Non-invasive Imaging of Netherton Syndrome with Reflectance Confocal Microscopy and Line-field Confocal Optical Coherence Tomography

Netherton syndrome (NS) is a rare autosomal recessive genodermatosis with an incidence of 1 : 200 000 [1].The pathogenesis of NS leads to the dysfunction of the epidermal barrier.Under physiological conditions, epidermal integrity and keratinocyte turnover are regulated by a balance between the activity of serine proteases, such as kallikrein-related peptidase 5, 7 and 14 (KLK5, KLK7, KLK14), and their inhibitors, mainly by lymphoepithelial Kazal-type related inhibitor (LEKTI) [2,3].Serine proteases facilitate the exfoliation of mature keratinocytes through the degradation of corneodesmosomal components: desmoglein 1, desmocollin 1 and corneodesmosin.Moreover, KLK5 initiates the production of pro-inflammatory cytokines via the stimulation of protease-activated receptor 2 (PAR2).In NS, the mutation in the SPINK5 gene results in a reduction in the secretion of LEKTI.This leads to an uncontrolled and increased activation of KLK5, which causes the loss of ABSTRACT Introduction: Netherton syndrome is a genodermatosis caused by a mutation in the SPINK5 gene, which encodes serine protease inhibitor LEKTI.LEKTI deficiency overactivates kallikrein-related peptidases, causing epidermal and hair shaft keratinization abnormalities.The characteristic clinical triad includes congenital ichthyosiform erythroderma or ichthyosis linearis circumflexa, atopic diathesis and trichorrhexis invaginata.Objective: To demonstrate how reflectance confocal microscopy and line-field confocal optical coherence tomography support the diagnosis of Netherton syndrome.Case report: A 3-year-old girl presented with erythematous, polycyclic plaques with peripheral scaling located on the face, trunk, upper and lower extremities.Trichoscopy showed bamboo hairs and golf tee-like endings.Reflectance confocal microscopy and line-field confocal optical coherence tomography revealed scale, parakeratosis, acanthosis, spongiosis and perivascular inflammatory infiltrates, which were confirmed by histopathological examination.Conclusions: Trichoscopy, reflectance confocal microscopy and linefield confocal optical coherence tomography can facilitate the diagnosis of patients presenting with eczema-like lesions and brittle hair to identify Netherton syndrome.To our knowledge, this is the first line-field confocal optical coherence tomography documentation of Netherton syndrome.