Ichthyosis

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Background

Ichthyosis refers to a relatively uncommon group of skin disorders characterized by the presence of excessive amounts of dry surface scales. It is regarded as a disorder of keratinization or cornification, and it is due to abnormal epidermal differentiation or metabolism.

The ichthyosiform dermatoses may be classified according to clinical manifestations, genetic presentation,[1] and histologic findings. Inherited and acquired forms of ichthyosis have been described, and ocular alterations may occur in specific subtypes. Five distinct types of inherited ichthyosis are noted, as follows: ichthyosis vulgaris, lamellar ichthyosis, epidermolytic hyperkeratosis, congenital ichthyosiform erythroderma, and X-linked ichthyosis.

Pathophysiology

Ichthyosis vulgaris is characterized by onset in early childhood, usually between age 3 and 12 months, with fine scales and varying degrees of dryness of the skin. Scaling is most prominent over the trunk, abdomen, buttocks, and legs. The flexural areas, such as the antecubital fossa, are spared. An association may be present between ichthyosis vulgaris and atopic diseases because one third to one half of patients show features of atopic disease and a similar proportion have relatives with atopic disease. A reported 11.5% association is noted between atopic dermatitis and primary hereditary ichthyosis. Ichthyosis vulgaris typically produces no significant ocular findings; however, scaling may be present on the eyelid skin, which could lead to punctate epithelial keratitis and recurrent corneal erosion. Linkage analysis has identified an ichthyosis vulgaris locus on band 1q22.

Two loss-of-function mutations in the coding of the filaggrin gene have been identified in both ichthyosis vulgaris and atopic dermatitis. Keratohyalin synthesis is affected because of the filaggrin mutation. Filaggrin is an epidermal protein that normally functions as a barrier molecule against environmental allergens, water loss, and infection.

In epidermolytic hyperkeratosis (bullous ichthyosiform erythroderma), a mild generalized erythroderma is present at birth. Bullae formation may occur, which may become infected and give rise to a foul skin odor.Erythrederma fades in infancy while the characteristic grey, waxy scale progresses. They are particularly prominent in the flexural creases. A mutation in the keratin genes (ie, KRT1, KRT10) is the cause of this autosomal dominant disorder.

Lamellar ichthyosis is a rare, autosomal recessive, genetically heterogeneous skin disease caused by mutations involving multiple genetic loci. Type 1 maps to band 14q11.2 and is caused by mutations in the gene for keratinocyte transglutaminase 1, an enzyme responsible for the assembly of the keratinized envelope.[2] Type 2, which is clinically indistinguishable from type 1, maps to band 2q33-q35. In classic lamellar ichthyosis, children with the disease are referred to as collodion babies and are covered at birth by a thickened membrane that subsequently is shed. The scaling of the skin involves the whole body with no sparing of the flexural creases. Approximately one third of children affected with this disorder develop bilateral ectropion of the cicatricial type that appears to result from excessive dryness of the skin and subsequent contracture. Secondary corneal ulceration may occur secondary to long-term exposure.

In X-linked ichthyosis, generalized scaling is present at or shortly after birth. This scaling is most prominent over the extremities, neck, trunk, and buttocks. The flexural creases may be involved but palms, and soles are spared. Irregular stromal corneal opacities that are located anterior to the Descemet membrane are found in 16-50% of male patients, and this finding may be used to distinguish this form of ichthyosis from all other forms. Approximately 25% of female carriers have minor corneal opacities. The corneal opacities are not known to affect visual acuity. An example of findings in X-linked ichthyosis is shown in the image below.


View Image

This slit beam illumination photograph of the cornea localizes the corneal opacity to the posterior stroma and the pre-Descemet membrane region. This ....

Previous studies have shown a deficiency of steroid sulfatase (STS) in skin fibroblasts and a marked elevation of plasma cholesterol sulfate in patients with X-linked ichthyosis. In most cases, STS deficiency is caused by a partial or complete deletion of the STS gene mapped on band Xp22.3. Deletions of the STS gene have systemic effects, such as corneal opacities, cryptorchidism, and failed progression during labor. Deletions to flank regions of the STS gene have been linked with mental retardation. These deletions involve portions of the VCXA and VCXB1 genes.

