Lamellar Ichthyosis

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Background

Lamellar ichthyosis (LI) is an autosomal recessive disorder that is apparent at birth and is present throughout life. The newborn is born encased in a collodion membrane that sheds within 10-14 days. The shedding of the membrane reveals generalized scaling with variable redness of the skin. The scaling may be fine or platelike, resembling fish skin. Although the disorder is not life threatening, it is quite disfiguring and causes considerable psychological stress to affected patients.

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Collodion baby with translucent membrane of the body.

Pathophysiology

Patients with lamellar ichthyosis have accelerated epidermal turnover with proliferative hyperkeratosis, in contrast to retention hyperkeratosis. This involves a mutation in the gene for transglutaminase 1 (TGM1). The transglutaminase 1 enzyme is involved in the formation of the cornified cell envelope. The formation of the cornified cell envelope is an essential scaffold upon which normal intercellular lipid layer formation in the stratum corneum occurs. Thus, mutations in the TGM1 secondarily cause defects in the intercellular lipid layers in the stratum corneum, leading to defective barrier function of the stratum corneum and to the ichthyotic phenotype seen in lamellar ichthyosis patients and in transglutaminase 1 knockout mice. How much a defective cornified cell envelope alone contributes to the barrier abnormality in ichthyoses remains unclear.[1]

To date, 6 genes for lamellar ichthyosis have been localized and 5 of them identified, as follows[2] :

Epidemiology

Frequency

United States

Prevalence is less than 1 case per 300,000 individuals.

Mortality/Morbidity

Race

Sex

Age

Physical

Newborn period

The newborn presents encased in a tough, filmlike membrane that fissures when stretched. This collodion membrane is shed by 10-14 days, revealing generalized erythema and scaling.

Childhood and adulthood

Causes

Lamellar ichthyosis is an autosomal recessive disorder in almost all cases. Genetic linkage studies have been performed on families with classic lamellar ichthyosis and show markers on band 14q11 in the region of the TGM1 gene locus. An autosomal dominant form of lamellar ichthyosis has been described.[6, 7]

Laboratory Studies

Procedures

Histologic Findings

Skin biopsy results show a normal or thickened granular layer, mild-to-moderate hyperkeratosis with increased mitoses, and a perivascular lymphocytic infiltrate. In autosomal dominant lamellar ichthyosis, the stratum granulosum and stratum corneum are separated by a prominent transforming zone and scales contain elevated triglyceride and fatty acid levels, which aids in differentiation from autosomal recessive lamellar ichthyosis.

Medical Care

Transfer the newborn to the neonatal intensive care unit for close monitoring of fluids, electrolytes, and signs of sepsis and placement in a high-humidity incubator. Manual debridement of the collodion membrane is not recommended.

Surgical Care

Surgery is occasionally necessary for severe ectropion.

Consultations

Consult a dermatologist for the evaluation and treatment of the skin. Consult an ophthalmologist for the evaluation and management of ectropion from birth. Consult a genetics counselor for a discussion of the risks of subsequent children being affected.

Activity

A potential for heat intolerance and heat stroke is present; however, with proper counseling, activity does not need to be limited.

Medication Summary

This disorder has no cure; therefore, treatment is directed at decreasing symptoms.

Emollients should be applied after showering or bathing. The stratum corneum can absorb 6 times its weight in water, and a heavy emollient, such as petrolatum jelly (Vaseline) or water-in-oil preparations (eg, Eucerin) should be applied while the skin is still wet. Alpha-hydroxy acids, such as lactic acid (eg, Lac-Hydrin), help reduce corneocyte adhesion and decrease the thickness of the epidermis. Urea creams can help soften scales. Salicylic acids in combination with propylene glycol help to remove dark scaling. Care must be taken when using topical salicylates over large areas, especially in children, because of reports of systemic salicylate intoxication. Topical retinoic acids (eg, Retin-A) decrease thickened scaling. Antiseptics and antimicrobials can be used topically to control odor. Because of the significant long-term adverse effects, reserve systemic retinoids for severe disease that is refractory to conventional therapy.

Newer therapies that have resulted in clinical improvement are Locobase fatty cream, which is 5% lactic acid and 20% propylene glycol in a lipophilic cream base[9] ; topical N -acetylcysteine, which has an antiproliferative effect[10, 11] ; tazarotene topical 0.05%, a receptor-selective retinoid[12] ; and calcipotriol, a synthetic derivative of vitamin D-3.[13]

Alternatively, ex vivo gene therapy has been reported for lamellar ichthyosis, with which normal gene expression of TGM1 has been restored and the phenotype correction was observed in engrafted lesional skin in vivo on the back of immunodeficient mice. Gene therapy serves to be a novel therapeutic approach to lamellar ichthyosis.[1]

Ammonium lactate (Lac-Hydrin)

Clinical Context:  Relieves itching and aids healing of skin in mild eczemas and dermatoses, itching skin, minor wounds, and minor skin irritations. Twelve percent ammonium lactate in base containing propylene glycol.

Class Summary

Decrease thickness of the epidermis and reduce corneocyte adhesion.

