Epidermal nevus is a benign, congenital malformation
or hamartoma of epidermal cells derived from embryonic ectoderm. Epidermal
nevus is classified into specific variants with pertinent, incriminated
epidermal structure besides clinical appearance, degree of involvement and
distribution of lesions. Adjunctive categories of epidermal nevus are comprised
of malformations of squamous epithelium which layers various cutaneous adnexa
and are designated as “organoid” variant of epidermal nevus. Inflammatory
linear verrucous epidermal nevus was initially scripted by Unna in 1896 and is
contemplated as an exceptional variant of verrucous epidermal nevus. The
condition commonly implicates the female population and is essentially
refractory to therapy.
Keywords: Verrucous, Epidermal nevus, Inflammatory
DISEASE CHARACTERISTICS
Linear verrucous epidermal nevus commonly
appears as linearly configured, verrucous papules or plaques distributed along
Blaschko’s lines which are embryonic lines situated along the planes of
ectodermal cleavage. Linear verrucous epidermal nevus demonstrates a unilateral
lesion as cogitated with nevus unis lateralis or extensive bilateral
incrimination as enunciated with ichthyosis hystrix. Linear verrucous epidermal
nevus is associated with aberrations of central nervous system and/or skeletal
deformities. However, oral mucosal lesions are infrequent. Linear verrucous
epidermal nevus appears with the incidence of an estimated 1 to 3 neonates per
1000 live births. The condition is commonly congenital, can appear in children
or adolescents and is equally distributed amongst males and females.
Alternative clinical representation of epidermal nevus is contingent to linear,
unilateral and extensive variants. Epidermal nevus is frequently localized
although extra-cutaneous anomalies can concur. Specific syndromes can be
associated with epidermal nevus such as keratitis, erythrokeratoderma and
sensorineural deafness (KID syndrome), congenital hemidysplasia, ichthyosiform
erythroderma and limb defects (CHILD syndrome) and Gardner’s syndrome.
Epidermal nevus can clinically and histologically simulate lesions of psoriasis
[1,3]. Epidermal nevus syndrome exemplifies the association of epidermal nevus
with various skeletal, neurological and ophthalmic anomalies. Extensive epidermal
nevi and concurrent systemic anomalies can indicate the appearance of an
epidermal nevus syndrome. Inflammatory linear verrucous epidermal nevus is an
infrequent variant of epidermal nevus which commonly appears at birth, infancy
or early childhood although adults can be implicated. Inflammatory verrucous
epidermal nevus generally enunciates as a sporadic disorder although familial
instances can occur and the condition demonstrates a female predominance with a
female to male ratio of 4:1. Classic clinical criterions for diagnosing
inflammatory linear verrucous epidermal nevus were described by Altman and
Mehregan in 1971 [1] with subsequent modifications from Morag and Metzker in
1985 [2]. Criterion are specified as
early age of disease onset, predominance
in females, frequent incrimination of the left lower limb, pruritus, distinctive
psoriasis-like appearance and resistance to therapy. Features such as
unilateral, pruritic linear epidermal nevus, bifid uvula, hypoplasia of enamel,
alopecia cutis and skeletal anomalies as cogitated with spina bifida,
intracranial lipomas and calcification are suggestive of inflammatory linear
verrucous epidermal nevus. Bilateral lesions can occur. Inflammatory linear
verrucous epidermal nevus should be contemplated with the appearance of
extensive verrucous and pruritic epidermal nevi with or without co-existent
systemic abnormalities. Inflammatory linear verrucous epidermal nevus is a potentially premalignant
DISEASE PATHOGENESIS
Inflammatory linear verrucous epidermal nevus
is engendered by somatic mutations as a component of genetic mosaicism and is
associated with enhanced production of interleukins 1 and 6, tumor necrosis
factor alpha (TNFα) and intercellular adhesion molecules. Exposure to
ultraviolet radiation and chemical carcinogens accounts for predilection for
malignant transformation which can manifest as rapid growth or superficial
ulceration of lesion. Basal cell carcinoma, keratoacanthoma and squamous cell
carcinoma can exceptionally develop in cutaneous linear epidermal nevus.
