Topical treatment of CHILD nevus and Sjögren-Larsson Syndrome with combined lovastatin and cholesterol

ARTICLE

ejd.2011.1549

Auteur(s) : Nayra Merino De Paz nayradepaz@hotmail.com, Marina Rodriguez-Martin, Patricia Contreras-Ferrer, Marta Garcia Bustinduy, Itamar Gonzalez Perera, Tirso Virgos Aller, Antonio Martin Herrera, Antonio Noda Cabrera

Hospital Universitario de Canarias, Ofra s/n La Cuesta, 38320 La Laguna, Spain

Ichthyoses are a large group of inherited disorders of cornification. Currently classification distinguishes syndromic versus non-syndromic forms. Treatments are mainly symptomatic [1].

Lipids are the main components of cell membranes and adequate proportions of ceramides, cholesterol and free fatty acids are necessary to form a competent barrier. The most recent pharmacological studies try to get substances to equilibrate or repair the lack of these lipid components on the stratum corneum (SC) [2, 3]. We present three cases of syndromic ichthyoses and their different responses to an experimental treatment.

A 22 year-old woman, with a clinical history of osseous malformations, was referred to our department to evaluate a linear lesion located on the upper right limb. She was first treated in Colombia with cryotherapy once a week for a year, with no improvement. There were no other family members affected. On physical examination, the patient showed a linear verrucous plaque with red-yellowish scales over an erythematous surface on the dorsum of the right hand and forearm. She presented a small plaque on the left hand with similar features (figure 1A). Histological examination showed hyperkeratosis, parakeratosis, acanthosis, perivascular lymphohistiocytic infiltrate and foamy histiocytes in dermal papillae (figure 1C , D). It was compatible with CHILD nevus. Complementary studies only revealed an 80% hearing loss on the right side. With these features CHILD Syndrome (Congenital Hemidysplasia with Ichthyosiform nevus and limb defects) was diagnosed. Genetic studies confirmed a compatible nonsense mutation in NSDHL gene (c.317C>A; p.S106X).

Two sisters, aged 31 and 27, with consanguineous parents, were referred to our Department to evaluate skin lesions present since birth. They associated the following neurological features: mental retardation and spastic diplegia. Sjögren Larsson Syndrome (SLS) was diagnosed by the Neurology Department. Physical examination showed generalized hyperkeratosis with fine grayish scales with focal accentuation, on the neck, abdominal folds and dorsum of both hands (figure 1E, G), with occasional pruritus. Cutaneous biopsies showed hyperkeratosis, papillomatosis, minimal acanthosis and mild dermal inflammatory infiltrate.

Lovastatin 2% and cholesterol 2% water solution used as foments during 10 minutes once a day was established. A great improvement was observed after three weeks in the CHILD patient (figure 1B). One year later the plaque had disappeared and only a slightly hyperpigmented macule remained. A slight improvement was observed in SLS after one month of treatment (figure 1F, H).

Here we describe two rare ichthyosiform syndromes with extracutaneous defects: CHILD and SSL. CHILD Syndrome is an X-linked dominant disorder. A loss of function of an enzyme in cholesterol biosynthesis located in the NSDHL gene is involved (3beta-hydroxysterol dehydrogenase). Fewer than fifty cases have been described in the literature. It is usually lethal in males. It mostly presents a right hemicorporal distribution. Our patient presented a mild affectation on the left side. The most characteristic cutaneous presentation is the CHILD nevus [3, 4].

SSL is a rare, autosomal recessive disorder characterized by ichthyosis, mental retardation and spastic diplegia or tetraplegia. SLS is caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase enzyme [5].

Ultrastructural studies of these diseases have revealed abnormal lipid inclusions in the cytoplasm of granular keratinocytes and in the SC. These changes could be secondary to pathway metabolite accumulation that may interfere with the formation of normal lamellar bodies [3, 6]. Cholesterol could improve the lipidic defect and lovastatin could avoid metabolite accumulation [3]. The treatment is more specific for the CHILD pathway defect, so better results were observed.

Cutaneous manifestations of syndromic ichthyoses with a lipid pathway mutation have a poor resolution with classic treatments. So, a cholesterol2%/lovastatin2% water solution could be a new option for these conditions.

Disclosure

Financial support: none. Conflicts of interest: none.

References

1. Oji V, Tadini G, Akiyama M, Blanchet Bardon C, et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Sorèze 2009. J Am Acad Dermatol 2010 ; 63 : 607-641.

2. Feingold KR, Man MQ, Proksch E, Menon GK, Brown BE, Elias P.M. The lovastatin-treated rodent: a new model of barrier disruption and epidermal hyperplasia. J Invest Dermatol 1991 ; 96 : 201-209.

3. Paller AS, van Steensel MA, Rodriguez-Martín M, et al. Pathogenesis-Based Therapy Reverses Cutaneous Abnormalities in an Inherited Disorder of Distal Cholesterol Metabolism. J Invest Dermatol 2011 [Epub ahead of print].

4. Happle R. The group of epidermal nevus syndromes: Part I. Well defined phenotypes. Journal of the American Academy of Dermatology. J Am Acad Dermatol 2010 ; 63 : 1-22.

5. Rizzo W.B. Sjögren-Larsson Syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab 2007 ; 90 : 1-9.

6. Rizzo WB, S’Aulis D, Jennings MA, et al. Ichthyosis in Sjögren-Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion. Arch Dermatol Res 2010 ; 302 : 443-451.