Netherton Syndrome

Rare autosomal recessive disease with variable expressions. Clinical features of the disease include variable ICHTHYOSIFORM ERYTHRODERMA, CONGENITAL; bamboo hair (trichorrhexis invaginata); and ATOPIC DERMATITIS. The disease is caused by mutations in the SPINK5 gene.

Also Known As:

Networked: 201 relevant articles (8 outcomes, 6 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Ichthyosis (Xeroderma)
2.	Atopic Dermatitis (Atopic Eczema)
3.	Lamellar Ichthyosis (Harlequin Ichthyosis)
4.	Psoriasis (Pustulosis Palmaris et Plantaris)
5.	Congenital Ichthyosiform Erythroderma

Experts

1.	Hovnanian, Alain: 31 articles (01/2022 - 02/2002)
2.	Wang, Yichen: 7 articles (01/2021 - 01/2019)
3.	Furio, Laetitia: 7 articles (01/2015 - 11/2011)
4.	Jayakumar, Arumugam: 7 articles (07/2012 - 04/2003)
5.	Zambruno, Giovanna: 7 articles (05/2012 - 02/2002)
6.	Bonnart, Chrystelle: 7 articles (08/2010 - 10/2003)
7.	Pampalakis, Georgios: 6 articles (01/2022 - 01/2019)
8.	Sotiropoulou, Georgia: 6 articles (01/2022 - 01/2019)
9.	Zingkou, Eleni: 6 articles (01/2022 - 01/2019)
10.	Ishida-Yamamoto, Akemi: 6 articles (11/2018 - 01/2005)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Netherton Syndrome:

