American Journal of Clinical Dermatology

, Volume 10, Issue 6, pp 351–364 | Cite as


Clinical Manifestations and Practical Treatment Options
  • Vinzenz Oji
  • Heiko Traupe
Therapy In Practice


Ichthyoses constitute a large group of cornification disorders that affect the entire integument. The skin is characterized by visible scaling and in many cases by inflammation, for example, in bullous/keratinopathic ichthyosis or Netherton syndrome. From the viewpoint of classification it is useful to distinguish nonsyndromic from syndromic types of ichthyosis. Ichthyosis vulgaris and recessive X-linked ichthyosis are common disorders—often of delayed onset, in contrast to congenital ichthyoses, which belong to the group of rare diseases and present at birth with either the features of collodion membrane or congenital ichthyosiform erythroderma.

The diagnostic steps are based on clinical data, analyses such as the steroid sulfatase activity test, skin biopsies, and genetic results. However, the dramatic increase in knowledge about the pathophysiology of these conditions has not led to a curative therapy so far. The therapeutic management is multidisciplinary and involves ichthyosis patient organizations in many countries. The mainstay of treatment remains with moisturizing creams containing, for example, urea, lactic acid and other humectants and keratolytics, regular bathing, and mechanical scale removal. Patients with lamellar ichthyosis or ichthyosiform erythroderma in particular profit from oral therapy with retinoids or retinoic acid metabolism-blocking agents.


Tazarotene Steroid Sulfatase Liarozole Netherton Syndrome Congenital Ichthyosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We are grateful to all our patients and to Selbsthilfe Ichthyose e.V., and want to thank Mrs Bückmann and Mr Wissel for help with the photographs. Our work is supported by the Network for Ichthyoses and Related Keratinization disorders (NIRK, Bundesministerium für Bildung und Forschung, GFGM01143901), the ichthyosis patient organization of Germany (Selbsthilfe Ichthyose e.V.), and the Foundation for Ichthyosis and Related Skin Types (F.I.R.S.T., North Wales, PA, USA). The authors have no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    Traupe H. The ichthyosis: a guide to clinical diagnosis, genetic counseling, and therapy. Berlin: Springer Verlag, 1989: 111–34Google Scholar
  2. 2.
    Oji V, Traupe H. Ichthyoses: differential diagnosis and molecular genetics. Eur J Dermatol 2006; 16: 349–59PubMedGoogle Scholar
  3. 3.
    Oji, V, Tadini, G, Akiyama, M, et al. Revised nomenclature and classification of inherited ichthyoses. Ichthyosis Consensus Conference; 2009 Jan 23-24; Sorèze [online]. Available from URL: [Accessed 2009 Sep 21]Google Scholar
  4. 4.
    Oji V. Update of themoderation process of the ichthyosis classification. Ichthyosis Consensus Conference; 2009 Jan 23-24; Sorèze [online]. Available from URL: [Accessed 2009 Sep 21].Google Scholar
  5. 5.
    Classification of congenital ichthyosis. First World Conference on Ichthyosis; 2007 Aug 31-Sep 2; MünsterGoogle Scholar
  6. 6.
    Elias PM, Williams ML, Holleran WM, et al. Thematic review series: skin lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism. J Lipid Res 2008; 49: 697–714Google Scholar
  7. 7.
    Schmuth M, Gruber R, Elias PM, et al. Ichthyosis update: towards a functiondriven model of pathogenesis of the disorders of cornification and the role of corneocyte proteins in these disorders. Adv Dermatol 2007; 23: 231–56PubMedCrossRefGoogle Scholar
  8. 8.
    DiGiovanna JJ. Ichthyosiform dermatoses: so many discoveries, so little progress. J Am Acad Dermatol 2004; 51: S31–4CrossRefGoogle Scholar
  9. 9.
    Wells RS, Kerr CB. Genetic classification of ichthyosis. Arch Dermatol 1965; 92: 1–6PubMedCrossRefGoogle Scholar
  10. 10.
    Wells RS, Jennings MC. X-linked ichthyosis and ichthyosis vulgaris: clinical and genetic distinctions in a second series of families. JAMA 1967; 202: 485–8PubMedCrossRefGoogle Scholar
  11. 11.
