Infliximab therapy for Netherton syndrome: A case report

Roda, Ângela; Mendonça-Sanches, Maria; Travassos, Ana Rita; Soares‐de‐Almeida, Luís; Metze, Dieter

doi:10.1016/j.jdcr.2017.07.019

Cited by 48 publications

(54 citation statements)

References 10 publications

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“…Treatment modalities such as topical corticosteroids, topical calcineurin inhibitors, topical retinoids, narrowband ultraviolet B phototherapy, psoralen and ultraviolet irradiation, and oral acitretin have been used with varying success as we did. Intravenous immunoglobulin and anti-TNF-α are therapeutic options for severe illness (13,14). Our reported case demonstrated in consistent with other similar cases, the importance of attention to other differential diagnoses in severe and refractory eruptions, especially with early onset disorders at neonatal age.…”

Section: Case Presentationsupporting

confidence: 89%

Netherton Syndrome: A Case Report With Literature Review

et al. 2019

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Introduction: Netherton Syndrome (NS) is a rare hereditary autosomal recessive disorder with ichthyosiform cutaneous lesions, specific hair shaft defect and atopic diathesis. The incidence of Netherton syndrome is estimated to be approximately 1 in 200,000. The objective of this case report is to illustrate the Netherton Syndrome in a patient with severe eczema atopic dermatitislike eruption. Case presentation: A 41-month old boy referred to the clinic of Allergy and Immunology, Hazrat Rasoul Hospital with generalized erythema and scaling cutaneous lesions. The patient underwent clinical examinations and laboratory analysis. Laboratory data revealed only an elevated IgE level, leukocyte count was 7800/μl with 10% eosinophil, and his hair shaft indicated classic trichorrhexis invaginata (Bamboo hair). Based on the clinical and laboratory findings, N.S was diagnosed. A brief review was also done related to this case. Conclusion: The case was reported because of the severity of the disorder and other differential diagnoses in severe and refractory atopic dermatitis-like eruptions. The importance of the case is related to other differential diagnoses, especially with early onset disorders at neonatal age.

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Section: Case Presentationsupporting

confidence: 89%

Netherton Syndrome: A Case Report With Literature Review

et al. 2019

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“…Given that SPINK5 variations have been identified in atopic dermatitis [5][6][7] and that Spink5 À/À mice are a model for atopic dermatitis [3], it is possible that KLK6 inhibition will be beneficial for the treatment of atopic dermatitis. Indeed, anti-inflammatory therapies with anti-TNFα agents have been used in severe cases of atopic dermatitis [30,31] and for alleviating the inflammatory phenotype in NS patients [32,33]. Our results presented here pinpoint KLK6 as an alternative pharmacological target.…”

Section: Discussionmentioning

confidence: 62%

A proinflammatory role of KLK6 protease in Netherton syndrome

Zingkou

Pampalakis

Charla

et al. 2019

Journal of Dermatological Science

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Background: Netherton syndrome (NS) is a rare but severe type of ichthyosis characterized by atopy, allergies, and potentially lethal skin overdesquamation associated with highly elevated proteolytic activities in LEKTI-deficient epidermis. NS symptoms are recapitulated in Spink5 À/À mouse where the gene encoding Lekti has been invalidated. Spink5 À/À mice die within 5 h from birth due to their severe skin barrier defect leading to dehydration. Spink5 À/À mice also serve as a model for atopic dermatitis. The KLK6 protease is expressed by epidermal keratinocytes and shown in vitro to cleave desmosomal components. Objective: To investigate in vivo whether KLK6 is implicated in epidermal overdesquamation and/or inflammation associated with NS. Methods: The role of KLK6 was evaluated by generating Spink5 À/À Klk6 À/À double knockout mice. The phenotype was assessed by macroscopic observation, immunohistochemistry for differentiation markers, in situ zymography for proteolysis, and quantification of proinflammatory cytokines. Results: Elimination of Klk6 in Spink5 À/À remarkably suppresses the expression of Tslp, a major itchinginducing factor and driver of allergic reactions. Tnfα and the Th17 promoting cytokine Il-23 were also suppressed. Spink5 À/À Klk6 À/À mice display normalized keratinocyte differentiation, nevertheless, epidermal proteolytic activities and the associated overdesquamation were not ameliorated, and Spink5 À/À Klk6 À/À still died from a severe epidermal barrier defect as the Spink5 À/À. Conclusions: Ablation of Klk6 largely suppresses epidermal inflammation but cannot rescue overdesquamation leading to the lethal NS phenotype. Nonetheless, our findings demonstrate for the first time that KLK6 is implicated in skin inflammation and may represent a novel druggable target for NS and other inflammatory conditions e.g. atopic dermatitis.

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“…Infliximab was reported as improving skin inflammation in two patients with NS . We cannot recommend such therapy (LoE 3, GoR D), based on the following arguments: paucity of data about TNF‐α inhibitors in NS, skin cancers (see below) and recurrent infections reported in NS, significantly increased risk of infections and nonmelanoma skin cancers for patients treated with TNF‐α inhibitors and some cancers being aggressive .…”

Section: Particularities Of Congenital Ichthyosismentioning

confidence: 99%

Management of congenital ichthyoses: European guidelines of care, part two

et al. 2018

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These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert-based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis.

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Infliximab therapy for Netherton syndrome: A case report

Cited by 48 publications

References 10 publications

Netherton Syndrome: A Case Report With Literature Review

Netherton Syndrome: A Case Report With Literature Review

A proinflammatory role of KLK6 protease in Netherton syndrome

Management of congenital ichthyoses: European guidelines of care, part two

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