Hereditary and Acquired Ichthyosis Vulgaris 

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Apr 25, 2011
 

Background

Hereditary ichthyosis vulgaris and acquired ichthyosis vulgaris, members of a group of cutaneous disorders of keratinization, appear similar both clinically and histologically. The term ichthyosis is derived from the ancient Greek root ichthys, meaning fish. Although the resemblance is rather fanciful, it nevertheless conveys the characteristic features of these diseases. References to ichthyosis have been found in ancient medical texts aged more than 2000 years. Robert Wilan first made the most accurate description of ichthyosis in the English literature in 1808. Later modifications classified the diseases into hereditary and acquired forms.

Hereditary ichthyosis vulgaris is an autosomal dominant genetic disorder first evident in early childhood. It is the most common form of ichthyosis, accounting for more than 95% of ichthyosis cases. It is caused by altered profilaggrin expression leading to scaling and desquamation. Visible scales are retained for longer periods and sloughed off in clumps. Hereditary ichthyosis is also associated with atopy. The protein filaggrin is important in maintaining effective skin barrier function. Loss-of-function mutations in the profilaggrin gene (FLG) are evident in up to 10% of the population, causing ichthyosis vulgaris and representing a major risk factor for the development of atopic dermatitis.[1]

Acquired ichthyosis, usually appearing for the first time in adulthood, is a nonhereditary condition associated with internal disease. Acquired ichthyosis is rare and must be viewed as a marker of systemic disease, including malignancy. Cases have been attributed to the use of certain medications.

Other eMedicine articles on ichthyosis include the following:

Next

Pathophysiology

Ichthyosis vulgaris is classified as a retention hyperkeratosis. The only known molecular marker affected by hereditary ichthyosis vulgaris is profilaggrin, a high molecular weight filaggrin precursor. Profilaggrin, synthesized in the granular layer of the epidermis, is a major component of keratohyalin granules. Through various posttranslational modifications, profilaggrin is converted to filaggrin, which aggregates keratin intermediate filaments in the lower stratum corneum. Filaggrin is proteolyzed and metabolized, producing free amino acids that may play a critical role as water-binding compounds in the upper stratum corneum. Normal cycles of skin hydration and dehydration contribute to normal desquamation. These cycles are disrupted in ichthyosis vulgaris.

Normal expression of the profilaggrin gene can be first detected in the granular layer. In ichthyosis vulgaris, the expression of profilaggrin is absent or reduced in the epidermis. This biochemical abnormality correlates with the decreased numbers of keratohyalin granules and the clinical severity of the condition. Analyses of cultured keratinocytes have shown reduced profilaggrin mRNA. Compared with normal amounts, one study found only 50% of the profilaggrin mRNA and 10% of the profilaggrin protein present. Research has shown that defective posttranscriptional regulation leads to decreased stability of profilaggrin mRNA.

The profilaggrin gene is part of a cluster of genes on 1q21 that encodes for structural proteins expressed in terminally differentiating epidermis. This complex, called the epidermal differentiation complex, involves many genes involved in this process. An adjacent region on 1q22 may also be involved.[2] The underlying molecular mechanisms contributing to the pathophysiology of this disease have not yet been determined. Studies are currently underway in humans and mouse models.

An association exists between filaggrin null mutations of ichthyosis vulgaris and atopic dermatitis.[3] Two common filaggrin (FLG) null mutations cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases. Comprehensive analysis of the gene encoding filaggrin uncovered prevalent and rare mutations in ichthyosis vulgaris and atopic eczema.[4] These common European mutations are ancestral variants carried on conserved haplotypes. Fifteen variants were described, including 7 that are prevalent, all being either nonsense or frameshift mutations that, in representative cases, resulted in loss of filaggrin production in the epidermis.

Filaggrin mutations p.R501X and c.2282del4 were analyzed in patients with ichthyosis vulgaris.[5] Homozygotes and compound heterozygotes may be severely affected, whereas heterozygotes showed mild disease or were asymptomatic, suggesting semidominant inheritance with incomplete penetrance in heterozygotes. The presence of FLG mutations in 15 of 21 ichthyosis vulgaris patients were studied with a marked generalized scaling phenotype, including 8 affected members of a 4-generation family. In this group, heterozygous patients for p.R501X and c.2282del4 also displayed a pronounced phenotype. Filaggrin mutation c.3321delA was identified in a Korean patient with ichthyosis vulgaris and atopic dermatitis.[6] Mutations R501X and 2282del4 represent the most frequent genetic cause in German ichthyosis vulgaris patients, but are probably population and family specific.[7]

Mutations in the gene encoding filaggrin have been identified as the cause of ichthyosis vulgaris and shown to be major predisposing factors for atopic dermatitis both in European and Japanese populations.[8, 9]

Mutations at any site within FLG appear to cause significant effects, possibly accounting for the lack of genotype-phenotype correlation observed in patients with FLG mutations.[10]

Previous
Next

Epidemiology

Frequency

United States

Hereditary ichthyosis vulgaris is a common disease in the United States, with a prevalence of approximately 1 case in 300 persons. Because symptoms improve with age, the true prevalence is probably higher. Acquired ichthyosis is extremely rare. Its prevalence in the United States is unknown.