    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: 337–42PubMedCrossRefGoogle Scholar
  12. 12.
    Liao H, Waters AJ, Goudie DR, et al. Filaggrin mutations are genetic modifying factors exacerbating X-linked ichthyosis. J Invest Dermatol 2007; 127: 2795–8PubMedCrossRefGoogle Scholar
  13. 13.
    Webster D, France JT, Shapiro LJ, et al. X-linked ichthyosis due to steroidsulphatase deficiency. Lancet 1978; I: 70–2Google Scholar
  14. 14.
    Ballabio A, Parenti G, Carrozzo R, et al. Isolation and characterization of a steroid sulfatase cDNA clone: genomic deletions in patients with X-chromosome-linked ichthyosis. Proc Natl Acad Sci USA 1987; 84: 4519–23PubMedCrossRefGoogle Scholar
  15. 15.
    Hernandez-Martin A, Gonzalez-Sarmiento R, De Unamuno P. X-linked ichthyosis: an update. Br J Dermatol 1999; 141: 617–27PubMedCrossRefGoogle Scholar
  16. 16.
    Akiyama M, Sakai K, Sato T, et al. Compound heterozygous ABCA12 mutations including a novel nonsense mutation underlie harlequin ichthyosis. Dermatology 2007; 215: 155–9PubMedCrossRefGoogle Scholar
  17. 17.
    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: 794–803PubMedCrossRefGoogle Scholar
  18. 18.
    Lefevre C, Audebert S, Jobard F, et al. Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2. Hum Mol Genet 2003; 12: 2369–78PubMedCrossRefGoogle Scholar
  19. 19.
    Akiyama M, Sawamura D, Shimizu H. The clinical spectrum of nonbullous congenital ichthyosiform erythroderma and lamellar ichthyosis. Clin Exp Dermatol 2003; 28: 235–40PubMedCrossRefGoogle Scholar
  20. 20.
    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: 3083–97PubMedCrossRefGoogle Scholar
  21. 21.
    Raghunath M, Hennies HC, Ahvazi B, et al. Self-healing collodion baby: a dynamic phenotype explained by a particular transglutaminase-1 mutation. J Invest Dermatol 2003; 120: 224–8PubMedCrossRefGoogle Scholar
  22. 22.
    Harting M, Brunetti-Pierri N, Chan CS, et al. Self-healing collodionmembrane and mild nonbullous congenital ichthyosiform erythroderma due to 2 novel mutations in the ALOX12B gene. Arch Dermatol 2008; 144: 351–6PubMedCrossRefGoogle Scholar
  23. 23.
    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: 767–76PubMedCrossRefGoogle Scholar
  24. 24.
    Jobard F, Lefevre C, Karaduman A, et al. Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1. Hum Mol Genet 2002; 11: 107–13PubMedCrossRefGoogle Scholar
  25. 25.
    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: 2473–82PubMedCrossRefGoogle Scholar
  26. 26.
    Compton JG, DiGiovanna JJ, Santucci SK, et al. Linkage of epidermolytic hyperkeratosis to the type II keratin gene cluster on chromosome 12q. Nat Genet 1992; 1: 301–5PubMedCrossRefGoogle Scholar
  27. 27.
    Rothnagel JA, Dominey AM, Dempsey LD, et al. Mutations in the rod domains of keratins 1 and 10 in epidermolytic hyperkeratosis. Science 1992; 257: 1128–30PubMedCrossRefGoogle Scholar
  28. 28.
    Steijlen PM, Perret CM, Schuurmans Stekhoven JH, et al. Ichthyosis bullosa of Siemens: further delineation of the phenotype. Arch Dermatol Res 1990; 282: 1–5PubMedCrossRefGoogle Scholar
  29. 29.
    Jansen GA, Ofman R, Ferdinandusse S, et al. Refsum disease is caused by mutations in the phytanoyl-CoAhydroxylase gene. Nat Genet 1997; 17: 190–3PubMedCrossRefGoogle Scholar
  30. 30.
    Jansen GA, Waterham HR, Wanders RJ. Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7). Hum Mutat 2004; 23: 209–18PubMedCrossRefGoogle Scholar
  31. 31.
