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Epidermolytic ichthyosis(BCIE; BIE; EI)

MedGen UID:
38179
Concept ID:
C0079153
Disease or Syndrome
Synonyms: Bullous erythroderma ichthyosiformis congenita of Brocq; Bullous ichthyosiform erythroderma; Bullous ichthyosiform erythroderma congenita; Congenital bullous ichthyosiform erythroderma; Epidermolytic Hyperkeratosis; KRT1-Related Epidermolytic Hyperkeratosis; KRT10-Related Epidermolytic Hyperkeratosis
SNOMED CT: Congenital bullous ichthyosiform erythroderma (254167000); Dominant ichthyosis vulgaris (254167000); Epidermolytic palmoplantar hyperkeratosis (239071005); Bullous ichthyosis (254167000); Bullous ichthyosiform erythroderma (254167000); Epidermolytic hyperkeratosis (254167000); BIE - Bullous ichthyosiform erythroderma (254167000)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Related genes: KRT10, KRT1
 
HPO: HP:0007475
Monarch Initiative: MONDO:0007239
OMIM®: 113800
OMIM® Phenotypic series: PS113800
Orphanet: ORPHA312

Definition

Epidermolytic hyperkeratosis is a skin disorder that is present at birth. Affected babies may have very red skin (erythroderma) and severe blisters. Because newborns with this disorder are missing the protection provided by normal skin, they are at risk of becoming dehydrated and developing infections in the skin or throughout the body (sepsis).

As affected individuals get older, blistering is less frequent, erythroderma becomes less evident, and the skin becomes thick (hyperkeratotic), especially over joints, on areas of skin that come into contact with each other, or on the scalp or neck. This thickened skin is usually darker than normal. Bacteria can grow in the thick skin, often causing a distinct odor.

Epidermolytic hyperkeratosis can be categorized into two types. People with PS-type epidermolytic hyperkeratosis have thick skin on the palms of their hands and soles of their feet (palmoplantar or palm/sole hyperkeratosis) in addition to other areas of the body. People with the other type, NPS-type, do not have extensive palmoplantar hyperkeratosis but do have hyperkeratosis on other areas of the body.

Epidermolytic hyperkeratosis is part of a group of conditions called ichthyoses, which refers to the scaly skin seen in individuals with related disorders. However, in epidermolytic hyperkeratosis, the skin is thick but not scaly as in some of the other conditions in the group. [from MedlinePlus Genetics]

Conditions with this feature

Ichthyosis bullosa of Siemens
MedGen UID:
98153
Concept ID:
C0432306
Congenital Abnormality
Ichthyosis bullosa of Siemens (IBS) is an autosomal dominant congenital bullous ichthyosis without erythroderma. Blistering occurs in response to mild physical trauma and results in superficial erosion ('molting') of the outer skin, particularly on flexures, shins, and the periumbilical region. Keratin filament aggregates are seen by electron microscopy in the granular and upper spinous layers of the epidermis (summary by McLean et al., 1994).
Annular epidermolytic ichthyosis
MedGen UID:
334410
Concept ID:
C1843463
Disease or Syndrome
A rare clinical variant of epidermolytic ichthyosis, with manifestations of blistering phenotype at birth and the development from early infancy of annular polycyclic erythematous scales on the trunk and extremities. It has been reported in less than 10 families. The disease is caused by mutations in the KRT1 (12q11-q13) and KRT10 (17q21-q23) genes, encoding keratins 1 and 10 respectively. These mutations impair keratin filament formation and weaken the structural stability of the keratinocyte cytoskeleton. Transmission is autosomal dominant.
Ectodermal dysplasia-cutaneous syndactyly syndrome
MedGen UID:
462159
Concept ID:
C3150809
Disease or Syndrome
Palmoplantar keratoderma, nonepidermolytic, focal 1
MedGen UID:
1644485
Concept ID:
C4552049
Disease or Syndrome
Focal nonepidermolytic palmoplantar keratoderma-1 (FNEPPK1) is an autosomal dominant skin disorder characterized by large, hard, compact, painful masses of keratin that develop at sites of recurrent friction, principally on the feet, though also on the palms and other sites, without evidence of epidermolysis (summary by Kelsell et al., 1995).
Epidermolytic hyperkeratosis 1
MedGen UID:
1826137
Concept ID:
C5781874
Disease or Syndrome
Epidermolytic hyperkeratosis-1 (EHK1) is a rare autosomal dominant disorder of cornification. The disorder usually presents at birth with erythema and blistering and is characterized in adulthood by warty flexural hyperkeratosis with fewer erosions and blisters. Ultrastructural analysis reveals clumping of the intermediate filaments within keratinocytes of the spinous and granular layers (summary by Whittock et al., 2001). A form of epidermolytic hyperkeratosis that is limited to the palms and soles, designated palmoplantar keratoderma (EPPK; 144200), can also be caused by mutation in KRT1, as well KRT9 (607606). Genetic Heterogeneity of Epidermolytic Hyperkeratosis Mutation in the KRT10 gene (148080) results in both autosomal dominant (EHK2A; 620150) and autosomal recessive (EHK2B; 620707) forms of epidermolytic hyperkeratosis.

