Inflammatory Linear Verrucous Research Articles

Extensive, Adolescent-Onset Inflammatory Linear Verrucous Epidermal Nevus – Treated Successfully with Oral Retinoids

Extensive, Adolescent-Onset Inflammatory Linear Verrucous Epidermal Nevus – Treated Successfully with Oral Retinoids

Dermoscopy of Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects Nevus with Unilateral Limb Defects

Here, we report the dermoscopic findings of congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) nevus with left-sided ichthyosiform erythroderma and left upper-limb aplasia in a 4-month-old baby. The presence of ptychotropism and strict midline demarcation are unique features described in CHILD nevus. Dermoscopy of the CHILD nevus showed linear and dotted vessels with yellowish waxy scales on a pink background. These characteristic dermoscopic findings would also help us to differentiate it from inflammatory linear verrucous epidermal nevus.

Inflammatory linear verrucous epidermal nevus should be genotyped to direct treatment and genetic counseling

Inflammatory linear verrucous epidermal nevus should be genotyped to direct treatment and genetic counseling

O07 CHILD syndrome and ILVEN: disorders on the same spectrum?

Abstract Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects (CHILD syndrome) is a rare X-linked dominant disorder caused by hemizygous variants in the NSDHL gene. Typically, affected girls are born with unilateral skin lesions in a Blaschkoid distribution due to random X-inactivation, and ipsilateral limb reductions. We report a genetically confirmed case without significant limb reductions and consider the relationship of CHILD syndrome to inflammatory linear verrucous epidermal naevus (ILVEN) also sometimes caused by mosaic variants in NSDHL. A 9-month-old girl presented with extensive congenital red, scaly lesions in a Blaschkoid distribution confined to the right side of her body. Examination was otherwise normal apart from sensorineural deafness in the right ear and overlapping right 4th and 5th toes. Histology showed the characteristic foamy histiocytes of CHILD syndrome and genetic testing revealed a heterozygous pathogenic variant of NSDHL, c.262C>T p.(Arg88*) previously reported in CHILD syndrome. Patients clinically diagnosed with ILVEN but with NSDHL mutations have sometimes been reclassified as CHILD syndrome (König A et al. ILVEN encompasses a spectrum of inflammatory mosaic disorders. Am. J.Med.Genet. 2000;90:339-46). The histology of ILVEN is less specific than CHILD syndrome, without the characteristic foamy histiocytes. Nonetheless these conditions could be on a spectrum, with limb defects arising if mutant skin cells overlie the primitive limb bud (Moss C, Burn J. Hypothesis: CHILD+ILVEN=PEN or PENCIL J.Med.Genet. 1990;27:390-391). NSDHL controls cholesterol synthesis and the topical treatment with statins plus cholesterol effective in CHILD syndrome could be considered in some cases of ILVEN.

Inflammatory Linear Verrucous Epidermal Nevus – Rare Presentation in a Young Female

Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare variant of epidermal nevus characterized by psoriasiform epidermal hyperplasia, pruritic, warty lesions, in a linear configuration, following the lines of Blaschko. We report a rarer incidence of ILVEN in a young adult female presented with pruritic linear focally warty lesion over dorsum of right foot since birth. Histopathological examination of excision biopsy was suggestive of ILVEN. Although generally considered benign, 15-20% ILVEN cases can show malignant transformation. Despite variable treatment options, treatment is custom-made depending upon the nature and extent of the lesion. Therefore, the correct diagnosis of ILVEN is vital for choosing early and prompt treatment planning. Keywords: Adult, ILVEN, Female, Epidermal, Nevus

Epidermal nevi and epidermal nevus syndromes in pediatric practice

Epidermal nevi are hamartomas of ectodermal origin. Epidermal nevus syndromes are defined as the presence of an epidermal nevus with the involvement of other organ systems. Epidermal nevi are a manifestation of cutaneous mosaicism. Mosaicism may result from postzygotic somatic mutations. Epidermal nevi are usually located along the Blaschkos lines. There are organoid (sebaceous nevus, comedonic nevus, eccrine nevus) and non-organoid epidermal nevus (keratinocytic epidermal nevus, inflammatory linear verrucous epidermal nevus). Epidermal nevi can be combined with extracutaneous malformations: skeletal anomalies, neurological changes, eye defects, and then it can be related with epidermal nevus syndrome. The presence in a child of large epidermal nevi and nevi located on the face and scalp requires a multidisciplinary approach involving a pediatrician, neurologist, ophthalmologist and geneticist. Currently, several well-defined epidermal nevus syndromes characterized by organoid and non-organoid (keratocytic) nevi have been described: Schimmelpennings syndrome, phakomatosis pigmentosa, Beckers nevus syndrome, comedonal nevus syndrome, angora hairy nevus syndrome, Proteus syndrome, and CHILD syndrome (congenital hemidisplasia with ichthiosiform nevus and limb defects). Thus, follow-up of patients with epidermal nevus syndromes should be individualized and include a thorough history, clinical examination, and, if necessary, genetic testing. Typically, children with small, isolated epidermal nevus do not require further evaluation.