Tretinoin topical (Retin-A, Avita)

Clinical Context:  Inhibits microcomedo formation and eliminates lesions. Makes keratinocytes in sebaceous follicles less adherent and easier to remove. Use 0.01% gel.

Tazarotene (Tazorac)

Clinical Context:  Topical gel 0.05%. Retinoid prodrug whose active metabolite modulates differentiation and proliferation of epithelial tissue; may also have anti-inflammatory and immunomodulatory properties. Make sure skin is dry before applying gel

Class Summary

Appear to decrease the cohesiveness of follicular epithelial cells and stimulate mitotic activity, resulting in an increase in turnover of follicular epithelial cells.

Isotretinoin (Accutane)

Clinical Context:  Oral agent that treats serious dermatologic conditions. Synthetic 13-cis isomer of naturally occurring tretinoin (trans -retinoic acid). Both agents are structurally related to vitamin A. Decreases sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization.

A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

Acitretin (Soriatane)

Clinical Context:  Retinoic acid analog, similar to etretinate and isotretinoin. Etretinate is main metabolite and has demonstrated clinical effects similar to those seen with etretinate. Mechanism of action is unknown.

Class Summary

Inhibit sebaceous gland function and keratinization.

Further Outpatient Care

Transfer

Deterrence/Prevention

Prognosis

Author

Heather Kiraly Orkwis, Philadelphia College of Osteopathic Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio

Disclosure: Nothing to disclose.

Theresa Dressler Conologue, DO, FAAD, Physician, Department of Dermatology, Geisinger Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Daniel J Hogan, MD, Clinical Professor of Internal Medicine (Dermatology), Nova Southeastern University College of Osteopathic Medicine; Investigator, Hill Top Research, Florida Research Center

Disclosure: Nothing to disclose.

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

Disclosure: Nothing to disclose.

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Disclosure: Nothing to disclose.

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD, Director, Ackerman Academy of Dermatopathology, New York

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous Chief Editor, William D. James, MD, to the development and writing of this article.

References

  1. Akiyama M, Shimizu H. An update on molecular aspects of the non-syndromic ichthyoses. Experimental Dermatology [serial online]. March 13, 2008;17:373-382. Available from: Medline. Accessed January 17, 2009. . Available at http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0625.2007.00691.x/pdf[View Abstract]
  2. Oji V, Traupe H. Ichthyoses: differential diagnosis and molecular genetics. Eur J Dermatol. Jul-Aug 2006;16(4):349-59. [View Abstract]
  3. Arita K, Jacyk WK, Wessagowit V, et al. The South African "bathing suit ichthyosis" is a form of lamellar ichthyosis caused by a homozygous missense mutation, p.R315L, in transglutaminase 1. J Invest Dermatol. Feb 2007;127(2):490-3. [View Abstract]
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  5. Alavi A, Shahshahani MM, Klotzle B, Fan JB, Ronaghi M, Elahi E. Manifestation of diffuse yellowish keratoderma on the palms and soles in autosomal recessive congenital ichthyosis patients may be indicative of mutations in NIPAL4. J Dermatol. Nov 21 2011;[View Abstract]
  6. Huber M, Rettler I, Bernasconi K, et al. Mutations of keratinocyte transglutaminase in lamellar ichthyosis. Science. Jan 27 1995;267(5197):525-8. [View Abstract]
  7. Hernández-Martín A, Garcia-Doval I, Aranegui B, de Unamuno P, Rodríguez-Pazos L, González-Enseñat MA, et al. Prevalence of autosomal recessive congenital ichthyosis: A population-based study using the capture-recapture method in Spain. J Am Acad Dermatol. Oct 13 2011;[View Abstract]
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  13. 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. May 1995;131(5):556-60. [View Abstract]
  14. Basgul AY, Kavak ZN, Guducu N, Durukan B, Isci H. Prenatal diagnosis of congenital harlequin ichthyosis with 2D, 3D, and 4D ultrasonography. Clin Exp Obstet Gynecol. 2011;38(3):283-5. [View Abstract]
  15. Abdel-Magid EH, el-Awad Ahmed FR. Salicylate intoxication in an infant with ichthyosis transmitted through skin ointment--a case report. Pediatrics. Dec 1994;94(6 Pt 1):939-40. [View Abstract]
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Collodion baby with translucent membrane of the body.

Keratoderma of the palms in a patient with lamellar ichthyosis. Courtesy of Dirk Elston, MD.

Nail dystrophy and inflammation of the nail folds. Courtesy of M. Bryan, MD.

Inflexible fingers due to taut skin in a young patient with lamellar ichthyosis. Courtesy of Dirk Elston, MD.

Collodion baby with translucent membrane of the body.

Keratoderma of the palms in a patient with lamellar ichthyosis. Courtesy of Dirk Elston, MD.

Inflexible fingers due to taut skin in a young patient with lamellar ichthyosis. Courtesy of Dirk Elston, MD.

Nail dystrophy and inflammation of the nail folds. Courtesy of M. Bryan, MD.