Introduction
Netherton syndrome (NS) is a rare autosomal recessive genodermatosis
(OMIM #256500) characterized by superficial scaling, atopic
manifestations, and multisystemic complications, a triad of congenital
ichthyosiform erythroderma or ichthyosis linearis circumflexa, hair
shaft abnormalities, and immune dysregulation. Its incidence is one in
200 000 newborns. It may represent up to 18% of infants with congenital
erythroderma.1 NS is caused by loss-of-function
mutations in Serine Protease Inhibitor Kazal type 5 (SPINK5) gene, which
is located on chromosome 5q31-32 and encodes Lympho-Epithelial
Kazal-type-related protease inhibitor (LEKTI).2 To
date, a total of 108 variants have been found, encompassing all types of
mutations.3 LEKTI, expressed in the thymus and
epithelia, is a direct inhibitor of kallikrein-related peptidases and
cathepsin G and affects epidermal desquamation and altered skin barrier
function. Skin manifestations in NS include ichthyosiform erythroderma
(IE) or ichthyosis linearis circumflexa (ILC), a specific hair shaft
defect called trichorrhexis invaginata (bamboo hair), and an atopic
diathesis. Indeed, NS is a multisystemic disease with characteristic
cutaneous and numerous extracutaneous manifestations.4Diagnosis of NS can be enhanced with histologic
examination;5 immunostaining shows the absence or
reduction of LEKTI expression in the granular layer of the epidermis and
in the hair follicles.6 Abnormalities of the hair
shaft could be detected in only 20-50% of affected
hairs.7 Laboratory findings show peripheral
eosinophilia and elevated IgE levels. It is very difficult to
distinguish atypical NS from other types of ichthyosis; detection of
gene mutations in SPINK5 is crucial for diagnosis. Current therapy for
patients with NS is mainly supportive, as there is no curative or
specific treatment, especially for children with NS, but targeted
therapies are being developed.
We describe a child with genetically proven Netherton syndrome, for whom
intravenous immunoglobulin for 5 months proven beneficial.