Background

This developmental malformation arises in early childhood as a raised wart-like proliferation of epidermis. They arise on the neck, trunk, and extremities. Several clinical variants are described below.

Common skin tumors including basal cell and squamous cell carcinomas have arisen within these nevi. The nevi have also been reported in association with polyostotic fibrous dysplasia and the Proteus syndrome.

The histology varies but usually shows hyperkeratosis with papillomatosis and acanthosis. These features are very similar if not identical to a seborrheic keratosis. The pathologist should always check the age of the patient before diagnosing this pattern as a seborrheic keratosis. In a child, this pattern is almost always an epidermal nevus.

The epidermal nevus syndrome is the association of epidermal nevi with various abnormalities including epilepsy, mental retardation, cataracts, kyphoscoliosis, and limb hypertrophy. Systemic cancers may also arise.

One other variant is the inflammatory linear verrucous epidermal nevus (ILVEN) which presents as a pruritic eruption on the lower extremities. Rarely it is associated with the epidermal nevus syndrome. The microscopic picture shows psoriasiform hyperplasia with characteristic ortho- and parakeratosis alternating in both a horizontal and vertical plane. The clinical history is helpful for the pathologist to exclude either psoriasis or pityriasis rubra pilaris.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/ Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

 

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Linear verrucous epidermal nevus
AGE RANGE-MEDIAN	Most occur at birth but occasionally occur as late as puberty

 

DISEASE ASSOCIATIONS	CHARACTERIZATION
ARTHRITIS
Inflammatory linear verrucous epidermal nevus and arthritis: a new association. Al-Enezi S, Huber AM, Krafchik BR, Laxer RM. Division of Rheumatology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.	J Pediatr 2001 Apr;138(4):602-4 Abstract quote Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare, chronic skin condition that begins in early childhood. We present two children with ILVEN and arthritis, a previously undescribed association. We discuss the relevance of this association and suggest appropriate management for this arthritis.
LICHEN AMYLOIDOSIS
Inflammatory linear verrucose epidermal nevus coexisting with lichen amyloidosus. Zhuang L, Zhu W. Department of Dermatology, First Affiliated Hospital of Nanjing Medical University, People's Republic of China	J Dermatol 1996 Jun;23(6):415-8 Abstract quote The clinical and histopathological findings in a case of inflammatory linear verrucose epidermal nevus coexisting with lichen amyloidosus are presented. A 33-year-old woman had had linear verrucose lesions which were histopathologically compatible with ILVEN, and with which no amyloid deposits were associated, on her left lower leg for 30 years. She had noticed keratotic papules around the verrucose lesions on the left leg for the last 3 years. Histopathology of these papules revealed amyloid deposits in the upper dermis under the hyperkeratotic and acanthotic epidermis. Topical application of DMSO liniment with dexamethasone successfully treated the ILVEN. This remission of both lesions and itching also alleviated the keratotic papules on the left leg.
THYROIDITIS
Inflammatory linear verrucous epidermal naevus with auto-immune thyroiditis: coexistence of two auto-immune epithelial inflammations? Dereure O, Paillet C, Bonnel F, Guilhou JJ. Department of Dermatology-Phlebology, Hopital Saint-Charles, Montpellier, France.	Acta Derm Venereol 1994 May;74(3):208-9 Abstract quote We report a patient with an inflammatory linear verrucous epidermal naevus (ILVEN) coexisting with an auto-immune lymphocytic thyroiditis. The occurrence of two epithelial inflammatory processes could be linked and raises the question of auto-immune involvement in the inflammatory part of ILVEN. Moreover, expression of a membrane antigen, OKM5, usually assigned to antigen-presenting cells, especially macrophages, has been demonstrated on keratinocytes in some dermatological diseases including ILVEN. These data suggest that keratinocytes in ILVEN could present some antigens and perhaps auto-antigens modified by the hamartomatous process, leading to an (auto-immune?) inflammatory reaction.