Linear Psoriasis: A Rare and Often Underdiagnosed form of Psoriasis in Children

Blaschko-linear psoriasis (PBL) is a rare form of psoriasis that presents as longitudinal lines on the skin, along Blaschko lines. This form of psoriasis is often observed in children and can be difficult to distinguish from other acquired Blaschko linear dermatoses such as inflammatory linear verrucous epidermal nevus (ILVEN) and lichen striatus. The prevalence of PBL is unknown, but it is generally observed in children and is more common in boys than in girls. The clinical and histological similarity of PBL to ILVEN presents a diagnostic challenge. In this case report, we present the case of a 7-year-old child with PBL and discuss the diagnostic and therapeutic aspects of this rare form of psoriasis. We were able to confirm the diagnosis of PBL after treatment with white petroleum jelly and salicylic acid petroleum jelly 5% resulted in a significant improvement of the lesions. Topical treatments, phototherapy, and systemic medications can be used in the case of PBL. It is important to select the most appropriate treatment based on the severity of the lesions, the location, and the patient's tolerance, and to keep in mind that PBL can have long-term effects on the quality of life of patients and their families.

An Unusual Presentation of Lichen Striatus.

An Unusual Presentation of Lichen Striatus.

Giant inflammatory linear verrucous epidermal nevus: difficulties in the management.

Giant inflammatory linear verrucous epidermal nevus: difficulties in the management.

262 The Role of Cholesterol in Rare Inflammatory Skin Disease

Inflammatory linear verrucous epidermal naevus (ILVEN) is a rare congenital disease characterised by Blaschko-linear erythematous scaly skin. It is highly pruritic, disfiguring, and notoriously treatment-resistant. The genetic basis is heterogeneous: causes so far established are a single case of GJA1- and two of CARD14- mosaicism. However, clinical overlap with the skin lesions of CHILD syndrome led us to hypothesise that there may be a common biological pathway abnormality in ILVEN skin centred on cholesterol metabolic pathways.

35376 Inflammatory linear verrucous epidermal nevi. A therapeutic proposal

Inflammatory linear verrucous epidermal nevi (ILVEN) represents around 6% of epidermal nevis, it is seen in infancy, more common in the lower extremities, and is characterized by linear psoriasiform plaques, following the Blaschko’s lines. A 6-year-old male presented with a linear erythematous-squamous plaque. It started at the age of 5 at the internal malleolus, accompanied by pain and itching. The patient had seen several doctors and used multiple treatments, without improvement. The plaque expanded during the last months difficulting use of footwear.

Inflammatory linear verrucous epidermal nevus (ILVEN) encompasses a spectrum of inflammatory mosaic disorders.

Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare skin disease characterized by pruritic erythematous scaly plaques distributed along the lines of Blaschko. Two cases of ILVEN with CARD14 mutations and one case with a GJA1 mutation have been previously reported. To elucidate the genetic cause of a cohort of patients diagnosed based on clinical and histopathological evaluation with ILVEN. We recruited patients diagnosed with ILVEN based on clinical and histopathological criteria. Exome sequencing of affected skin with or without blood/saliva was performed and germline and somatic pathogenic variants were identified. Five patients were enrolled. All had skin lesions from birth or early childhood. Two patients developed psoriasis vulgaris after the diagnosis of ILVEN. The first had a germline heterozygous CARD14 mutation and a post-zygotic hotspot mutation in KRT10. The histopathologic evaluation did not show epidermolytic hyperkeratosis. The second had a post-zygotic hotspot mutation in HRAS. Her ILVEN became itchy once psoriasis developed. One patient was re-diagnosed with linear porokeratosis based on a germline mutation in PMVK and a post-zygotic second-hit mutation. Two patients were re-diagnosed with congenital hemidysplasia with ichthyosiform nevus and limb defect nevus based on germline NSDHL mutations. ILVEN is a clinical descriptor for a heterogenous group of mosaic inflammatory disorders. Genetic analysis has the potential to more precisely categorize ILVEN and permits pathogenesis-directed therapies in some cases.

