Case Report: Infantile Urticaria as a Herald of Neonatal Onset Multisystem Inflammatory Disease With a Novel Mutation in NLRP3

Neonatal multisystem onset inflammatory disorder (NOMID) is a severe autoinflammatory syndrome that can have an initial presentation as infantile urticaria. Thus, an immediate recognition of the clinical symptoms is essential for obtaining a genetic diagnosis and initiation of early therapies to pre...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Anna E. Patrick, Eden M. Lyons, Lisa Ishii, Alan S. Boyd, Joseph M. Choi, Anna K. Dewan, Janet G. Markle
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Urticaria NOMID NLRP3 gene variant pediatric autoinflammatory disease inflammasome Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/6246c04228bb42069b6f4edfdf1ee275
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6246c04228bb42069b6f4edfdf1ee275
record_format	dspace
spelling	oai:doaj.org-article:6246c04228bb42069b6f4edfdf1ee2752021-11-18T06:45:49ZCase Report: Infantile Urticaria as a Herald of Neonatal Onset Multisystem Inflammatory Disease With a Novel Mutation in NLRP31664-322410.3389/fimmu.2021.775140https://doaj.org/article/6246c04228bb42069b6f4edfdf1ee2752021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.775140/fullhttps://doaj.org/toc/1664-3224Neonatal multisystem onset inflammatory disorder (NOMID) is a severe autoinflammatory syndrome that can have an initial presentation as infantile urticaria. Thus, an immediate recognition of the clinical symptoms is essential for obtaining a genetic diagnosis and initiation of early therapies to prevent morbidity and mortality. Herein, we describe a neonate presenting with urticaria and systemic inflammation within hours after birth who developed arthropathy and neurologic findings. Pathologic evaluation of the skin revealed an infiltration of lymphocytes, eosinophils, and scattered neutrophils. Genetic analysis identified a novel heterozygous germline variant of unknown significance in the NLRP3 gene, causing the missense mutation M408T. Variants of unknown significance are common in genetic sequencing studies and are diagnostically challenging. Functional studies of the M408T variant demonstrated enhanced formation and activity of the NLRP3 inflammasome, with increased cleavage of the inflammatory cytokine IL-1β. Upon initiation of IL-1 pathway blockade, the infant had a robust response and improvement in clinical and laboratory findings. Our experimental data support that this novel variant in NLRP3 is causal for this infant’s diagnosis of NOMID. Rapid assessment of infantile urticaria with biopsy and genetic diagnosis led to early recognition and targeted anti-cytokine therapy. This observation expands the NOMID-causing variants in NLRP3 and underscores the role of genetic sequencing in rapidly identifying and treating autoinflammatory disease in infants. In addition, these findings highlight the importance of establishing the functional impact of variants of unknown significance, and the impact this knowledge may have on therapeutic decision making.Anna E. PatrickEden M. LyonsLisa IshiiAlan S. BoydJoseph M. ChoiAnna K. DewanJanet G. MarkleFrontiers Media S.A.articleUrticariaNOMIDNLRP3gene variantpediatric autoinflammatory diseaseinflammasomeImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Urticaria NOMID NLRP3 gene variant pediatric autoinflammatory disease inflammasome Immunologic diseases. Allergy RC581-607
spellingShingle	Urticaria NOMID NLRP3 gene variant pediatric autoinflammatory disease inflammasome Immunologic diseases. Allergy RC581-607 Anna E. Patrick Eden M. Lyons Lisa Ishii Alan S. Boyd Joseph M. Choi Anna K. Dewan Janet G. Markle Case Report: Infantile Urticaria as a Herald of Neonatal Onset Multisystem Inflammatory Disease With a Novel Mutation in NLRP3
