RESUMO
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. The family opted for palliative care, and the infant died at the age of 2 months after discharge. This report documents a case of Netherton syndrome caused by the SPINK5 gene mutation in the neonatal period, and highlights multidisciplinary diagnosis and therapy for this condition.
Assuntos
Exantema , Síndrome de Netherton , Lactente , Recém-Nascido , Humanos , Masculino , Síndrome de Netherton/diagnóstico , Síndrome de Netherton/genética , Reinfecção , Dispneia , HomozigotoRESUMO
This case report describes a 28-year-old woman with Netherton syndrome who had large erythematous migratory patches with serpiginous double-edged scales on her face, neck, trunk, and extremities.
Assuntos
Síndrome de Netherton , Humanos , Síndrome de Netherton/diagnóstico , Síndrome de Netherton/tratamento farmacológico , Pirimidinas , SulfonamidasRESUMO
Comel-Netherton syndrome, or Netherton syndrome (NS), is a rare chronic genetic skin condition affecting the daily life of patients, which often results in poorly developed social skills and anxiety. Genetic predisposition plays a key role alongside the clinical findings, and clinicians must be aware of it as it can mimic other well-known skin conditions. Diagnosis is challenging both clinically and histologically. Clinically, it can mimic a severe form of atopic dermatitis, psoriasiform dermatitis overlapping with atopic dermatitis, or erythrokeratodermia variabilis. The difficulties in making histological diagnosis are similar, and it is often necessary to take several biopsies in order to clarify the diagnosis. Although retinoids are used for both psoriasis, erythrokeratodermia variabilis, and other congenital forms of keratodermia, the recommended treatment doses are different. This often results in poor treatment outcome. We present a 16-year-old patient previously diagnosed as erythrokeratodermia variabilis and treated with little to no improvement. Systemic therapy with acitretin 10â¯mg daily, local pimecrolimus 1%, emollients, and bilastine 20â¯mg once daily was initiated. Due to the limited application of retinoids and the difficulties in achieving permanent remission, modern medicine is faced with the challenge of seeking innovative therapeutic solutions. New hopes are placed on targeted or anti-cytokine therapy, based on inhibiting the inflammatory component of the disease. This article is mainly focused on innovative therapeutic options, including modern medications such as dupilumab, infliximab, secukinumab, anakinra, omalizumab, and others.
Assuntos
Dermatite Atópica , Eritroceratodermia Variável , Síndrome de Netherton , Humanos , Adolescente , Dermatite Atópica/diagnóstico , Dermatite Atópica/genética , Síndrome de Netherton/diagnóstico , Síndrome de Netherton/tratamento farmacológico , Síndrome de Netherton/genética , Bulgária , AcitretinaRESUMO
This case report describes dry skin with marked redness of the face and hands as well as trichorrhexis invaginata.
Assuntos
Dermatite Esfoliativa , Síndrome de Netherton , Humanos , Síndrome de Netherton/complicações , Síndrome de Netherton/diagnóstico , Síndrome de Netherton/genética , DermoscopiaRESUMO
BACKGROUND: Scant data are currently available on the allergen-specific immunoglobulin (Ig)E sensitization profile in primary immunodeficiencies with hyper IgE. Netherton syndrome (NS, OMIM 266500) is an extremely rare form of congenital ichthyosis characterized by congenital scaly erythroderma, hair abnormalities, and deregulated IgE reactivity associated with severe atopic manifestations. OBJECTIVE: The aim of this study was to evaluate the feasibility and reliability of a multiplex proteomic approach in the detection of specific IgE in NS. METHODS: Specific IgE was evaluated in 10 individuals with an established molecular diagnosis of NS using an allergenic molecules microarray (immuno-solid-phase allergen chip). RESULTS: Polireactivity to airway allergens, mainly house dust mites and olive tree pollen, and food allergens were observed in NS. Eighty per cent of patients were responsive to LTP or profilins. A clinical history suggestive of severe egg, milk, and fish allergy was confirmed by reactivity to the thermostable molecules Gal d 1, Bod 8, and parvalbumin Gad c 1, respectively. Latex reactivity was associated with Hev b 5 and 6 reactivity. Two distinct clusters of reactivity were observed after hierarchical analysis. Extremely high IgE levels (> 10,000 kU/L) do not affect the results obtained with microarrays. CONCLUSION: IgE multiplex evaluation allows (i) to profile IgE polyreactivity pictures, in the presence of LTP and profilin sensitization, (ii) to verify the clinical history of food allergy to milk, egg, and seafood, (iii) to confirm the allergic events associated with latex exposure, and (iv) to disclose the presence of preclinical sensitizations in patients affected by primary immunodeficiencies with hyper IgE, such as the NS.
Assuntos
Hipersensibilidade Alimentar , Síndrome de Netherton , Animais , Látex , Síndrome de Netherton/diagnóstico , Proteômica , Reprodutibilidade dos Testes , Reações Cruzadas , Imunoglobulina E , Alérgenos , Profilinas , Hipersensibilidade Alimentar/diagnósticoRESUMO
Generalized inflammatory peeling skin syndrome (PSS) is a rare autosomal recessive genodermatosis caused by loss-of-function disease-causing variants of the corneodesmosin gene (CDSN), resulting in excessive shedding of the superficial layers of the epidermis. We describe a case of generalized inflammatory PSS in an infant, presenting at day two of life with ichthyosiform erythroderma and superficial peeling of the skin. Hair microscopy showed trichorrhexis invaginata. Normal amounts of skin LEKT1, a product of SPINK5 on immunohistochemical staining excluded a diagnosis of Netherton syndrome. Genetic analysis revealed a homozygous novel complete CDSN deletion, estimated 4.6 kb in size, supporting the diagnosis of generalized inflammatory PSS.