International

Hereditary ichthyosis vulgaris is found worldwide, and the prevalence depends on the location. One study in Berkshire, England, observed a frequency of 1 case in 250 schoolchildren. Acquired ichthyosis is extremely rare. Its prevalence worldwide is unknown.

Mortality/Morbidity

Children and adolescents with hereditary ichthyosis vulgaris may experience some morbidity in terms of cosmesis. Secondary infections may occur in fissures of the hands and feet. The morbidity and mortality of acquired ichthyosis in adults is due to associated internal disease.

Race

Hereditary and acquired ichthyosis vulgaris have no known racial predisposition.

Sex

Hereditary and acquired ichthyosis occur equally in men and women.

Age

Hereditary ichthyosis vulgaris typically is absent at birth. It appears in most patients during the first year of life and in the vast majority by age 5 years. The extent of scaling usually intensifies up until puberty and subsequently decreases with age.

Acquired ichthyosis usually first appears in adulthood; however, age-associated systemic diseases do occur in children.

Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Jason F Okulicz, MD  Assistant Professor of Medicine, Uniformed Services University of the Health Sciences; Staff, Infectious Disease Service, Brooke Army Medical Center

Jason F Okulicz, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Albert C Yan, MD  Section Chief, Associate Professor, Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia and University of Pennsylvania

Albert C Yan, MD is a member of the following medical societies: American Academy of Dermatology, American Academy of Pediatrics, Society for Investigative Dermatology, and Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Lester F Libow, MD  Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Texas Medical Association

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References

  1. McGrath JA, Uitto J. The filaggrin story: novel insights into skin-barrier function and disease. Trends Mol Med. Jan 2008;14(1):20-7. [Medline].

  2. 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. [Medline].

  3. Hanifin JM. Evolving concepts of pathogenesis in atopic dermatitis and other eczemas. J Invest Dermatol. Feb 2009;129(2):320-2. [Medline].

  4. Sandilands A, Terron-Kwiatkowski A, Hull PR, et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet. May 2007;39(5):650-4. [Medline].

  5. Gruber R, Janecke AR, Fauth C, Utermann G, Fritsch PO, Schmuth M. Filaggrin mutations p.R501X and c.2282del4 in ichthyosis vulgaris. Eur J Hum Genet. Feb 2007;15(2):179-84. [Medline].

  6. Kang TW, Lee JS, Oh SW, Kim SC. Filaggrin mutation c.3321delA in a Korean patient with ichthyosis vulgaris and atopic dermatitis. Dermatology. 2009;218(2):186-7. [Medline].

  7. Oji V, Seller N, Sandilands A, et al. Ichthyosis vulgaris: novel FLG mutations in the German population and high presence of CD1a+ cells in the epidermis of the atopic subgroup. Br J Dermatol. Apr 2009;160(4):771-81. [Medline].

  8. Nomura T, Sandilands A, Akiyama M, et al. Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis. J Allergy Clin Immunol. Feb 2007;119(2):434-40. [Medline].

  9. Nomura T, Akiyama M, Sandilands A, et al. Specific filaggrin mutations cause ichthyosis vulgaris and are significantly associated with atopic dermatitis in Japan. J Invest Dermatol. Jun 2008;128(6):1436-41. [Medline].

  10. Akiyama M. FLG mutations in ichthyosis vulgaris and atopic eczema: spectrum of mutations and population genetics. Br J Dermatol. Mar 2010;162(3):472-7. [Medline].

  11. London RD, Lebwohl M. Acquired ichthyosis and hyperparathyroidism. J Am Acad Dermatol. Oct 1989;21(4 Pt 1):801-2. [Medline].

  12. Spelman LJ, Strutton GM, Robertson IM, Weedon D. Acquired ichthyosis in bone marrow transplant recipients. J Am Acad Dermatol. Jul 1996;35(1):17-20. [Medline].

  13. 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. [Medline].

  14. 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. [Medline].

  15. Urrutia S, Vazquez F, Requena L, Sanchez Yus E. Acquired ichthyosis associated with dermatomyositis. J Am Acad Dermatol. Mar 1987;16(3 Pt 1):627-9. [Medline].

