Ichthyosis with confetti: clinics, molecular genetics and management

Ichthyosis with confetti (IWC) is an autosomal dominant congenital ichthyosis also known as ichthyosis variegata or congenital reticular ichthyosiform erythroderma. It manifests at birth with generalized ichthyosiform erythroderma or with a collodion baby picture. The erythrodermic and ichthyotic phenotype persists during life and its severity may modify. However, the hallmark of the disease is the appearance, in childhood or later in life, of healthy skin confetti-like spots, which increase in number and size with time. IWC is a very rare genodermatosis, with a prevalence <1/1,000,000 and only 40 cases reported worldwide. The most important associated clinical features include ear deformities, mammillae hypoplasia, palmoplantar keratoderma, hypertrichosis and ectropion. IWC is due to dominant negative mutations in the KRT10 and KRT1 genes, encoding for keratins 10 and keratin 1, respectively. In this context, healthy skin confetti-like spots represent “repaired” skin due to independent events of reversion of keratin gene mutations via mitotic recombination. In most cases, IWC clinical suspicion is delayed until the detection of white skin spots. Clinical features, which may represent hint to the diagnosis of IWC even before appearance of confetti-like spots, include ear and mammillae hypoplasia, the progressive development of hypertrichosis and, in some patients, of adherent verrucous plaques of hyperkeratosis. Altogether the histopathological finding of keratinocyte vacuolization and the nuclear staining for keratin 10 and keratin 1 by immunofluorescence are pathognomonic. Nevertheless, mutational analysis of KRT10 or KRT1 genes is at present the gold standard to confirm the diagnosis. IWC has to be differentiated mainly from congenital ichthyosiform erythroderma. Differential diagnosis also includes syndromic ichthyoses, in particular Netherton syndrome, and the keratinopathic ichthyoses. Most of reported IWC cases are sporadic, but familial cases with autosomal dominant mode of inheritance have been also described. Therefore, knowledge of the mutation is the only way to properly counsel the couples. No specific and satisfactory therapy is currently available for IWC. Like for other congenital ichthyoses, topical treatments (mainly emollients and keratolytics) are symptomatic and offer only temporary relief. Among systemic treatments, retinoids, in particular acitretin, improve disease symptoms in most patients. Although at present there is no curative therapy for ichthyoses, treatments have improved considerably over the years and the best therapy for each patient is always the result of both physician and patient efforts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-015-0336-4) contains supplementary material, which is available to authorized users.