Professional guidelines

PubMed

Clabbers J, van Oosten NV, Bolling M, Vreeburg M, van Geel M, Steijlen P, Gostynski A
Dermatology 2024;240(1):170-177. Epub 2023 Sep 4 doi: 10.1159/000533934. PMID: 37666225
Vahlquist A, Fischer J, Törmä H
Am J Clin Dermatol 2018 Feb;19(1):51-66. doi: 10.1007/s40257-017-0313-x. PMID: 28815464Free PMC Article
Arin MJ, Oji V, Emmert S, Hausser I, Traupe H, Krieg T, Grimberg G
Br J Dermatol 2011 Feb;164(2):442-7. doi: 10.1111/j.1365-2133.2010.10096.x. PMID: 21271994

Recent clinical studies

Etiology

Kiener S, Castilla E, Jagannathan V, Welle M, Leeb T
Anim Genet 2023 Aug;54(4):562-565. Epub 2023 Mar 26 doi: 10.1111/age.13319. PMID: 36967672
Lefferdink R, Rangel SM, Chima M, Ibler E, Pavel AB, Kim H, Wu B, Abu-Zayed H, Wu J, Jackson K, Singer G, Choate KA, Guttman-Yassky E, Paller AS
Arch Dermatol Res 2023 Mar;315(2):305-315. Epub 2022 Feb 26 doi: 10.1007/s00403-022-02325-3. PMID: 35218370Free PMC Article
Tham KC, Lefferdink R, Duan K, Lim SS, Wong XFCC, Ibler E, Wu B, Abu-Zayed H, Rangel SM, Del Duca E, Chowdhury M, Chima M, Kim HJ, Lee B, Guttman-Yassky E, Paller AS, Common JEA
Br J Dermatol 2022 Oct;187(4):557-570. Epub 2022 Jul 4 doi: 10.1111/bjd.21687. PMID: 35633118Free PMC Article
Traupe H, Fischer J, Oji V
J Dtsch Dermatol Ges 2014 Feb;12(2):109-21. Epub 2013 Oct 11 doi: 10.1111/ddg.12229. PMID: 24119255
Hamada T, Tsuruta D, Fukuda S, Ishii N, Teye K, Numata S, Dainichi T, Karashima T, Ohata C, Furumura M, Hashimoto T
Exp Dermatol 2013 Feb;22(2):83-7. Epub 2012 Oct 8 doi: 10.1111/exd.12021. PMID: 23039137

Diagnosis

Pan S, Leszczynska MA, Parekh P, Hendrick SJ
J Pediatr 2023 Dec;263:113711. Epub 2023 Aug 30 doi: 10.1016/j.jpeds.2023.113711. PMID: 37657660
Almuqarrab FJ, Alakloby OM, Alqahtani JM, Hennies HC
Am J Case Rep 2022 Feb 24;23:e935393. doi: 10.12659/AJCR.935393. PMID: 35202349Free PMC Article
Shah KM, Silverman RA, Mauskar MM
Pediatr Dermatol 2022 Jan;39(1):128-129. doi: 10.1111/pde.14880. PMID: 35106818
Mendes SR, Gameiro AR, Cardoso JC, Reis JP
BMJ Case Rep 2021 Feb 18;14(2) doi: 10.1136/bcr-2020-240424. PMID: 33602779Free PMC Article
Eskin-Schwartz M, Drozhdina M, Sarig O, Gat A, Jackman T, Isakov O, Shomron N, Samuelov L, Malchin N, Peled A, Vodo D, Hovnanian A, Ruzicka T, Koshkin S, Harmon RM, Koetsier JL, Green KJ, Paller AS, Sprecher E
Am J Dermatopathol 2017 Jun;39(6):440-444. doi: 10.1097/DAD.0000000000000674. PMID: 28121638Free PMC Article