 

PATHOGENESIS	CHARACTERIZATION
Inflammatory linear verrucous epidermal nevus. Epidermal protein analysis in four patients. Bernhard JD, Owen WR, Steinman HK, Kaplan LA, Menkes AB, Baden HP.	Arch Dermatol 1984 Feb;120(2):214-5 Abstract quote Inflammatory linear verrucous epidermal nevus (ILVEN) may be difficult to differentiate clinically from psoriasis. We report four cases of ILVEN that confirm the observation that the analysis of epidermal proteins by sodium lauryl sulfate-polyacrylamide gel electrophoresis (SLS-PAGE) discloses a pattern different from that seen in psoriasis. We have also found, however, that the SLS-PAGE epidermal protein pattern is not identical in each case of ILVEN.
Histopathogenesis of inflammatory linear verrucose epidermal naevus: histochemistry, immunohistochemistry and ultrastructure. Ito M, Shimizu N, Fujiwara H, Maruyama T, Tezuka M. Department of Dermatology, Niigata University School of Medicine, Japan.	Arch Dermatol Res 1991;283(8):491-9 Abstract quote Skin lesions of three patients with inflammatory linear verrucose epidermal naevus (ILVEN) were examined. Histologically, orthokeratosis and parakeratosis were alternately seen in the acanthotic epidermis. By N-(7-dimethylamino-4-methyl-3-coumarinyl)maleimide staining, the horny cells in the parakeratotic epidermis showed a cytoplasmic SH pattern and a weak membranous SS pattern. The orthokeratotic epidermis revealed an increased involucrin expression, whereas the parakeratotic epidermis showed almost no involucrin expression. Ultrastructurally, in the parakeratotic epidermis, the living keratinocytes had prominent Golgi apparatuses and vesicles in the cytoplasm. In the intercellular spaces in the upper spinous layer through to the lower horny layer, an electron dense, homogeneous substance was deposited. The cytoplasm of the horny cells was filled with keratin filaments and contained remnants of nucleus and cytoplasmic membrane structures, and some lipid droplets. The marginal band formation was incomplete. Most of these ultrastructural abnormalities were not found in the orthokeratotic epidermis. There are both similarities and differences in histopathogenesis of the parakeratotic epidermis between ILVEN and psoriasis. A unique finding was the lack of involucrin expression in the ILVEN parakeratotic epidermis.