Nonbullous congenital ichthyosiform erythroderma (NBIE) or congenital ichthyosiform erythroderma (CIE) is a milder form of the disease that is autosomal recessive in inheritance.CIE has been found to be caused by mutations in the genes coding for transglutaminase 1, 12R-lipoxygenase, and/or lipoxygenase 3. The lipoxygenase genes play a role in the epidermal permeability layer. As with lamellar ichthyosis, neonates with CIE are referred to as collodion babies, but, as children and adults, they show generalized red skin with thin, white scaling. Other manifestations include persistent ectropion and scarring alopecia.

Multiple congenital ectodermal dysplastic syndromes are associated with scaling and other system defects. The keratitis, ichthyosis, and deafness (KID) syndrome is a congenital disorder of ectoderm that affects not only the epidermis but also other ectodermal tissues, such as the corneal epithelium and the inner ear.[3, 4] KID syndrome may present with the Hutchinson triad (the combination of notched, widely spaced peg teeth, interstitial keratitis, and deafness). KID syndrome has been linked to mutations in the connexin 26 gene (GJB2) on band 13q11-q12.

The colobomas of the eye, heart defects, ichthyosiform dermatosis, mental retardation, and ear defects (CHIME) syndrome comprise a rare neuroectodermal disorder.

Netherton syndrome is an autosomal recessive condition that consists of an ichthyosiform dermatosis with variable erythroderma, hair shaft defects, and atopic features. Netherton syndrome has been linked to a mutation on band 5q32, specifically encoding for LEKTI (lymphoepithelial Kazal-type—related inhibitor), a serine protease inhibitor.

Sjögren-Larsson syndrome is an autosomal recessive condition that comprises ichthyosis, spastic diplegia, pigmentary retinopathy, and mental retardation.

Congenital hemidysplasia with ichthyosiform erythroderma or nevus and limb defects (CHILD) syndrome is a rare X-linked dominant malformation syndrome characterized by unilaterally distributed ichthyosiform erythroderma or nevi, often sharply delimited at the midline, and ipsilateral limb defects. This syndrome is caused by a loss-of-function mutation of nicotinamide adenine dinucleotide phosphate (NADPH) steroid dehydrogenase-like (NSDHL) protein at band Xq28.

Acquired ichthyosis usually occurs in adults and manifests as small, white, fishlike scales that frequently are concentrated on the extremities but may be seen in a generalized distribution. This form of ichthyosis may be associated with internal neoplasia (eg, Hodgkin lymphoma, leukemia), systemic illness (eg, sarcoidosis, HIV infection, hypothyroidism, chronic hepatitis, malabsorption), bone marrow transplantation, or the intake of certain medications that interfere with sterol synthesis in epidermal cells (eg, nicotinic acid).

Newborns with type 2 Gaucher disease (glucosyl cerebroside lipidosis) may present with ichthyotic skin at birth prior to neurologic manifestations, which could be mistaken for a congenital form of ichthyosis.

Epidemiology

Frequency

United States

Ichthyosis vulgaris is the most common form and is an autosomal dominant trait with an incidence of 1 case per 300 population. Epidermolytic hyperkeratosis is an autosomal dominant disorder with an incidence of 1 case per 300,000 population. Lamellar ichthyosis, a more severe form of dermatosis, is an autosomal recessive trait with an incidence of 1 case per 300,000 population. X-linked recessive ichthyosis has an incidence of 1 case per 6000 males.

International

Studies show that a higher prevalence of X-linked ichthyosis as compared to ichthyosis vulgaris may be noted in Mexico, which is markedly different from the experience in the United States. In the United Kingdom, the incidence of ichthyosis vulgaris was reported to be 1 case per 250 population, in a study population of 6501 healthy school children. Similarly, in another large epidemiological study, the incidence of X-linked recessive ichthyosis was 1 case in 6190 males. In a Danish population study, the predicted incidence of X-linked recessive ichthyosis was 1 case per 2000 males. In a Danish study, Bygum et al concluded that epidermolytic ichthyosis had a prevalence of approximately 1 in 350,000, with a high percentage of de novo mutations (75%).[5] In southern coastal Italy, the frequency of X-linked recessive ichthyosis was estimated at 1.98 in 10,000 males. In China, ichthyosis vulgaris has a prevalence of 2.29%.

