Netherton Syndrome
November 2019
in “
Harper's Textbook of Pediatric Dermatology
”
Netherton syndrome ichthyosiform erythroderma trichorrhexis invaginata SPINK5 gene LEKTI protein serine protease inhibitor kallikreins KLK5 KLK7 skin barrier emollients topical steroids calcineurin inhibitors intravenous immunoglobulin serine protease inhibitor therapy gene therapy skin barrier protection IVIG
TLDR Netherton syndrome is a genetic skin disorder causing severe skin issues and requires careful treatment to protect the skin barrier.
Netherton syndrome (NS) was described as an autosomal recessive disorder characterized by ichthyosiform erythroderma, trichorrhexis invaginata, and atopic manifestations. It was caused by mutations in the SPINK5 gene, which encodes the LEKTI protein, a serine protease inhibitor. Deficient LEKTI expression led to increased serine proteases, particularly kallikreins KLK5 and 7, compromising the skin barrier. Infants with NS often faced life-threatening complications such as hypernatraemic dehydration, hypothermia, and sepsis. Severe cases persisted as generalized erythroderma, while milder cases evolved into ichthyosis linearis circumflexa. Treatment focused on protecting the skin barrier with emollients, while topical steroids and calcineurin inhibitors were generally avoided due to increased systemic absorption risks. Intravenous immunoglobulin showed some benefit, and experimental treatments included serine protease inhibitor therapy and potential gene therapy.
