Netherton syndrome Q80.9

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 17.07.2023

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Bamboo Hair Syndrome; Comèl-Netherton syndrome; Erythroderma ichthyosiforme congenitum; Ichthyosis linearis circumflexa (Rille-Comel) and trichorrhexis invaginata; Ichthyosis linearis circumflexa (Rille-Comèl) and trichorrhexis invaginata; OMIM: 256500; Trichorrhexis Syndromes

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Comel, 1949; Netherton, 1958

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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.

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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.

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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) .

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Usually at birth or shortly after.

Clinical features
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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.

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Increase of inflammation parameters; partly clear eosinophilia, almost always clear increase of ECP and IgE (> 1000 IU/ml). Rare evidence of aminoaciduria.

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Psoriasiform epithelial reaction with missing str. granulosum. Parakeratosis. Intraepithelial are single granulocytes. In the upper dermis a non-specific, perivascular, lympho-histiocytic infiltrate with single neutrophil and eosinophilic granulocytes is visible.

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

General therapy
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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).

External therapy
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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.

Internal therapy
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Retinoids such as Acitretin (Neotigason) not only have a positive effect on the skin changes, but also cause a partial normalization of the hair shaft changes. Adults initially 25-30 mg/day, low maintenance dose of 5-10 mg/day p.o. Cave! It can come to dose-dependent heavy skin irritations! Dose reduction is partly sufficient in such cases. The use of Ciclosporin A is discussed differently. As long-term therapy is necessary, caution is recommended.

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The first description of the clinical picture, which was wrongly named after Netherton, goes back to the Italian Comèl, who in 1949 reported on the clinical picture under the name " Ichthyosis linearis circumflexa".

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  1. Beljan G et al (2003) Comèl-Netherton syndrome with bacterial superinfection. Dermatologist 54: 1198-1202
  2. ComèI M (1949) Ichthyosis linearis circumflexa. Dermatologica 978: 133-136
  3. Godic A, Dragos V (2004) Successful treatment of Netherton's syndrome with topical calcipotriol. Eur J Dermatol 14: 115-117
  4. Green SL et al (1995) Netherton's syndrome. Report of a case and review of the literature. J Am Acad Dermatol 13: 329-337
  5. Hammer C et al (2013) Generalized erythema, scaling and hair anomaly. Dermatologist 64: 516-518
  6. Haußer I et al (1989) Netherton's syndrome: ultrastructure of the active lesion under retinoid therapy. Arch Dermatol Res 281: 165-1720
  7. Kato A et al (2003) Association of SPINK5 gene polymorphisms with atopic dermatitis in the Japanese population. Br J Dermatol 148: 665-669
  8. Mitsudo K et al (2003) Inhibition of serine proteinases plasmin, trypsin, subtilisin A, cathepsin G, and elastase by LEKTI: a kinetic analysis. Biochemistry 42: 3874-3881
  9. Netherton EW (1958) A unique case of trichorrhexis nodosa; bamboo hairs. Arch Dermatol 78: 483-487
  10. salt M (2015) Netherton syndrome. A new mutation leads to the entire spectrum of typical features of Netherton syndrome. JDDG 13: 691-692
  11. Yerebakan O et al (2002) Netherton syndrome associated with idiopathic congenital hemihypertrophy. Pediatric dermatol 19: 345-348


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