- Epidermolytic hyperkeratosis
Epidermolytic hyperkeratosis Classification and external resources ICD-10 Q80.3 OMIM 113800 DiseasesDB 33392 eMedicine derm/590 MeSH D017488
Epidermolytic hyperkeratosis, (also known as "Bullous congenital ichthyosiform erythroderma," "Bullous ichthyosiform erythroderma,":482 or "bullous congenital ichthyosiform erythroderma Brocq") is a rare skin disease in the ichthyosis family affecting around 1 in 250,000 people.
At birth, affected babies are called "enfant brûlé", from the French for "burned child", because they look red and have a fragile top layer of skin which easily forms blisters and wounds. Such injury can be caused by diapers, or just by touching the baby. The wounds should be properly cared for, otherwise they are at risk from infection.
The skin is stressed by birth. It gets better after some weeks and fewer blisters are formed. Some months later the skin starts scaling; this is caused by hyperkeratosis. There is a fairly large variation in the degree and extent of the scaling and the blisters.
In particular, some patients have scaling and blisters on the palms and soles of the feet, whereas others do not. Usually scaling is seen on the rest of the body, often concentrated around the joints.
Additionally, the skin develops blisters (hence the bullous part of the name). Typically these will be more common in children than in adults. Depending on the form of the disease patients may also experience palmoplantar keratoderma and frequent superimposed infections.
It is possible to classify epidermolytic hyperkeratosis based upon palm and sole hyperkeratosis.
- Keratin 1 is associated with the variants affecting the palms and soles.
- Keratin 10 is associated with the variants in which these are unaffected.
generalized redness; thick, generally dark, scales that tend to form parallel rows of spines or ridges,especially near large joints; the skin is fragile and blisters easily following trauma; extent of blistering and amount of scale is variable
Gene Therapy is really the only true therapy on the horizon for sufferers of EHK.
Over the past 10 years since the first EHK mouse model was developed, many ideas have been discussed about how best to cure EHK. Back as far as 1994 researchers were discussing new promising ideas such as topical lotions that would deliver ribozymes in a liposom cream. Ribozymes are a small piece of synthetic RNA which can digest RNA molecules. When cells make a protein from a gene on a chromosome sitting in the nucleus, the gene is first transcribed as a piece of RNA. This RNA is then translated into a protein. Ribozymes can be designed to destroy RNA molecules with specific sequences. In theory, this will stop the production of the protein encoded by the mutant alleles of the gene. This sounded like a promising theory however virtually no research funding has been applied to this idea over the past 10 years.
Luckily other new ideas have moved to the foreground that are even more promising. Successful gene therapy solutions have been recently achieved on mouse models by Jiang Chen M.D., a post-doctoral fellow in the laboratory of Dennis Roop, Ph.D., in the Center for Cutaneous Molecular Biology at Baylor College of Medicine's departments of molecular and cellular biology and dermatology in Houston.
In 1998 they developed an inducible mouse model for epidermolysis hyperkeratosis which is viable, because the expression of a mutant K10 allele can be restricted to a focal area of the skin. "Once the mutant K10 allele is activated in epidermal stem cells by topical application of an inducer, these stem cells continuously give rise to defective progeny that form hyperkeratotic lesions which persist for the life of the mouse. It was observed that partial suppression of the mutant K10 gene may be sufficient to eliminate the disorder."
To test this observation, Dr. Chen and his team of researchers developed siRNAs that target the mutant K10 gene products for degradation, without affecting normal K10 gene products. Dr. Chen observed that under these conditions, an efficient knock-down of mutant, but not normal, K10 genes could be achieved. The results allowed the normal K10 genes to function properly building healthy skin tissues. He claims that these results may prove to be a very vital step forward in forging a novel gene therapy and possible permanent corrective therapy for this debilitating skin disease.
Larger animal models are the next step required to determine the safety and efficacy of novel in vivo therapies before testing in human subjects. A spontaneously occurring large animal model has been identified as the recessive dystrophic EB in golden retrievers where type-VII collagen is absent. This disease has successfully been corrected using retroviral vectors and ex vivo gene transfer. Norfolk Terriers have been identified as having epidermolytic hyperkeratosis naturally. Once these cases have been cured as the golden retrievers have been cured for EB, EHK will be ready for human clinical trials. If anyone is aware of this next critical step being worked on, please post details about it here.
Until gene therapy solutions finally become reality, EHK sufferers must treat their fragile skin carefully. Most have learned that taking regular extended baths allows patients to care for their fragile skin and keep it manageable. Baths that include sea salt seem to improve the process of softening and removing the thickened skin.
- Nonbullous ichthyosiform erythroderma
- Ichthyosis bullosa of Siemens
- Isotretinoin (Accutane)
- List of cutaneous conditions
- ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.
- ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0071380760.
- ^ synd/1036 at Who Named It?
- ^ Cheng J, Syder AJ, Yu QC, Letai A, Paller AS, Fuchs E (September 1992). "The genetic basis of epidermolytic hyperkeratosis: a disorder of differentiation-specific epidermal keratin genes". Cell 70 (5): 811–9. doi:10.1016/0092-8674(92)90314-3. PMID 1381287. http://linkinghub.elsevier.com/retrieve/pii/0092-8674(92)90314-3.
- ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0721629210.
- ^ DiGiovanna JJ, Bale SJ (August 1994). "Clinical heterogeneity in epidermolytic hyperkeratosis". Arch Dermatol 130 (8): 1026–35. doi:10.1001/archderm.130.8.1026. PMID 8053700.
