Congenital Reticular Ichthyosiform Erythroderma

DISEASE CARD

Disease group Keratinization disorders
DISEASE NAME CONGENITAL RETICULAR ICHTHYOSIFORM ERYTHORDERMA
Synonymous Ichthyosis with confetti, Congenital Erythrokeratoderma, Ichthyosis Variegata
Estimated prevalence 1 / 1 000 000
OMIM 609165
Inheritance Autosomal dominant
Gene (s) KRT10 (148080)

Definition

In a consensus conference in 2009, a new classification system and terminology has been established for ichthyoses [1]. Ichthyoses are determined as Mendelian disorders of cornification (MeDOC) that are characterized by universal scaling of the skin. In two main categories, non-syndromic forms (phenotype restricted to the skin) are distinguished from syndromic forms (involvement of other organs). A further distinction is made between common and rare forms. Within the non-syndromic forms the term keratinopathic ichthyosis is used as an umbrella term to describe all forms of ichthyosis that are based on mutations in keratin genes. The keratinopathic ichthyoses manifest at birth and sometimes involve blistering [2, 3].

Congenital reticular ichthyosiform erythroderma (CRIE) is a rare skin disorder caused by mutations in the KRT10 gene (17q21.2).

Clinical Description

CRIE patients are born with severe ichthyosiform erythroderma, which is seen throughout the first years of life. Clinical appearance further includes keratotic lichenification and palmoplantar keratoderma. Ichthyotic patches appear in a reticulated pattern. Defective skin barrier function and poor skin integrity can lead to early death, due to bacterial infections. During the age of 3-10 years, white islands start to appear over the body surface. With time, these confetti-like spots increase in number and size. The white spots are considered to be areas of localized spontaneous healing due to recombination events [3, 4].

Pathogenesis

Keratin 10 levels are reduced in diseased skin. Ultrastructurally, a reduction of cytokeratin filaments can be seen with poor contact to desmosomes. CRIE is caused by frameshift mutations in the KRT10 gene. These mutations result in an alternative reading frame that produces an arginine-rich C-terminal peptide, that redirects keratin 10 from the cytokeratin network to the nucleolus. The full consequences of nucleolar localization of KRT10 are unknown, but the high arginine content suggests a possible interference with RNA molecules. Ribosome biogenesis, protein synthesis, cell cycle, DNA repair and replication could also be affected [4].

Diagnosis

Histopathological findings include band-like parakeratosis, psoriasiform acanthosis, vacuolization of the keratinocytes with binuclear cells in the upper epidermis and deposition of amyloid in the dermis [5]. Ultrastructural findings are reduced intermediate filaments in the suprabasal layers of the epidermis. Mislocalization of mutant KRT10 to the nucleolus can be determined by co-staining with fibrillarin. Molecular genetic testing by DNA sequencing of the KRT10 gene [4].

Treatment

Standard treatment is the use of emollients. Oral retinoids have been reported effective in CRIE [6, 7, 8].

References

1
Oji V, Tadini G, Akiyama M, Blanchet Bardon C, Bodemer C, Bourrat E, Coudiere P, DiGiovanna JJ, Elias P, Fischer J, Fleckman P, Gina M, Harper J, Hashimoto T, Hausser I, Hennies HC, Hohl D, Hovnanian A, Ishida-Yamamoto A, Jacyk WK, Leachman S, Leigh I, Mazereeuw-Hautier J, Milstone L, Morice-Picard F, Paller AS, Richard G, Schmuth M, Shimizu H, Sprecher E, Van Steensel M, Taïeb A, Toro JR, Vabres P, Vahlquist A, Williams M, Traupe H. (2010) Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Sorèze 2009. J Am Acad Dermatol 63:607-641.

2
Schmuth M, Martinz V, Janecke AR, Fauth C, Schossig A, Zschocke J, Gruber R. (2013) Inherited ichthyoses/generalized Mendelian disorders of cornification. Eur J Hum Genet 21:123-133.

3
Traupe H, Fischer J, Oji V. (2013) Nonsyndromic types of ichthyoses – an update. J Dtsch Dermatol Ges Oct 11. doi: 10.1111/ddg.12229. [Epub ahead of print]

4
Choate KA, Lu Y, Zhou J, Choi M, Elias PM, Farhi A, Nelson-Williams C, Crumrine D, Williams ML, Nopper AJ, Bree A, Milstone LM, Lifton RP. (2010) Mitotic recombination in patients with ichthyosis causes reversion of dominant mutations in KRT10. Science 330:94-97.

5
Krunic L, Palcesky D, Busbey S, Medenica M. (2003) Congenital Reticular Ichthyosiform Erythroderma — Ichthyosis Variegata: a Case Report and Review of the Literature. Acta Derm Venereol 83:36-39.

6
Marghescu S, Anton-Lamprecht I, Rudolph PO, Kaste R. (1984) Kongentiale retikulare ichthyosiforme erythrodermie. Hautarzt 35:522-529.

7
Camenzind M, Harms M, Chavaz O, Saurat JH. (1984) Ichthyose en confettis. Ann Dermatol Venereol 111:675-676 .

8
Rufli T, Schneider BV, Schnyder UW. (1990) Nichtbullose Erythrodermie (congenitale) ichthyosiforme mit peri- nuklearen Schalen. Hautarzt 41:442-447.