Assuntos
Dermatite Esfoliativa , Eosinofilia , Doenças do Cabelo , Síndrome de Netherton , Dermatopatias Genéticas , Dermatite Esfoliativa/diagnóstico , Dermatite Esfoliativa/genética , Dermatite Esfoliativa/patologia , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intercelular , Síndrome de Netherton/diagnóstico , Síndrome de Netherton/genética , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/genéticaRESUMO
Netherton syndrome (NS) is a rare autosomal recessive genetic disease caused by SPINK5 gene mutation without specific effective therapies available. We report a case of NS confirmed by whole exome sequencing of DNA using peripheral blood, and Sanger sequencing found two new mutations associated with her clinical presentation located at SPINK5 gene c.1220+5G>A from her father and c.1870delA from her mother. The patient was treated with dupilumab (600 mg at week 0, then 300 mg every 2 weeks, s.c.). The clinical manifestation and dermoscopic images of the patient's hair showed remarkable improvement after dupilumab treatment with no adverse effects. We also reviewed previous reports to learn more about the therapeutic effect and adverse reactions of NS treated with dupilumab.
Assuntos
Síndrome de Netherton , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Mutação , Síndrome de Netherton/diagnóstico , Síndrome de Netherton/tratamento farmacológico , Síndrome de Netherton/genética , Proteínas Secretadas Inibidoras de Proteinases/genética , Inibidor de Serinopeptidase do Tipo Kazal 5/genéticaRESUMO
Netherton syndrome (NS) is a rare autosomal recessive condition caused by mutations in the serine peptidase inhibitor, Kazal type 5 (SPINK5) gene which encodes for a serine protease inhibitor, lymphoepithelial Kazal-typerelated inhibitor (LEKT1). NS is characterized by a triad of ichthyosiform erythroderma, trichorrhexis invaginata, and atopic diathesis with elevated IgE levels. The syndrome typically presents in infancy, where life-threatening complications are frequent, and evolves into a less severe condition with milder clinical symptoms in adulthood. This case report details the clinical history and genetic testing of a mother and two children with clinically symptomatic and genetically proven NS.
Assuntos
Eritrodermia Ictiosiforme Congênita , Síndrome de Netherton , Humanos , Criança , Feminino , Síndrome de Netherton/complicações , Síndrome de Netherton/diagnóstico , Síndrome de Netherton/genética , Mães , Inibidor de Serinopeptidase do Tipo Kazal 5/genética , Eritrodermia Ictiosiforme Congênita/genética , Mutação , Inibidores de Serina Proteinase/genéticaRESUMO
Netherton syndrome (NS) is an autosomal recessive primary immunodeficiency. It is characterised by substantial skin barrier defects and is often misdiagnosed as severe atopic dermatitis or hyper-immunoglobulin E syndrome. Although more than 80 NS-associated pathogenic mutations in the serine peptidase inhibitor kazal type 5 (SPINK5) gene have been reported worldwide, only one has been reported in the Arab population to date. We report the case of a novel association between the c.1887+1G>A mutation in the SPINK5 gene and NS in an Omani-Arab patient born in 2014 who was managed at a paediatric immunology clinic in Muscat, Oman. Accurate genetic diagnosis facilitated tailored clinical management of the index patient and enabled the provision of genetic counselling and offering of future reproductive options to the individuals related to the index patient.
Assuntos
Síndrome de Netherton , Criança , Humanos , Mutação , Síndrome de Netherton/diagnóstico , Síndrome de Netherton/genética , Omã , Proteínas Secretadas Inibidoras de Proteinases/genética , Inibidor de Serinopeptidase do Tipo Kazal 5/genéticaAssuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Ictiose/tratamento farmacológico , Síndrome de Netherton/tratamento farmacológico , Adolescente , Adulto , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Feminino , Humanos , Ictiose/diagnóstico , Ictiose/imunologia , Síndrome de Netherton/complicações , Síndrome de Netherton/diagnóstico , Síndrome de Netherton/imunologia , Índice de Gravidade de Doença , Resultado do TratamentoAssuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Glucocorticoides/administração & dosagem , Síndrome de Netherton/diagnóstico , Administração Cutânea , Adulto , Terapia Combinada/métodos , Feminino , Humanos , Quimioterapia de Indução/métodos , Injeções Subcutâneas , Quimioterapia de Manutenção/métodos , Masculino , Síndrome de Netherton/tratamento farmacológico , Síndrome de Netherton/imunologia , Síndrome de Netherton/patologia , Índice de Gravidade de Doença , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Resultado do Tratamento , Adulto JovemRESUMO
Netherton syndrome (NS) is an orphan disease characterized by congenital ichthyosis, hair abnormalities, and atopy, with limited treatment options. We achieved temporary improvement only during the initial 6 weeks of treatment with dupilumab, which differs from the sustained improvement observed in 2 other recently published cases. Although the clinical presentation of atopy and increased pre-allergic cytokines in NS patients suggest that dupilumab may be beneficial, larger studies are required.
Assuntos
Doenças do Cabelo , Eritrodermia Ictiosiforme Congênita , Síndrome de Netherton , Anticorpos Monoclonais Humanizados , Humanos , Síndrome de Netherton/diagnóstico , Síndrome de Netherton/tratamento farmacológico , Síndrome de Netherton/genéticaRESUMO
Netherton syndrome (NS) is a rare skin disorder involving the skin, hair, and immune system. Pathological manifestations are due to unopposed kallikrein peptidase activity because of a SPINK5 gene deficiency. In their article, Gouin et al. explore the role of kallikrein 14 in the stratum granulosum, defining it as an important player implicated in the pathogenesis of NS hair shaft anomalies.