Inflammatory linear verrucous epidermal nevus

Last updated
Inflammatory linear verrucous epidermal nevus
Other namesILVEN
Inflammatory verrucous linear epidermal nevus.jpg
Verrucous linear plaque following the lines of Blaschko over the right upper arm of a young girl
Usual onsetLVEN usually presents in childhood, typically within the first 6 months of life. Rare onset in adulthood has also been reported
DurationChronic
Causes Somatic mutations in keratinocyte precursor cells during embryogenesis
Diagnostic method Clinical findings, histopathological examination for confirmation
Differential diagnosis linear psoriasis, lichen striatus, linear porokeratosis, Incontinentia pigmenti
PreventionNone
Treatment surgical removal, laser ablation, cryotherapy, skin grafts
Medication retinoids, corticosteroids or calcipotriol
Prognosis Rarely, can become cancerous if not removed (for example, basal cell carcinoma or squamous cell carcinoma)

Inflammatory Linear Verrucous Epidermal Nevus (ILVEN) is an uncommon skin (cutaneous) disorder characterized by itchy (pruritic), red (erythematous) and raised (hyperkeratotic) plaques that follow the lines of skin cell development (Blaschko lines). The rash typically presents in infancy or early childhood, with a female predominance and most frequently affects the lower limbs. ILVEN is caused by somatic mutations during the embryonic stage that results in visible genetic mosaicism. [1] [2] [3] There is no cure, but different medical treatments can alleviate the symptoms.

Contents

The plaques can vary significantly, but tend to be slightly warty (psoriaform) or scaly (eczema-like).

Mosaicism

Initially, ILVEN was regarded as a distinct disease, which was diagnosed by the "warty" appearance (psoriaform epidermal hyperplasia with orthokeratosis and parakeratosis), and the number of lymphocytes invading the tissue (perivascular lymphocytic infiltrate), as well as the tendency of these plaques to roughly follow lines on the skin.

However, it is now recognized that the disease arises from a collection of different molecular mechanisms, but look similarly with overlapping clinical features. [4] [5]

Appearance

ILVEN typically affects one side of the body (unilateral) which is 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, or "itchiness" (5) marked refractoriness to therapy, and (6) a distinctive psoriasiform and inflammatory histologic appearance. [6]

Genetics

ILVEN is increasingly understood as a mosaic inflammatory disorder caused by post-zygotic (somatic) mutations in keratinocyte-related genes.

Recent genomic reports have implicated mutations in genes including GJA1 (connexin 43) and CARD14 among others; however, the genetic landscape is heterogeneous and research is evolving.

The molecular findings help explain phenotypic overlap with other inflammatory disorders.

Most cases are sporadic, but a familial cases do exis, with the condition occurring in a mother and her daughter. Another case was described in a father and son. [7]

It also has been proposed that activation of an autosomal dominant 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. [8]

Associated Mutations

Histopathology

-The plaques are characterized histologically by hyperkeratosis which is a thickening of the outer layer of skin. Hyperkeratosis is often associated with an abnormal amount of keratin production. Also characteristic is moderate acanthosis a thickening of the stratum spinosum with elongation of rete ridges.[ citation needed ]

- 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) 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. [23]

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. [23] 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, cryotherapy, laser therapy, and surgical excision. These therapies have a high failure rate because of incomplete relief of symptoms, scarring, or recurrence [ citation needed ].

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. [24] CO2 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. [25] ILVEN appears very similar to psoriasis. 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. [6] The Dupre and Christol described histopathological criteria in 1977. [26]

Prognosis and complications

ILVEN is benign but chronic as the lesions usually persist long-term.

Pruritus can be severe and impair quality of life.

Rarely, ILVEN can be part of an epidermal nevus syndrome with extracutaneous abnormalities (skeletal, neurologic, ocular). Such associations are uncommon but reported and warrant assessment when lesions are extensive or accompanied by developmental findings.

Malignant transformation is rare in young children, but there are isolated case reports of adnexal tumors or other neoplasms arising in longstanding epidermal nevi. Vigilance for new changes (ulceration, rapid growth) is prudent. [10]

