Inflammatory Linear Verrucous Epidermal Nevus and Epilepsy: Remission During Valproic Acid Therapy

January 2013 | Volume 12 | Issue 1 | Editorials | 18 | Copyright © January 2013

Laura Diluvio MDa, Elena Campione PhDa, Cristina Mordenti MDa, Valentina Bagnolo MDb, Caterina Cerminara MDb, Sergio Chimenti MDa, and Luca Bianchi MDa

aDepartment of Dermatology and bDepartment of Neuropsychiatry, University of Rome “Tor Vergata”, Rome, Italy

Inflammatory linear verrucous epidermal nevus (ILVEN) is an uncommon cutaneous disorder characterized by a linearly arranged psoriasiform eruption that mostly occurs during infancy.1 The diagnostic criteria are early age of onset, female predominance, frequent involvement of the left lower extremity, pruritus, distinctive inflammatory histological appearance, persistent lesions with disappointing therapeutic results.2 ILVEN is rarely described with endocrinologic, ocular, dermatologic, musculoskeletal, and neurologic abnormalities. We present the unexpected successful clearing of ILVEN during valproic acid (VPA) therapy in 2 children affected by epilepsy.
A 6-year-old Caucasian male without a familial or personal history of cutaneous disorders presented with a psoriasiform and pruritic eruption on his left upper extremity, consistent with a diagnosis of ILVEN. Moreover, he complained of high-frequency episodes of psychomotor arrest that lasted 10 to 15 seconds. The electroencephalogram showed diffuse discharges of generalized high-amplitude spikes and slow wave complexes, rhythmic at around 3 Hz, compatible with a diagnosis of absence epilepsy. VPA at 25 mg/kg/day brought total crisis remission. After the seizures were controlled, almost complete clearance of ILVEN, preceded by remission of the severe itching, could be surprisingly observed at 7 months of continuous VPA treatment. Any dermatological systemic or topical treatments had been otherwise proposed.
The second case concerns a 7-year-old Moldovan boy with a pruritic linear eruption on his dorsal left hand that aroused 1 year before and subsequently extended to the upper extremity. The patient was adopted, so there was no information available about his familial or personal medical history. No cutaneous or nail psoriatic features was observed. The diagnosis of ILVEN was proposed. Also this child was affected by epilepsy, which presented as psychomotor arrests many times a day, combined with eyelid myoclonia. The electroencephalogram confirmed the diagnosis of absence epilepsy.VPA (25 mg/kg/day) was prescribed and resulted in complete control of manifestations. A significant improvement of ILVEN was achieved after 6 months of VPA therapy, without the addition of any concomitant dermatological treatments.
The association of ILVEN with absence-type idiopathic generalized epilepsy is rare, and probably merely coincidental, but we noticed the therapeutic effect of antiepileptic VPA on the skin. The clinical and histological similarities between ILVEN and psoriasis are well-known. Indeed, patients previously diagnosed with linear psoriasis may actually have a diagnosis of ILVEN. Furthermore, ILVEN has been also reported with concomitant plaque-type psoriasis, leading to a suggestion that ILVEN may otherwise predispose to psoriasis. In particular, the typical histopathological features are characterized by epidermal acanthosis, elongated rete ridges and dermal papillae, alternating areas of hypergranulosis and hypogranulosis, orthokeratosis and parakeratosis, and a lymphocytic infiltrate in the upper dermis, all consistent with a psoriasiform appearance.3 In light of these findings, antipsoriatic agents have been proposed for ILVEN, with variable therapeutic results.4 Other possible treatments include corticosteroids, retinoids, podophyllin, cryotherapy, CO2 laser therapy, or dermabrasion.5
Recently, the antipsoriatic tumor necrosis factor (TNF)-α blockers have been successfully tested on ILVEN.6-7 Epilepsy comprises a group of neurological disorders characterized by periodic occurrence of spontaneous seizures. A potential contributor to the mechanism of epileptogenesis is an excessive glial activation and the associated increase in proinflammatory cytokine production, including interleukin (IL)-1β and TNF-α.8 VPA is an agent widely used in the treatment of seizure disorders. Interestingly, in vitro studies showed that VPA suppresses TNF-α and IL-6 production via nuclear factor (NF)-kB inhibition. The exact mechanism remains unknown, but this drug may modulate the binding of NF-kB to DNA during the nuclear translocation.9 Indeed, the pleiotropic cytokine TNF-α is one of the leading proinflammatory mediators in several inflammatory skin conditions such as psoriasis. Feily and Namazi recently speculated that VPA may be able to reduce the enhanced susceptibility to seizures and to significantly improve cutaneous plaques in patients simultaneously affected by epilepsy and psoriasis, outside from any dermatologic concomitant therapeutic protocol.10
The potential link between ILVEN and epilepsy remains elusive and is probably coincidental. We believe that the almost complete and stable clearing of the skin linear eruption during VPA therapy could be at least partially explained by the inhibitory effect of this drug on TNF-α production, a cytokine known to be elevated in epilepsy and in inflammatory psoriasiform skin conditions. This observation raises the debated