- ^ Ross R, DiGiovanna JJ, Capaldi L, Argenyi Z, Fleckman P, Robinson-Bostom L (July 2008). "Histopathologic characterization of epidermolytic hyperkeratosis: a systematic review of histology from the National Registry for Ichthyosis and Related Skin Disorders". J. Am. Acad. Dermatol. 59 (1): 86–90. doi:10.1016/j.jaad.2008.02.031. PMC 2517215. PMID 18571597. http://linkinghub.elsevier.com/retrieve/pii/S0190-9622(08)00263-6.
- ^ Brecher AR, Orlow SJ (2003). "Oral retinoid therapy for dermatologic conditions in children and adolescents". J. Am. Acad. Dermatol. 49 (2): 171–82; quiz 183–6. doi:10.1067/S0190-9622(03)01564-0. PMID 12894062.
- ^ "Gene Therapy - Gene therapy progress and prospects: the skin - easily accessible, but still far away". http://www.nature.com/gt/journal/v13/n22/full/3302855a.html. Retrieved 2008-01-03.
Congenital malformations and deformations of integument / skin disease (Q80–Q82, 757.0–757.3) GenodermatosisCongenital ichthyosis/
erythrokeratodermiaADARUngroupedIchthyosis bullosa of Siemens · Ichthyosis follicularis · Ichthyosis prematurity syndrome · Ichthyosis–sclerosing cholangitis syndrome · Nonbullous congenital ichthyosiform erythroderma · Ichthyosis linearis circumflexa · Ichthyosis hystrixEB
keratinopathydiffuse: Diffuse epidermolytic palmoplantar keratoderma • Diffuse nonepidermolytic palmoplantar keratoderma • Palmoplantar keratoderma of Sybert • Mal de Meleda •syndromic (connexin (Bart–Pumphrey syndrome • Clouston's hidrotic ectodermal dysplasia • Vohwinkel syndrome) • Corneodermatoosseous syndrome • plakoglobin (Naxos syndrome) • Scleroatrophic syndrome of Huriez • Olmsted syndrome • Cathepsin C (Papillon–Lefèvre syndrome • Haim–Munk syndrome) • Camisa diseasefocal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis • Focal palmoplantar and gingival keratosis • Howel–Evans syndrome • Pachyonychia congenita (Pachyonychia congenita type I • Pachyonychia congenita type II) • Striate palmoplantar keratoderma • Tyrosinemia type II)punctate: Acrokeratoelastoidosis of Costa • Focal acral hyperkeratosis • Keratosis punctata palmaris et plantaris • Keratosis punctata of the palmar creases • Schöpf–Schulz–Passarge syndrome • Porokeratosis plantaris discreta • Spiny keratodermaOtherMeleda disease · Keratosis pilaris · ATP2A2 (Darier's disease) · Dyskeratosis congenita · Lelis syndromeOtherTemplate:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder
anomaliesMidlineOther/ungrouped· Bronchogenic cyst · Congenital cartilaginous rest of the neck · Congenital hypertrophy of the lateral fold of the hallux · Congenital lip pit · Congenital malformations of the dermatoglyphs · Congenital preauricular fistula · Congenital smooth muscle hamartoma · Cystic lymphatic malformation · Median raphe cyst · Melanotic neuroectodermal tumor of infancy · Mongolian spot · Nasolacrimal duct cyst · Omphalomesenteric duct cyst · Poland anomaly · Rapidly involuting congenital hemangioma · Rosenthal–Kloepfer syndrome · Skin dimple · Superficial lymphatic malformation · Thyroglossal duct cyst · Verrucous vascular malformation · Birthmark
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epidermolytic hyperkeratosis — an autosomal dominant disorder of keratinization caused by mutation in the keratin genes KRT1 (locus: 12q13) and KRT10 (locus: 17q21 q22), resulting in structural defects in tonofibrils. It is present at birth and characterized by generalized… … Medical dictionary
Hyperkeratosis — Infobox Disease Name = PAGENAME Caption = DiseasesDB = 20624 ICD10 = ICD9 = ICD9|701.1 ICDO = OMIM = MedlinePlus = eMedicineSubj = eMedicineTopic = MeshID = Hyperkeratosis results when an excess of proteins called keratins are produced. In humans … Wikipedia
epidermolytic palmoplantar keratoderma — the most common type of diffuse palmoplantar keratoderma, a genetically heterogeneous, autosomal dominant disorder characterized by epidermolytic hyperkeratosis (q.v.) … Medical dictionary
hyperkeratosis — Thickening of the horny layer of the epidermis or mucous membrane. SEE ALSO: keratoderma, keratosis. SYN: hyperkeratinization. h. congenita SYN: ichthyosis vulgaris. diffuse h. of palms and soles an … Medical dictionary
Focal palmoplantar keratoderma with oral mucosal hyperkeratosis — Classification and external resources OMIM 114140 Focal palmoplantar keratoderma with oral mucosal hyperkeratosis (also known as Focal epidermolytic palmoplantar keratoderma,  Hereditary painful cal … Wikipedia
EHK — epidermolytic hyperkeratosis … Medical dictionary
EHK — • epidermolytic hyperkeratosis … Dictionary of medical acronyms & abbreviations
List of cutaneous conditions — This is an incomplete list, which may never be able to satisfy particular standards for completeness. You can help by expanding it with reliably sourced entries. See also: Cutaneous conditions, Category:Cutaneous conditions, and ICD 10… … Wikipedia
Keratin 10 — Identifiers Symbols KRT10; BCIE; BIE; CK10; EHK; K10; KPP External IDs OM … Wikipedia
Palmoplantar keratoderma — Classification and external resources A picture of a 40 y/o Caucasian female with only the soles of the feet affected. The amputation was prior to this admission ICD 10 L … Wikipedia