Cutis. 2001 Nov. 68(5):327-30. [Medline].