Background

Epidermolytic ichthyosis (EI), formerly known as epidermolytic hyperkeratosis (EHK) or bullous congenital ichthyosiform erythroderma (bullous CIE),^[1]is a form of congenital ichthyosis. It is inherited in an autosomal dominant fashion, with about 50% of cases representing spontaneous mutations. Epidermolytic ichthyosis presents at birth with erythroderma, blisters, and erosions and evolves over time into varying degrees of hyperkeratosis.

Next: Pathophysiology

Pathophysiology

Epidermolytic ichthyosis results from heterozygous mutations in the genes encoding keratin 1 (KRT1) and keratin 10 (KRT10).^[2]Mutations cause defects that compromise keratin alignment and assembly of intermediate filaments, leading to cellular collapse, blistering, and impaired barrier function. Compensatory hyperproliferation leads to hyperkeratosis.

Next: Pathophysiology

Etiology of Epidermolytic Ichthyosis

Defects in genes for keratin 1 (KRT1) and 10 (KRT10) are the cause of epidermolytic ichthyosis.^{[3, 4, 5, 6, 7]}Usually, these mutations are missense substitutions into the highly conserved alpha-helical rod and the nonhelical H1 domains of the keratin proteins.^[8]

Palmoplantar keratoderma is usually associated with KRT1 mutations; however, in rare cases, palmoplantar keratoderma may be observed in patients with KRT10 mutations.^[9]Novel mutations in both genes continue to be reported.

Patients with generalized epidermolytic ichthyosis may be born to parents with epidermolytic epidermal nevi (mosaic epidermolytic ichthyosis).^{[10, 11]}Epidermal nevi with histologic changes of epidermolytic hyperkeratosis are caused by postzygotic mutations in keratin 1 or keratin 10. If the mutation also involves gonadal cells, which is thought to be more likely in patients with more extensive cutaneous involvement, affected individuals can have offspring with generalized epidermolytic ichthyosis.

Next: Pathophysiology

Epidemiology

Frequency

The incidence of epidermolytic hyperkeratosis is estimated to be 1 in 200,000-300,000.

Race

No racial predilection is apparent for epidermolytic ichthyosis.

Sex

No sex predilection is recognized for epidermolytic ichthyosis.

Age

Epidermolytic ichthyosis is a lifelong condition with an onset at birth or in the neonatal period.

Next: Pathophysiology

Prognosis

Epidermolytic ichthyosis is a lifelong condition. Some patients may experience amelioration of symptoms as they age. Risk for morbidity and mortality is highest in the neonatal period, where infants are at increased risk for complications such as sepsis and dehydration because of impaired barrier function. Later in life, affected patients may experience recurrent skin infections.

Next: Pathophysiology

Patient Education

Educate patients with epidermolytic ichthyosis about the potential of passing the genetic defect on to offspring.