  16. Roselino AM, Souza CS, Andrade JM, et al. Dermatomyositis and acquired ichthyosis as paraneoplastic manifestations of ovarian tumor. Int J Dermatol. Aug 1997;36(8):611-4. [Medline].

  17. Ennibi K, Rabhi M, Al Bouzidi A, et al. [Acquired ichthyosis revealing an Hodgkin's disease]. Rev Med Interne. May 2008;29(5):418-20. [Medline].

  18. Parsons WB Jr, Flinn JH. Reduction of serum cholesterol levels and beta-lipoprotein cholesterol levels by nicotinic acid. AMA Arch Intern Med. May 1959;103(5):783-90. [Medline].

  19. Williams ML, Feingold KR, Grubauer G, Elias PM. Ichthyosis induced by cholesterol-lowering drugs. Implications for epidermal cholesterol homeostasis. Arch Dermatol. Nov 1987;123(11):1535-8. [Medline].

  20. Poulsen J. Hair loss, depigmentation of hair, ichthyosis, and blepharoconjunctivitis produced by dixyrazine. Acta Derm Venereol. 1981;61(1):85-8. [Medline].

  21. Caver CV. Clofazimine-induced ichthyosis and its treatment. Cutis. Apr 1982;29(4):341-3. [Medline].

  22. 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. Nov 1 2006;15(21):3083-97. [Medline].

  23. Dar NR, Raza N, Khan A, Amin MU. Paraneoplastic Addisonian pigmentation and acquired ichthyosis as presenting features of multiple myeloma. J Coll Physicians Surg Pak. Jan 2011;21(1):40-2. [Medline].

  24. Biver-Dalle C, Gil H, Meaux-Ruault N, et al. [Acquired ichthyosis and livedoid palmoplantar keratoderma: Two unusual skin manifestations of systemic lupus erythematosus.]. Rev Med Interne. Mar 21 2011;[Medline].

  25. Cather JC, Cohen PR. Ichthyosiform sarcoidosis. J Am Acad Dermatol. May 1999;40(5 Pt 2):862-5. [Medline].

  26. Matarasso SL, Bruce S. Ichthyosiform sarcoidosis: report of a case. Cutis. Jun 1991;47(6):405-8. [Medline].

  27. Grahovac M, Budimcic D. Unrecognized dermatophyte infection in ichthyosis vulgaris. Acta Dermatovenerol Croat. 2009;17(2):127-30. [Medline].

  28. Haas AA, Arndt KA. Selected therapeutic applications of topical tretinoin. J Am Acad Dermatol. Oct 1986;15(4 Pt 2):870-7. [Medline].

  29. Hofmann B, Stege H, Ruzicka T, Lehmann P. Effect of topical tazarotene in the treatment of congenital ichthyoses. Br J Dermatol. Oct 1999;141(4):642-6. [Medline].

  30. Osawa R, Akiyama M, Shimizu H. Filaggrin gene defects and the risk of developing allergic disorders. Allergol Int. Mar 2011;60(1):1-9. [Medline].

  31. Anton-Lamprecht I, Hofbauer M. Ultrastructural distinction of autosomal dominant ichthyosis vulgaris and X-linked recessive ichthyosis. Humangenetik. 1972;15(3):261-4. [Medline].

  32. Aram H. Acquired ichthyosis and related conditions. Int J Dermatol. Sep 1984;23(7):458-61. [Medline].

  33. Brenner S. Acquired ichthyosis in AIDS. Cutis. May 1987;39(5):421-3. [Medline].

  34. Buxman M, Hickman J, Ragsdale W, Stretcher G, Krochmal L, Wehr RF. Therapeutic activity of lactate 12% lotion in the treatment of ichthyosis. Active versus vehicle and active versus a petrolatum cream. J Am Acad Dermatol. Dec 1986;15(6):1253-8. [Medline].

  35. Compton JG, DiGiovanna JJ, Johnston KA, Fleckman P, Bale SJ. Mapping of the associated phenotype of an absent granular layer in ichthyosis vulgaris to the epidermal differentiation complex on chromosome 1. Exp Dermatol. Dec 2002;11(6):518-26. [Medline].

  36. Cooper MF, Wilson PD, Hartop PJ, Shuster S. Acquired ichthyosis and impaired dermal lipogenesis in Hodgkin's disease. Br J Dermatol. Jun 1980;102(6):689-93. [Medline].

  37. Dykes PJ, Marks R. Acquired ichthyosis: multiple causes for an acquired generalized distrubance in desquamation. Br J Dermatol. Sep 1977;97(3):327-34. [Medline].

