Nethertone syndrome

Netherton syndrome (NTS) is a genetic disorder that predominantly affects the hair and the skin, and it can have a wide variety of presentations. The genetic syndrome is more common with consanguineous parents. Given the rarity and varying presentation of the condition, a few cases have been reported in the literature. We present an unusual case of two incidental diagnoses of NTS in siblings of consanguineous parents, manifesting as erythroderma and other symptoms that were initially diagnosed as pityriasis rubra pilaris and psoriasis in separate visits...

KEY CLINICAL MESSAGE: High-dose intravenous immunoglobulin exhibits great potential in the treatment of Netherton syndrome. ABSTRACT: Netherton syndrome (NS) is a rare autosomal recessive genodermatosis (OMIM #256500) characterized by superficial scaling, atopic manifestations, and multisystemic complications. It is caused by loss-of-function mutations in the SPINK5 gene, which encode a key kallikrein protease inhibitor. There are two subtypes of the syndrome that differ in clinical presentation and immune profile: ichthyosiform erythroderma and ichthyosis linearis circumflexa...

BACKGROUND: Netherton syndrome, a rare autosomal recessive genetic disease, lacks effective treatment options. This article presents a novel case of successful Upadacitinib therapy in a 14-year-old boy with Netherton syndrome. CASE PRESENTATION: A 14-year-old male with a lifelong history of dry skin, erythema, scaling, itching, and notable body odor was evaluated. These symptoms, accompanied by irregular hair growth and delayed development, prompted an initial diagnosis of atopic dermatitis at a local hospital...

Netherton syndrome is a rare, autosomal recessive disorder that clinically presents with a triad of congenital ichthyosiform erythroderma, hair shaft abnormalities, and immune dysregulation, which is confirmed with genetic testing for mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene. This diagnosis was included in our differential due to the patient's recurring and unimproving rash with desquamating skin. While eczema was included in our differential diagnoses, the patient's systemic symptoms, including failure to thrive, prompted our team to consider other diagnoses...

The lympho-epithelial Kazal-type inhibitors (LEKTI) are key to control skin turnover, and their absence causes Netherton syndrome. For clinical sample testing of LEKTI-based therapies, a robust analytical method to measure LEKTI-like activity in skin is required. This work reports on the development of a back-titration method to determine incremental LEKTI-like activity in skin samples. The method meets the analytical requirements for study sample testing, and reliable quantification can be achieved with negligible skin matrix interference...

Erythrokeratodermia variabilis (EKV) is a rare genodermatosis characterized by well-demarcated erythematous patches and hyperkeratotic plaques. EKV is most often transmitted in an autosomal dominant manner. Until recently, only mutations in connexins such as GJB3 (connexin 31), GJB4 (connexin 30.3), and occasionally GJA1 (connexin 43) were known to cause EKV. In recent years, mutations in other genes have been described as rare causes of EKV, including the genes KDSR , KRT83 , and TRPM4 . Features of the EKV phenotype can also appear with other genodermatoses: for example, in Netherton syndrome, which hampers correct diagnosis...

BACKGROUND: Patients with inherited ichthyosis suffer from scaling due to mutations affecting the epidermal barrier. Symptomatic treatment with ointments, bathing and mechanical scale removal can alleviate the disease, but therapy is time and cost intensive. OBJECTIVES: We investigated costs, time and disease burden of ichthyoses. The study addresses difficulties of the healthcare situation for patients with ichthyoses and reveals potential improvements. MATERIALS AND METHODS: We developed a questionnaire addressing time and financial effort for the treatment...

No abstract text is available yet for this article.

Netherton syndrome (NS) is a rare autosomal recessive genodermatosis. In this article, we present two siblings with NS who harbour a novel variant in the SPINK5 gene and were treated with infliximab infusions. Both patients exhibited the characteristic clinical triad of NS, and their whole exome sequencing analysis revealed a homozygous variant, c.1820+53G>A, in the SPINK5 gene. Notably, this is the first documented instance of homozygosity for this particular variant. Despite the absence of a specific treatment, both patients achieved total clearance of the skin lesions, and a significant decrease in total IgE levels was documented...

INTRODUCTION: Netherton syndrome (NS) is a rare autosomal recessive genodermatosis in the group of congenital ichthyosis. The clinical manifestations of the syndrome vary from a very mild clinical manifestation occurring with the picture of ichthyosis linearis circumflexa to exfoliative erythroderma. It can be fatal in the first days of a newborn's life due to dehydration, hypothermia, weight loss, respiratory infections, and sepsis. A specific anomaly of the hair trichorrexis invaginata is considered pathognomonic for the syndrome...