1.	dupilumabIBA 01/01/2023 - "Effective treatment of Netherton syndrome in children with dupilumab: a case report and review of the literature." 01/01/2022 - "Dupilumab may be an effective and safe treatment option in a subset of pediatric patients with Netherton syndrome, especially in improving itch and the quality of life. " 02/24/2022 - "Additional studies are needed to confirm the effect of dupilumab for Netherton syndrome, which currently lack any effective treatment strategies." 02/24/2022 - "Although studies have previously described cases who used dupilumab for Netherton syndrome, reported effects have been limited or transient. " 01/01/2023 - "Dupilumab in paediatric Netherton syndrome: Can we do better?"
2.	pimecrolimus (Elidel)FDA Link 01/01/2010 - "The safety and efficacy of pimecrolimus, 1%, cream for the treatment of Netherton syndrome: results from an exploratory study." 11/01/2005 - "Topical pimecrolimus: a novel therapeutic option for Netherton syndrome." 01/01/2006 - "[Improvement of Netherton syndrome associated erythroderma in two adult sisters through use of topical pimecrolimus]." 03/01/2007 - "Netherton syndrome: successful use of topical tacrolimus and pimecrolimus in four siblings."
3.	Protease Inhibitors (Protease Inhibitor)IBA 01/01/2022 - "Netherton syndrome (NS) is a rare recessive skin disorder caused by loss-of-function mutations in SPINK5 encoding the protease inhibitor LEKTI (lymphoepithelial Kazal-type-related inhibitor). " 01/01/2022 - "Cocktails of KLK5 Protease Inhibitors and Anti-TNFα Therapeutics: an Effective Treatment for Netherton Syndrome." 01/01/2020 - "Netherton syndrome (NS) is a monogenic skin disease resulting from loss of function of lymphoepithelial Kazal-type-related protease inhibitor (LEKTI-1). " 03/10/2014 - "Netherton syndrome (NS) is a severe genetic skin disease in which absence of a key protease inhibitor causes congenital exfoliative erythroderma, eczematous-like lesions, and atopic manifestations. " 04/01/2018 - "In Netherton syndrome, which is caused by an absence of the protease inhibitor lymphoepithelial Kazal-type-related inhibitor, premature degradation of corneodesmosomes occurs due to the overactivation of proteases involved in corneodesmosome degradation. "
4.	Immunoglobulins (Immunoglobulin)IBA 11/01/2020 - "Our case report also verifies and supports the safety and efficacy of subcutaneous immunoglobulin substitution in chronic generalized skin disorders associated with primary immunodeficiencies such as Netherton syndrome." 11/01/2020 - "A novel SPINK5 mutation and successful subcutaneous immunoglobulin replacement therapy in a child with Netherton syndrome." 01/01/2016 - "A case of netherton syndrome: successful treatment with omalizumab and pulse prednisolone and its effects on cytokines and immunoglobulin levels."
5.	pembrolizumabIBA 09/01/2022 - "Pembrolizumab had a effective and safe treatment profile when it was used as a monotherapy for treating a Netherton syndrome patient diagnosed with locally advanced and recurrent/metastatic cSCC." 09/01/2022 - "Significant response to Pembrolizumab for metastatic cutaneous squamous cell carcinoma in patient with Netherton syndrome." 09/01/2022 - "Pembrolizumab, an immune checkpoint inhibitors (ICIs) showed a benefit in patients with various tumors including squamous cell carcinoma, but using this drug which is working by enhancing the immunity against tumor in patient with altered immunity like Netherton syndrome was a bit of a challenge, in terms of both effectiveness and safety. "
6.	Serine Peptidase Inhibitor Kazal-Type 5IBA 03/01/2002 - "The findings in this study suggest that the defective inhibitory regulation of desquamation due to the serine protease inhibitor Kazal-type 5 gene mutations may cause over-desquamation of corneocytes in Netherton syndrome, leading to severe skin permeability barrier dysfunction." 12/01/2023 - "Netherton syndrome is caused by a genetic mutation causing loss of function of the SPINK5 gene it encodes for the LEKTI protein, normally expressed in epithelia. " 01/01/2022 - "Netherton syndrome is a rare but severe autosomal recessive disorder with dominant impaired skin barrier function, caused by mutations in the SPINK5 (serine protease inhibitor Kazal-type 5) gene, which encodes LEKTI (lymphoepithelial Kazal-type-related inhibitor). " 03/01/2002 - "Here, we describe the serine protease inhibitor Kazal-type 5 gene mutations, including two novel non-sense mutations, and genotype-phenotype correlation in three Netherton syndrome patients in two unrelated Japanese families. " 03/01/2002 - "The mutations of the secretory serine protease inhibitor Kazal-type 5 gene have been identified in Netherton syndrome patients; however, the actual physiologic substrates of the serine protease inhibitor Kazal-type 5 proprotein are unknown, and how the genetic defects cause characteristic skin phenotype remains uncertain. "
7.	Proteins (Proteins, Gene)FDA Link 01/01/2023 - "Netherton syndrome (NS) is a rare autosomal recessive disorder caused by SPINK5 mutations, resulting in a deficiency in its processed protein LEKTI. " 02/01/2013 - "Netherton syndrome and its multifaceted defective protein LEKTI." 11/01/2011 - "Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is the defective protein of the ichthyosiform condition Netherton syndrome (NS). " 11/01/2011 - "Proteolytic activation cascade of the Netherton syndrome-defective protein, LEKTI, in the epidermis: implications for skin homeostasis." 11/01/2005 - "LEKTI is a 120-kDa protein that plays an important role in skin development, as mutations affecting LEKTI synthesis underlie Netherton syndrome, an inherited skin disorder producing severe scaling. "
8.	Ointments (Pastes)IBA 06/01/2006 - "We report a female patient with previously undiagnosed Netherton syndrome who presented to participate in a clinical research trial investigating the benefit of topical tacrolimus 0.03% ointment [Protopic (Fujisawa Pharmaceutical Co. " 10/01/2006 - "Low but detectable serum levels of tacrolimus seen with the use of very dilute, extemporaneously compounded formulations of tacrolimus ointment in the treatment of patients with netherton syndrome." 06/01/2001 - "Three patients previously diagnosed as having Netherton syndrome were treated at different centers with 0.1% tacrolimus ointment twice daily. " 01/01/2007 - "This presentation illustrates that even low-potency steroid ointments should be used with caution in Netherton syndrome and warns about the use of long-term topical medications with potential systemic side effects when used in large quantities in any chronic skin disease." 01/01/2007 - "We report an 11-year-old boy with Netherton syndrome who developed Cushing syndrome after application of 1% hydrocortisone ointment to his entire body for more than 1 year. "
9.	Tacrolimus (Prograf)FDA LinkGeneric 12/01/2003 - "Tacrolimus was administered intermittently and not during acute flares, thus avoiding systemic resorption even after long-time treatment despite the disturbed epidermal barrier in Comel-Netherton syndrome. " 06/01/2001 - "Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome." 06/01/2006 - "Current literature suggests a relative contraindication for use of topical tacrolimus in patients with Netherton syndrome owing to concern for increased systemic absorption of the drug. " 06/01/2006 - "We report a female patient with previously undiagnosed Netherton syndrome who presented to participate in a clinical research trial investigating the benefit of topical tacrolimus 0.03% ointment [Protopic (Fujisawa Pharmaceutical Co. " 03/01/2007 - "Netherton syndrome: successful use of topical tacrolimus and pimecrolimus in four siblings."
10.	Serine Proteinase Inhibitors (Serine Protease Inhibitors)IBA 01/01/2019 - "The genetic bases of Netherton syndrome are mutations in the gene SPINK5, and the Lymphoepitheial Kazal type related inhibitor, a serine protease inhibitor, is encoded by SPINK. " 01/01/2017 - "The identification of SPINK5, which encodes for the serine protease inhibitor LEKTI, as the gene responsible for Netherton syndrome, enabled the search for causative mutations in Netherton syndrome patients and families. " 01/01/2016 - "Netherton syndrome (NS) is associated with the mutation in the SPINK5 gene, which codes LEKTI (lymphoepithelial Kazaltype related inhibitor), a serine protease inhibitor. " 06/01/2015 - "These barrier abnormalities were reminiscent of (albeit less severe than in) Netherton syndrome, which results from a deficiency of the serine protease inhibitor LEKTI. " 03/01/2014 - "Netherton syndrome (NS) is a rare autosomal recessive disorder which is caused by mutations in the SPINK5 gene encoding the serine-protease inhibitor LEKTI. "