Mortality/Morbidity

An increased risk of testicular cancer in men with ichthyosis vulgaris has been suggested. In addition, an increased incidence of testicular maldescent, cryptorchidism, abnormalities of the sperm count or motility leading to infertility, and testicular cancer has been reported in patients with X-linked recessive ichthyosis.

Race

In general, all races may be affected in the inherited and acquired forms of ichthyosis.

Sex

X-linked recessive ichthyosis is much more prevalent in males. It is caused by a deficiency of STS. Because this enzyme plays an important role in androgen metabolism, men with this ailment do not show androgenetic alopecia or develop only mild forms of this common type of hair loss.

History

See Pathophysiology.

Physical

Ocular and periocular manifestations that may be seen in the ichthyosiform syndromes include the following:

Causes

See Pathophysiology.

Laboratory Studies

Imaging Studies

Other Tests

Procedures

Histologic Findings

Medical Care

Surgical Care

Consultations

Diet

Medication Summary

Oral retinoids display an impressive antikeratinizing action in ichthyosiform dermatoses. Acitretin (25-50 mg/d) and Isotretinoin (0.5-2 mg/kg/d) have been shown to reduce scaling, discomfort, and disfigurement. However, when these drugs are discontinued, the ichthyotic skin recurs, thereby necessitating long-term use.

Liarozole (150 mg bid), an imidazole derivative, inhibits the cytochrome P450-dependent 4-hydroxylation of retinoic acid, resulting in increased tissue levels of retinoic acid and a reduction in epidermal proliferation and scaling. It is a broad-spectrum antifungal agent; inhibits cytochrome P450 metabolic pathways, increasing levels of cytochrome P450 metabolized drugs. The US FDA has not approved this medication for use.Patients with epidermolytic hyperkeratosis may develop chronic bacterial infections of the skin necessitating long-term antibiotic therapy.

N-acetylcysteine 10% emulsion, a nontoxic and hypoallergenic amino acid derivative, can be safely and efficaciously used in the topical treatment of neonatal ichthyosis.

Isotretinoin (Amnesteem, Claravis, Sotret)

Clinical Context:  The synthetic 13-cis isomer of the naturally occurring tretinoin (trans -retinoic acid). Both agents are structurally related to vitamin A.

Acitretin (Soriatane)

Clinical Context:  Metabolite of etretinate and related to retinoic acid and retinol (vitamin A). Mechanism of action unknown but thought to exert therapeutic effect by modulating keratinocyte differentiation, keratinocyte hyperproliferation, and tissue infiltration by inflammatory cells.

Class Summary

These agents decrease cohesiveness of abnormal hyperproliferative keratinocytes and may reduce potential for malignant degeneration. They modulate keratinocyte differentiation and have been shown to reduce risk of skin cancer formation in renal transplant patients.

Erythromycin (EES, Ery-Tab, Erythrocin)

Clinical Context:  This is for patients with epidermolytic hyperkeratosis who develop bacterial infections of the skin .

Class Summary

Patients with epidermolytic hyperkeratosis may develop chronic bacterial infections of the skin necessitating long-term antibiotic therapy.

Urea (Ureacin, Carmol, Keralac)

Clinical Context:  Promotes hydration and removal of excess keratin in conditions of hyperkeratosis.

Class Summary

These agents are used to prevent cicatricial ectropion in lamellar ichthyosis, a humidified atmosphere combined with the use of topical moisturizing agents is beneficial. Petrolatum ointment and 10% urea cream applied to the eyelid skin several times daily helps to prevent skin contracture. Salicylic acid 2% and retinoic acid 0.1% ointments are also effective, but local irritation may limit their frequency of use.

Carboxymethylcellulose 0.5 to 1% (Optive, Refresh Plus)

Clinical Context:  Lubricates and relieves dry eyes and eye irritation associated with deficient tear production.

Class Summary

In chronic ocular surface disorders associated with ichthyosis, nonpreserved artificial tears (carboxymethylcellulose sodium 0.5-1.0%) and ointment (white petrolatum 56.8%, mineral oil 41.5%) are preferred to prevent complications from dryness and exposure. Preservative-free lubricants may be used as often as needed while decreasing the incidence of preservative-related allergies. In cases where poor corneal epithelial adhesion is present, bandage contact lenses and temporary collagen shields may decrease symptoms and promote surface healing.

