Abstract
The ichthyoses are a heterogeneous group of disorders with both inherited and acquired forms. Clinical presentation, pattern of inheritance, and laboratory evaluation may establish a precise diagnosis, which can assist in prognosis and genetic counseling.
Congenital autosomal recessive ichthyosis (CARI) usually presents at birth, often as a collodion baby. CARI can progress into any one of a spectrum of disorders. Lamellar ichthyosis is characterized by dark, plate (armor)-like scale. This disease is often caused by mutations in the gene encoding the enzyme transglutaminase 1. Congenital ichthyosiform erythroderma is another phenotype within CARI, marked by generalized redness and fine white scale.
Epidermolytic hyperkeratosis is an autosomal dominant disorder characterized by hyperkeratosis and blistering, and at least six clinical phenotypes have been described. It may be due to mutations in the gene encoding the intermediate filament proteins keratin 1 and 10.
Ichthyosis vulgaris is the most common ichthyosis, and is inherited in an autosomal dominant pattern. Involvement is generally mild and may vary greatly with climate and humidity. X-linked ichthyosis, due to a defect in the enzyme steroid sulfatase, affects males with generalized scaling that usually begins soon after birth. There may be associated corneal opacities that do not affect vision.
Sjögren-Larsson syndrome is an autosomal recessive ichthyosis associated with progressive spastic paralysis and mental retardation. This condition is caused by mutations in the gene for fatty aldehyde dehydrogenase. Refsum’s disease, due to accumulation of phytanic acid, results in ichthyosis and progressive neurologic dysfunction.
The erythrokeratodermas are characterized by hyperkeratosis and localized erythema. Erythrokeratodermia variabilis is autosomal dominant and characterized by generalized or localized hyperkeratosis and migratory red patches. Mutations in the genes encoding the gap junction proteins, connexins, underlie this disorder.
Netherton’s syndrome is an autosomal recessive disorder characterized by ichthyosis, a hair shaft abnormality and atopy. The ichthyosis may present at birth with erythroderma or in some cases a collodion presentation. However, a frequent characteristic skin manifestation is ichthyosis linearis circumflexa. Netherton’s syndrome has been found to be due to an abnormality in a serum protease inhibitor. Acquired ichthyosis can have a variety of underlying causes including neoplastic, infectious, drugs, endocrine, metabolic, autoimmune, malabsorptive states, and hereditary. Topical, and in more severe cases, systemic, therapy are useful in managing this array of disorders of cornification.
Similar content being viewed by others
Notes
Use of tradenames is for product identification only and does not imply endorsement.
References
Williams ML, Elias PM. Genetically transmitted, generalized disorders of cornification: the ichthyoses. Dermatol Clin 1987; 5 (1): 155–178
Williams ML, Elias PM. From basket weave to barrier: unifying concepts for the pathogenesis of the disorders of cornification [editorial]. Arch Dermatol 1993; 129 (5): 626–629
DiGiovanna JJ. Ichthyosiform dermatoses. In: Freedberg IM, Eisen AZ, Wolff K, et al., editors. Fitzpatrick’s dermatology in general medicine. New York: McGraw-Hill, 1999: 581–603
Williams ML, Elias PM. Heterogeneity in autosomal recessive ichthyosis: clinical and biochemical differentiation of lamellar ichthyosis and nonbullous congenital ichthyosiform erythroderma. Arch Dermatol 1985; 121 (4): 477–488
