Comment
Presentation
Inflammatory linear verrucous epidermal nevus is a rare type of keratinocytic epidermal nevus4 that clinically presents as small, discrete, pruritic, scaly plaques coalescing into a linear plaque along the lines of Blaschko.9 Considerable pruritus and resistance to treatment are hallmarks of the disease.10 Histopathologically, ILVEN is characterized by alternating orthokeratosis and parakeratosis with a lack of neutrophils in an acanthotic epidermis.11-13 Inflammatory linear verrucous epidermal nevus presents at birth or in early childhood. Adult onset is rare.9,14 Approximately 75% of lesions present by 5 years of age, with a majority occurring within the first 6 months of life.15 The differential diagnosis includes linear psoriasis, epidermal nevi, linear lichen planus, linear verrucae, linear lichen simplex chronicus, and mycosis fungoides.4,11
Differentiation From Psoriasis
Despite the histopathologic overlap with psoriasis, ILVEN exhibits fewer Ki-67-positive keratinocyte nuclei (proliferative marker) and more cytokeratin 10-positive cells (epidermal differentiation marker) than psoriasis.16 Furthermore, ILVEN has demonstrated fewer CD4−, CD8−, CD45RO−, CD2−, CD25−, CD94−, and CD161+ cells within the dermis and epidermis than psoriasis.16
The clinical presentations of ILVEN and psoriasis may be similar, as some patients with linear psoriasis also present with psoriatic plaques along the lines of Blaschko.17 Additionally, ILVEN may be a precursor to psoriasis. Altman and Mehregan1 found that ILVEN patients who developed psoriasis did so in areas previously affected by ILVEN; however, they continued to distinguish the 2 pathologies as distinct entities. Another early report also hypothesized that the dermoepidermal defect caused by epidermal nevi provided a site for the development of psoriatic lesions because of the Koebner phenomenon.18
Patients with ILVEN also have been found to have extracutaneous manifestations and symptoms commonly seen in psoriasis patients. A 2012 retrospective review revealed that 37% (7/19) of patients with ILVEN also had psoriatic arthritis, cutaneous psoriatic lesions, and/or nail pitting. The authors concluded that ILVEN may lead to the onset of psoriasis later in life and may indicate an underlying psoriatic predisposition.19 Genetic theories also have been proposed, stating that ILVEN may be a mosaic of psoriasis2 or that a postzygotic mutation leads to the predisposition for developing psoriasis.20
Treatment
Inflammatory linear verrucous epidermal nevus frequently is refractory to treatment; however, the associated pruritus and distressing cosmesis make treatment attempts worthwhile.11 No single therapy has been found to be successful in all patients. A widely used first-line treatment is topical or intralesional corticosteroids, with the former typically used with occlusion.13 Other treatments include adalimumab, calcipotriol,22,23 tretinoin,24 and 5-fluorouracil.24 Physical modalities such as cryotherapy, electrodesiccation, and dermabrasion have been reported with varying success.15,24 Surgical treatments include tangential25 and full-thickness excisions.26
The CO2 laser also has demonstrated success. One study showed considerable improvement of pruritus and partial resolution of lesions only 5 weeks following a single CO2 laser treatment.5 Another study showed promising results when combining CO2 pulsed laser therapy with fractional CO2 laser treatment.6 Other laser therapies including the argon27 and flashlamp-pumped pulsed dye lasers8 have been used with limited success. The use of light therapy and lasers in psoriasis have now increased the treatment options for ILVEN based on the rationale of their shared histopathologic characteristics. Photodynamic therapy also has been attempted because of its successful use in psoriasis patients. It has been found to be successful in diminishing ILVEN lesions and associated pruritus after a few weeks of therapy; however, treatment is limited by the associated pain and requirement for local anesthesia.28
The excimer laser is a form of targeted phototherapy that emits monochromatic light at 308 nm.29 It is ideal for inflammatory skin lesions because the UVB light induces apoptosis.30 Psoriasis lesions treated with the excimer laser show a decrease in keratinocyte proliferation, which in turn reverses epidermal acanthosis and causes T-cell depletion due to upregulation of p53.29,31 This mechanism of action addresses the overproliferation of keratinocytes mediated by T cells in psoriasis and contributes to the success of excimer laser treatment.31 A considerable advantage is its localized treatment, resulting in lower cumulative doses of UVB and reducing the possible carcinogenic and phototoxic risks of whole-body phototherapy.32
One study examined the antipruritic effects of the excimer laser following the treatment of epidermal hyperinnervation leading to intractable pruritus in patients with atopic dermatitis. The researchers suggested that a potential explanation for the antipruritic effect of the excimer laser may be secondary to nerve degeneration.33 Additionally, low doses of UVB light also may inhibit mast cell degranulation and prevent histamine release, further supporting the antipruritic properties of excimer laser.34
In our patient, failed treatment with other modalities led to trial of excimer laser therapy because of the overlapping clinical and histopathologic findings with psoriasis. Excimer laser improved the clinical appearance and overall texture of the ILVEN lesions and decreased pruritus. The reasons for treatment success may be two-fold. By decreasing the number of keratinocytes and mast cells, the excimer laser may have improved the epidermal hyperplasia and pruritus in the ILVEN lesions. Alternatively, because the patient had ILVEN lesions since infancy, psoriasis may have developed in the location of the ILVEN lesions due to koebnerization, resulting in the clinical response to excimer therapy; however, she had no other clinical evidence of psoriasis.
Because of the recalcitrance of ILVEN lesions to conventional therapies, it is important to investigate therapies that may be of possible benefit. Our novel case documents successful use of the excimer laser in the treatment of ILVEN.
Conclusion
Our case of ILVEN in a woman that had been present since infancy highlights the disease pathology as well as a potential new treatment modality. The patient was refractory to first-line treatments and was concerned about the cosmetic appearance of the lesions. The patient was subsequently treated with a trial of a 308-nm excimer laser with clinical improvement of the lesions. It is possible that the similarity of ILVEN and psoriasis may have contributed to the clinical improvement in our patient, but the mechanism of action remains unknown. Due to the paucity of evidence regarding optimal treatment of ILVEN, the current case offers dermatologists an option for patients who are refractory to other treatments.