Differences in clinical characteristics and lesion proteomics between inflammatory linear verrucous epidermal nevus and local verrucous epidermal nevus

BackgroundVerrucous epidermal nevus (VEN) are keratinocytic epidermal nevus that appear at birth or in early childhood. They exhibit a range of manifestations, depending on the patient's age. VEN are rarely encountered in clinical practice, and the systemic and comprehensive clinical characteristics of VEN have not been well investigated. Furthermore, the association between tandem mass tag (TMT)-based quantitative proteomics and the VEN phenotype is still unclear. ObjectivesThis study investigated the differences in the clinical characteristics and lesion proteomics between inflammatory linear VEN (ILVEN) and local VEN. MethodsThis retrospective study enrolled 125 patients with histopathologically diagnosed VEN who presented to our hospital between 2019 and 2021. We collected the clinical data of all patients with VEN using a self-designed questionnaire. The expression of proteins in VEN lesions was analyzed using TMT proteomics technology. ResultsIn total, there were 125 patients with VEN that were evaluated, including 67 (53.60%) patients with local VEN and 58 (46.40%) with ILVEN. No significant differences were found in sex, onset age, and lesion location between patients with local VEN and those with ILVEN (all P > 0.05). Significant differences were found in the onset site and pruritus scores between patients with ILVEN and those with local VEN (all P < 0.05). According to the TMT proteomics results, 89 proteins were up or downregulated with at least 1.3-fold (upregulated: 38, downregulated: 51; P < 0.05) in ILVEN lesions relative to VEN lesions. The top 10 differentially expressed proteins between ILVEN and local VEN lesions were OGN, NT5C3A, ADD1, OLFML1, DHRS1, CALML5, SAMHD1, SFRP2, SPRR1B, and SERPINB13. The upregulated proteins are mainly involved in neutrophil activation, neutrophil-mediated immunity, and p53 signaling pathway (hsa04115). The downregulated proteins are mainly involved in cellular response to cytokine stimulus, cell adhesion, Th1 and Th2 cell differentiation. In total, based on the differentially expressed proteins between ILVEN and local VEN, five pathways that may be associated with the pathogenesis of inflammation, including CAMs (P = 0.006), Th1 and Th2 cell differentiation (P = 0.017), PPAR signaling pathway (P = 0.023), Th17 cell differentiation (P = 0.024), and p53 signaling pathway (P = 0.041). ConclusionsClinical data of the patients revealed that ILVEN lesions presented with intense pruritus and inflammatory change. Differentially expressed proteins between ILVEN and local VEN are mainly involved in multiple inflammation related pathways associated with the pathogenesis mechanisms of pruritus. LimitationsThe small sample size in clinical characteristic and proteomics study is one of the most significant limitations in our study. The inflammation associated proteins and signal pathways in the pathogenesis of pruritus in ILVEN is not explored. SignificanceIn this study, we found the lesions of ILVEN patients presented with intense pruritus and inflammational change. A total of 89 proteins were up or downregulated with at least 1.3-fold (upregulated: 38, downregulated: 51; P < 0.05) in ILVEN lesions relative to VEN lesions. On the other hand, the etiology of itch in ILVEN mainly associated with inflammation, but the exact mechanisms was still unclear. We found the differentially expressed proteins between ILVEN and local VEN enriched five pathways that may be associated with the pathogenesis of inflammation and pruritus.

Benign skin neoplasms in children

There are many different types of skin neoplasms in children and most are benign. Dermatologists should be able to differentiate between the various types of benign skin neoplasms and be able to recommend optimal treatment to concerned patients. Surgical removal of benign skin neoplasms is often the only treatment option. The aim of this paper is to provide a general overview of epidermal lesions (e.g., inflammatory linear verrucous epidermal nevus [ILVEN], nevus sebaceous), tumors of the epidermal appendages (e.g. pilomatrixoma), cutaneous neoplasms (e.g. angiofibroma), fibromatoses (e.g., knuckle pads), tumors comprised of fat, muscle, or bone tissue (e.g., osteoma cutis, subungual exostosis), epidermal cysts and pseudocysts, and pathologic fibrosis reactions after dermal injury (keloid). Scientific data are scarce and only in the last decade has it been possible to perform histopathological examinations and genetic studies together with detailed phenotyping to gain new understanding of the pathogenetic mechanisms.

Verrucous epidermal nevus: diagnostic difficulties.

