Netherton Syndrome: Case Report and Review of the Literature

Abstract

Netherton syndrome (NS) is a rare genodermatosis with an autosomal recessive pattern of inheritance caused by pathogenic variants in the SPINK5 gene. It is characterized by a triad consisting of atopic diathesis, ichthyosis linearis circumflexa, and hair shaft abnormalities. Ichthyosis linearis circumflexa can be confused with atopic dermatitis leading to a delayed diagnosis. Furthermore, difficulty in making the differential diagnosis with other atopiform, erythrodermic, and ichthyosiform entities that exhibit hair shaft abnormalities represent a challenge. Trichoscopy is an accessible and noninvasive auxiliary diagnostic tool in these cases; the hair shaft abnormalities found in NS are bamboo, golf tee, and matchstick hairs. Identification of a pathogenic variant in the SPINK5 gene through genetic testing is necessary to confirm the diagnosis. Multiple treatment options are available including topical therapy with emollients, corticosteroids, calcineurin inhibitors, antiseptics, and narrowband UVB phototherapy. Systemic treatments comprehend intravenous immunoglobulins, and advances in the understanding of the pathophysiology of NS have led to more directed therapies with biologics such as infliximab, ixekizumab, secukinumab, ustekinumab, and dupilumab. Treatments currently under investigation include inhibitors of kallikrein 5, cathelicidins, drugs activating the transcription factor nuclear factor erythroid-derived 2-like 2, and gene therapy using autologous keratinocytes induced with a lentiviral vector encoding SPINK5.

Keywords: Ichthyosis linearis circumflexa; Netherton syndrome; Trichorrhexis invaginata.

Fig. 1

a Erythematous and serpiginous plaques with characteristic double-edged marginal scale. b Eczematous lesions involving the eyelids and oral commissures. Lack of external portion of the eyebrows.

Fig. 2

a Dermoscopy of eyebrows. Bamboo hairs (green), golf tee hairs (yellow) and matchsticks hairs (red). b Trichorrhexis invaginata, confirmed with optical microscope from a sample of the occipital region. c Histopathology with hematoxylin and eosin stain at ×20 magnification showing hyperkeratosis, acanthosis, focal hypergranulosis, and superficial perivascular lymphocytic infiltrate.