Hazell M, Marks R. Clinical, histologic, and cell kinetic discriminants between lamellar ichthyosis and nonbullous congenital ichthyosiform erythroderma. Arch Dermatol 1985; 121 (4): 489–493
Laiho E, Ignatius J, Mikkola H, et al. Transglutaminase 1 mutations in autosomal recessive congenital ichthyosis: private and recurrent mutations in an isolated population. Am J Hum Genet 1997; 61 (3): 529–538
Bale SJ, Russell LJ, Lee ML, et al. Congenital recessive ichthyosis unlinked to loci for epidermal transglutaminases. J Invest Dermatol 1996; 107 (6): 808–811
Fischer J, Faure A, Bouadjar B, et al. Two new loci for autosomal recessive ichthyosis on chromosomes 3p21 and 19p12-q12 and evidence for further genetic heterogeneity. Am J Hum Genet 2000 Mar; 66 (3): 904–913
Virolainen E, Wessman M, Hovatta I, et al. Assignment of a novel locus for autosomal recessive congenital ichthyosis to chromosome 19p13.1-p13.2. Am J Hum Genet 2000; 66 (3): 1132–1137
Frenk E, de Techtermann F. Self-healing collodion baby: evidence for autosomal recessive inheritance. Pediatr Dermatol 1992; 9 (2): 95–97
DiGiovanna JJ, Bale SJ. Clinical heterogeneity in epidermolytic hyperkeratosis. Arch Dermatol 1994; 130 (8): 1026–1035
DiGiovanna JJ, Bale SJ. Epidermolytic hyperkeratosis: applied molecular genetics. J Invest Dermatol 1994; 102 (3): 390–394
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 (4): 485–490
Wells RS, Kerr CB. Clinical features of autosomal dominant and sex-linked ichthyosis in an English population. BMJ 1966; 1: 947–950
Anton-Lamprecht I, Hofbauer M. Ultrastructural distinctive features of autosomal dominant ichthyosis vulgaris and X-linked recessive ichthyosis. Dermatologica 1972; 145 (1): 60–64
Sybert VP, Dale BA, Holbrook KA. Ichthyosis vulgaris: identification of a defect in synthesis of filaggrin correlated with an absence of keratohyaline granules. J Invest Dermatol 1985; 84 (3): 191–194
Nirunsuksiri W, Presland RB, Brumbaugh SG, et al. Decreased profilaggrin expression in ichthyosis vulgaris is a result of selectively impaired posttranscriptional control. J Biol Chem 1995; 270 (2): 871–876
Richard G, Lin JP, Smith L, et al. Linkage studies in erythrokeratodermias: fine mapping, genetic heterogeneity and analysis of candidate genes. J Invest Dermatol 1997; 109 (5): 666–671
Richard G, Smith LE, Bailey RA, et al. Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis. Nat Genet 1998; 20 (4): 366–369
Rizzo WB, Craft DA. Sjogren-Larsson syndrome, deficient activity of the fatty aldehyde dehydrogenase component of fatty alcohol: NAD+ oxidoreductase in cultured fibroblasts. J Clin Invest 1991; 88 (5): 1643–1648
Rizzo WB, Carney G, Lin Z. The molecular basis of Sjogren-Larsson syndrome: mutation analysis of the fatty aldehyde dehydrogenase gene. Am J Hum Genet 1999; 65 (6): 1547–1560
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 (1): 52–57
Rizzo WB, Craft DA, Kelson TL, et al. Prenatal diagnosis of Sjogren-Larsson syndrome using enzymatic methods. Prenat Diagn 1994; 14 (7): 577–581
Chavanas S, Bodemer C, Rochat A, et al. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet 2000 Jun; 25 (2): 141–142
Hochner I, Blickle JF, Brogard JM. Refsum disease. Rev Med Interne 1996; 17 (5): 391–398
Kitareewan S, Burka LT, Tomer KB, et al. Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR. Mol Biol Cell 1996; 7 (8): 1153–1166
Itin PH, Sarasin A, Pittelkow MR. Trichothiodystrophy: update on the sulfur-deficient brittle hair syndromes. J Am Acad Dermatol 2001; 44 (6): 891–920
Takayama K, Salazar EP, Broughton BC, et al. Defects in the DNA repair and transcription gene ERCC2 (XPD) in trichothiodystrophy. Am J Hum Genet 1996; 58 (2): 263–270