N-acetylcysteine (Acetadote)

Clinical Context:  N-acetylcysteine is a glutathione precursor. It may provide effective photoprotection by increasing the availability of glutathione, a potent antioxidant. A nontoxic 10% emulsion and hypoallergenic amino acid derivative can be safely and efficaciously used in the topical treatment of neonatal ichthyosis.

Class Summary

Agents in this category may prove effective in the topical treatment of neonatal ichthyosis.

Further Outpatient Care

Complications

Prognosis

Author

Kenneth M Goins, MD, Professor of Clinical Ophthalmology, Director of Cornea and External Diseases and Refractive Surgery, Department of Ophthalmology, University of Iowa Hospitals and Clinics; Medical Director of Iowa Lions Eye Bank

Disclosure: Nothing to disclose.

Coauthor(s)

Matthew Rauen, MD, Fellow in Corneal, External Diseases and Refractive Surgery, Department of Ophthalmology and Visual Sciences, University of Iowa Health Care

Disclosure: Nothing to disclose.

Seth Adam Anderson, Des Moines University College of Osteopathic Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Arash Taheri, MD, Research Fellow, Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Steven R Feldman, MD, PhD, Professor, Departments of Dermatology, Pathology and Public Health Sciences, Wake Forest University Health Sciences; Director, Center for Dermatology Research, Director, Psoriasis Treatment Center, Director of Industry Relations, Department of Dermatology, Wake Forest University School of Medicine

Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Galderma Honoraria Speaking and teaching; Taro Consulting fee Consulting; www.DrScore.com Ownership interest Management position; Causa Reseasrch Ownership interest Management position; Janssen Consulting; Pfizer Honoraria Speaking and teaching; Novartis Consulting fee Consulting; Celgene Consulting fee Consulting

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Disclosure: Nothing to disclose.