Along Blachko’s lines are distributed diseases with Mendelian inheritance such as incontinentia pigmenti, polygenic hereditary diseases such as psoriasis or atopic dermatitis (3), nevi such as verrucous epidermal nevus (VEN) and its inflammatory variant (1), and acquired diseases such as lichen striatus (LS). All these diseases share a condition of mosaicism, that is, they presuppose the existence of a gene mutation, often post-zygotic, that gives rise to a clone of cells different from all the others. The type of mutated gene is responsible for the different morphology of these diseases, but the distribution on the skin of the mutated clone is always the same; therefore, it does not depend on the gene, but on the time in which the mutation occurred and on the stereotyped movements of the migrations that skin cells undergo during fetal life. If the nevus is very extensive and therefore secondary to an early mutation, other organs may be involved such as the nervous system, the eye, the skeletal system, as happening in epidermal nevus syndrome (4) or even some gonadal cells with the risk that the mutation is transmitted to the zygote of the offspring thus giving rise to a generalized inherited disease (5). VEN is usually present at birth; when it is localized in hidden locations or when it initially manifests with just hyperpigmented lesions it may become evident later. However, it is exceptional that it manifests itself at 8 years as in the present case. Its earliness and its morphology are able in most cases to easily differentiate it from an acquired inflammatory condition such as LS. LS is a self-healing inflammatory skin disease, usually asymptomatic, which affects the first years of age, usually between 5 and 15 years, and is distributed linearly along Blaschko’s lines, suggesting that on the line in which it occurs there is a clone of mutated cells as a result of a post-zygotic mutation: this mutation would give the cells involved a particular susceptibility towards an exogenous agent that, upon its arrival, would cause the transient inflammatory reaction (2). There are various hypotheses on the pathogenetic mechanisms that lead to the inflammatory reaction and its spontaneous regression. The present case has posed problems of differential diagnosis between VEN and LS. The histological findings were not able to eliminate the clinical doubt, indeed they added another possible differential diagnosis, i.e. inflammatory linear verrucous epidermal nevus. The latter diagnosis was discarded due to the lack of itching and obvious clinical signs of inflammation. Only prolonged clinical observation over time resolved the diagnostic doubt thanks to the persistence of the lesions and the greater evidence of papillomatous and warty structures.

25959 Clinical and histopathologic evolution of inflammatory linear verrucous epidermal nevus in a pediatric patient

An 11-year-old girl presented with lines of “pink bumps” down her right arm, which first appeared 2 years prior and had worsened over the preceding 2-3 months. The lesions were intensely pruritic. She denied exposures or trauma to the area. She reported a history of asthma, seasonal allergies, and eczema. Physical examination revealed 50 4- to 9-mm pink-brown, flat-topped erythematous and scaly papules arranged linearly following a Blaschkoid distribution along the right dorsolateral arm, forearm, and wrist. Punch biopsy demonstrated superficial and deep perivascular and perieccrine lymphocytic inflammation, suggestive of lichen striatus (LS), which correlated with the initial clinical presentation. The patient was counseled regarding the self-limited nature of LS; however, she remained symptomatic for 2 more years with minimal response to topical or intralesional steroids. The papules became more verrucous and inflammatory, and this change, coupled with the lack of expected resolution, led to rebiopsy. Histopathology revealed areas of parakeratosis overlying an absent granular layer alternating with orthokeratosis overlying a thickened granular layer, a pattern indicative of inflammatory linear verrucous epidermal nevus (ILVEN). ILVEN is a rare form of congenital epidermal nevus that, unlike LS, may be characterized by a chronic, progressive course. Early ILVEN can mimic LS and linear hyperkeratotic lesions including linear psoriasis, linear lichen planus, and linear verruca. This case highlights the clinical and histopathological evolution of ILVEN and emphasizes the importance of subsequent biopsies for definitive diagnosis in refractory cases. Recognition of ILVEN points clinicians toward alternative treatments, including laser therapy, which is currently under consideration.

Molecular Genetic Dissection of Inflammatory Linear Verrucous Epidermal Naevus Leads to Successful Targeted Therapy

Molecular Genetic Dissection of Inflammatory Linear Verrucous Epidermal Naevus Leads to Successful Targeted Therapy

Dermatoscopic and confocal microscopy features of widespread inflammatory linear verrucous epidermal nevus.

article: Dermatoscopic and confocal microscopy features of widespread inflammatory linear verrucous epidermal nevus - Italian Journal of Dermatology and Venereology 2022 February;157(1):117-8 - Minerva Medica - Journals

Bilateral Systematized Inflammatory Linear Verrucous Epidermal Nevus Treated with Topical and Systemic Retinoids: A Case Report

Bilateral Systematized Inflammatory Linear Verrucous Epidermal Nevus Treated with Topical and Systemic Retinoids: A Case Report

A Rare Case of Bilateral Inflammatory Linear Verrucous Epidermal Nevus

Inflammatory linear verrucous epidermal nevus (ILVEN) is rare, mosaicism-induced linear inflammatory dermatoses with early childhood presentation and persistence for whole life in majority of cases. No definite gene or genetic locus has been nominated yet. Treatment is mostly aimed for relief of symptoms and for cosmetic concerns.Here, authors are reporting a case of 6-year-old girl presented with history of extremely pruritic, erythematous, linear plaques following the lines of Blaschko over all 4 limbs, trunk and flexures since infancy.Clinical impression of bilateral ILVEN was confirmed by histopathology. No systemic abnormality was detected.Bilateral ILVEN is extremely rare entity and it should be documented whenever encounter.