Inflammatory Linear Verrucous Epidermal Nevus is a rare disease of the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

that presents as multiple, discrete, red

papule A papule is a small, well-defined bump in the skin. It may have a rounded, pointed or flat top, and may have a dip. It can appear with a stalk, be thread-like or look warty. It can be soft or firm and its surface may be rough or smooth. Some ha ...

s that tend to coalesce into linear plaques that follow the

Lines of Blaschko Blaschko's lines, also called the lines of Blaschko, are lines of normal cell development in the skin. These lines are only visible in those with a Mosaic (genetics), mosaic skin condition or in Chimera (genetics), chimeras where different cell li ...

. The plaques can be slightly warty (psoriaform) or scaly (eczema-like). ILVEN is caused by somatic

mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...

that result in genetic

mosaicism Mosaicism or genetic mosaicism is a condition in multicellular organisms in which a single organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized ...

. There is no cure, but different medical treatments can alleviate the symptoms.

Classification

ILVEN is a condition that normally only affects one side of the body (unilateral). Usually the left side of patients is affected. The condition is persistent and forms along characteristic lines. It usually appears on an extremity in infancy or childhood. Altman and Mehregan described six characteristic features of ILVEN: (1) early age of onset, (2) predominance in females (4:1 female-male ratio), (3) frequent involvement of the left leg, (4)

pruritus Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

, or "itchiness" (5) marked refractoriness to therapy, and (6) a distinctive psoriasiform and inflammatory histologic appearance.

Genetics

Most cases are sporadic, but a familial case, with the condition occurring in a mother and her daughter, has been described. It also has been proposed that activation of an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...

lethal mutation that survives by mosaicism may be the cause of the lesions. The mutated cells may survive in the due to proximity of normal cells. Another theory is that retrotransposable elements may be the cause of all skin conditions along the Lines of Blashko. Some dogs have a coat variation based upon a similar mechanism. The classification of the disease has much to do with the appearance and location of the lesions (

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prop ...

characteristics). As this is a rare condition, it is possible that more than one genotype could cause a similar phenotype. Different genes have been implicated, but the number of patients studied in each case is very low. There is some evidence that interleukins 1 and 6, tumor necrosis factor α, and intercellular adhesion molecule-1 are upregulated in ILVEN, similar to psoriasis.

Histopathology

-The plaques are characterized histologically by

hyperkeratosis Hyperkeratosis is thickening of the stratum corneum (the outermost layer of the epidermis, or skin), often associated with the presence of an abnormal quantity of keratin,Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathologi ...

which is a thickening of the outer layer of skin. Hyperkeratosis is often associated with an abnormal amount of

keratin Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, ...

production. Also characteristic is moderate

acanthosis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rel ...

a thickening of the

stratum spinosum The stratum spinosum (or spinous layer/prickle cell layer) is a layer of the epidermis found between the stratum granulosum and stratum basale. This layer is composed of polyhedral keratinocytes. These are joined with desmosomes. Their spiny ( ...

with elongation of rete ridges. - Characteristic histologic feature is regular alternation of slightly raised parakeratotic areas without a granular layer ( hypogranulosis) and slightly depressed orthokeratotic areas with prominent granular layer ( hypergranulosis). Orthokeratotic hyperkeratosis is characterised by hyperkeratosis with non-nucleated cells. Parakeratotic hyperkeratosis is characterised by hyperkeratosis with nucleated cells. - The orthokeratotic area shows a basket-weave-pattern. - The dermis shows scattering of chronic inflammatory infiltrate (

Munro's microabscess Munro's microabscess is an abscess (collection of neutrophils) in the stratum corneum of the epidermis due to the infiltration of neutrophils from papillary dermis into the epidermal stratum corneum. They are a cardinal sign of psoriasis Psor ...

) sometimes giving a spongiform appearance. This is very similar to linear psoriasis, but it has been noted that the diseases are distinct entities by immunohistochemical analyses.

Immunohistochemistry

Patients with ILVEN with and without associated psoriasis, the number of Ki-67 positive nuclei, tended to be lower than is typically found in psoriasis. Additionally, the number of keratin-10 positive cells and HLA-DR expression was higher as compared to psoriasis. In ILVEN without associated psoriasis all T-cell subsets and cells expressing NK receptors were reduced as compared to psoriasis, except for CD45RA+ cells. In particular the density of CD8+, CD45RO+ and CD2+, CD94 and CD161 showed a marked difference between ILVEN without psoriasis and psoriasis itself. T cells relevant in the pathogenesis of psoriasis are markedly reduced in ILVEN without psoriasis as compared to psoriasis.

Treatment

Reported treatments include topical agents,

dermabrasion Dermabrasion is a type of surgical skin planing, generally with the goal of removing acne, scarring and other skin or tissue irregularities, typically performed in a professional medical setting by a dermatologist or plastic surgeon trained spe ...

cryotherapy Cryotherapy, sometimes known as cold therapy, is the local or general use of low temperatures in medical therapy. Cryotherapy may be used to treat a variety of tissue lesions. The most prominent use of the term refers to the surgical treatment, s ...

, laser therapy, and surgical excision. These therapies have a high failure rate because of incomplete relief of symptoms, scarring, or recurrence . Though similar in appearance, ILVEN will not respond to therapies known to affect psoriasis. ILVEN can be very difficult to live with but can be treated. The most effective method is full-thickness excision of the lesion. laser surgery can resurface the skin to give a flat, smoother and more normal appearance, but does not remove the lesion.

History

The condition later known as ILVEN was first described by Paul Gerson Unna in 1896. ILVEN appears very similar to

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complet ...

. However, it was not until 1971 that the disorder was described and clearly defined as a distinct entity by Altman and Mehregan in a case study of 25 patients. The Dupre and Christol described histopathological criteria in 1977.

Epidemiology

ILVEN usually appears in infancy or early childhood. The condition is very rarely begun in adulthood. ILVEN occurs predominantly in females (female-male ratio, 4:1) with no racial predominance.

References

External links

{{Skin tumors, epidermis Epidermal nevi, neoplasms, and cysts