Therapy

Tanahashi K, Kono M, Yoshikawa T, Suzuki Y, Inoie M, Kuwatsuka Y, Kinoshita F, Takeichi T, Akiyama M
Br J Dermatol 2024 Aug 14;191(3):397-404. doi: 10.1093/bjd/ljae193. PMID: 38739763
Lefferdink R, Rangel SM, Chima M, Ibler E, Pavel AB, Kim H, Wu B, Abu-Zayed H, Wu J, Jackson K, Singer G, Choate KA, Guttman-Yassky E, Paller AS
Arch Dermatol Res 2023 Mar;315(2):305-315. Epub 2022 Feb 26 doi: 10.1007/s00403-022-02325-3. PMID: 35218370Free PMC Article
Vahlquist A, Fischer J, Törmä H
Am J Clin Dermatol 2018 Feb;19(1):51-66. doi: 10.1007/s40257-017-0313-x. PMID: 28815464Free PMC Article
Sethuraman G, Marwaha RK, Challa A, Yenamandra VK, Ramakrishnan L, Thulkar S, Sharma VK
Pediatrics 2016 Jan;137(1) Epub 2015 Dec 31 doi: 10.1542/peds.2015-1313. PMID: 26721572
Bygum A, Virtanen M, Brandrup F, Gånemo A, Sommerlund M, Strauss G, Vahlquist A
Acta Derm Venereol 2013 May;93(3):309-13. doi: 10.2340/00015555-1447. PMID: 22930352

Prognosis

Nelson JM, Isaac JM, Mervak JE, Mancuso JB, Chan MP, Arreola A, Cha KB
Pediatr Dermatol 2024 Sep-Oct;41(5):780-785. Epub 2024 Jun 19 doi: 10.1111/pde.15676. PMID: 38898621
Mo R, Lin M, Lee M, Yan W, Wang H, Lin Z
J Eur Acad Dermatol Venereol 2022 Oct;36(10):1857-1862. Epub 2022 May 12 doi: 10.1111/jdv.18189. PMID: 35490383
Vahlquist A, Fischer J, Törmä H
Am J Clin Dermatol 2018 Feb;19(1):51-66. doi: 10.1007/s40257-017-0313-x. PMID: 28815464Free PMC Article
Eskin-Schwartz M, Drozhdina M, Sarig O, Gat A, Jackman T, Isakov O, Shomron N, Samuelov L, Malchin N, Peled A, Vodo D, Hovnanian A, Ruzicka T, Koshkin S, Harmon RM, Koetsier JL, Green KJ, Paller AS, Sprecher E
Am J Dermatopathol 2017 Jun;39(6):440-444. doi: 10.1097/DAD.0000000000000674. PMID: 28121638Free PMC Article
Chamcheu JC, Siddiqui IA, Syed DN, Adhami VM, Liovic M, Mukhtar H
Arch Biochem Biophys 2011 Apr 15;508(2):123-37. Epub 2010 Dec 19 doi: 10.1016/j.abb.2010.12.019. PMID: 21176769Free PMC Article

Clinical prediction guides

Nelson JM, Isaac JM, Mervak JE, Mancuso JB, Chan MP, Arreola A, Cha KB
Pediatr Dermatol 2024 Sep-Oct;41(5):780-785. Epub 2024 Jun 19 doi: 10.1111/pde.15676. PMID: 38898621
Lefferdink R, Rangel SM, Chima M, Ibler E, Pavel AB, Kim H, Wu B, Abu-Zayed H, Wu J, Jackson K, Singer G, Choate KA, Guttman-Yassky E, Paller AS
Arch Dermatol Res 2023 Mar;315(2):305-315. Epub 2022 Feb 26 doi: 10.1007/s00403-022-02325-3. PMID: 35218370Free PMC Article
Tham KC, Lefferdink R, Duan K, Lim SS, Wong XFCC, Ibler E, Wu B, Abu-Zayed H, Rangel SM, Del Duca E, Chowdhury M, Chima M, Kim HJ, Lee B, Guttman-Yassky E, Paller AS, Common JEA
Br J Dermatol 2022 Oct;187(4):557-570. Epub 2022 Jul 4 doi: 10.1111/bjd.21687. PMID: 35633118Free PMC Article
Eskin-Schwartz M, Drozhdina M, Sarig O, Gat A, Jackman T, Isakov O, Shomron N, Samuelov L, Malchin N, Peled A, Vodo D, Hovnanian A, Ruzicka T, Koshkin S, Harmon RM, Koetsier JL, Green KJ, Paller AS, Sprecher E
Am J Dermatopathol 2017 Jun;39(6):440-444. doi: 10.1097/DAD.0000000000000674. PMID: 28121638Free PMC Article
Knöbel M, O'Toole EA, Smith FJ
Cell Tissue Res 2015 Jun;360(3):583-9. Epub 2015 Jan 27 doi: 10.1007/s00441-014-2105-4. PMID: 25620412

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