References

  1. [Guideline] Moeschler JB, Shevell M. Clinical genetic evaluation of the child with mental retardation or developmental delays. Pediatrics. Jun 2006;117(6):2304-16. [View Abstract]
  2. Pietrusinski M, Stanczyk-Przyluska A, Chlebna-Sokól D, Borkowska E, Kaluzewski B, Borowiec M. Identification and clinical consequences of a novel mutation in the gene for transglutaminase 1 in a patient with lamellar ichthyosis. Clin Exp Dermatol. Sep 23 2014;[View Abstract]
  3. Djalilian AR, Kim JY, Saeed HN, Holland EJ, Chan CC. Histopathology and treatment of corneal disease in keratitis, ichthyosis, and deafness (KID) syndrome. Eye (Lond). Jul 10 2009;[View Abstract]
  4. Levit NA, Sellitto C, Wang HZ, Li L, Srinivas M, Brink PR, et al. Aberrant Connexin26 Hemichannels Underlying Keratitis-Ichthyosis-Deafness Syndrome are Potently Inhibited by Mefloquine. J Invest Dermatol. Sep 17 2014;[View Abstract]
  5. Bygum A, Virtanen M, Brandrup F, Gånemo A, Sommerlund M, Strauss G, et al. Generalized and Naevoid Epidermolytic Ichthyosis in Denmark: Clinical and Mutational Findings. Acta Derm Venereol. Aug 29 2012;[View Abstract]
  6. Scott CA, Rajpopat S, Di WL. Harlequin ichthyosis: ABCA12 mutations underlie defective lipid transport, reduced protease regulation and skin-barrier dysfunction. Cell Tissue Res. Aug 4 2012;[View Abstract]
  7. Sigurdsson H, Baldursson BT. Inverting Sutures With Systemic Retinoids and Lubrication Can Correct Ectropion in Ichthyosis. Ophthal Plast Reconstr Surg. Sep 11 2014;[View Abstract]
  8. Akiyama M, Suzumori K, Shimizu H. Prenatal diagnosis of harlequin ichthyosis by the examination of keratinized hair canals and amniotic fluid cells at 19 weeks' estimated gestational age. Prenat Diagn. Feb 1999;19(2):167-71. [View Abstract]
  9. Al-Akloby OM. Association of atopic dermatitis with primary hereditary ichthyoses. Saudi Med J. Aug 2004;25(8):1097-9. [View Abstract]
  10. Baden HP, Imber M. Ichthyosis with an unusual constellation of ectodermal dysplasias. Clin Genet. Jun 1989;35(6):455-61. [View Abstract]
  11. Bale SJ, DiGiovanna JJ. Genetic approaches to understanding the keratinopathies. Adv Dermatol. 1997;12:99-113; discussion 114. [View Abstract]
  12. Banse-Kupin L, Pelachyk JM. Ichthyosiform sarcoidosis. Report of two cases and a review of the literature. J Am Acad Dermatol. Oct 1987;17(4):616-20. [View Abstract]
  13. Bitoun E, Chavanas S, Irvine AD, Lonie L, Bodemer C, Paradisi M. Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families. J Invest Dermatol. Feb 2002;118(2):352-61. [View Abstract]
  14. Caceres-Rios H, Tamayo-Sanchez L, Duran-Mckinster C, de la Luz Orozco M, Ruiz-Maldonado R. Keratitis, ichthyosis, and deafness (KID syndrome): review of the literature and proposal of a new terminology. Pediatr Dermatol. Mar-Apr 1996;13(2):105-13. [View Abstract]
  15. Casaroli Marano RP, Ortiz Stradtmann MA, Uxo M, Iglesias E. Ocular findings associated with congenital X-linked ichthyosis. Ann Ophthalmol. May 1991;23(5):167-72. [View Abstract]
  16. Chiaretti A, Schembri Wismayer D, Tortorolo L, Piastra M, Polidori G. Salicylate intoxication using a skin ointment. Acta Paediatr. Mar 1997;86(3):330-1. [View Abstract]
  17. Costagliola C, Fabbrocini G, Illiano GM, Scibelli G, Delfino M. Ocular findings in X-linked ichthyosis: a survey on 38 cases. Ophthalmologica. 1991;202(3):152-5. [View Abstract]
  18. Cuevas-Covarrubias SA, Diaz-Zagoya JC, Rivera-Vega MR, et al. Higher prevalence of X-linked ichthyosis vs. ichthyosis vulgaris in Mexico. Int J Dermatol. Jul 1999;38(7):555-6. [View Abstract]
  19. Culican SM, Custer PL. Repair of cicatricial ectropion in an infant with harlequin ichthyosis using engineered human skin. Am J Ophthalmol. Sep 2002;134(3):442-3. [View Abstract]
  20. Derse M, Wannke E, Payer H, Rohrbach JM, Zierhut M. [Successful topical cyclosporin A in the therapy of progressive vascularising keratitis in keratitis-ichthyosis-deafness (KID) syndrome (Senter syndrome)]. Klin Monatsbl Augenheilkd. May 2002;219(5):383-6. [View Abstract]
