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: 92 relevant articles (3 outcomes, 3 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Skin Diseases
2.	Ichthyosis (Xeroderma)
3.	Atopic Dermatitis (Atopic Eczema)
4.	Lamellar Ichthyosis (Harlequin Ichthyosis)
5.	Genetic Skin Diseases

Experts

1.	Hovnanian, Alain: 17 articles (01/2015 - 02/2002)
2.	Bonnart, Chrystelle: 7 articles (08/2010 - 10/2003)
3.	Furio, Laetitia: 6 articles (01/2015 - 03/2012)
4.	Jayakumar, Arumugam: 6 articles (07/2012 - 04/2003)
5.	Zambruno, Giovanna: 6 articles (05/2012 - 02/2002)
6.	Deraison, Céline: 6 articles (03/2012 - 01/2005)
7.	Clayman, Gary L: 5 articles (07/2012 - 04/2003)
8.	Ishida-Yamamoto, Akemi: 4 articles (05/2014 - 01/2005)
9.	Di, Wei-Li: 4 articles (12/2013 - 02/2011)
10.	Lacroix, Matthieu: 4 articles (03/2012 - 05/2009)

Drugs and Biologics

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

1.	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."
2.	Serine Proteases (Serine Protease)IBA 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." 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. " 12/01/2013 - "Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations in the serine protease inhibitor Kazal type 5 gene (SPINK5), which encodes for a serine protease inhibitor lymphoepithelial Kazal type-related inhibitor (LEKTI). " 05/01/2012 - "Netherton syndrome (NS) is a rare, life-threatening ichthyosiform syndrome caused by recessive loss-of-function mutations in SPINK5 gene encoding lymphoepithelial Kazal-type-related inhibitor (LEKTI), a serine protease inhibitor expressed in the most differentiated epidermal layers and crucial for skin barrier function. "
3.	Tacrolimus (Prograf)FDA LinkGeneric 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." 06/01/2006 - "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. " 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 - "Three patients previously diagnosed as having Netherton syndrome were treated at different centers with 0.1% tacrolimus ointment twice daily. " 06/01/2001 - "Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome."
4.	Carbon MonoxideIBA 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. " 07/16/2012 - "Using confocal microscopy and Netherton syndrome skin sections, we confirmed the co-localisation of LEKTI with dermcidin and demonstrated altered trafficking of dermcidin in these patients. "
5.	Immunoglobulin E (IgE)IBA 10/01/2014 - "IgE allergen component-based profiling and atopic manifestations in patients with Netherton syndrome." 12/01/2010 - "Mutations in the SPINK5 gene result in Netherton syndrome, a disorder characterised by AD, ichthyosis, and elevated serum IgE levels. " 09/01/2006 - "Netherton syndrome (NS) (OMIM 256500) was suspected due to very high serum IgE levels, growth retardation, severe food allergies and typical hair finding (trichorrhexis invaginata). " 02/01/2002 - "Netherton syndrome is a severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. " 08/01/2001 - "The Comèl-Netherton syndrome is an autosomal recessive multisystemic disorder characterized by localized or generalized congenital ichthyosis, hair shaft abnormalities, immune deficiency, and markedly elevated IgE levels. "
6.	Kallikreins (Kallikrein)IBA 03/10/2014 - "Transgenic kallikrein 5 mice reproduce major cutaneous and systemic hallmarks of Netherton syndrome." 01/01/2013 - "Netherton syndrome is caused by loss-of-function mutations in SPINK5 encoding the Kazal-type inhibitor LEKTI-1 leading to dysregulation of proteolytic cascades involving several kallikreins. " 09/01/2014 - "Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy." 07/01/2014 - "SPINK5 knockdown in organotypic human skin culture as a model system for Netherton syndrome: effect of genetic inhibition of serine proteases kallikrein 5 and kallikrein 7." 08/01/2010 - "Here we show that the membrane protease matriptase initiates Netherton syndrome in a LEKTI-deficient mouse model by premature activation of a pro-kallikrein cascade. "