  38. Feinstein A, Ackerman AB, Ziprkowski L. Histology of autosomal dominant ichthyosis vulgaris and X-linked ichthyosis. Arch Dermatol. May 1970;101(5):524-7. [Medline].

  39. Fleckman P, Holbrook KA, Dale BA, Sybert VP. Keratinocytes cultured from subjects with ichthyosis vulgaris are phenotypically abnormal. J Invest Dermatol. May 1987;88(5):640-5. [Medline].

  40. Goldsmith LA, Baden HP. Management and treatment of ichthyosis. N Engl J Med. Apr 13 1972;286(15):821-3. [Medline].

  41. Humbert P, Agache P. Acquired ichthyosis: a new cutaneous marker of autoimmunity. Arch Dermatol. Feb 1991;127(2):263-4. [Medline].

  42. Kato N, Yasukawa K, Kimura K, Yoshida K. Anaplastic large-cell lymphoma associated with acquired ichthyosis. J Am Acad Dermatol. May 2000;42(5 Pt 2):914-20. [Medline].

  43. Kuokkanen K. Ichthyosis vulgaris. A clinical and histopathological study of patients and their close relatives in the autosomal dominant and sex-linked forms of the disease. Acta Derm Venereol Suppl (Stockh). 1969;62:1-72. [Medline].

  44. Liu P, Yang Q, Wang X, et al. Identification of a genetic locus for ichthyosis vulgaris on chromosome 10q22.3-q24.2. J Invest Dermatol. Jun 2008;128(6):1418-22. [Medline].

  45. Nirunsuksiri W, Presland RB, Brumbaugh SG, Dale BA, Fleckman P. Decreased profilaggrin expression in ichthyosis vulgaris is a result of selectively impaired posttranscriptional control. J Biol Chem. Jan 13 1995;270(2):871-6. [Medline].

  46. Nirunsuksiri W, Zhang SH, Fleckman P. Reduced stability and bi-allelic, coequal expression of profilaggrin mRNA in keratinocytes cultured from subjects with ichthyosis vulgaris. J Invest Dermatol. Jun 1998;110(6):854-61. [Medline].

  47. Patel N, Spencer LA, English JC 3rd, Zirwas MJ. Acquired ichthyosis. J Am Acad Dermatol. Oct 2006;55(4):647-56. [Medline].

  48. Presland RB, Boggess D, Lewis SP, Hull C, Fleckman P, Sundberg JP. Loss of normal profilaggrin and filaggrin in flaky tail (ft/ft) mice: an animal model for the filaggrin-deficient skin disease ichthyosis vulgaris. J Invest Dermatol. Dec 2000;115(6):1072-81. [Medline].

  49. Rawlings AV, Scott IR, Harding CR, Bowser PA. Stratum corneum moisturization at the molecular level. J Invest Dermatol. Nov 1994;103(5):731-41. [Medline].

  50. Schwartz JL, Goldsmith LA. The history of genodermatoses. Clin Dermatol. Jan-Mar 1985;3(1):7-13. [Medline].

  51. Schwartz RA, Williams ML. Acquired ichthyosis: a marker for internal disease. Am Fam Physician. Feb 1984;29(2):181-4. [Medline].

  52. Scott IR, Harding CR, Barrett JG. Histidine-rich protein of the keratohyalin granules. Source of the free amino acids, urocanic acid and pyrrolidone carboxylic acid in the stratum corneum. Biochim Biophys Acta. Oct 28 1982;719(1):110-7. [Medline].

  53. Shwayder T, Ott F. All about ichthyosis. Pediatr Clin North Am. Aug 1991;38(4):835-57. [Medline].

  54. 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. Mar 1985;84(3):191-4. [Medline].

  55. Thomas JR 3rd, Doyle JA. The therapeutic uses of topical vitamin A acid. J Am Acad Dermatol. May 1981;4(5):505-13. [Medline].

  56. Wells RS. Ichthyosis. Br Med J. Dec 17 1966;2(5528):1504-6. [Medline].

  57. Wells RS, Kerr CB. Clinical features of autosomal dominant and sex-linked ichthyosis in an English population. Brit Med J. April 1966;1:947-50.

  58. Wells RS, Kerr CB. The histology of ichthyosis. J Invest Dermatol. 1966;46:530-5.

  59. Ziprkowski L, Feinstein A. A survey of ichthyosis vulgaris in Israel. Br J Dermatol. Jan 1972;86(1):1-8. [Medline].

 
Previous
Next
 
Hereditary ichthyosis vulgaris with thick scaling of the anterior shins.
Hematoxylin and eosin staining of acquired ichthyosis vulgaris in an adult. Shows epidermal atrophy with thinning of the granular layer. No dermal infiltrate is evident.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.