Acta Dermato-Venereologica 99-3CompleteContent | Page 27

SHORT COMMUNICATION 345 Tazarotene 0.015% Cream as a Potential Topical Agent for Management of Ichthyosis in Dorfman- Chanarin Syndrome Luana NICULESCU 1 , Cristel RUINI 1 , Jerome SROUR 1 , Suzanna SALZER 1 , Ines SCHÖNBUCHNER 2 , Tanja VON BRAUNMÜHL 1 , Thomas RUZICKA 1 , Ulrich HOHENLEUTNER 3 , Kathrin A. GIEHL 1 , Judith FISCHER 4 and Andreas WOLLENBERG 1 * Department of Dermatology and Allergy, Ludwig Maximilian University, Frauenlobstr. 9-11, DE-80337 Munich, 2 Department of Human Genetics and 3 Department of Dermatology, University Medical Center Regensburg, Regensburg, and 4 Department of Human Genetics, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany. *E-mail: [email protected] 1 Accepted Nov 20, 2018; E-published Nov 21, 2018 Dorfman-Chanarin syndrome (DCS), known as neutral lipid storage disease with ichthyosis, is an autosomal re- cessive disorder caused by mutations in the ABHD5 gene responsible for triglyceride degradation (1, 2). Lipid dro- plets accumulate in various cells, including granulocytes, keratinocytes, hepatocytes, Schwann cells and epidermal Langerhans cells (3). Currently, there is no treatment for DCS and the management of symptoms and potential complications requires multidisciplinary coordination. Skin involvement is characterized by ichthyosiform non-bullous erythroderma, and adequate treatment poses a challenge to dermatologists. Various topical therapies, including emollients and keratolytic agents, have been proposed to improve ichthyosis, with mostly unsatisfac- tory results (4). While systemic therapy with retinoids has been used successfully in patients with ichthyosis, co-morbidities limit its use in DCS. We report here overall clinical improvement with local use of tazarotene 0.015% cream in a female patient with DCS manifesting with ichthyosis, hepatomegaly and cataracts. CASE REPORT An 18-year-old woman born to a consanguineous Kurdish family presented with a history of generalized congenital ichthyosis. Previous genetic testing revealed the homozygous mutation c.594dupC (p.Arg199Glnfs*11) in the ABHD5 gene, consistent with DCS (1). Furthermore, pathognomonic lipid droplets were identified in granulocytes by lipid-specific blood smear coloration. Topical therapy was initiated with tazarotene 0.015% cream (15 g tazarotene 0.1%, Zorac ®, EMRA-MED Arzneimittel GmbH (Trittau, Germany), diluted in 100 g cream base) on the face and left side of the body once daily. The patient was informed about the teratogenic potential of retinoids, and contraception during treatment was advised. As an internal control, the other half of the patient’s body was treated with emollient containing 10% urea in the same vehicle as the diluted tazarotene cream. The treatment was not blinded. Blood samples were taken prior to and 8 weeks after treatment. The liver enzymes, which were elevated prior to therapy, remained stable with no further increase. After 8 weeks, a clear delineation of the side treated with tazarotene 0.015% was evident. The left side had significantly less scaling than the right side treated with 10% urea, where skin findings were similar to baseline, and the patient observed sweating on the left side of her body (Fig. 1e). To assess these findings, transepidermal water loss (TEWL) was measured using TEWAMETER TM210 ® and stratum cor- neum hydration (SCH) using Corneometer ® 825 at baseline and 8 weeks after therapy. An increase in TEWL is seen in patients with a disrupted skin barrier, indicating increased water loss and decreased hydration of stratum corneum (4). The side treated with tazarotene showed lower TEWL and higher SCH values than the side treated with urea 10%, indicating overall improvement in skin barrier function following tazarotene treatment (Table SI 1 ). Optical coherence tomography (OCT), a non-invasive method to examine skin changes, was performed at baseline and after 8 weeks using VivoSight OCT ® , Firma Michelson Diagnostics Deutschland GmbH (Schwarzenbruck-Altenthann, Germany), which allows an imaging depth of approximately 1.5–2 mm (5). A coherent interpretation of the OCT image was performed by using histopathological images from a previous biopsy as a template. At baseline, OCT identified an abnormal hyper-reflective stratum corneum indicative of hyperkeratosis, an increased epidermal thickness, a thinned granular layer and papillomatosis, all consis- tent with the histopathology. Following treatment, OCT showed an absence of scales, normalization of the epidermal thickness and of the granular layers (Fig. 1a, b). The epidermal thickness decreased from 0.2094  ±  0.03560 mm to 0.1508  ±  0.03121 mm after 8 weeks of therapy (p < 0.0001) (6). After 8 weeks, urea 10% was stopped and tazarotene 0.015% cream was applied to the whole body. Follow-up after 13 months of topical therapy revealed satisfactory clinical improvement. DISCUSSION DCS is a disorder with many systemic implications. The most obvious is physical appearance, since patients have congenital erythrodermic ichthyosis (7, 8). Keratolytic agents were not considered as treatment options for our patient, due to side-effects following systemic absorption. Although the use of systemic retinoids has been reported in individual cases of DCS with satisfactory results and tolerability, concerns regarding worsening of the elevated liver enzymes precluded its use (7). Tazarotene is a retinoic acid that has shown favourable results in patients with ichthyosis when used topically in a 0.1% formulation. We diluted tazarotene to 0.015% and tested this formulation on half of the patient’s body. She reported good tolerability, which allowed for full adherence to therapy. While many authors have published their experience with different types of ichthyosis, this is the first report of topical tazarotene treatment in a patient with DCS (9, 10). Tazarotene is a retinoid that binds selectively to the RARß and RARγ receptors, mostly expressed in the epi- dermis. The rapid conversion of the hydrophobic prodrug tazarotene to the hydrophilic active metabolite tazarotenic acid ensures a low level of retinoid in the fatty tissue (11). https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3087 1 This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3087 Acta Derm Venereol 2019; 99: 345–346