{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T03:25:32Z","timestamp":1762917932064,"version":"3.41.2"},"reference-count":31,"publisher":"American Academy of Pediatrics (AAP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:p>Multicentric Castleman disease (MCD) is a rare entity that, unlike unicentric Castleman disease, involves generalized polyclonal lymphoproliferation, systemic inflammation, and multiple-organ system failure resulting from proinflammatory hypercytokinemia, including, in particular, interleukin-6. A subset of MCD is caused by human herpesvirus-8 (HHV-8), although the etiology for HHV-8\u2013negative, idiopathic MCD (iMCD) cases is unknown at present. Recently, a consensus was reached on the diagnostic criteria for iMCD to aid in diagnosis, recognize mimics, and initiate prompt treatment. Pediatric iMCD remains particularly rare, and differentiation from MCD mimics in children presenting with systemic inflammation and lymphoproliferation is a challenge. We report on a young boy who presented with a HHV-8\u2013negative, iMCD-like phenotype and was found to suffer from the monogenic disorder deficiency of adenosine deaminase 2 (DADA2), which is caused by loss-of-function mutations in CECR1. DADA2 prototypic features include early-onset ischemic and hemorrhagic strokes, livedoid rash, systemic inflammation, and polyarteritis nodosa vasculopathy, but marked clinical heterogeneity has been observed. Our patient\u2019s presentation remains unique, with predominant systemic inflammation, lymphoproliferation, and polyclonal hypergammaglobulinemia but without apparent immunodeficiency. On the basis of the iMCD-like phenotype with elevated interleukin-6 expression, treatment with tocilizumab was initiated, resulting in immediate normalization of clinical and biochemical parameters. In conclusion, iMCD and DADA2 should be considered in the differential diagnosis of children presenting with systemic inflammation and lymphoproliferation. We describe the first case of DADA2 that mimics the clinicopathologic features of iMCD, and our report extends the clinical spectrum of DADA2 to include predominant immune activation and lymphoproliferation.<\/jats:p>","DOI":"10.1542\/peds.2017-2266","type":"journal-article","created":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T07:25:22Z","timestamp":1535009122000},"source":"Crossref","is-referenced-by-count":28,"title":["ADA2 Deficiency Mimicking Idiopathic Multicentric Castleman Disease"],"prefix":"10.1542","volume":"142","author":[{"given":"Erika","family":"Van Nieuwenhove","sequence":"first","affiliation":[{"name":"Departments of Microbiology and Immunology and"},{"name":"VIB and KU Leuven Center for Brain and Disease Research, Leuven, Belgium;"},{"name":"University Hospitals Leuven, Leuven, Belgium; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Humblet-Baron","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and"},{"name":"VIB and KU Leuven Center for Brain and Disease Research, Leuven, Belgium;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lien","family":"Van Eyck","sequence":"additional","affiliation":[{"name":"University Hospitals Leuven, Leuven, Belgium; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lien","family":"De Somer","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and"},{"name":"University Hospitals Leuven, Leuven, Belgium; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Dooley","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and"},{"name":"VIB and KU Leuven Center for Brain and Disease Research, Leuven, Belgium;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Tousseyn","sequence":"additional","affiliation":[{"name":"Imaging and Pathology, Translational Cell and Tissue Research, Katholieke Universiteit Leuven, Leuven, Belgium;"},{"name":"Department of Pathology,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hershfield","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Duke University, Durham, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Liston","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and"},{"name":"VIB and KU Leuven Center for Brain and Disease Research, Leuven, Belgium;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carine","family":"Wouters","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and"},{"name":"University Hospitals Leuven, Leuven, Belgium; 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