Neue Erkenntnisse zum Thema Ichthyose^[*]

Zusammenfassung

Ichthyosen umfassen eine ätiologisch heterogene Gruppe von Verhornungsstörungen, die die gesamte Haut betreffen und durch sichtbare Schuppung und Verdickung der Hornhaut charakterisiert sind. Häufig besteht zusätzlich ein Erythem. Neben der Unterteilung in kongenital und nicht-kongenital unterscheidet man isolierte Ichthyosen, wie die X-chromosomal rezessive Ichthyose oder lamelläre Ichthyose, von Ichthyose-Syndromen, wie das Comèl-Netherton- oder Sjögren-Larsson-Syndrom. Kongenitale Ichthyosen sind selten und manifestieren sich unter dem Bild eines Kollodiumbabys oder als kongenitale ichthyosiforme Erythrodermie. In den letzten Jahren wurden erneut wichtige Meilensteine der Ichthyoseforschung passiert, z. B. die molekulargenetische Aufklärung der Harlekin-Ichthyose und Ichthyosis vulgaris. Trotz meist fehlender kausaler Therapiemöglichkeit stellt die verbesserte Diagnostik einen großen Gewinn für Betroffene dar. Darüber hinaus existieren mannigfache symptomatische Therapieoptionen. Hilfreiche Organisationen in Deutschland stellen die Selbsthilfe Ichthyose e. V. (www.ichthyose.de) und das Netzwerk für Ichthyose und verwandte Verhornungsstörungen (NIRK) (www.netzwerk-ichthyose.de) dar.

Summary

Ichthyoses comprise a heterogeneous group of cornification disorders which affect the entire skin and are characterized by visible scaling and a thickening of the stratum corneum. In addition, in many cases an erythema of the skin can be seen. From a nosologic point of view it is useful to distinguish congenital from non-congenital types and to separate isolated types of ichthyosis such as X-linked recessive ichthyosis or lamellar ichthyosis from ichthyosis syndromes such as Comèl-Netherton or Sjögren-Larsson syndrome. Congenital ichthyoses are uncommon and present at birth either the features of collodion baby or those of congenital ichthyosiform erythroderma. Recently, new molecular genetic insights were obtained in Harlequin ichthyosis and in ichthyosis vulgaris. Although in the vast majority of cases a causative therapy is still lacking, advances in the molecular and biochemical diagnosis clearly benefit those persons who are affected by ichthyosis. Moreover, manifold symptom relieving therapy options exist. In Germany, structures that provide help with diagnosis and management of these rare disorders are the patient organization Selbsthilfe Ichthyose e. V. (www.ichthyose.de) and the network for ichthyoses and related keratinization disorders (NIRK) (www.netzwerk-ichthyose.de).

Schlüsselwörter

Genetik - Ichthyose - Verhornungsstörung - Erythem

Keywords

Genetics - ichthyosis - cornification disorder - erythema

^* Wir widmen diese Arbeit unserem langjährigen Freund und Kollegen Prof. Dr. med. Wolfgang Küster, der unerwartet am 24. Juli 2006 verstorben ist.

• Literatur

• 1 Akiyama M. Harlequin ichthyosis and other autosomal recessive congenital ichthyoses: The underlying genetic defects and pathomechanisms. J Dermatol Sci 2006; 42: 83-9.
• 2 Chavanas S, Bodemer C, Rochat A. et al. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet 2000; 25: 141-2.
• 3 Eckl KM, Krieg P, Kuster W. et al. Mutation spectrum and functional analysis of epidermis-type lipoxygenases in patients with autosomal recessive congenital ichthyosis. Hum Mutat 2005; 26: 351-61.
• 4 Has C, Bruckner-Tuderman L, Muller D. et al. The Conradi-Hunermann-Happle syndrome (CDPX2) and emopamil binding protein: novel mutations, and somatic and gonadal mosaicism. Hum Mol Genet 2000; 9: 1951-5.
• 5 Haug S, Braun-Falco M. Adeno-associated virus vectors are able to restore fatty aldehyde dehydrogenase-deficiency. Implications for gene therapy in Sjogren-Larsson syndrome. Arch Dermatol Res 2005; 296: 568-72.
• 6 Hernandez-Martin A, Gonzalez-Sarmiento R, De UP. X-linked ichthyosis: an update. Br J Dermatol 1999; 141: 617-27.
• 7 Kalinin AE, Kajava AV, Steinert PM. Epithelial barrier function: assembly and structural features of the cornified cell envelope. Bioassays 2002; 24: 789-800.
• 8 Kelsell DP, Norgett EE, Unsworth H. et al. Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. Am J Hum Genet 2005; 76 (05) 794-803.
• 9 Küster W. Ichthyoses: suggestions for an improved therapy. Deutsches Ärzteblatt 2006; 103: A-1484-9.
• 10 Lefevre C, Bouadjar B, Ferrand V. et al. Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. Hum Mol Genet 2006; 15: 767-76.
• 11 Lefevre C, Bouadjar B, Karaduman A. et al. Mutations in ichthyin, a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis. Hum Mol Genet 2004; 13: 2473-82.
• 12 Leung TF, Ma KC, Cheung LT. et al. A randomized, single-blind and crossover study of an amino acid-based milk formula in treating young children with atopic dermatitis. Pediatr Allergy Immunol 2004; 15: 558-61.
• 13 Muller FB, Huber M, Kinaciyan T. et al. A human keratin 10 knockout causes recessive epidermolytic hyperkeratosis. Hum Mol Genet 2006; 15: 1133-41.
• 14 Oji V, Hautier JM, Ahvazi B. et al. Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for a temperature-sensitive phenotype. Hum Mol Genet 2006; 15 (21) 3083-97.
• 15 Oji V, Traupe H. Ichthyoses: differential diagnosis and molecular genetics. Eur J Dermatol 2006; 16 (04) 349-59.
• 16 Palmer CN, Irvine AD, Terron-Kwiatkowski A. et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006; 38: 441-6.
• 17 Raghunath M, Hennies HC, Ahvazi B. et al. Selfhealing collodion baby: a dynamic phenotype explained by a particular transglutaminase-1 mutation. J Invest Dermatol 2003; 120: 224-28.
• 18 Raghunath M, Tontsidou L, Oji V. et al. SPINK5 and Netherton syndrome: novel mutations, demonstration of missing LEKTI, and differential expression of transglutaminases. J Invest Dermatol 2004; 123: 474-83.
• 19 Rothnagel JA, Traupe H, Wojcik S. et al. Mutations in the rod domain of keratin 2e in patients with ichthyosis bullosa of Siemens. Nat Genet 1994; 7: 485-90.
• 20 Smith FJ, Irvine AD, Terron-Kwiatkowski A. et al. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 2006; 38: 337-42.
• 21 Sprecher E, Ishida-Yamamoto A, Becker OM. et al. Evidence for novel functions of the keratin tail emerging from a mutation causing ichthyosis hystrix. J Invest Dermatol 2001; 116: 511-19.
• 22 Traupe H. The ichthyosis. A guide to clinical diagnosis, genetic counseling, and therapy. Berlin, Heidelberg: Springer Verlag; 1989
• 23 Wells RS, Kerr CB. Genetic classification of ichthyosis. Arch Dermatol 1965; 92: 1-6.