Bowen’s disease, verrucous carcinoma and adnexal carcinoma can also originate
within an epidermal nevus [4,5].
CLINICAL ELUCIDATION
Lesions are initially miniature, squamoid, pruritic
and extend gradually to incriminate adjacent regions. However, lesions can be
stationary and devoid of progression.
Clinical evaluation demonstrates enlarged,
erythematous, well defined keratotic or verrucous patches with foci of hemorrhagic
crust and multiple, confluent plaques and papules. Localized, verrucous papules
or plaques which appear on the extremities, trunk or head and neck are
denominated. Epidermal nevus can emerge as elevated, painless, erythematous and
papillary lesion or delineate multiple, unilateral, patches and plaques
recapitulating a wart-like appearance. Accompanying lesions appear as painless,
linear and yellowish macules depicting a focal blaschkoid and linear
distribution [5,6]. Inflammatory linear verrucous epidermal nevus
characteristically exhibits unilateral, recurrent, inflammatory manifestations
with features of chronic eczema or psoriasis associated with severe pruritus is
exemplified. Typical clinical symptoms demonstrate intensely pruritic,
inflammatory, erythematous papules which coalesce to configure well defined
verrucous plaques. Aforesaid lesions emerge on the extremities along the
distribution of Blaschko’s lines and infrequently in a curvilinear arrangement
on the trunk. Dark tinged or brownish, mossy, pruritic papules with a linear
configuration are elucidated on the neck, lumbar region, axilla, chest,
shoulders and upper extremities. Verrucous papules can appear on the face,
cheek, external ear, pre-auricular region, forehead and scalp with linear
extensions. Intraoral papules appear as diffuse, sessile, linear and papillary
lesions on the dorsum of tongue. Gingival inflammation is generalized and
accompanied by gingival desquamation, enamel hyperplasia and dental caries.
Subjects can delineate hemorrhagic features such as bleeding gums, skeletal
abnormalities as delineated with scoliosis, asymmetrical lower extremities with
anterior bowing and alopecia cutis [3,4].
HISTOLOGICAL
ELUCIDATION
Epidermal nevus displays moderate
hyperkeratosis, acanthosis, papillomatosis with a psoriasiform, inflammatory
infiltration of the dermis or occurrence of Munro’s micro-abscesses. Elongated
rete ridges and focal thickening of granular epithelial layer are accompanied
by expansive columns of parakeratosis. Basal layer can occasionally depict
mildly enhanced melanin pigment, thereby generating typical hues of tan or
brownish lesions. Also, perimeter of the lesion is microscopically well
demarcated from surrounding epithelium. Acanthosis and hyperkeratosis are
accompanied by thick, shallow papillomatosis. Morphology often simulates the
papillomatous variant of seborrheic keratosis. Occasionally, epidermolytic
hyperkeratosis can arise within the lesion.
Certain exceptional histological patterns can
originate in the epidermal nevus such as configurations recapitulating
acanthosis nigricans, Hailey-Hailey disease, acantholytic dyskeratosis or
associated conditions [5,6] (Figures
1-9).
DISEASE VARIANTS
Aplasia cutis congenita is a cutaneous
deformity commonly arising in midline scalp and can be associated with
epidermal nevus syndrome (ENS). Aplasia cutis congenita typically displays
hairless, solitary cutaneous lesions with a distinct margin. Skeletal anomalies
are cogitated in one half to two third (50% to 66%) individuals. Predominant
primary osseous manifestations are described as incomplete bony development at
various sites, vertebral defects, camptodactyly, clinodactyly, aberrant
clavicles, rib asymmetry, shortened bones of extremities, posterior luxation of
ankle joint and asymmetry of skull [3,5]. Secondary bony manifestations include
kyphoscoliosis and limb hypertrophy. Radiographic assessment of skeletal bones demonstrate expansile bony
lesions, thickening of bone cortex, sclerosis, bony trabeculae with designated
radiolucent areas a uniform ground glass appearance and bony deformities.
