Successful Amelioration of Inflammatory Linear Verrucous Epidermal Nevus with Topical Sirolimus

Dear Editor:

Inflammatory linear verrucous epidermal nevus (ILVEN) is distinctive type of epidermal nevus characterized by intensely pruritic linear confluent, scaly, erythematous papules and plaques. For diagnosis, Altman and Mehregan clinical criteria is used which includes early age of onset, 4:1 female preponderance, frequent involvement of left lower extremity, pruritus, inflammatory linear appearance following the lines of blaschko and persistent lesions showing marked refractoriness to treatment. Similarly for histological diagnosis, Dupre and Cristol criteria mentioning hypergranulosis and parakeratosis alternating with hypogranulosis and orthokeratosis is utilized. This entity is quite resistant to various therapies including topical & intralesional steroids, topical retinoids and cryotherapy¹. Eighteen years old female presented to department of dermatology with complaint of skin lesion over right hand which had been present since her infancy. Lesion has gradually developed significant redness and itching over a period of last 8 years. On examination well defined erythematous, dry, scaly plaque involving palmer aspect of right hand with involvement of index finger, base of middle finger, ring finger and little finger. Associated reducible Swan-Neck flexure deformity of ring finger was also present (Fig. 1A, 2A; patient's consent for publication of images was obtained). Potassium hydroxide mount of skin scrapping was negative for any fungal element. There was no associated systemic finding. Skin biopsy from lesion revealed psoriasiform hyperplasia with alternating parakeratosis and orthokeratosis and focal hypogranulosis. Papillary dermis showing dilated tortuous capillaries with band like lymphohistocytic infiltrate (Fig. 2B, C).

Fig. 1. (A) Inflammatory linear verrucous epidermal nevus involving right palm with reducible ‘Swan-neck’ deformity of ring finger. (B) Remarkable amelioration of skin lesion 3 months post starting topical sirolimus.

Fig. 2. (A) X-ray of involved hand ruling out underlying bone or joint involvement. (B, C) Findings of skin biopsy showing characteristic feature of inflammatory linear verrucous epidermal nevus (B: H&E, ×4; C: H&E, ×10).

Based on clinical and histological findings diagnosis of ILVEN was made. Patient was not willing for any ablative procedure; previous medical records showed poor response to topical steroid, retinoid and calcipotriol. Patient was offered off label use of topical sirolimus after written consent for off label use. Based on previously published reports, topical sirolimus 0.4% was prepared by mixing 40 crushed tablets of 1 mg sirolimus with 10 g white petrolatum ointment². Patient was advised to apply 1 finger tip unit uniformly over lesion once in the evening at least 3 hours before retiring to bed and to be kept overnight. Patient was advised to avoid any work from affected hand for at least 3 hours after application. Four weeks post initiation of topical sirolimus patient achieved significant improvement in itching and skin lesion. There was remarkable amelioration of itching and skin lesion 3 months post starting topical sirolimus (Fig. 1B). At the time of writing of this report patient is under regular monthly follow-up, frequency of application of topical sirolmus has been reduced to twice a week after initial 3 months and she is maintaining clinical remission. Patient had no local or systemic adverse event throughout treatment and follow up period. Sirolimus is inhibitor of mammalian target of rapamycin protein which has antiproliferative, antiangiogenic and immunosuppressive action³. Sirolimus down regulates T cell proliferation and thereby various cytokine production. There is evidence of role of interleukin (IL)-1,6 and tumor necrosis factor (TNF) alpha in ILVEN⁴. Of late topical sirolimus is increasingly being tried in infantile haemangiomas⁵, epidermal nevus⁶ and genodermatoses like facial angiofibromas of tuberous sclerosis⁷, plantar keratoderma of pachyonychia congenita. Antiproliferative, down regulation of T cell proliferation and resultant decrease in proinflammatory cytokines (IL-1,6 and TNF-α) could be mechanism behind excellent response of topical sirolimus in our patient. Topical sirolimus has opened up a new avenue in management of difficult to treat dermatological disorders and further detailed study can provide promising future treatment option for ILVEN. Limited published literature is available for effect of sirolimus on ILVEN, our experience is based on single case report, large case series or randomized controlled study is required to draw more robust scientific inference.

DATA SHARING STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.