eMedicine Specialties > Dermatology > Pediatric Diseases

Ichthyosis, Lamellar

Heather Kiraly Orkwis, Philadelphia College of Osteopathic Medicine
Theresa Dressler Conologue, DO, FAAD, Physician, Department of Dermatology, Geisinger Medical Center; Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas Health Science Center-San Antonio

Updated: Mar 23, 2009

Introduction

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.

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 follows² :

• TGM1 (14q11)
• ABCA12 (2q34)
• 19p12-q12
• 19p13
• ALOXE3-ALOX12B (17p13)
• ichthyin (5q33)

Frequency

United States

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

Mortality/Morbidity

• In the neonatal period, following the shedding of the collodion membrane, the newborn is at risk for secondary sepsis and hypernatremic dehydration.
• As the child ages, the hyperkeratosis can interfere with normal sweat gland function, which can predispose to heat intolerance and possible heat shock. Ectropion may result in the inability to fully close the eyelids and can cause exposure keratitis.

Race

• Lamellar ichthyosis affects all populations.

Sex

• Incidence in males and females is equal.

Age

• The disease is present at birth and continues throughout life.
• A rare phenotype of lamellar ichthyosis has been described in South Africa. The term bathing-suit ichthyosis describes the characteristic distribution of the lesions, which involve the trunk, the proximal parts of the upper limbs, the scalp, and the neck, with sparing of the central face and extremities. This form of lamellar ichthyosis is caused by a homozygous missense mutation in TGM1.^3,4

Clinical

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

• Skin: The disease is characterized by generalized scales, which range from fine and white to thick, dark, and platelike. The scales are arranged in a mosaic pattern resembling fish skin. The lesions involve the entire body and are increased in flexural surfaces such as the axilla, groin, antecubital fossa, and neck. The individual scales tend to be larger over the legs and, in some areas, are centrally attached and raised at the edges.

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

• Nail abnormalities: These include secondary dystrophy with nail fold inflammation, subungual hyperkeratosis, and longitudinal or transverse stippling. The nails may grow 2-3 times the normal rate.

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

• Scalp: Scarring alopecia can result from the overall tightness of skin and the thick stratum corneum entrapping hairs. The hair may be thin and fine but, similar to the nails, can grow at 2-3 times the normal rate.
• Other findings: The lips and mucous membranes tend to be spared. Other associated features are ectropion, eclabium, bilateral conjunctivitis, small and deformed ears, and inflexible digits due to taut skin.

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

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.⁵

Differential Diagnoses

Ichthyosis Fetalis
Ichthyosis Vulgaris, Hereditary and Acquired
Ichthyosis, X-Linked
Rud Syndrome
Sjogren-Larsson Syndrome

Other Problems to Be Considered

Congenital ichthyosiform erythroderma
Conradi disease
Netherton syndrome
Trichothiodystrophy
Lamellar exfoliation of the newborn

Workup

Laboratory Studies

• As a result of the abnormal skin barrier, neonatal sepsis is a significant risk in the newborn period. If sepsis is considered, perform a sepsis workup. Chemistries and fluids need to be monitored closely because of the high incidence of hypernatremia observed.

Procedures

• Skin biopsies can aid in the diagnosis of lamellar ichthyosis and detection of transglutaminase-1 expression. At birth, electron microscopy can be used to differentiate a severe collodion baby affected by lamellar ichthyosis from a baby affected by harlequin ichthyosis by demonstrating the absence of the marginal band.⁶

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.

Treatment

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

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 base⁷ ; topical N -acetylcysteine, which has an antiproliferative effect⁸ ; tazarotene topical 0.05%, a receptor-selective retinoid⁹ ; and calcipotriol, a synthetic derivative of vitamin D-3.¹⁰

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

Alpha-hydroxy acids

Decrease thickness of the epidermis and reduce corneocyte adhesion.

Lactic acid (Lac-Hydrin)

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.

Dosing

Adult

Apply topically to affected areas bid after bathing

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause stinging and burning at application site; caution when using on face (potential irritation)

Topical retinoids

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

Tretinoin (Retin-A, Avita)

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

Dosing

Adult

Apply topically to affected areas qhs

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

Toxicity increases with coadministration of benzoyl peroxide, salicylic acid, or resorcinol; avoid topical sulfur, resorcinol, salicylic acid, other keratolytics, abrasives, astringents, spices, and lime

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Gels are flammable; photosensitivity may occur with excessive sunlight exposure; caution in eczema; do not apply to mucous membranes, mouth, and angles of nose

Tazarotene (Tazorac)

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

Dosing

Adult

Apply thin film qd to cover lesion (2 mg/cm²); not to exceed >20% of BSA

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; pregnancy

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

May cause burning or stinging; discontinue if excessive irritation; rinse thoroughly if contact with eyes, eyelids, or mouth; may cause severe irritation in eczematous skin; photosensitivity may occur

Systemic retinoids

Inhibit sebaceous gland function and keratinization.