Weeda G, Eveno E, Donker I, et al. A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy. Am J Hum Genet 1997; 60 (2): 320–329
Stefanini M, Vermeulen W, Weeda G, et al. A new nucleotide-excision-repair gene associated with the disorder trichothiodystrophy. Am J Hum Genet 1993; 53 (4): 817–821
Griffiths WAD, Judge MR, Leigh IM. Disorders of keratinization. In: Champion RH, Burton JL, Burns DA, et al., editors. Rook/Wilkinson/Ebling textbook of dermatology. Oxford: Blackwell Science, 1998: 1483–1530
Sneddon IB. Acquired ichthyosis in Hodgkin’s disease. Br J Dermatol 1955; 1: 763–764
Lucker GP, Steijlen PM. Acrokeratosis paraneoplastica (Bazex syndrome) occurring with acquired ichthyosis in Hodgkin’ disease. Br J Dermatol 1995; 133 (2): 322–325
Cheesbrough MJ. Acquired ichthyosis and unclassified lymphoma. Br J Dermatol 1978; 99 Suppl. 16: 26–27
Tamura J, Shinohara M, Matsushima T, et al. Acquired ichthyosis as a manifestation of abdominal recurrence of non-Hodgkin’s lymphoma [letter]. Am J Hematol 1994; 45 (2): 191–192
Kutting B, Metze D, Luger TA, et al. Mycosis fungoides presenting as an acquired ichthyosis. J Am Acad Dermatol 1996; 34 (5 Pt 2): 887–889
Ikada J, Oki M. Concurrent pityriasis rotunda and acquired ichthyosis with IgG myeloma. Br J Dermatol 1974; 91 (5): 585–586
Haste AR. Acquired ichthyosis from breast cancer. BMJ 1967; 4 (571): 96
Polisky RB, Bronson DM. Acquired ichthyosis in a patient with adenocarcinoma of the breast. Cutis 1986; 38 (6): 359–360
Flint GL, Flam M, Soter NA. Acquired ichthyosis: a sign of nonlymphoproliferative malignant disorders. Arch Dermatol 1975; 111 (11): 1446–1447
Krakowski A, Brenner S, Covo J, et al. Acquired ichthyosis in Kaposi’s sarcoma. Dermatologica 1973; 147 (5): 348–351
Bechtel MA, Callen JP. Disseminated Kaposi’s sarcoma in a patient with acquired ichthyosis. J Surg Oncol 1984; 26 (1): 22–26
Young L, Steinman HK. Acquired ichthyosis in a patient with acquired immunodeficiency syndrome and Kaposi’s sarcoma [letter]. J Am Acad Dermatol 1987; 16 (2 Pt 1): 395–396
Grattan CE, Williams DM, Raafat F, et al. Acquired ichthyosis in a child with rhabdomyosarcoma. Pediatr Dermatol 1988; 5 (3): 167–169
Farrell AM, Ross JS, Thomas JM, et al. Acquired ichthyosis, alopecia and loss of hair pigment associated with leiomyosarcoma. J Eur Acad Dermatol Venereol 1998; 10 (2): 159–163
Majekodunmi AE, Femi-Pearse D. Ichthyosis: early manifestation of intestinal leiomyosarcoma. BMJ 1974; 3 (5933): 724
Bergman R, Friedman-Birnbaum R, Carter A. Acquired ichthyosis in a patient with polycythemia rubra vera. Cutis 1985; 36 (2): 157–158
Kato N, Yasukawa K, Kimura K, et al. Anaplastic large-cell lymphoma associated with acquired ichthyosis. J Am Acad Dermatol 2000 May; 42 (5 Pt 2): 914–920
Yokote R, Iwatsuki K, Hashizume H, et al. Lymphomatoid papulosis associated with acquired ichthyosis. J Am Acad Dermatol 1994; 30 (5 Pt 2): 889–892
Schulz EJ. Ichthyosiform conditions occurring in leprosy. Br J Dermatol 1965; 77: 151–157
Goodman DS, Teplitz ED, Wishner A, et al. Prevalence of cutaneous disease in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. J Am Acad Dermatol 1987; 17 (2 Pt 1): 210–220
Coldiron BM, Bergstresser PR. Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus. Arch Dermatol 1989; 125 (3): 357–361
Singh M, Kaur S, Kumar B, et al. The associated diseases with leprosy. Indian J Lepr 1987; 59 (3): 315–321
Kaplan MH, Sadick NS, McNutt NS, et al. Acquired ichthyosis in concomitant HIV-1 and HTLV-II infection: a new association with intravenous drug abuse. J Am Acad Dermatol 1993; 29 (5 Pt 1): 701–708