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
General
Verrucous Epidermal Nevus
Localized Nevus verrucosus	Localized wart-like proliferations
Systematized
Nevus unius lateris	Long, linear, usually unilateral lesions on the extremities
Ichthyosis hystrix	Large and disfiguring with bilateral truncal distribution
Inflammatory linear verrucous epidermal nevus (ILVEN)
VARIANTS
Nevus sebaceous
Nevus comedonicus
Eccrine nevus
Apocrine nevus
Becker's nevus
White sponge nevus
ADULT ONSET
Adult onset of inflammatory linear verrucous epidermal nevus in a mother and her daughter. Goldman K, Don PC. Department of Dermatology, New York Medical College-Metropolitan Hospital Center, New York City 10029	Dermatology 1994;189(2):170-2 Abstract quote Inflammatory linear verrucous epidermal nevus (ILVEN) is a rather uncommon dermatosis that typically has an early age of onset, is unilateral, localized, pruritic and relatively refractory to treatment. Atypical presentations of ILVEN have also been described and include late onset in life, widespread involvement and response to treatment. We report the adult onset of an extremely pruritic systemized eruption in both mother and her daughter that clinically and histologically was most compatible with ILVEN. The eruptions were also partially responsive to therapy.
Adult onset of inflammatory linear verrucous epidermal nevus. Kawaguchi H, Takeuchi M, Ono H, Nakajima H. Department of Dermatology, Yokohama City University, School of Medicine, Japan.	J Dermatol 1999 Sep;26(9):599-602 Abstract quote Adult onset of inflammatory linear verrucous epidermal nevus (ILVEN) is reported in a 44-year-old Japanese man. A mild pruritic eruption appeared one year earlier and extended from the left dorsal foot to the gluteal region. Histologically, acanthosis and papillomatous thickening of epidermis as well as spongiotic edema and exocytosis with lymphocytes and neutrophils were observed. Topical tacalcitol was not effective, but the pruritus as well as the eruption slightly improved with topical corticosteroid and vaseline containing salicylic acid. This adult onset of ILVEN is considered to be a rare case.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
General	Hyperkeratosis, acanthosis, papillomatosis with elongation of the rete ridges Epidermolytic hyperkeratosis may be present
Inflammatory linear verrucose epidermal nevus. A pathologic study. Dupre A, Christol B.	Arch Dermatol 1977 Jun;113(6):767-9 Abstract quote We saw three patients with inflammatory linear verrucose epidermal nevus (ILVEN). The purpose of this study is to better delineate the histopathologic features of this type of nevus. In fact, in all three cases very particular, specific histologic lesions have been noted that permit us to better distinguish this recently outlined entity. The histologic features were depressed, cup-like areas of hyper-granulosis with overlying orthokeratotic hyperkeratosis, alternating (with sharp dermacation) with raised, level areas of agranulosis with overlying parakeratotic hyperkeratosis.
VARIANTS
ACANTHOLYSIS
Acantholytic dyskeratotic epidermal nevus: a rare histopathologic feature J. Mazereeuw-Hautier, I. Thibaut and J. L. Bonafé	J Cutan Pathol 2002;29:52 Abstract quote Background: Epidermal nevus is a congenital malformation of the epidermis consisting of verrucoid scaly plaques on the skin, often in a linear fashion. Different histologic features have been seen and, at times, acantholytic dyskeratosis has been observed. We report a new case of acantholytic dyskeratotic epidermal nevus. Case report: A 3-year-old girl presented, since birth, asymptomatic keratotic scaly lesions on the left hemithorax and left arm that followed Blaschko's lines. Histology: Biopsies revealed acanthosis, papillomatosis, hyperkeratosis and focal areas of suprabasal clefting with acantholysis, as well as individual dyskeratotic cells (corps ronds et grains) in the upper layers of the epidermis. In the literature, this histologic feature has been reported twice. Generalized or localized Darier's disease are well-established clinical entities with characteristic histologic features of acantholytic dyskeratosis. Because of the linear clinical appearance and the onset at birth or early chilhood, the lesions should be regarded as epidermal nevi and not linear Darier's disease. Conclusion: We report here an additional case of dyskeratotic epidermal nevus, which is a rare histopathologic feature.

 

SPECIAL STAINS/ IMMUNO-HISTOCHEMISTRY

CHARACTERIZATION

Immunohistochemical features in inflammatory linear verrucous epidermal nevi suggest a distinctive pattern of clonal dysregulation of growth. Military Medical Consortium for the Advancement of Retroviral Research. Welch ML, Smith KJ, Skelton HG, Frisman DM, Yeager J, Angritt P, Wagner KF. Walter Reed Army Medical Center, Department of Dermatology, Washington, D.C.

Am Acad Dermatol 1993 Aug;29(2 Pt 1):242-8 Abstract quote BACKGROUND: We studied biopsy material from four patients with inflammatory linear verrucous epidermal nevi (ILVEN) that had a psoriasiform appearance histologically and seven cases of linear epidermal nevi (LEN). Of the seven LEN, five showed hyperkeratosis, papillomatosis, and varying degrees of acanthosis; two had features of epidermolytic hyperkeratosis. Because these lesions have distinctive histologic patterns, we wanted to determine whether we could also demonstrate a distinctive pattern of immunohistochemical markers. METHODS: On all 11 cases we performed immunohistochemical stains for PCNA, factor XIIIa, MAC-387, UCHL-1, and OPD-4. In addition, on one case of ILVEN we performed ICAM-1, ELAM-1, and HLA-DR stains. RESULTS: The pattern of staining of PCNA, factor XIIIa, MAC-387, UCHL-1, and OPD-4 was distinctly different in ILVEN and LEN. Staining for ICAM-1 was present on keratinocytes, and ELAM-1 was present on endothelial cells in two cases of ILVEN. HLA-DR in these same two cases of ILVEN stained mainly dendritic cells in the epidermis. CONCLUSION: The different pattern of staining of PCNA, factor XIIIa, MAC-387, UCHL-1, and OPD-4 in LEN and ILVEN indicates a different mechanism of growth dysregulation. Stains for ICAM-1, ELAM-1, and HLA-DR in ILVEN suggest that an inability to down-regulate the inflammatory infiltrate may be important in the growth dysregulation in ILVEN. In addition, the onset of ILVEN at the time of HIV-1 infection in one patient suggests that HIV-1 infection may be one of many factors that initiates ILVEN in a susceptible person.