Central nervous system (CNS) manifestations of epidermal nevus syndrome occur
in around half to three fourths (50% to 70%) subjects and are commonly defined
by seizures and mental retardation. Associated neurologic features are
denominated by hypotonia, hyperkinesia, hemiparesis, hemiplegia, cranial nerve
palsies, hydrocephalus, hemi-megalencephaly, cortical lesions, cortical
atrophy, ventricular abnormalities and intracerebral calcification [7,8].
Intra-spinal and intracranial lipomas, ocular
defects such as astigmatism, choristomas, colobomas of eyelid, iris, choroid
and retina, cortical blindness, nystagmus, oculomotor dysfunction, optic nerve
dysfunction, ptosis and strabismus are additional complications of epidermal
nevus syndrome. Oral lesions exceptionally appear in epidermal nevus syndrome
and define unilateral or midline papules or nodules. Lesions with papillary or
verrucous superficial surface appear on the lips, tongue, buccal mucosa, hard
palate, tonsils, pharynx, soft palate and gingiva. Tooth anomalies include
missing tooth, impacted tooth, and tooth of atypical magnitude, tooth
hypoplasia, odontodysplasia and anomalous spacing between teeth. Intra-oral
lesions can appear as wart-like, condylomata, mammilated or verrucous lesions
and demonstrate various hues as of normal oral mucosa, yellow-white, tan, dark
brown or grey [4,6].
DIFFERENTIAL
DIAGNOSIS
Inflammatory linear verrucous epidermal nevus
necessitates a distinction from various dermatoses such as adjunctive variants
of epidermal nevus, Darier’s disease, linear porokeratosis, linear lichen
planus, linear psoriasis and lichen striatus. Lichen striatus is a
self-limiting condition which can clinically simulate inflammatory linear
verrucous epidermal nevus and can be distinguished on account of early disease
onset and lack of spontaneous regression. Segregation of epidermal nevus is
required from acanthosis nigricans, a condition which usually depicts lesser
quantities of hyperkeratosis and papillomatosis than a typical epidermal nevus.
However, acanthosis nigricans-like variant of epidermal nevus can ensue.
Confluent and reticulated papillomatosis of Gougerot and Carteaud (CARP) also
necessitates a distinction from epidermal nevus. Papillomatous articulations
within lesions of CARP are subtle and can be absent [7,8]. Epidermal nevus can
recapitulate associated conditions with epidermal proliferation and
papillomatosis within the epidermal arrangements. Adequate clinical information
is mandated in cogent instances for appropriate distinction. Seborrheic
keratosis often demonstrates an identical histology. However, epidermal nevus
morphologically resembling seborrheic keratosis is often enunciated in children
or young individuals or can emerge as congenital lesions. Verruca vulgaris can
simulate epidermal nevus [9].
INVESTIGATIVE ASSAY
Dermoscopic examination of epidermal nevus
typically reveals filiform zones exemplifying irregular and linear blood
vessels with peripheral accentuation superimposed upon an erythematous
backdrop. Few centroidal, enlarged, brownish spheres and circles can accompany
the yellowish, homogenous foci. Histological assessment and a bi-annual
clinical examination are necessitated to further elucidate an epidermal nevus.
Dental radiographs can depict an absence of teeth or deviated nasal septum.
Axial computerized tomography (CT) of the brain displays miniature, calcific
foci enunciated within the frontal or parietal regions, radio-dense adipose
tissue deposits accumulated upon bilateral cistern and cerebellopontine angle
is indicative of intracranial lipomas. Lumbar radiographs delineate mild
scoliosis with congenital schmorl’s node and spina bifida. Anterior bowing of
lower extremity can occur with sclerosis of tibia [7,9].