    Eldjarn L, Try K, Stokke O, et al. Dietary effects on serum-phytanic-acid levels and on clinical manifestations in heredopathia atactica polyneuritiformis. Lancet 1966; I: 691–3CrossRefGoogle Scholar
  32. 32.
    Sprecher E, Chavanas S, DiGiovanna JJ, et al. The spectrum of pathogenic mutations in SPINK5 in 19 families with Netherton syndrome: implications for mutation detection and first case of prenatal diagnosis. J Invest Dermatol 2001; 117: 179–87PubMedCrossRefGoogle Scholar
  33. 33.
    Chavanas S, Bodemer C, Rochat A, et al. Mutations in SPINK5, encoding a serine protease inhibitor, causeNetherton syndrome. Nat Genet 2000; 25: 141–2PubMedCrossRefGoogle Scholar
  34. 34.
    Komatsu N, Takata M, Otsuki N, et al. Elevated stratum corneum hydrolytic activity in Netherton syndrome suggests an inhibitory regulation of desquamation by SPINK5-derived peptides. J Invest Dermatol 2002; 118: 436–43PubMedCrossRefGoogle Scholar
  35. 35.
    De Laurenzi V, Rogers GR, Hamrock DJ, et al. Sjogren-Larsson syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene. Nat Genet 1996; 12: 52–7PubMedCrossRefGoogle Scholar
  36. 36.
    Gordon N. Sjogren-Larsson syndrome. Dev Med Child Neurol 2007; 49: 152–4PubMedCrossRefGoogle Scholar
  37. 37.
    Lefevre C, Jobard F, Caux F, et al. Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin- Dorfman syndrome. Am J Hum Genet 2001; 69: 1002–12PubMedCrossRefGoogle Scholar
  38. 38.
    Angelini C, Philippart M, Borrone C, et al. Multisystem triglyceride storage disorder with impaired long-chain fatty acid oxidation. Ann Neurol 1980; 7: 5–10PubMedCrossRefGoogle Scholar
  39. 39.
    Faghri S, Tamura D, Kraemer KH, et al. Trichothiodystrophy: a systematic review of 112 published cases characterises a wide spectrum of clinical manifestations. J Med Genet 2008; 45: 609–21PubMedCrossRefGoogle Scholar
  40. 40.
    Patel N, Spencer LA, English III JC, et al. Acquired ichthyosis. J Am Acad Dermatol 2006; 55: 647–56PubMedCrossRefGoogle Scholar
  41. 41.
    Dale BA, Holbrook KA, Fleckman P, et al. Heterogeneity in harlequin ichthyosis, an inborn error of epidermal keratinization: variable morphology and structural protein expression and a defect in lamellar granules. J Invest Dermatol 1990; 94: 6–18PubMedCrossRefGoogle Scholar
  42. 42.
    Elias PM, Williams ML. Neutral lipid storage disease with ichthyosis: defective lamellar body contents and intracellular dispersion. Arch Dermatol 1985; 121: 1000–8PubMedCrossRefGoogle Scholar
  43. 43.
    Dahlqvist J, Klar J, Hausser I, et al. Congenital ichthyosis: mutations in ichthyin are associated with specific structural abnormalities in the granular layer of epidermis. J Med Genet 2007; 44: 615–20PubMedCrossRefGoogle Scholar
  44. 44.
    Ishida-Yamamoto A, Richard G, Takahashi H, et al. In vivo studies of mutant keratin 1 in ichthyosis hystrix Curth-Macklin. J Invest Dermatol 2003; 120: 498–500PubMedCrossRefGoogle Scholar
  45. 45.
    Ong C, O’Toole EA, Ghali L, et al. LEKTI demonstrable by immunohistochemistry of the skin: a potential diagnostic skin test for Netherton syndrome. Br J Dermatol 2004; 151: 1253–7PubMedCrossRefGoogle Scholar
  46. 46.
    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: 474–83PubMedCrossRefGoogle Scholar
  47. 47.
    Raghunath M, Hennies HC, Velten F, et al. A novel in situ method for the detection of deficient transglutaminase activity in the skin. Arch Dermatol Res 1998; 290: 621–7PubMedCrossRefGoogle Scholar
  48. 48.