Griffiths CE, Leonard JN, Walker MM. Acquired ichthyosis and sarcoidosis. Clin Exp Dermatol 1986; 11 (3): 296–298
Banse-Kupin L, Pelachyk JM. Ichthyosiform sarcoidosis: report of two cases and a review of the literature. J Am Acad Dermatol 1987; 17 (4): 616–620
Cather JC, Cohen PR. Ichthyosiform sarcoidosis. J Am Acad Dermatol 1999; 40 (5 Pt 2): 862–865
London RD, Lebwohl M. Acquired ichthyosis and hyperparathyroidism. J Am Acad Dermatol 1989; 21 (4 Pt 1): 801–802
Font J, Bosch X, Ingelmo M, et al. Acquired ichthyosis in a patient with systemic lupus erythematosus [letter]. Arch Dermatol 1990; 126 (6): 829
Duvic M, Jegasothy BV. Acquired ichthyosis with systemic lupus erythematosus. Arch Dermatol 1980; 116 (8): 952–954
Urrutia S, Vazquez F, Requena L, et al. Acquired ichthyosis associated with dermatomyositis [letter]. J Am Acad Dermatol 1987; 16 (3 Pt 1): 627–629
Roselino AM, Souza CS, Andrade JM, et al. Dermatomyositis and acquired ichthyosis as paraneoplastic manifestations of ovarian tumor. Int J Dermatol 1997; 36 (8): 611–614
de la Cruz-Alvarez J, Allegue F, Oliver J. Acquired ichthyosis associated with eosinophilic fasciitis. J Am Acad Dermatol 1996; 34 (6): 1079–1080
Spelman LJ, Strutton GM, Robertson IM, et al. Acquired ichthyosis in bone marrow transplant recipients. J Am Acad Dermatol 1996; 35 (1): 17–20
Dilek I, Demirer T, Ustun C, et al. Acquired ichthyosis associated with chronic graft-versus-host disease following allogeneic peripheral blood stem cell transplantation in a patient with chronic myelogenous leukemia. Bone Marrow Transplant 1998; 21 (11): 1159–1161
Parsons Jr WB. Treatment of hypercholesteremia by nicotinic acid: progress report with review of studies regarding mechanism of action. Arch Intern Med (Chicago) 1961; 107: 639–652
Winkelmann RK, Perry HO, Achor RW, et al. Cutaneous syndromes produced as side effects of triparanol therapy. Arch Derm (Chicago) 1963; 87: 372–377
Greist MC, Epinette WW. Cimetidine-induced xerosis and asteatotic dermatitis. Arch Dermatol 1982; 118 (4): 253–254
Caver CV. Clofazimine-induced ichthyosis and its treatment. Cutis 1982; 29 (4): 341–343
Williams ML, Feingold KR, Grubauer G, et al. Ichthyosis induced by cholesterollowering drugs: implications for epidermal cholesterol homeostasis. Arch Dermatol 1987; 123 (11): 1535–1538
Niederauer HH, Bacharach-Buhles M, Altmeyer P. Ichthyosis and alopecia after maprotiline: corneolysis caused by temporary disorder of keratinization [in German]. Hautarzt 1991; 42 (7): 455–458
Epstein Jr EH, Bonifas JM. Recessive X-linked ichthyosis: lack of immunologically detectable steroid sulfatase enzyme protein. Hum Genet 1985; 71 (3): 201–205
Epstein Jr EH, Krauss RM, Shackleton CH. X-linked ichthyosis: increased blood cholesterol sulfate and electrophoretic mobility of low-density lipoprotein. Science 1981; 214 (4521): 659–660
Chipev CC, Yang JM, DiGiovanna JJ, et al. Preferential sites in keratin 10 that are mutated in epidermolytic hyperkeratosis. Am J Hum Genet 1994; 54 (2): 179–190
Bale SJ, DiGiovanna JJ. Genetic approaches to understanding the keratinopathies. Adv Dermatol 1997; 12: 99–114
GeneTests GeneClinics. Laboratory directory [online]. Available from URL: www.genetests.org [Accessed 2002 Dec 6]
Frost P, Van Scott EJ. Ichthyosiform dermatoses: classification based on anatomic and biometric observations. Arch Dermatol 1966; 94 (2): 113–126
Ishida-Yamamoto A, McGrath JA, Judge MR, et al. Selective involvement of keratins K1 and K10 in the cytoskeletal abnormality of epidermolytic hyperkeratosis (bullous congenital ichthyosiform erythroderma). J Invest Dermatol 1992; 99 (1): 19–26