Therapies and Procedures

1.	Phototherapy (Light Therapy) 06/01/2012 - "Narrowband UVB phototherapy as a novel treatment for Netherton syndrome." 06/01/2012 - "Narrowband ultraviolet B phototherapy associated with improvement in Netherton syndrome." 01/01/2004 - "UVA1 phototherapy of Netherton syndrome."
2.	Therapeutics 01/01/2019 - "The finding of underlying mutations contributes to the understanding of Netherton syndrome and is instrumental in indicating a specific therapy. " 11/01/2011 - "To our knowledge, this is the first report of a successful complex excision of a giant condyloma in Netherton syndrome, the subsequent reconstruction, and periodic maintenance with topical therapies." 01/01/1984 - "[The Netherton syndrome: clinical characteristics, differential diagnosis and new ways of therapy]." 07/01/2022 - "This therapy has been used in the genodermatosis Netherton syndrome, which has been associated with the increased risk of Staphylococcus aureus infections. " 01/01/2022 - "Furthermore, a lot of case series report that biological therapeutics are effective treatment options, mainly for Netherton syndrome and autosomal recessive congenital ichthyosis. "
3.	Precision Medicine 07/07/2021 - "Epidermal application of the ABP-inhibitor on Spink5-/-Klk5-/- mice, a Netherton syndrome model, reversed disease hallmarks, providing preclinical proof-of-concept for using ABPs as theranostics." 01/01/2022 - "Precision medicine treatment was performed in 85.7% (6/7) of the patients, including hydrochlorothiazide and indomethacin for 57.1% (4/7) with arginine vasopressin receptor 2 (AVPR2) deficiency-associated congenital nephrogenic diabetes insipidus; a special diet of fructose formula for 1 patient with solute carrier family 5 member 1 deficiency-associated congenital glucose-galactose malabsorption (1/7, 14.3%); and kallikrein-inhibiting ointment for 1 patient with serine protease inhibitor of Kazal-type 5 deficiency-associated Netherton syndrome (1/7, 14.3%). "
4.	Negative-Pressure Wound Therapy 11/01/2017 - "This case indicates that surgery and topical negative-pressure therapy is a safe and reasonable treatment for individuals with Netherton syndrome."
5.	Dye Lasers 10/04/2023 - "Pulsed dye laser for facial erythema in Netherton syndrome."