    Verfaille CJ, Vanhoutte FP, Blanchet-Bardon C, et al. Oral liarozole versus acitretin in the treatment of ichthyosis: a phase II/III multicentre, doubleblind, randomized, active-controlled study. Br J Dermatol 2007; 156: 965–73PubMedCrossRefGoogle Scholar
  49. 49.
    Okano M. Assessment of the clinical effect of topical tacalcitol on ichthyoses with retentive hyperkeratosis. Dermatology 2001; 202: 116–8PubMedCrossRefGoogle Scholar
  50. 50.
    Lucker GP, Heremans AM, Boegheim PJ, et al. Oral treatment of ichthyosis by the cytochrome P-450 inhibitor liarozole. Br J Dermatol 1997; 136: 71–5PubMedCrossRefGoogle Scholar
  51. 51.
    Lucker GP, Verfaille CJ, Heremans AM, et al. Topical liarozole in ichthyosis: a double-blind, left-right comparative study followed by a long-term open maintenance study. Br J Dermatol 2005; 152: 566–9PubMedCrossRefGoogle Scholar
  52. 52.
    Kuster W, Bohnsack K, Rippke F, et al. Efficacy of urea therapy in children with ichthyosis: a multicenter randomized, placebo-controlled, double-blind, semilateral study. Dermatology 1998; 196: 217–22PubMedCrossRefGoogle Scholar
  53. 53.
    Kragballe K, Steijlen PM, Ibsen HH, et al. Efficacy, tolerability, and safety of calcipotriol ointment in disorders of keratinization: results of a randomized, double-blind, vehicle-controlled, right/left comparative study. Arch Dermatol 1995; 131: 556–60PubMedCrossRefGoogle Scholar
  54. 54.
    Kempers S, Katz HI, Wildnauer R, et al. An evaluation of the effect of an alpha hydroxy acid-blend skin cream in the cosmetic improvement of symptoms of moderate to severe xerosis, epidermolytic hyperkeratosis, and ichthyosis. Cutis 1998; 61: 347–50PubMedGoogle Scholar
  55. 55.
    Ganemo A, Virtanen M, Vahlquist A. Improved topical treatment of lamellar ichthyosis: a double-blind study of four different cream formulations. Br J Dermatol 1999; 141: 1027–32PubMedCrossRefGoogle Scholar
  56. 56.
    DiGiovanna JJ, Robinson-Bostom L. Ichthyosis: etiology, diagnosis, and management. Am J Clin Dermatol 2003; 4: 81–95PubMedCrossRefGoogle Scholar
  57. 57.
    Kuster W. Ichthyoses: suggestions for an improved therapy. Deutsches Ärzteblatt 2006; 103: 1484–9Google Scholar
  58. 58.
    Shwayder T. Disorders of keratinization: diagnosis and management. Am J Clin Dermatol 2004; 5: 17–29PubMedCrossRefGoogle Scholar
  59. 59.
    Traupe H, Burgdorf WHC. Treatment of ichthyosis: there is always something you can do! In memoriam: Wolfgang Küster. Am Acad Dermatol 2007; 57: 542–7CrossRefGoogle Scholar
  60. 60.
    Vahlquist A, Ganemo A, Virtanen M. Congenital ichthyosis: an overview of current and emerging therapies. Acta Derm Venereol 2008; 88: 4–14PubMedCrossRefGoogle Scholar
  61. 61.
    Elias PM, Williams ML, Holleran WM, et al. Thematic review series: skin lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism. J Lipid Res 2008; 49: 697–714Google Scholar
  62. 62.
    Hofmann B, Stege H, Ruzicka T, et al. Effect of topical tazarotene in the treatment of congenital ichthyoses. Br J Dermatol 1999; 141: 642–6PubMedCrossRefGoogle Scholar
  63. 63.
    Nguyen V, Cunningham BB, Eichenfield LF, et al. Treatment of ichthyosiform diseases with topically applied tazarotene: risk of systemic absorption. J Am Acad Dermatol 2007; 57 (5 Suppl.): S123–5CrossRefGoogle Scholar
  64. 64.