Robinson-Bostom L, McDonald CJ. Ichthyosis. In: McDonald CJ, editor. Immunomodulatory and cytotoxic agents in dermatology. New York: Marcel Deckker, 1997: 293–300
Allen A, Siegfried E, Silverman R, et al. Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome. Arch Dermatol 2001; 137 (6): 747–750
Gibberd FB, Billimoria JD, Page NG, et al. Heredopathia atactica polyneuritiformis (Refsum’s disease) treated by diet and plasma-exchange. Lancet 1979; I (8116): 575–578
Moser HW, Braine H, Pyeritz RE, et al. Therapeutic trial of plasmapheresis in Refsum disease and in Fabry disease. Birth Defects Orig Artic Ser 1980; 16 (1): 491–497
Goldsmith LA, Baden HP. Propylene glycol with occlusion for treatment of ichthyosis. JAMA 1972; 220 (4): 579–580
Germann R, Schindera I, Kuch M, et al. Life threatening salicylate poisoning caused by percutaneous absorption in severe ichthyosis vulgaris [in German]. Hautarzt 1996; 47 (8): 624–627
Chiaretti A, Schembri Wismayer D, Tortorolo L, et al. Salicylate intoxication using a skin ointment. Acta Paediatr 1997; 86 (3): 330–331
Redondo P, Bauza A. Topical N-acetylcysteine for lamellar ichthyosis [letter]. Lancet 1999; 354 (9193): 1880
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 (5): 556–560
Lucker GP, van de Kerkhof PC, van Dijk MR, et al. Effect of topical calcipotriol on congenital ichthyoses. Br J Dermatol 1994; 131 (4): 546–550
Lucker GP, van de Kerkhof PC, Cruysberg JR, et al. Topical treatment of Sjogren-Larsson syndrome with calcipotriol. Dermatology 1995; 190 (4): 292–294
Steijlen PM, Reifenschweiler DO, Ramaekers FC, et al. Topical treatment of ichthyoses and Darier’s disease with 13-cis- retinoic acid: a clinical and immunohistochemical study. Arch Dermatol Res 1993; 285 (4): 221–226
Hofmann B, Stege H, Ruzicka T, et al. Effect of topical tazarotene in the treatment of congenital ichthyoses. Br J Dermatol 1999; 141 (4): 642–646
Jensen TG, Jensen UB, Jensen PK, et al. Correction of steroid sulfatase deficiency by gene transfer into basal cells of tissue-cultured epidermis from patients with recessive X-linked ichthyosis. Exp Cell Res 1993; 209 (2): 392–397
Choate KA, Medalie DA, Morgan JR, et al. Corrective gene transfer in the human skin disorder lamellar ichthyosis. Nat Med 1996; 2 (11): 1263–1267
Peck GL, DiGiovanna JJ. The retinoids. In: Freedberg IM, Eisen AZ, Wolff K, et al., editors. Fitzpatrick’s dermatology in general medicine. New York: McGraw-Hill, 1999: 2810–2820
DiGiovanna JJ, Peck GL. Oral synthetic retinoid treatment in children. Pediatr Dermatol 1983; 1 (1): 77–88
Virtanen M, Gedde-Dahl Jr T, Mork NJ, et al. Phenotypic/genotypic correlations in patients with epidermolytic hyperkeratosis and the effects of retinoid therapy on keratin expression. Acta Derm Venereol 2001; 81 (3): 163–170
Soriatane package insert. Nutley (NJ): Roche Laboratories Inc., 2001 Jan
Isotretinoin package insert. Nutley (NJ): Roche Laboratories Inc., 2002 Jun
DiGiovanna JJ. Isotretinoin effects on bone. J Am Acad Dermatol 2001; 45 (5): S176–S182
Lucker GP, Heremans AM, Boegheim PJ, et al. Oral treatment of ichthyosis by the cytochrome P-450 inhibitor liarozole. Br J Dermatol 1997; 136 (1): 71–75
Acknowledgements
Dr DiGiovanna has received travel and speaking honoraria and clinical research support from Hoffman-LaRoche, and clinical research support from Allergan, who market retinoid drugs.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
DiGiovanna, J.J., Robinson-Bostom, L. Ichthyosis. Am J Clin Dermatol 4, 81–95 (2003). https://doi.org/10.2165/00128071-200304020-00002
Published:
Issue Date:
DOI: https://doi.org/10.2165/00128071-200304020-00002