7.	Protease Inhibitors (Protease Inhibitor)IBA 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. " 07/01/2006 - "SPINK5 (serine protease inhibitor Kazal-type 5), encoding the protease inhibitor LEKTI (lympho-epithelial Kazal-type related inhibitor), is the defective gene in Netherton syndrome (NS), a severe inherited keratinizing disorder. " 07/01/2014 - "Netherton syndrome (NS; OMIM 256500) is a genetic skin disease resulting from defects in the serine protease inhibitor Kazal-type 5 (SPINK5) gene, which encodes the protease inhibitor lympho-epithelial Kazal type inhibitor (LEKTI). " 05/11/2009 - "Netherton syndrome (NS) is a severe genetic skin disease with constant atopic manifestations that is caused by mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene, which encodes the protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI). "
8.	TrypsinIBA 03/01/2002 - "This hypothesis is supported by the marked increase of trypsin-like hydrolytic activity demonstrated in stratum corneum samples from our Netherton syndrome patients. " 01/01/2013 - "We used both structure-based and ligand-based virtual screening computations to identify commercially available non-covalent inhibitors of human kallikrein 5 (hK5), a serine protease (trypsin-like) that plays a central role in the initiation of the molecular cascades leading to the Netherton syndrome phenotype. " 07/01/2006 - "Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsin-like hyperactivity in Netherton syndrome."
9.	Growth Hormone (Somatotropin)IBA 01/01/2014 - "Netherton syndrome associated with growth hormone deficiency." 01/01/2015 - "Netherton Syndrome in a Neonate with Possible Growth Hormone Deficiency and Transient Hyperaldosteronism." 01/01/2015 - "Corrigendum to "Netherton Syndrome in a Neonate with Possible Growth Hormone Deficiency and Transient Hyperaldosteronism"."
10.	TrichothiodystrophyIBA 03/01/2007 - "Reassessment of a previously published case report allowed correction of a misdiagnosis: a neonatal aspect of collodion baby with pilar dystrophy is evocative of trichothiodystrophy and not Netherton syndrome. " 03/01/2007 - "[Collodion baby with neonatal signs of trichothiodystrophy misdiagnosed as Netherton syndrome: reassessment of a previous diagnostic error]." 01/01/2014 - "Thirty-seven patients (31%) showed morphologic changes compatible with specific diagnoses of various genetic conditions, including 25 cases of loose anagen hair syndrome, 6 cases of uncombable hair syndrome, 2 cases of Netherton syndrome, 3 cases of Menkes syndrome, and 1 case of trichothiodystrophy. " 01/01/2014 - "Examples of genetic disorders with associated hair abnormalities include Menkes syndrome, Netherton syndrome, uncombable hair syndrome, trichothiodystrophy, and loose anagen hair syndrome. " 07/07/2008 - "Our results show that characteristic light microscopy features of Netherton syndrome, monilethrix, woolly hair syndrome, pili torti, pili annulati and trichothiodystrophy may be visualized by trichoscopy. "

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.	Transplants (Transplant) 02/01/2011 - "Ex-vivo gene therapy restores LEKTI activity and corrects the architecture of Netherton syndrome-derived skin grafts." 01/01/2012 - "We conclude that skin grafts modified with lentiviral vectors encoding INVOp offer a suitable platform for therapeutic gene therapy in Netherton syndrome, and our experience highlights unanticipated effects of transgene codon optimization." 01/01/2012 - "We have previously described efficient lentiviral vector-mediated gene transfer to keratinocyte stem cells and the generation of human skin grafts for the inherited skin disease, Netherton syndrome, which arises due to mutations in serine protease inhibitor Kazal-type 5 (SPINK5). "
3.	Extracorporeal Membrane Oxygenation (ECMO) 05/01/2008 - "An infant with Netherton syndrome and persistent pulmonary hypertension requiring extracorporeal membrane oxygenation."