  21. 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. Jun 1998;21(11):1159-61. [View Abstract]
  22. Gicquel JJ, Lami MC, Catier A, Balayre S, Dighiero P. [Limbal stem cell deficiency associated with KID syndrome, about a case]. J Fr Ophtalmol. Dec 2002;25(10):1061-4. [View Abstract]
  23. Gloerich J, Ijlst L, Wanders RJ, Ferdinandusse S. Bezafibrate induces FALDH in human fibroblasts; implications for Sjögren-Larsson syndrome. Mol Genet Metab. Sep-Oct 2006;89(1-2):111-5. [View Abstract]
  24. Happle R, Hoffmann R. Absence of male-pattern baldness in men with X-linked recessive ichthyosis? A hypothesis to be challenged. Dermatology. 1999;198(3):231-2. [View Abstract]
  25. Hazan C, Orlow SJ, Schaffer JV. X-linked recessive ichthyosis. Dermatol Online J. 2005;11(4):12. [View Abstract]
  26. Hoffjan S, Stemmler S. On the role of the epidermal differentiation complex in ichthyosis vulgaris, atopic dermatitis and psoriasis. Br J Dermatol. Sep 2007;157(3):441-9. [View Abstract]
  27. Hosomi N, Oiso N, Fukai K, Hanada K, Fujita H, Ishii M. Deletion of distal promoter of VCXA in a patient with X-linked ichthyosis associated with borderline mental retardation. J Dermatol Sci. Jan 2007;45(1):31-6. [View Abstract]
  28. Hummel M, Cunningham D, Mullett CJ, Kelley RI, Herman GE. Left-sided CHILD syndrome caused by a nonsense mutation in the NSDHL gene. Am J Med Genet A. Oct 15 2003;122(3):246-51. [View Abstract]
  29. Ingordo V, D'Andria G, Gentile C, Decuzzi M, Mascia E, Naldi L. Frequency of X-linked ichthyosis in coastal southern Italy: a study on a representative sample of a young male population. Dermatology. 2003;207(2):148-50. [View Abstract]
  30. Kaplan MH, Sadick NS, McNutt NS, Talmor M, Coronesi M, Hall WW. Acquired ichthyosis in concomitant HIV-1 and HTLV-II infection: a new association with intravenous drug abuse. J Am Acad Dermatol. Nov 1993;29(5 Pt 1):701-8. [View Abstract]
  31. Kawashima J, Akiyama M, Takizawa Y, Takahashi S, Matsuo I, Shimizu H. Structural, enzymatic and molecular studies in a series of nonbullous congenital ichthyosiform erythroderma patients. Clin Exp Dermatol. Jul 2005;30(4):429-31. [View Abstract]
  32. 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(2):217-22. [View Abstract]
  33. König A, Happle R, Bornholdt D, Engel H, Grzeschik KH. Mutations in the NSDHL gene, encoding a 3beta-hydroxysteroid dehydrogenase, cause CHILD syndrome. Am J Med Genet. Feb 14 2000;90(4):339-46. [View Abstract]
  34. Lacz NL, Schwartz RA, Kihiczak G. Epidermolytic hyperkeratosis: a keratin 1 or 10 mutational event. Int J Dermatol. Jan 2005;44(1):1-6. [View Abstract]
  35. Lee HW, Ahn SJ, Choi JC, et al. Acquired ichthyosis associated with an overlap syndrome of systemic sclerosis and systemic lupus erythematosus. J Dermatol. Jan 2006;33(1):52-4. [View Abstract]
  36. Leung PC, Ma GF. Ectropion of all four eyelids associated with severe ichthyosis congenita: a case report. Br J Plast Surg. Jul 1981;34(3):302-4. [View Abstract]
  37. Lucker GP, Heremans AM, Boegheim PJ, van de Kerkhof PC, Steijlen PM. Oral treatment of ichthyosis by the cytochrome P-450 inhibitor liarozole. Br J Dermatol. Jan 1997;136(1):71-5. [View Abstract]
  38. Marulli GC, Campione E, Chimenti MS, Terrinoni A, Melino G, Bianchi L. Type I lamellar ichthyosis improved by tazarotene 0.1% gel. Clin Exp Dermatol. Jul 2003;28(4):391-3. [View Abstract]
  39. Mayuzumi N, Ikeda S, Kawada H, Ogawa H. Effects of drugs and anticytokine antibodies on expression of ATP2A2 and ATP2C1 in cultured normal human keratinocytes. Br J Dermatol. May 2005;152(5):920-4. [View Abstract]
  40. Messmer EM, Kenyon KR, Rittinger O, Janecke AR, Kampik A. Ocular manifestations of keratitis-ichthyosis-deafness (KID) syndrome. Ophthalmology. Feb 2005;112(2):e1-6. [View Abstract]
  41. Montague I, Fox R, Mann R. Intra-amniotic debris identified at ultrasound scanning: a feature of congenital ichthyosis. Ultrasound Obstet Gynecol. May 1997;9(5):350-1. [View Abstract]
