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Case Report: Susceptibility to viral infections and secondary hemophagocytic lymphohistiocytosis responsive to intravenous immunoglobulin as primary manifestations of adenosine deaminase 2 deficiency

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Title: Case Report: Susceptibility to viral infections and secondary hemophagocytic lymphohistiocytosis responsive to intravenous immunoglobulin as primary manifestations of adenosine deaminase 2 deficiency
Authors: Enrico Drago, Francesca Garbarino, Sara Signa, Alice Grossi, Francesca Schena, Federica Penco, Elettra Santori, Fabio Candotti, Kaan Boztug, Stefano Volpi, Marco Gattorno, Roberta Caorsi
Source: Frontiers in Immunology, Vol 13 (2022)
Publisher Information: Frontiers Media S.A., 2022.
Publication Year: 2022
Collection: LCC:Immunologic diseases. Allergy
Subject Terms: dada2, hemophagocitic lymphohistiocytosis, viral infection, therapy, immunoglobulin, Immunologic diseases. Allergy, RC581-607
More Details: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease associated with a highly variable clinical presentation, including systemic vasculitis, immunodeficiency, and cytopenia. We report a case of a 16-year-old girl affected by recurrent viral infections [including cytomegalovirus (CMV)-related hepatitis and measles vaccine virus-associated manifestations] and persistent inflammation, which occurred after Parvovirus infection and complicated by secondary hemophagocytic lymphohistiocytosis (HLH). HLH’s first episode presented at 6 years of age and was preceded by persistent fever and arthralgia with evidence of Parvovirus B19 infection. The episode responded to intravenous steroids but relapsed during steroids tapering. High-dose intravenous immunoglobulin (IVIG) helped manage her clinical symptoms and systemic inflammation. The frequency of IVIG administration and the dosage were progressively reduced. At the age of 9, she experienced varicella zoster virus (VZV) reactivation followed by the recurrence of the inflammatory phenotype complicated by HLH with neurological involvement. Again, high-dose steroids and monthly IVIG resulted in a quick response. Targeted next-generation sequencing (NGS) for autoinflammatory diseases and immunodeficiencies revealed the homozygous Leu183Pro ADA2 mutation, which was confirmed by Sanger analysis. ADA2 enzymatic test showed a complete loss of ADA2 activity. For about 3 years, IVIG alone was completely effective in preventing flares of inflammation and neurological manifestations. Anti-TNF treatment was started at the age of 13 for the appearance of recurrent genital ulcers, with a complete response. This case further expands the clinical spectrum of DADA2 and emphasizes the importance of extensive genetic testing in clinical phenotypes characterized by persistent unspecific inflammatory syndromes. The use of high doses of IVIG might represent a possible effective immune modulator, especially in combination with anti-TNF treatment.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-3224
Relation: https://www.frontiersin.org/articles/10.3389/fimmu.2022.937108/full; https://doaj.org/toc/1664-3224
DOI: 10.3389/fimmu.2022.937108
Access URL: https://doaj.org/article/f42672116ab34efa9419e70b7a20d6a5
Accession Number: edsdoj.f42672116ab34efa9419e70b7a20d6a5
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  Data: Case Report: Susceptibility to viral infections and secondary hemophagocytic lymphohistiocytosis responsive to intravenous immunoglobulin as primary manifestations of adenosine deaminase 2 deficiency
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  Data: <searchLink fieldCode="AR" term="%22Enrico+Drago%22">Enrico Drago</searchLink><br /><searchLink fieldCode="AR" term="%22Francesca+Garbarino%22">Francesca Garbarino</searchLink><br /><searchLink fieldCode="AR" term="%22Sara+Signa%22">Sara Signa</searchLink><br /><searchLink fieldCode="AR" term="%22Alice+Grossi%22">Alice Grossi</searchLink><br /><searchLink fieldCode="AR" term="%22Francesca+Schena%22">Francesca Schena</searchLink><br /><searchLink fieldCode="AR" term="%22Federica+Penco%22">Federica Penco</searchLink><br /><searchLink fieldCode="AR" term="%22Elettra+Santori%22">Elettra Santori</searchLink><br /><searchLink fieldCode="AR" term="%22Fabio+Candotti%22">Fabio Candotti</searchLink><br /><searchLink fieldCode="AR" term="%22Kaan+Boztug%22">Kaan Boztug</searchLink><br /><searchLink fieldCode="AR" term="%22Stefano+Volpi%22">Stefano Volpi</searchLink><br /><searchLink fieldCode="AR" term="%22Marco+Gattorno%22">Marco Gattorno</searchLink><br /><searchLink fieldCode="AR" term="%22Roberta+Caorsi%22">Roberta Caorsi</searchLink>
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  Data: Frontiers in Immunology, Vol 13 (2022)
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  Data: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease associated with a highly variable clinical presentation, including systemic vasculitis, immunodeficiency, and cytopenia. We report a case of a 16-year-old girl affected by recurrent viral infections [including cytomegalovirus (CMV)-related hepatitis and measles vaccine virus-associated manifestations] and persistent inflammation, which occurred after Parvovirus infection and complicated by secondary hemophagocytic lymphohistiocytosis (HLH). HLH’s first episode presented at 6 years of age and was preceded by persistent fever and arthralgia with evidence of Parvovirus B19 infection. The episode responded to intravenous steroids but relapsed during steroids tapering. High-dose intravenous immunoglobulin (IVIG) helped manage her clinical symptoms and systemic inflammation. The frequency of IVIG administration and the dosage were progressively reduced. At the age of 9, she experienced varicella zoster virus (VZV) reactivation followed by the recurrence of the inflammatory phenotype complicated by HLH with neurological involvement. Again, high-dose steroids and monthly IVIG resulted in a quick response. Targeted next-generation sequencing (NGS) for autoinflammatory diseases and immunodeficiencies revealed the homozygous Leu183Pro ADA2 mutation, which was confirmed by Sanger analysis. ADA2 enzymatic test showed a complete loss of ADA2 activity. For about 3 years, IVIG alone was completely effective in preventing flares of inflammation and neurological manifestations. Anti-TNF treatment was started at the age of 13 for the appearance of recurrent genital ulcers, with a complete response. This case further expands the clinical spectrum of DADA2 and emphasizes the importance of extensive genetic testing in clinical phenotypes characterized by persistent unspecific inflammatory syndromes. The use of high doses of IVIG might represent a possible effective immune modulator, especially in combination with anti-TNF treatment.
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      – Text: English
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