description	Neonatal multisystem onset inflammatory disorder (NOMID) is a severe autoinflammatory syndrome that can have an initial presentation as infantile urticaria. Thus, an immediate recognition of the clinical symptoms is essential for obtaining a genetic diagnosis and initiation of early therapies to prevent morbidity and mortality. Herein, we describe a neonate presenting with urticaria and systemic inflammation within hours after birth who developed arthropathy and neurologic findings. Pathologic evaluation of the skin revealed an infiltration of lymphocytes, eosinophils, and scattered neutrophils. Genetic analysis identified a novel heterozygous germline variant of unknown significance in the NLRP3 gene, causing the missense mutation M408T. Variants of unknown significance are common in genetic sequencing studies and are diagnostically challenging. Functional studies of the M408T variant demonstrated enhanced formation and activity of the NLRP3 inflammasome, with increased cleavage of the inflammatory cytokine IL-1β. Upon initiation of IL-1 pathway blockade, the infant had a robust response and improvement in clinical and laboratory findings. Our experimental data support that this novel variant in NLRP3 is causal for this infant’s diagnosis of NOMID. Rapid assessment of infantile urticaria with biopsy and genetic diagnosis led to early recognition and targeted anti-cytokine therapy. This observation expands the NOMID-causing variants in NLRP3 and underscores the role of genetic sequencing in rapidly identifying and treating autoinflammatory disease in infants. In addition, these findings highlight the importance of establishing the functional impact of variants of unknown significance, and the impact this knowledge may have on therapeutic decision making.
format	article
author	Anna E. Patrick Eden M. Lyons Lisa Ishii Alan S. Boyd Joseph M. Choi Anna K. Dewan Janet G. Markle
author_facet	Anna E. Patrick Eden M. Lyons Lisa Ishii Alan S. Boyd Joseph M. Choi Anna K. Dewan Janet G. Markle
author_sort	Anna E. Patrick
title	Case Report: Infantile Urticaria as a Herald of Neonatal Onset Multisystem Inflammatory Disease With a Novel Mutation in NLRP3
title_short	Case Report: Infantile Urticaria as a Herald of Neonatal Onset Multisystem Inflammatory Disease With a Novel Mutation in NLRP3
title_full	Case Report: Infantile Urticaria as a Herald of Neonatal Onset Multisystem Inflammatory Disease With a Novel Mutation in NLRP3
title_fullStr	Case Report: Infantile Urticaria as a Herald of Neonatal Onset Multisystem Inflammatory Disease With a Novel Mutation in NLRP3
title_full_unstemmed	Case Report: Infantile Urticaria as a Herald of Neonatal Onset Multisystem Inflammatory Disease With a Novel Mutation in NLRP3
title_sort	case report: infantile urticaria as a herald of neonatal onset multisystem inflammatory disease with a novel mutation in nlrp3
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6246c04228bb42069b6f4edfdf1ee275
work_keys_str_mv	AT annaepatrick casereportinfantileurticariaasaheraldofneonatalonsetmultisysteminflammatorydiseasewithanovelmutationinnlrp3 AT edenmlyons casereportinfantileurticariaasaheraldofneonatalonsetmultisysteminflammatorydiseasewithanovelmutationinnlrp3 AT lisaishii casereportinfantileurticariaasaheraldofneonatalonsetmultisysteminflammatorydiseasewithanovelmutationinnlrp3 AT alansboyd casereportinfantileurticariaasaheraldofneonatalonsetmultisysteminflammatorydiseasewithanovelmutationinnlrp3 AT josephmchoi casereportinfantileurticariaasaheraldofneonatalonsetmultisysteminflammatorydiseasewithanovelmutationinnlrp3 AT annakdewan casereportinfantileurticariaasaheraldofneonatalonsetmultisysteminflammatorydiseasewithanovelmutationinnlrp3 AT janetgmarkle casereportinfantileurticariaasaheraldofneonatalonsetmultisysteminflammatorydiseasewithanovelmutationinnlrp3
_version_	1718424418545303552

Case Report: Infantile Urticaria as a Herald of Neonatal Onset Multisystem Inflammatory Disease With a Novel Mutation in NLRP3

Ejemplares similares