 

DIFFERENTIAL DIAGNOSIS

CHARACTERIZATION

Inflammatory linear verrucous epidermal naevus (ILVEN) versus linear psoriasis. A clinical, histological and immunohistochemical study. de Jong E, Rulo HF, van de Kerkhof PC. Department of Dermatology, University of Nijmegen, The Netherlands.

Acta Derm Venereol 1991;71(4):343-6 Abstract quote Inflammatory Linear Verrucous Epidermal Nevus (ILVEN) has been suggested to be a separate disease entity. However, the distinction from linear psoriasis has been discussed in the literature over recent decades. The aim of the present study was to investigate, in addition to the clinical and histological criteria, the immunohistochemical aspects of inflammation, epidermal proliferation and keratinization. From a clinical and histological point of view, ILVEN and psoriasis, according to the established criteria, have been proved to overlap. The immunohistochemical study suggests that the following procedures have an additional diagnostic impact: assessment of elastase-positive cells, assessment of keratin 16 and of keratin 10.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Treatment	Excision if possible but this may not anatomically or cosmetically feasible Excision should include the deep dermis
	Laser Electrofulguration Liquid nitrogen cryotherapy Dermabrasion Chemical peels These modalities frequently remove only the superficial portions with recurrence frequent
Full-thickness surgical excision for the treatment of inflammatory linear verrucous epidermal nevus. Lee BJ, Mancini AJ, Renucci J, Paller AS, Bauer BS. Department of Pediatrics, Northwestern University Medical School, Chicago, IL, USA.	Ann Plast Surg 2001 Sep;47(3):285-92 Abstract quote Inflammatory linear verrucous epidermal nevus (ILVEN) is a benign cutaneous hamartoma characterized by intensely erythematous, pruritic, inflammatory papules that occur as linear bands along the lines of Blaschko. Because of its chronic and unremitting symptomatology, patients with ILVEN seek medical treatment for relief of discomfort as well as concerns regarding cosmetic appearance. Reported therapeutic approaches include topical agents, dermabrasion, cryotherapy, laser therapy, and partial-thickness excision. Unfortunately, no one therapy has been successful consistently. Medical management is often unsatisfactory, because improvement tends to be temporary. Surgical modalities have met with better success in relief of symptoms but at the risk of marked scarring and a high rate of recurrence. Furthermore, the occurrence of extensive ILVEN or localization to certain anatomic regions has been considered previously a relative contraindication to excision. The authors report 4 patients with extensive ILVEN treated successfully with full-thickness surgical excision. Our report underscores the effectiveness of this surgical modality for the definitive treatment of ILVEN.
Resurfacing CO2 laser treatment of linear verrucous epidermal nevus. Michel JL, Has C, Has V. 42000 Saint-Etienne, France.	Eur J Dermatol 2001 Sep-Oct;11(5):436-9 Abstract quote The term linear epidermal nevus (LVEN) refers to benign hyperplasia of the epidermis. Three types of LVEN can be distinguished: localized, systemic and inflammatory form. All have in common resistance to treatment and risk of recurrence. We report the observations of 5 patients with inflammatory linear verrucous epidermal nevus and 5 patients with linear verrucous epidermal nevus. Management by superpulsed CO2 laser was performed as follows: test treatment, completed by removal of the lesion in one or more sessions. Treatment was effective in all cases but 2. Satisfactory cosmetic results were obtained; slight hyperpigmentation, transitory desquamation and erythematous papules were observed. There was no recurrence in two years follow-up. We suppose that for the two patients with recurrence, our treatment failure is due to the lower laser parameters used in these patients compared to the others, because of their younger age.

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Last Updated July 18, 2005

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