    Cotellessa C, Cuevas-Covarrubias SA, Valeri P, et al. Topical tazarotene 0.05% versus glycolic acid 70% treatment in X-linked ichthyosis due to extensive deletion of the STS gene. Acta Derm Venereol 2005; 85: 346–8PubMedGoogle Scholar
  65. 65.
    Yamamura S, Kinoshita Y, Kitamura N, et al. Neonatal salicylate poisoning during the treatment of a collodion baby. Clin Pediatr (Phila) 2002; 41: 451–2CrossRefGoogle Scholar
  66. 66.
    Singh S, Bhura M, Maheshwari A, et al. Successful treatment of harlequin ichthyosis with acitretin. Int J Dermatol 2001; 40: 472–3PubMedCrossRefGoogle Scholar
  67. 67.
    Lawlor F, Peiris S. Harlequin fetus successfully treated with etretinate. Br J Dermatol 1985; 112: 585–90PubMedCrossRefGoogle Scholar
  68. 68.
    Ozturk A, Caksen H, Cetin N, et al. A retrospective study on 16 collodion babies. Turk J Pediatr 1997; 39: 55–9PubMedGoogle Scholar
  69. 69.
    Hachem JP, Houben E, Crumrine D, et al. Serine protease signaling of epidermal permeability barrier homeostasis. J Invest Dermatol 2006; 126: 2074–86PubMedCrossRefGoogle Scholar
  70. 70.
    Haenssle HA, Finkenrath A, Hausser I, et al. Effective treatment of severe thermodysregulation by oral retinoids in a patient with recessive congenital lamellar ichthyosis. Clin Exp Dermatol 2008; 33 (5): 578–81PubMedCrossRefGoogle Scholar
  71. 71.
    Oji V, Beljan G, Beier K, et al. Topical pimecrolimus: a novel therapeutic option for Netherton syndrome. Br J Dermatol 2005; 153: 1067–8PubMedCrossRefGoogle Scholar
  72. 72.
    Allen A, Siegfried E, Silverman R, et al. Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome. Arch Dermatol 2001; 137: 747–50PubMedGoogle Scholar
  73. 73.
    Lacour M, Mehta-Nikhar B, Atherton DJ, et al. An appraisal of acitretin therapy in children with inherited disorders of keratinization. Br J Dermatol 1996; 134: 1023–9PubMedCrossRefGoogle Scholar
  74. 74.
    Steijlen PM, Van Dooren-Greebe RJ, Happle R, et al. Ichthyosis bullosa of Siemens responds well to low-dosage oral retinoids. Br J Dermatol 1991; 125: 469–71PubMedCrossRefGoogle Scholar
  75. 75.
    Berth-Jones J, Todd G, Hutchinson PE, et al. Treatment of psoriasis with oral liarozole: a dose-ranging study. Br J Dermatol 2000; 143: 1170–6PubMedCrossRefGoogle Scholar
  76. 76.
    Akiyama M, Titeux M, Sakai K, et al. DNA-based prenatal diagnosis of harlequin ichthyosis and characterization of ABCA12 mutation consequences. J Invest Dermatol 2007; 127: 568–73PubMedCrossRefGoogle Scholar
  77. 77.
    Bitoun E, Bodemer C, Amiel J, et al. Prenatal diagnosis of a lethal form of Netherton syndrome by SPINK5 mutation analysis. Prenat Diagn 2002; 22: 121–6PubMedCrossRefGoogle Scholar
  78. 78.
    Rothnagel JA, Lin MT, Longley MA, et al. Prenatal diagnosis for keratin mutations to exclude transmission of epidermolytic hyperkeratosis. Prenat Diagn 1998; 18: 826–30PubMedCrossRefGoogle Scholar
  79. 79.
    Fassihi H, Eady RA, Mellerio JE, et al. Prenatal diagnosis for severe inherited skin disorders: 25 years’ experience. Br J Dermatol 2006; 154: 106–13PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2009

Authors and Affiliations

  • Vinzenz Oji
    • 1
  • Heiko Traupe
    • 1
  1. 1.Department of DermatologyUniversity of MünsterMünsterGermany

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