No abstract text is available yet for this article.

Netherton syndrome (NS) is a rare skin disease caused by loss-of-function mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) gene. Disease severity and the lack of efficacious treatments call for a better understanding of NS mechanisms. Here we describe a novel and viable, Spink5 conditional knock-out (cKO) mouse model, allowing to study NS progression. By combining transcriptomics and proteomics, we determine a disease molecular profile common to mouse models and NS patients. Spink5 cKO mice and NS patients share skin barrier and inflammation signatures defined by up-regulation and increased activity of proteases, IL-17, IL-36, and IL-20 family cytokine signaling...

Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton's syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin...

A male infant, aged 6 days, was admitted to the hospital due to respiratory distress and systemic desquamative rash after birth. The infant presented with erythema and desquamative rash, respiratory failure, recurrent infections, chronic diarrhea, hypernatremic dehydration, and growth retardation. Comprehensive treatment, including anti-infection therapy, intravenous immunoglobulin administration, and skin care, resulted in improvement of the rash, but recurrent infections persisted. Second-generation sequencing revealed a homozygous mutation in the SPINK5 gene, consistent with the pathogenic variation of Netherton syndrome...

IL-36 is a most recent member of the IL-1 cytokine family, primarily expressed at barrier sites of the body such as the skin, lungs, and intestine. It plays a vital role in inflammation and is implicated in the development of various cutaneous; intestinal; and pulmonary disorders, including psoriasis, inflammatory bowel disease, and chronic obstructive pulmonary disease. IL-36 comprises 4 isoforms: the proinflammatory IL-36α, IL-36β, and IL-36γ and the anti-inflammatory IL-36R antagonist. An imbalance between proinflammatory and anti-inflammatory IL-36 isoforms can contribute to the inflammatory fate of cells and tissues...

BACKGROUND/OBJECTIVES: Recent literature highlights the potential of biologics in the management of inherited disorders of keratinisation. In this study, we conducted a systematic review of existing literature on treatment outcomes of inherited keratinisation disorders treated with biologics. METHODS: Eligible records were retrieved through searches of the electronic databases MEDLINE, Embase, PubMed and Scopus. Databases were searched from inception to July 2023 for eligible records...

Netherton syndrome (NS) is rare and multisystemic congenital skin disorder classically distinguied as a triad of congenital ichthyosiform erythroderma, trichorrhexis invaginata (TI), and an atopic diathesis. Recent advances in pathogenesis have explored the role of IL-23/Th17 pathway in NS. Herein, we present a 17 years old girl harbouring homozygous four base pair deletion in exon 26 of the SPINK5 gene, presented with pruritus, scaling, dry skin and generalized eczematous lesions. She was administered anti IL17A (subcutaneous secukinumab) therapy...

BACKGROUND: Since the early 1990s, Ultraviolet (UV) A1 phototherapy has been described as an effective and safe treatment of a multitude of skin disorders. However, after 30 years, its use has remained limited to few dermatological centers. OBJECTIVE: To analyze the changes over the years and the current position of UVA1 phototherapy through a Real-World Evidence (RWE) study at a single tertiary referral center. METHODS: We reviewed the medical files of 740 patients treated between 1998 and 2022...

Dehydrated human amnion chorion membrane (dHACM) allografts are synthetic skin substitutes derived from placental tissue. dHACM allografts are used for replacing lost or damaged dermal tissue, as they contain many of the components found within the extracellular matrix that are beneficial in wound healing. Common uses of dHACM allografts include the healing of diabetic and non-diabetic foot and leg ulcers, decubitus ulcers, and wounds following debridement. While these grafts have been proven to be beneficial in other disciplines of medicine, their potential for use in the field of dermatology is emerging...

Netherton syndrome is a rare, multisystem, autosomal recessive genodermatosis characterized by a triad of manifestations: congenital ichthyosis, immune dysregulation, and scalp anomalies. We report the case of a 1-month-old male infant evaluated for failure to thrive and feeding difficulties. At birth, the infant was admitted to intensive care for severe hypernatremia (natremia 186 mg/dL). Upon entering the ward, the general conditions were poor. He presented with diffuse erythrodermia. A dermatological evaluation showed evidence of "invaginated trichuriasis," a typical sign of Netherton syndrome...