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Epidermolytic hyperkeratosis 1(EHK1)

MedGen UID:
1826137
Concept ID:
C5781874
Disease or Syndrome
Synonyms: BULLOUS CONGENITAL ICHTHYOSIFORM ERYTHRODERMA; EHK1
 
Gene (location): KRT1 (12q13.13)
 
Monarch Initiative: MONDO:0700249
OMIM®: 113800

Definition

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. [from OMIM]

Clinical features

From HPO
Palmoplantar keratosis
MedGen UID:
44017
Concept ID:
C0022596
Disease or Syndrome
Abnormal thickening of the skin localized to the palm of the hand and the sole of the foot.
Erythroderma
MedGen UID:
3767
Concept ID:
C0011606
Disease or Syndrome
An inflammatory exfoliative dermatosis involving nearly all of the surface of the skin. Erythroderma develops suddenly. A patchy erythema may generalize and spread to affect most of the skin. Scaling may appear in 2-6 days and be accompanied by hot, red, dry skin, malaise, and fever.
Epidermolytic ichthyosis
MedGen UID:
38179
Concept ID:
C0079153
Disease or Syndrome
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).\n\nAs 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.\n\nEpidermolytic 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.\n\nEpidermolytic 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.
Epidermal acanthosis
MedGen UID:
65136
Concept ID:
C0221270
Finding
Diffuse hypertrophy or thickening of the stratum spinosum of the epidermis (prickle cell layer of the skin).
Scaling skin
MedGen UID:
472970
Concept ID:
C0237849
Finding
Refers to the loss of the outer layer of the epidermis in large, scale-like flakes.
Abnormal blistering of the skin
MedGen UID:
412159
Concept ID:
C2132198
Finding
The presence of one or more bullae on the skin, defined as fluid-filled blisters more than 5 mm in diameter with thin walls.

Professional guidelines

PubMed

Tsai JH, Tsai TF
Dermatitis 2024 Jan-Feb;35(1):24-42. Epub 2023 May 19 doi: 10.1089/derm.2022.0096. PMID: 37205852
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
DiGiovanna JJ, Robinson-Bostom L
Am J Clin Dermatol 2003;4(2):81-95. doi: 10.2165/00128071-200304020-00002. PMID: 12553849

Recent clinical studies

Etiology

Pondeljak N, Lugović-Mihić L, Tomić L, Parać E, Pedić L, Lazić-Mosler E
Int J Mol Sci 2023 Dec 23;25(1) doi: 10.3390/ijms25010236. PMID: 38203406Free PMC Article
Roy SF, Ghazawi FM, Choate KA, McNiff JM
J Cutan Pathol 2019 May;46(5):305-309. Epub 2019 Feb 8 doi: 10.1111/cup.13422. PMID: 30663082
DiGiovanna JJ, Robinson-Bostom L
Am J Clin Dermatol 2003;4(2):81-95. doi: 10.2165/00128071-200304020-00002. PMID: 12553849
DiGiovanna JJ, Bale SJ
Arch Dermatol 1994 Aug;130(8):1026-35. PMID: 8053700
Bale SJ, Compton JG, DiGiovanna JJ
Semin Dermatol 1993 Sep;12(3):202-9. PMID: 7692917

Diagnosis

Tsai JH, Tsai TF
Dermatitis 2024 Jan-Feb;35(1):24-42. Epub 2023 May 19 doi: 10.1089/derm.2022.0096. PMID: 37205852
Kumar P, Kumar R, Mandal RK, Hassan S
Dermatol Online J 2014 Jan 15;20(1):21248. PMID: 24456951
Lacz NL, Schwartz RA, Kihiczak G
Int J Dermatol 2005 Jan;44(1):1-6. doi: 10.1111/j.1365-4632.2004.02364.x. PMID: 15663649
Bale SJ, Compton JG, DiGiovanna JJ
Semin Dermatol 1993 Sep;12(3):202-9. PMID: 7692917
Brownstein MH
J Am Acad Dermatol 1988 Nov;19(5 Pt 1):783-6. doi: 10.1016/s0190-9622(88)70234-0. PMID: 2461398

Therapy

Tsai JH, Tsai TF
Dermatitis 2024 Jan-Feb;35(1):24-42. Epub 2023 May 19 doi: 10.1089/derm.2022.0096. PMID: 37205852
Dai C, Sokumbi O, Bruce A, Thielen JM, Sluzevich JC
Dermatol Online J 2021 Jan 15;27(1) PMID: 33560797
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
Lacz NL, Schwartz RA, Kihiczak G
Int J Dermatol 2005 Jan;44(1):1-6. doi: 10.1111/j.1365-4632.2004.02364.x. PMID: 15663649
DiGiovanna JJ, Robinson-Bostom L
Am J Clin Dermatol 2003;4(2):81-95. doi: 10.2165/00128071-200304020-00002. PMID: 12553849

Prognosis

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
Ross R, DiGiovanna JJ, Capaldi L, Argenyi Z, Fleckman P, Robinson-Bostom L
J Am Acad Dermatol 2008 Jul;59(1):86-90. doi: 10.1016/j.jaad.2008.02.031. PMID: 18571597Free PMC Article
DiGiovanna JJ, Robinson-Bostom L
Am J Clin Dermatol 2003;4(2):81-95. doi: 10.2165/00128071-200304020-00002. PMID: 12553849

Clinical prediction guides

Ansai O, Miyauchi T, Hayashi R, Katsumi T, Nishiguchi T, Hasegawa A, Shinkuma S, Natsuga K, Nomura T, Shimomura Y, Abe R
Clin Exp Dermatol 2023 Mar 1;48(3):199-210. doi: 10.1093/ced/llac069. PMID: 36656063
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
Putra PB, Radiono S, Danarti R
Dermatol Online J 2021 Feb 15;27(2) PMID: 33818988
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
Ross R, DiGiovanna JJ, Capaldi L, Argenyi Z, Fleckman P, Robinson-Bostom L
J Am Acad Dermatol 2008 Jul;59(1):86-90. doi: 10.1016/j.jaad.2008.02.031. PMID: 18571597Free PMC Article

Recent systematic reviews

Ross R, DiGiovanna JJ, Capaldi L, Argenyi Z, Fleckman P, Robinson-Bostom L
J Am Acad Dermatol 2008 Jul;59(1):86-90. doi: 10.1016/j.jaad.2008.02.031. PMID: 18571597Free PMC Article

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