See also

References

  1. ↑ Happle, R. (1995). "What is a nevus? A proposed definition of a common medical term". Dermatology. 191 (1): 1–5. doi:10.1159/000246468. PMID   8589475.
  2. ↑ Odom, Richard B.; Davidsohn, Israel; James, William D.; Henry, John Bernard; Berger, Timothy G.; Dirk M. Elston (2006). Andrews' diseases of the skin: clinical dermatology. Saunders Elsevier. ISBN   0-7216-2921-0.
  3. ↑ Freedberg; et al. (2003). Fitzpatrick's Dermatology in General Medicine (6th ed.). McGraw-Hill. ISBN   0-07-138076-0.
  4. ↑ https://doi.org/10.1111/jdv.70098
  5. ↑ Inflammatory linear verrucous epidermal nevus: A paradigm of progress Heymann, Warren R. Journal of the American Academy of Dermatology, Volume 90, Issue 6, 1159 - 1160
  6. 1 2 Altman J, Mehregan AH (1971). "Inflammatory linear verrucose epidermal nevus". Arch. Dermatol. 104 (4): 385–389. doi:10.1001/archderm.1971.04000220043008.
  7. 1 2 Guo BR, Cai HB, Zong WK, Li CS, Liu LZ, Qiao S, et al. A heterozygous mutation in GJA1 gene in Chinese family with serious erythrokeratodermia variabilis et progressive. Chin Med J (Engl). 2019; 132(1): 86–88.
  8. ↑ Happle, R. (2002). "Transposable elements and the lines of Blaschko: a new perspective". Dermatology. 204: 4–7. doi:10.1159/000051801.
  9. ↑ van Leersum FS, Seyger MMB, Theunissen TEJ, Bongers E, Steijlen PM, van Geel M. Recessive mosaicism in ABCA12 causes blaschkoid congenital ichthyosiform erythroderma. Br J Dermatol. 2020; 182(1): 208–211.
  10. 1 2 3 4 5 6 7 8 The evolving genetic landscape of ILVEN: A comprehensive review Marra Aghajani, Jessie Tong Lu, John W. Frew, Deshan F. Sebaratnam, First published: 09 October 2025 https://doi.org/10.1111/jdv.70098
  11. ↑ Wang M, Zhang S, Zheng G, Huang J, Songyang Z, Zhao X, et al. Gain-of-function mutation of Card14 leads to spontaneous psoriasis-like skin inflammation through enhanced keratinocyte response to IL-17A. Immunity. 2018; 49(1): 66–79.e5.
  12. ↑ Polubothu S, Riachi M, Stadnik P, Ogunbiyi O, Brändli-Wälchli R, Cullup T, Sebire N J, Pittman A, Kinsler VA. Inflammatory linear verrucous epidermal nevus should be genotyped to direct treatment and genetic counseling. Journal of the American Academy of Dermatology, Volume 90, Issue 6, 1279 - 1280
  13. ↑ Umegaki-Arao N, Sasaki T, Fujita H, Aoki S, Amagai M, Seishima M, et al. The identification of a postzygotic GJA1 mutation in a patient with an inflammatory linear verrucous epidermal nevus suggests that the disease is a mosaic of erythrokeratodermia variabilis et progressiva. J Invest Dermatol. 2017; 137(10 Suppl 2):S226.
  14. ↑ Atzmony L, Ugwu N, Hamilton C, Paller AS, Zech L, Antaya RJ, et al. Inflammatory linear verrucous epidermal nevus (ILVEN) encompasses a spectrum of inflammatory mosaic disorders. Pediatr Dermatol. 2022; 39(6): 903–907.
  15. ↑ Beyens A, Lietaer C, Claes K, De Baere E, Goeteyn M, Lerut B, et al. HRAS-related epidermal nevus syndromes: expansion of the spectrum with first branchial arch defects. Clin Genet. 2023; 103(6): 709–713.
  16. ↑ Li Z, Liu Q, Zhang F, Wang S. Successful treatment of generalized inflammatory linear verrucous epidermal nevus with a somatic mutation in KRT10 with crisaborole 2% ointment. Clin Exp Dermatol. 2025; 50: 1399–1402.
  17. ↑ Li H, Zuo J, Tang W. Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases. Front Pharmacol. 2018; 9:1048.
  18. ↑ Barney E, Prose NS, Ramirez M. Inflammatory linear verrucous epidermal nevus treated successfully with crisaborole ointment in a 5-year-old boy. Pediatr Dermatol. 2019; 36(3): 404–405.
  19. ↑ Garcia-Bravo B, Rodriguez-Pichardo A, Konig A, Grzeschik KH, Happle R, Camacho F. A new case of CHILD syndrome previously diagnosed as inflammatory linear verrucous epidermal nevus. Med Cutan Ibero Lat Am. 2002; 30(3): 120–125.
  20. ↑ Gantner S, Rütten A, Requena L, Gassenmaier G, Landthaler M, Hafner C. CHILD syndrome with mild skin lesions: histopathologic clues for the diagnosis. J Cutan Pathol. 2014; 41(10): 787–790.
  21. ↑ Kalmykova A, Lytvynenko B, Stovbyr A, Chepets O, Koshyk E. Different presentations of child syndrome. Am J Dermatopathol. 2020; 42(6):e80.
  22. ↑ Atzmony L, Lim YH, Hamilton C, Leventhal JS, Wagner A, Paller AS, et al. Topical cholesterol/lovastatin for the treatment of porokeratosis: a pathogenesis-directed therapy. J Am Acad Dermatol. 2020; 82(1): 123–131.
  23. 1 2 Vissers WH, Muys L, Erp PE, de Jong EM, van de Kerkhof PC (2004). "Immunohistochemical differentiation between inflammatory linear verrucous epidermal nevus (ILVEN) and psoriasis". Eur J Dermatol. 14 (4): 216–220.
  24. ↑ Binodini Behera; Basanti Devi; Bibhuti B Nayak; Bharti Sahu; Bhabani Singh & Manas R Puhan (2013). "Giant Inflammatory Linear Verrucous Epidermal Nevus: Successfully Treated with Full Thickness Excision and Skin Grafting". Indian J Dermatol. 58 (6): 461–463. doi: 10.4103/0019-5154.119959 . PMC   3827519 . PMID   24249899.
  25. ↑ Unna, Paul Gerson (1896). The Histopathology of the Diseases of the Skin. New York, NY: Macmillan.
  26. ↑ Dupre A, Christol B (1977). "Bilateral inflammatory linear verrucous epidermal nevus localized on the lip and with minimal histological lesions". Ann. Dermatol. Venereol. 104: 163–4.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.