  42. Moran JL, Qiu H, Turbe-Doan A, et al. A mouse mutation in the 12R-lipoxygenase, Alox12b, disrupts formation of the epidermal permeability barrier. J Invest Dermatol. Aug 2007;127(8):1893-7. [View Abstract]
  43. Moskowitz DG, Fowler AJ, Heyman MB, et al. Pathophysiologic basis for growth failure in children with ichthyosis: an evaluation of cutaneous ultrastructure, epidermal permeability barrier function, and energy expenditure. J Pediatr. Jul 2004;145(1):82-92. [View Abstract]
  44. Oji V, Beljan G, Beier K, Traupe H, Luger TA. Topical pimecrolimus: a novel therapeutic option for Netherton syndrome. Br J Dermatol. Nov 2005;153(5):1067-8. [View Abstract]
  45. Orth DH, Fretzin DF, Abramson V. Collodion baby with transient bilateral upper lid ectropion. Review of ocular manifestations in ichthyosis. Arch Ophthalmol. Mar 1974;91(3):206-7. [View Abstract]
  46. Pagliaro JA, White SI. Specific skin lesions occurring in a patient with Hodgkin's lymphoma. Australas J Dermatol. Feb 1999;40(1):41-3. [View Abstract]
  47. Patel N, Spencer LA, English JC 3rd, Zirwas MJ. Acquired ichthyosis. J Am Acad Dermatol. Oct 2006;55(4):647-56. [View Abstract]
  48. Richard G, Rouan F, Willoughby CE, et al. Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome. Am J Hum Genet. May 2002;70(5):1341-8. [View Abstract]
  49. Sarici SU, Sahin M, Yurdakök M. Topical N-acetylcysteine treatment in neonatal ichthyosis. Turk J Pediatr. Jul-Sep 2003;45(3):245-7. [View Abstract]
  50. Schnur RE, Greenbaum BH, Heymann WR, et al. Acute lymphoblastic leukemia in a child with the CHIME neuroectodermal dysplasia syndrome. Am J Med Genet. Oct 3 1997;72(1):24-9. [View Abstract]
  51. Schorderet DF, Huber M, Laurini RN, et al. Prenatal diagnosis of lamellar ichthyosis by direct mutational analysis of the keratinocyte transglutaminase gene. Prenat Diagn. May 1997;17(5):483-6. [View Abstract]
  52. Shwayder T. Disorders of keratinization: diagnosis and management. Am J Clin Dermatol. 2004;5(1):17-29. [View Abstract]
  53. Sun JD, Linden KG. Netherton syndrome: a case report and review of the literature. Int J Dermatol. Jun 2006;45(6):693-7. [View Abstract]
  54. Suresh S, Vijayalakshmi R, Indrani S, Lata M. Short foot length: a diagnostic pointer for harlequin ichthyosis. J Ultrasound Med. Dec 2004;23(12):1653-7. [View Abstract]
  55. Takechi K, Sekiguchi K, Goto S. [A case of keratitis, ichthyosis, and deafness syndrome with Hutchinson's triad-like symptoms]. Nippon Ganka Gakkai Zasshi. Apr 1999;103(4):322-6. [View Abstract]
  56. Thiers BH. The use of topical calcipotriene/calcipotriol in conditions other than plaque-type psoriasis. J Am Acad Dermatol. Sep 1997;37(3 Pt 2):S69-71. [View Abstract]
  57. Traboulsi E, Waked N, Megarbane H. Ocular findings in ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome. Ophthalmic Genet. Jun 2004;25(2):153-6. [View Abstract]
  58. Tsochatzis E, Vassilopoulos D, Deutsch M, Asvesti C, Sevastos N, Archimandritis AJ. Myelodysplastic syndrome presenting as acquired ichthyosis. Eur J Intern Med. Aug 2006;17(5):368-9. [View Abstract]
  59. Zhong W, Cui B, Zhang Y, et al. Linkage analysis suggests a locus of ichthyosis vulgaris on 1q22. J Hum Genet. 2003;48(7):390-2. [View Abstract]

This slit beam illumination photograph of the cornea localizes the corneal opacity to the posterior stroma and the pre-Descemet membrane region. This type of corneal opacity is commonly present in X-linked recessive ichthyosis.

This direct illumination slit lamp photograph discloses a reticular central corneal haze that is seen bilaterally. Visual acuity is 20/20 in both eyes. The patient's chief complaint is photophobia and dry scaly skin.

This slit beam illumination photograph of the cornea localizes the corneal opacity to the posterior stroma and the pre-Descemet membrane region. This type of corneal opacity is commonly present in X-linked recessive ichthyosis.

An orbital mass is shown on CT scan in a 38-year-old male with human immunodeficiency virus (HIV) who presented with a late onset generalized ichthyotic rash and proptosis.