THERAPEUTIC OPTIONS
Therapeutic modalities for managing epidermal
nevus are diverse although a singular, consistently successful therapeutic
option is lacking. Surgical eradication of the lesions is not a preferable mode
of treatment on account of extensive scarring and relapsing lesions. Several
treatment modalities can be applied in the management of inflammatory linear
verrucous epidermal nevus. Pertinent methodologies include administration of
intra-lesional and topical steroids, topical and systemic retinoids, topical 5-fluorouracil,
podophyllin, dermabrasion, cryosurgery and surgical extermination of the
lesions. However, an incomplete eradication of lesions or extensive scarring
can ensue. Lasers can be employed to manage epidermal nevus and several options
such as Argon, Erbium-YAG, pulsed dye and carbon dioxide laser are available.
The contemporary pulsed, scanned carbon dioxide laser is a preferential mode of
treatment [8,9].
Therapeutic response to the anti-psoriatic
drug calcipotriol and anti TNF antibody such as etanercept is enunciated.
Inflammatory linear verrucous epidermal nevus is markedly refractory to
therapeutic intervention. It can be managed with topical glucocorticoids,
intra-lesional corticosteroids, combined tretinoin and 5% fluorouracil.
Besides, agents such as anthralin, tar, analogues of vitamin D3 can be adopted.
Surgical extermination, cryotherapy with liquid nitrogen and carbon dioxide
laser therapy is recommended and beneficial. However, a singular therapeutic
option has not been consistently advantageous or deemed superior. However, as
treatment of inflammatory linear verrucous epidermal nevus is controversial and
invasive, an accurate determination of the condition is required [8,9].
1.
Altman
J, Mehregan AH (1971) Inflammatory linear verrucosae epidermal nevus. Arch
Dermatol 104: 385-389.
2.
Morag
C, Metzker A (1985) Inflammatory linear verrucous epidermal nevus - Report of
seven new cases and review of literature. Pediatr Dermatol 3: 15-18.
3.
Senhaji
G, Jouari OE, Gallouj S, Mernissi FZ (2018) Dermoscopy of inflammatory linear
verrucous epidermal nevus syndrome (ILVEN). Cosmetol 2: 000113.
4.
Kumar
CA, Yelluri G, Raghav N (2012) Inflammatory linear verrucous epidermal nevus
syndrome with its polymorphic presentation - A rare case report. Contemp Clin
Dent 3: 119-122.
5.
Avcioglu
SN, Altinkaya SO, Küçük M, Yüksel H, Demircan-Sezer S, et al. (2013) Vulvar and
perianal condyloma superimposed inflammatory linear verrucous epidermal nevus:
a case report and review of literature. Case Rep Dermatol Med 261574.
6.
Gianfaldoni
S, Tchernev G, Gianfaldoni R, Wollina U, Lotti T (2017) A case of inflammatory
linear verrucous epidermal nevus(ILVEN) treated with CO2 laser ablation. Open
Access Macd J Med Sci 5: 454-457.
7.
Behera
B, Devi B, Nayak BB, Sahu B, Singh B (2013) Giant inflammatory linear verrucous
epidermal nevus: Successfully treated with full thickness excision and skin
grafting. Indian J Dermatol 58: 461-463.
8.
Cabanillas
M, Aneiros A, Monteagudo B, Santos-García D, Suárez-Amor O, et al. (2009)
Epidermal nevus syndrome associated with polyostotic fibrous dysplasia, CNS
lipoma and aplasia cutis. Dermatol Online J 15: 7.
9.
Canyigit
M, Oguz KK (2006) Epidermal nevus syndrome with internal carotid artery
occlusion and intracranial and orbital lipomas. Am J Neuroradiol 27: 1559-1561.
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