Netherton syndrome Q80.9

Very rare hereditary genodermatosis characterized by the combination of ichthyosis linearis circumflexa, hair shaft abnormalities(bamboo hair = trichorrhexis invaginata), elevated IgE levels and immunodeficiency with failure to thrive. Optionally associated are disorders in amino acid metabolism, possibly oligophrenia and cerebral seizures.

The incidence is 1:200,000; the prevalence 1:100,000; to date, about 150 patients with Netherton syndrome (Comèl-Netherton syndrome) have been described.

Autosomal recessive inheritance. Mutations of the SPINK5 gene (5q31-q32) encoding LEKTI, a serine protease inhibitor, have been detected. LEKTI is expressed in epithelia, thymus, tonsils, parathyroid gland and trachea. Furthermore, it can be detected in the stratum corneum and granulosum as well as in skin appendages. This protein inhibits a number of serine proteases, such as plasmin, trypsin, subtilisin A, cathepsin G or elastase. The"hyperactivity" of these proteolytic enzymes caused by LEKTI deficiency leads to a substantial disturbance in the function of the epidermal barrier. This occurs via increased degradation of desmoglein 1 and increased degradation of desmosomes. The disrupted skin barrier facilitates the penetration of allergens into the skin.

Remark: The particular expression of the SPINK5 gene in the thymus leads to defective T cell differentiation, a consecutive unbalanced Th2 response and a highly elevated IgE (there are analogies to the hyper IgE syndrome) .

Integument: Often beginning in childhood with congenital ichthyotic erythroderma, which may regress to ichthyosis linearis circumflexa in clinically mild cases at adolescent age. In this case, large, often circular, migratory, garland-like, brown-red or red, surface-rough, scaly plaques form, fringed by a double scale. Varying degrees of severe itching in the affected skin. Lichenification of the large joints. Temporary blistering possible.

Concomitant hair shaft anomalies(bamboo hairs, trichorrhexis nodosa, pili torti), alopecia, rhagades in the corner of the mouth, and papillomas in the genital area are obligatory.

Evidence of increased activity of acid phosphatases, β-glucuronidase, transglutaminase in skin scales.

Extracutaneous manifestations: Recurrent superinfections with septicemia as a consequence of immunodeficiency are feared.

Type I sensitization to food and environmental allergens is almost obligatory.

A causal therapy does not exist. In this respect, depending on the degree of activity of the skin appearance, a symptomatic therapy is indicated.

Internal therapy (supplement):

Individual case reports indicate a good efficacy of Dupilumab in NS (Off-Label Use). The dosage corresponds to the approved dosage for atopic dermatitis (initial 600mg s.c., followed by 300mg every 14 days).

Ointments, creams or lotions containing urea/lactic acid/polidocanol as well as external agents containing ammonium lactate (e.g. Kerapil, Optiderm, rp. 102 , rp. 104 , rp. 113 ) have proven to be effective.

An application of local retinoids, e.g. Tazarotene, e.g. Zorac 0.05% or 0.1% can be tried. Their irritating potential limits the therapy.

An attempt with Tacrolimus (Protopic) is worthwhile.

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