Clinical Presentation

Rice AS, Crane JS. Epidermolytic Hyperkeratosis. Stat Pearls [Internet]. 2021 Jan. [QxMD MEDLINE Link]. [Full Text].
Chia SY, Tan EC, Wei H, Zhao Y, Koh MJA. Epidermolytic ichthyosis in a child and systematized epidermolytic nevi in the mosaic parent associated with a KRT1 variant. Eur J Med Genet. 2021 Nov. 64 (11):104324. [QxMD MEDLINE Link].
Lacz NL, Schwartz RA, Kihiczak G. Epidermolytic hyperkeratosis: a keratin 1 or 10 mutational event. Int J Dermatol. 2005 Jan. 44(1):1-6. [QxMD MEDLINE Link].
Math A, Frank J, Handisurya A, et al. Identification of a de novo keratin 1 mutation in epidermolytic hyperkeratosis with palmoplantar involvement. Eur J Dermatol. 2006 Sep-Oct. 16(5):507-10. [QxMD MEDLINE Link].
McGowan KA, Aradhya S, Fuchs H, de Angelis MH, Barsh GS. A mouse keratin 1 mutation causes dark skin and epidermolytic hyperkeratosis. J Invest Dermatol. 2006 May. 126(5):1013-6. [QxMD MEDLINE Link].
Muller FB, Huber M, Kinaciyan T, et al. A human keratin 10 knockout causes recessive epidermolytic hyperkeratosis. Hum Mol Genet. 2006 Apr 1. 15(7):1133-41. [QxMD MEDLINE Link].
Betlloch I, Lucas Costa A, Mataix J, Pérez-Crespo M, Ballester I. Bullous congenital ichthyosiform erythroderma: a sporadic case produced by a new KRT10 gene mutation. Pediatr Dermatol. 2009 Jul-Aug. 26(4):489-91. [QxMD MEDLINE Link].
Chamcheu JC, Siddiqui IA, Syed DN, Adhami VM, Liovic M, Mukhtar H. Keratin gene mutations in disorders of human skin and its appendages. Arch Biochem Biophys. 2011 Apr 15. 508(2):123-37. [QxMD MEDLINE Link]. [Full Text].
Morais P, Mota A, Baudrier T, et al. Epidermolytic hyperkeratosis with palmoplantar keratoderma in a patient with KRT10 mutation. Eur J Dermatol. 2009 Jul-Aug. 19(4):333-6. [QxMD MEDLINE Link].
Chassaing N, Kanitakis J, Sportich S, et al. Generalized epidermolytic hyperkeratosis in two unrelated children from parents with localized linear form, and prenatal diagnosis. J Invest Dermatol. 2006 Dec. 126(12):2715-7. [QxMD MEDLINE Link].
Akhyani M, Kiavash K, Kamyab K. Bullous ichthyosiform erythroderma in a child born to a parent with systematized linear epidermolytic hyperkeratosis. Int J Dermatol. 2009 Feb. 48(2):215-7. [QxMD MEDLINE Link].
Terheyden P, Grimberg G, Hausser I, et al. Recessive epidermolytic hyperkeratosis caused by a previously unreported termination codon mutation in the keratin 10 gene. J Invest Dermatol. 2009 Nov. 129(11):2721-3. [QxMD MEDLINE Link].
Tsubota A, Akiyama M, Kanitakis J, et al. Mild recessive bullous congenital ichthyosiform erythroderma due to a previously unidentified homozygous keratin 10 nonsense mutation. J Invest Dermatol. 2008 Jul. 128(7):1648-52. [QxMD MEDLINE Link].
el-Khateeb EA. Bullous congenital ichthyosiform erythroderma associated with hypocalcemic vitamin D-resistant rickets. Pediatr Dermatol. 2008 Mar-Apr. 25(2):279-82. [QxMD MEDLINE Link].
Bhat YJ, Baba AN, Manzoor S, Qayoom S, Ahmed SM. Bullous icthyosiform erythroderma with rickets in child of a parent with naevus unius lateralis. Indian J Dermatol Venereol Leprol. 2010 Mar-Apr. 76(2):192-4. [QxMD MEDLINE Link].
Blalock TW, Teague D, Sheehan DJ. Epidermolytic hyperkeratosis and congenital platelike osteoma cutis in a child. Cutis. 2011 Jun. 87(6):278-80. [QxMD MEDLINE Link].
Russell P, Valmadre S, Howard V. Localised epidermolytic hyperkeratosis of the vulva: a case of mistaken identity. Pathology. 2010. 42(5):483-5. [QxMD MEDLINE Link].
Bergman R, Khamaysi Z, Sprecher E. A unique pattern of dyskeratosis characterizes epidermolytic hyperkeratosis and epidermolytic palmoplantar keratoderma. Am J Dermatopathol. 2008 Apr. 30(2):101-5. [QxMD MEDLINE Link].
Ross R, DiGiovanna JJ, Capaldi L, Argenyi Z, Fleckman P, Robinson-Bostom L. Histopathologic characterization of epidermolytic hyperkeratosis: a systematic review of histology from the National Registry for Ichthyosis and Related Skin Disorders. J Am Acad Dermatol. 2008 Jul. 59(1):86-90. [QxMD MEDLINE Link]. [Full Text].
Rothnagel JA, Lin MT, Longley MA, et al. Prenatal diagnosis for keratin mutations to exclude transmission of epidermolytic hyperkeratosis. Prenat Diagn. 1998 Aug. 18(8):826-30. [QxMD MEDLINE Link].
Li H, Torma H. Retinoids reduce formation of keratin aggregates in heat-stressed immortalized keratinocytes from an epidermolytic ichthyosis patient with a KRT10 mutation*. Acta Derm Venereol. 2013 Jan. 93(1):44-9. [QxMD MEDLINE Link].
Digiovanna JJ, Mauro T, Milstone LM, Schmuth M, Toro JR. Systemic retinoids in the management of ichthyoses and related skin types. Dermatol Ther. 2013 Jan-Feb. 26 (1):26-38. [QxMD MEDLINE Link].

Media Gallery

Pathology of epidermolytic ichthyosis (hematoxylin and eosin stain).
Pathology of epidermolytic ichthyosis (hematoxylin and eosin stain).
The scale in epidermolytic ichthyosis is classically described as "corrugated". Patients often experience erosions as a result of skin fragility.
The scale in epidermolytic ichthyosis is classically described as "corrugated". Patients often experience erosions as a result of skin fragility.
Palms and soles may have varying degrees of hyperkeratosis.
Hyperkeratosis involving the abdomen.
Hyperkeratosis involving the knee.

of 7

#author-disclosures{display:block}#author-disclosures.modal-layer{position:relative}#author-disclosures .modal-content{max-height:none}#author-disclosures .close-modal{display:none}

Author

Brittany G Craiglow, MD Assistant Professor of Dermatology and Pediatrics, Yale University School of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Society for Investigative Dermatology, Association of Professors of Dermatology, North American Hair Research Society

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

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

Disclosure: Nothing to disclose.

Additional Contributors

Marjan Garmyn, MD, PhD Professor, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium; Chair and Adjunct Head, Department of Dermatology, University of Leuven, Belgium

Disclosure: Nothing to disclose.

Tina S Chen Twu, MD Pediatric Dermatologist/Dermatologist, Sharp Rees-Stealy Medical Group, San Diego, CA

Tina S Chen Twu, MD is a member of the following medical societies: American Academy of Dermatology, Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

Brandie J Metz, MD Assistant Clinical Professor of Dermatology and Pediatrics, Chief of Pediatric Dermatology, University of California, Irvine, School of Medicine

Brandie J Metz, MD is a member of the following medical societies: American Academy of Dermatology, Society for Pediatric Dermatology, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Jeffrey B Smith, MD Mohs Surgery, Kaiser Permanente, San Jose, CA

Jeffrey B Smith, MD is a member of the following medical societies: American Academy of Dermatology and American College of Mohs Surgery

Disclosure: Nothing to disclose.

Sidney B Smith, MD Medical Director, Dermatologist, Dermatology, Dermacare Laser and Skin Care Clinics of Tri-Cities

Sidney B Smith, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.