Nonbullous congenital ichthyosiform erythroderma (nonbullous CIE) includes genetic disorders that frequently present at birth as a collodion baby, with generalized red skin that is frequently cracked and has decreased barrier function and increased water loss; patients are at risk for systemic infection. Over a span of days to weeks, the skin becomes scaly, most frequently with small white scales, and remains red. Sometimes ectropion is present. This condition persists throughout the individual's life.

Several disorders, mostly with autosomal recessive inheritance and very rarely autosomal dominant inheritance, are included under this diagnosis. Some cases of harlequin ichthyosis may evolve into nonbullous CIE. These disorders are distinct from the lamellar ichthyosis form of nonbullous CIE, although at times this distinction is difficult.

Individuals may frequently have chronic secondary infection with dermatophytes, and rarely adults with this disorder have developed cutaneous squamous cell carcinomas.

Genes that are mutated and cause this condition include:

• ALOXE3 and ALOX12B – Genes involved with production of epidermal lipids.
• NIPAL4
• ABCA12 – Controls a liver transport protein and may cause severe forms of this disorder.
• Ichthyic mutations of a transmembrane protein.
• Some mutations of transglutaminase I may cause this form of nonbullous CIE.
• Patients with loss-of-function mutations in sphingosine-1-phosphate lyase may have nephrosis with ichthyosis and adrenal insufficiency.

Both sexes are equally affected, and all ethnic groups are involved. There may be consanguinity in some patients.