Isotretinoin (Accutane)

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.

Dosing

Adult

0.5-2 mg/kg/d divided bid

Pediatric

Not established

Interactions

Toxicity may occur with vitamin A coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; may reduce plasma levels of carbamazepine

Contraindications

Documented hypersensitivity; pregnant or planning to become pregnant while undergoing treatment

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Depression, psychosis, and (rarely) suicidal ideation have been reported but linkage is debatable; has been associated with cases of pseudotumor cerebri and physician should monitor for early signs of headache, papilledema, nausea, and vomiting; decreased night vision, cornea opacities, possible onset or exacerbation of inflammatory bowel disease, elevation of plasma triglyceride levels, hyperostosis, and hepatotoxicity may occur

Acitretin (Soriatane)

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.

Dosing

Adult

Initial dose: 25 or 50 mg/d PO single dose with main meal
Maintenance dose: 25-50 mg/d PO after initial response to treatment; terminate therapy when lesions have resolved sufficiently

Pediatric

Not established

Interactions

Increases toxicity of methotrexate (avoid concomitant use); interferes with effects of microdosed progestin "minipill"; coadministration with alcohol may enhance synthesis of etretinate, which has much longer half-life than acitretin (>120 d)

Contraindications

Documented hypersensitivity; pregnant or planning to become pregnant for 3 y following discontinuation of treatment

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Hepatotoxicity with elevation of AST, ALT, GGT, or LDH occurs in approximately 1 in 3 patients; lipid elevations occur in approximately 25-50% of patients and rarely result in pancreatitis; one case of fatal hemorrhagic pancreatitis has been reported; pseudotumor cerebri may occur; may experience dry eyes and loss of lashes; decreased night vision, blepharitis, Bell palsy, cortical cataract, photophobia, and posterior subcapsular cataract may occur; patients with visual changes should discontinue treatment; hyperostosis, elevation of triglyceride levels, and lowered HDL may occur

Follow-up

Further Outpatient Care

• The family should be aware of these patient and family support groups:
  • Foundation for Ichthyosis and Related Skin Types (F.I.R.S.T), 1364 Welsh Road G2,
    North Wales, PA 19454; telephone: 215-619-0670, fax: 215-619-0780, http://www.scalyskin.org, email: info@scalyskin.org, Executive Director: Jean Pickford
  • National Registry for Ichthyosis and Related Disorders, University of Washington, Dermatology Department, Rm. BB1353, Box 356524, 1959 NE Pacific St., Seattle, WA 98195-6524; telephone: (206) 616-3179 or (800) 595-1265, www.skinregistry.org, email: info@skinregistry.org

Transfer

• Transfer the newborn to the neonatal intensive care unit for close monitoring of fluids, electrolytes, and signs of sepsis. Manual debridement of the collodion membrane is not recommended.

Deterrence/Prevention

• Prenatal diagnosis is controversial. A fetal skin biopsy at 22 weeks may aid in prenatal diagnosis. In patients with a known gene locus, DNA linkage analysis may be useful.
• The quality of life of patients with the more severe congenital ichthyoses is often seriously affected and the parents' request for prenatal diagnosis is not easily ignored. Because the recent advances in the understanding of the causative genetic defects for severe congenital ichthyosis, making DNA-based prenatal diagnosis is now possible for several congenital ichthyosis, using chorionic villus or amniotic fluid sampling procedures early in pregnancy, with a lower risk to fetal health and with a reduced burden on the parents.¹

Prognosis

• Patients with lamellar ichthyosis have normal life spans.

Patient Education

• Educate patients on the potential for heat stress disorders. Access to support groups is critical for patients and their families. The following address is for the support group for lamellar ichthyosis: Foundation for Ichthyosis and Related Skin Types, PO Box 20921, Raleigh NC 27619, telephone: (800) 545-3286

Miscellaneous

Medicolegal Pitfalls

• As with most genetic testing, prenatal diagnosis is controversial and can be a potential area for medicolegal problems. For severe congenital ichthyosis, as is the case with other genetic conditions, perhaps even earlier prenatal diagnosis by completely noninvasive analysis of DNA from fetal cells in maternal circulation, and preimplantation genetic diagnosis will be available in the future.¹
• Many of the medications used for lamellar ichthyosis have a long list of potential adverse effects, and care must be taken to discuss the advantages and disadvantages of treatment. Salicylate toxicity has been reported with systemic absorption of topical salicylic acids in the treatment of children with ichthyosis.¹¹ A case of lactic acidosis has been reported, with clinical signs of irritability, agitation, myoclonia, and difficulty walking, all which resolved upon discontinuation of the topical treatment.¹²
• Topical tacrolimus, a macrolide immunosuppressant, should be used with caution because significantly elevated systemic tacrolimus levels have been reported in a patient with lamellar ichthyosis.¹³

Multimedia

Media file 1: Collodion baby with translucent membrane of the body.

