Hematological involvement in pediatric systemic lupus erythematosus: A multi-center study

Introductio

A20 haploinsufficiency (HA20) : Clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease

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

A20 haploinsufficiency (HA20) : Clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease

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

The characteristics of patients with COVID-19-associated pediatric vasculitis: an international, multicenter study

Objective: COVID-19 associated pediatric vasculitis other than Kawasaki disease (KD)-like vasculitis in multisystem inflammatory syndrome in children (MIS-C) is very rare. We aimed to analyze the characteristics, treatment and outcome in COVID-19-associated pediatric vasculitis (excluding KD-like vasculitis in MIS-C). Methods: The inclusion criteria were as follows: 1) <18 years at vasculitis onset; 2) evidence of vasculitis; 3) evidence of SARS-CoV-2 exposure; 4) ≤3 months between SARS-CoV-2 exposure and vasculitis onset. Patients with MIS-C were excluded. Results: Forty-one patients (median age 8.3 years; M/F=1.3) were included from 14 centers and six countries. The most frequent vasculitis subtype was IgA vasculitis/Henoch Schönlein purpura (IgAV/HSP) (n=30). The median duration between SARS-CoV-2 exposure and vasculitis onset was 13 days. Skin (92.7%) and gastrointestinal (61%) involvements were the most common manifestations of vasculitis. Most patients (68.3%) received corticosteroids; while 14.6% used additional immunosuppressive drugs. Remission was achieved in all. All IgAV/HSP patients had skin manifestations while 18 (60%) and 13 (43.3%) had gastrointestinal system and renal involvement, respectively. When we compared the features of these patients with those of a pre-pandemic pediatric IgAV/HSP cohort (n=159), fever (30% vs. 5%; p<0.001) and renal involvement (43.3% vs. 17.6%; p=0.002) were more common, while recovery without treatment (10% vs. 39%; p=0.002) and complete recovery (86.7% vs. 99.4%; p=0.002) were less frequent among COVID-19-associated IgAV/HSP patients. Conclusion: This is the largest cohort of children with COVID-19 associated vasculitis (excluding MIS-C). Our findings suggest a more severe disease course in COVID-19-associated pediatric IgAV/HSP patients compared to pre-pandemic patients. This article is protected by copyright. All rights reserved

The characteristics of patients with COVID-19-associated pediatric vasculitis: an international, multicenter study.

Objective: COVID-19 associated pediatric vasculitis other than Kawasaki disease (KD)-like vasculitis in multisystem inflammatory syndrome in children (MIS-C) is very rare. We aimed to analyze the characteristics, treatment and outcome in COVID-19-associated pediatric vasculitis (excluding KD-like vasculitis in MIS-C). Methods: The inclusion criteria were as follows: 1) <18 years at vasculitis onset; 2) evidence of vasculitis; 3) evidence of SARS-CoV-2 exposure; 4) ≤3 months between SARS-CoV-2 exposure and vasculitis onset. Patients with MIS-C were excluded. Results: Forty-one patients (median age 8.3 years; M/F=1.3) were included from 14 centers and six countries. The most frequent vasculitis subtype was IgA vasculitis/Henoch Schönlein purpura (IgAV/HSP) (n=30). The median duration between SARS-CoV-2 exposure and vasculitis onset was 13 days. Skin (92.7%) and gastrointestinal (61%) involvements were the most common manifestations of vasculitis. Most patients (68.3%) received corticosteroids; while 14.6% used additional immunosuppressive drugs. Remission was achieved in all. All IgAV/HSP patients had skin manifestations while 18 (60%) and 13 (43.3%) had gastrointestinal system and renal involvement, respectively. When we compared the features of these patients with those of a pre-pandemic pediatric IgAV/HSP cohort (n=159), fever (30% vs. 5%; p<0.001) and renal involvement (43.3% vs. 17.6%; p=0.002) were more common, while recovery without treatment (10% vs. 39%; p=0.002) and complete recovery (86.7% vs. 99.4%; p=0.002) were less frequent among COVID-19-associated IgAV/HSP patients. Conclusion: This is the largest cohort of children with COVID-19 associated vasculitis (excluding MIS-C). Our findings suggest a more severe disease course in COVID-19-associated pediatric IgAV/HSP patients compared to pre-pandemic patients. This article is protected by copyright. All rights reserved

Loss-Of-Function Mutations in Tnfaip3 Leading to A20 Haploinsufficiency Cause an Early-Onset Autoinflammatory Disease

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