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Congenital non-bullous ichthyosiform erythroderma
Congenital ichthyosiform erythroderma (CIE) is a variant of autosomal recessive congenital ichthyosis (ARCI; see this term), a rare epidermal disease, characterized by fine, whitish scales on a background of erythematous skin over the whole body.
Prevalence is estimated at approximately 1/200,000- 1/1,000,000 individuals.
Since birth, patients present with fine white-grayish scales of various sizes associated with erythroderma. Some newborns are encased in a mild collodion membrane (taut, shiny, translucent membrane appearing as an extra skin layer) and develop scales and erythroderma once the membrane has been shed. The clinical picture varies widely among patients with variable degrees in the severity of erythema and in the size of scales observed. The clinical picture can also change over time and in response to treatment. Skin is usually itchy or painful, and sensitivity may be reduced by the scales. Other additional clinical features can be observed in variable degrees of severity: persistent ectropion and associated eye complications (keratitis, corneal scarring), palmo-plantar keratoderma, alopecia, failure to thrive, short stature, intense pruritus, intolerance to heat, nail dystrophy, and hearing impairement (due to accumulation of scales in external ear).
CIE is a genetically heterogeneous disease. It is due to mutations in one of the following genes: TGM1, ABCA12, ALOX12B, ALOXE3, CYP4F22 and NIPAL4, and on locus 12p11.2-q13. Most mutations are found in the TGM1 gene encoding transglutaminase 1, involved in the formation of the epidermal cornified cell envelope. ABCA12 encodes an ATP-binding cassette (ABC) transporter, involved in lipid transport, and ALOX12B, ALOXE3, and CYP4F22 code respectively for arachidonate 12(R)-lipoxygenase, arachidonate lipoxygenase-3 and cytochrome P450 protein, all involved in lipid metabolism. NIPAL4 likely encodes a membrane receptor. There is no clear genotype-phenotype correlation.
The diagnosis is based on the clinical appearance of the skin. Histological aspect of the skin is not specific. Molecular testing is possible but is not available in general practice. Immunohistochemistry using antibodies directed against TGase 1 or TGase1 enzyme activity measurement is available in some centers.
At birth, differential diagnoses include other causes of neonatal erythroderma (e.g. congenital immunodeficiencies). Later in life, differential diagnosis includes syndromic forms of icthyosis, harlequin ichthyosis, lamellar ichthyosis, congenital reticular ichthyosiform erythroderma, and peeling skin syndrome (see these terms).
Prenatal diagnosis is based on DNA analysis of amniocentesis and chorion villus sampling materials. Ultrasonography can detect the collodion membrane.
The disease is transmitted as an autosomal recessive trait. Genetic counseling should be offered to the affected families informing them of the 25% risk of recurrence.
Management and treatment
Management is based on daily applications of emollients. Keratolytics can be used but are often not tolerated. Oral retinoids can be used in severe forms of the disease but are less tolerated than in the case of lamellar ichthyosis (LI) (usually lower doses than in LI, 10-25 mg/d in adults).
Prognosis is variable, ranging from mild to severe (especially during the neonatal period due to the risk of sepsis). For some patients there is a significant improvement with time but the disease often remains stable over the life, with periods of exacerbation. The life expectancy is normal. The disease has a strong impact on the quality of life due to the altered physical appearance, the troublesome symptoms, and the constraints due to disease and the treatment.