Media file 2: Keratoderma of the palms in a patient with lamellar ichthyosis. Courtesy of Dirk Elston, MD.

Media file 3: Inflexible fingers due to taut skin in a young patient with lamellar ichthyosis. Courtesy of Dirk Elston, MD.

Media file 4: Nail dystrophy and inflammation of the nail folds. Courtesy of M. Bryan, MD.

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. [Medline]. Available at http://www3.interscience.wiley.com/cgi-bin/fulltext/119407221/HTMLSTART.

2. Oji V, Traupe H. Ichthyoses: differential diagnosis and molecular genetics. Eur J Dermatol. Jul-Aug 2006;16(4):349-59. [Medline].

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. [Medline].

4. Jacyk WK. Bathing-suit ichthyosis. A peculiar phenotype of lamellar ichthyosis in South African blacks. Eur J Dermatol. Nov-Dec 2005;15(6):433-6. [Medline].

5. Huber M, Rettler I, Bernasconi K, et al. Mutations of keratinocyte transglutaminase in lamellar ichthyosis. Science. Jan 27 1995;267(5197):525-8. [Medline].

6. Sandler B, Hashimoto K. Collodion baby and lamellar ichthyosis. J Cutan Pathol. Feb 1998;25(2):116-21. [Medline].

7. Ganemo A, Virtanen M, Vahlquist A. Improved topical treatment of lamellar ichthyosis: a double-blind study of four different cream formulations. Br J Dermatol. Dec 1999;141(6):1027-32. [Medline].

8. Redondo P, Bauza A. Topical N-acetylcysteine for lamellar ichthyosis. Lancet. Nov 27 1999;354(9193):1880. [Medline].

9. Stege H, Hofmann B, Ruzicka T, Lehmann P. Topical application of tazarotene in the treatment of nonerythrodermic lamellar ichthyosis. Arch Dermatol. May 1998;134(5):640. [Medline].

10. 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. [Medline].

11. 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. [Medline].

12. Ramirez ME, Youseef WF, Romero RG, et al. Acute percutaneous lactic acid poisoning in a child. Pediatr Dermatol. May-Jun 2006;23(3):282-5. [Medline].

13. Allen DM, Esterly NB. Significant systemic absorption of tacrolimus after topical application in a patient with lamellar ichthyosis. Arch Dermatol. Sep 2002;138(9):1259-60. [Medline].

14. DiGiovanna JJ. Ichthyosiform Dermatoses. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, Fitzpatrick TB, eds. Fitzpatrick's Dermatology in General Medicine. Vol 1. 5^th ed. New York, NY: McGraw-Hill; 1999:587-8.

15. Novice FM, Collison DW, Burgdorf WHC, Esterly N, eds. Lamellar ichthyosis. In: Handbook of Genetic Skin Disorders. Philadelphia, Pa: WB Saunders; 1994:9-12.

16. Spitz JL. Lamellar ichthyosis. In: Spitz JL, ed. Genodermatoses. Baltimore, Md: Williams & Wilkins; 1996:8-9.

17. Sybert VP. Lamellar Ichthyosis. In: Sybert VP, ed. Genetic Skin Disorders. ed. New York, NY: Oxford University Press; 1997:27-30.

Keywords

lamellar ichthyosis, ichthyosis, congenital ichthyosis, nonbullous congenital ichthyosiform erythroderma, non-bullous congenital ichthyosiform erythroderma, autosomal recessive ichthyosis, erythrodermic autosomal recessive lamellar ichthyosis, EARI, nonerythrodermic autosomal recessive lamellar ichthyosis, NEARLI, non-erythrodermic autosomal recessive lamellar ichthyosis

Contributor Information and Disclosures

Author

Heather Kiraly Orkwis, Philadelphia College of Osteopathic Medicine
Heather Kiraly Orkwis is a member of the following medical societies: Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Theresa Dressler Conologue, DO, FAAD, Physician, Department of Dermatology, Geisinger Medical Center
Theresa Dressler Conologue, DO, FAAD is a member of the following medical societies: American Academy of Cosmetic Surgery, American Academy of Dermatology, and American Society for Laser Medicine and Surgery
Disclosure: Nothing to disclose.

Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas Health Science Center-San Antonio
Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society
Disclosure: Nothing to disclose.

Medical Editor

Daniel J Hogan, MD, Clinical Professor of Internal Medicine (Dermatology), NOVA Southeastern University; Investigator, Hill Top Research, Florida Research Center
Daniel J Hogan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Contact Dermatitis Society, and Canadian Dermatology Association
Disclosure: Nothing to disclose.

Pharmacy Editor

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.

Managing Editor

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas Health Science Center
Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery
Disclosure: Nothing to disclose.

CME Editor

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
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

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.

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

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)