TY - JOUR
T1 - A20 haploinsufficiency (HA20)
T2 - Clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease
AU - Aeschlimann, Florence A.
AU - Batu, Ezgi D.
AU - Canna, Scott W.
AU - Go, Ellen
AU - Gül, Ahmet
AU - Hoffmann, Patrycja
AU - Leavis, Helen L.
AU - Ozen, Seza
AU - Schwartz, Daniella M.
AU - Stone, Deborah L.
AU - Van Royen-Kerkhof, Annet
AU - Kastner, Daniel L.
AU - Aksentijevich, Ivona
AU - Laxer, Ronald M.
N1 - Funding Information:
Funding FAA was supported by grants from the rhyner-Bangerter Foundation, Starr-Foundation, Swiss League against rheumatism, Foundation W!, Alberta Children’s Hospital research Institute Foundation and SickKids Foundation.
Publisher Copyright:
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Objectives The association between mutations in TNFAIP3, encoding the NF-kB regulatory protein A20, and a new autoinflammatory disease has recently been recognised. This study aims at describing the clinical phenotypes and disease course of patients with A20 haploinsufficiency (HA20). Methods Data for all cases from the initial publication, and additional cases identified through collaborations since, were collected using standardised data collection forms. Results A total of 16 patients (13 female) from seven families with a genetic diagnosis of HA20 were included. The disease commonly manifested in early childhood (range: first week of life to 29 years of age). The main clinical symptoms were recurrent oral, genital and/or gastrointestinal ulcers (16/16), musculoskeletal (9/16) and gastrointestinal complaints (9/16), cutaneous lesions (8/16), episodic fever (7/16), and recurrent infections (7/16). Clinical phenotypes varied considerably, even within families. Relapsing-remitting disease course was most common, and one patient died. Laboratory abnormalities included elevated acute-phase reactants and fluctuating presence of various autoantibodies such as antinuclear antibodies (4/10 patients tested) and anti-dsDNA (2/5). Tissue biopsy of different sites revealed non-specific chronic inflammation (6/12 patients tested), findings consistent with class V lupus nephritis in one patient, and pustules and normal results in two patients each. All patients were treated: 4/16 received colchicine and 12/16 various immunosuppressive agents. Cytokine inhibitors effectively suppressed systemic inflammation in 7/9 patients. Conclusions Early-onset recurrent oral, genital and/or gastrointestinal ulcers are the hallmark feature of HA20. Frequency and intensity of other clinical manifestations varied highly. Treatment regimens should be based on disease severity, and cytokine inhibitors are often required to control relapses.
AB - Objectives The association between mutations in TNFAIP3, encoding the NF-kB regulatory protein A20, and a new autoinflammatory disease has recently been recognised. This study aims at describing the clinical phenotypes and disease course of patients with A20 haploinsufficiency (HA20). Methods Data for all cases from the initial publication, and additional cases identified through collaborations since, were collected using standardised data collection forms. Results A total of 16 patients (13 female) from seven families with a genetic diagnosis of HA20 were included. The disease commonly manifested in early childhood (range: first week of life to 29 years of age). The main clinical symptoms were recurrent oral, genital and/or gastrointestinal ulcers (16/16), musculoskeletal (9/16) and gastrointestinal complaints (9/16), cutaneous lesions (8/16), episodic fever (7/16), and recurrent infections (7/16). Clinical phenotypes varied considerably, even within families. Relapsing-remitting disease course was most common, and one patient died. Laboratory abnormalities included elevated acute-phase reactants and fluctuating presence of various autoantibodies such as antinuclear antibodies (4/10 patients tested) and anti-dsDNA (2/5). Tissue biopsy of different sites revealed non-specific chronic inflammation (6/12 patients tested), findings consistent with class V lupus nephritis in one patient, and pustules and normal results in two patients each. All patients were treated: 4/16 received colchicine and 12/16 various immunosuppressive agents. Cytokine inhibitors effectively suppressed systemic inflammation in 7/9 patients. Conclusions Early-onset recurrent oral, genital and/or gastrointestinal ulcers are the hallmark feature of HA20. Frequency and intensity of other clinical manifestations varied highly. Treatment regimens should be based on disease severity, and cytokine inhibitors are often required to control relapses.
KW - autoinflammatory disease
KW - pediatric rheumatology
KW - ulcers
UR - http://www.scopus.com/inward/record.url?scp=85042378129&partnerID=8YFLogxK
U2 - 10.1136/annrheumdis-2017-212403
DO - 10.1136/annrheumdis-2017-212403
M3 - Article
AN - SCOPUS:85042378129
SN - 0003-4967
VL - 77
SP - 728
EP - 735
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 5
ER -