Florence A. Aeschlimann

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.

TNF and IL-1 Targeted Treatment in Kawasaki Disease

Opinion statementKawasaki disease (KD) is a multisystemic vasculitis affecting young children and the most common cause of acquired heart disease in children in the developed world. Current treatment recommendations for acute KD include IVIG and aspirin, but there are no evidence-based guidelines for children who do not respond to IVIG treatment. Widely applicable risk stratification algorithms to identify patients at high-risk of treatment failure and poor coronary artery outcome are not available. Over the past few years, increasing knowledge of the pathophysiology of disease have resulted in the identification of key inflammatory mediators and the use of biologic pathway targeting agents such as TNF and IL-1 inhibitors for children with IVIG-resistant disease. However, despite considerable efforts, adequately powered, randomized, controlled and prospective trials are lacking. In this review, we summarize the recent advances in our understanding of disease pathobiology and provide an overview of the currently available studies on anti-TNF and IL-1 therapy in KD.

Presentation and disease course of childhood- versus adult-onset Takayasu Arteritis

To compare the clinical features, efficacy and safety of treatment regimens, and outcomes of childhood‐ and adult‐onset Takayasu arteritis (TAK).

Early Onset of Chronic Rheumatic Disease May Lead to Creative Expression: The Stories of Antoni Gaudí and Maud Lewis

Many famous artists had rheumatic diseases. Among them, the popular French impressionist painter Pierre-Auguste Renoir, the Russian expressionist painter Alexej von Jawlensky, and the French fauvist and “painter of the light” Raoul Dufy were diagnosed with rheumatoid arthritis (RA), and Paul Klee, a highly renowned Swiss-German painter, with systemic sclerosis. Their medical histories have been widely discussed, and they are examples of how creative art may help in coping with the disease1,2,3,4,5,6. Autoimmune diseases such as RA seem to occur with a higher frequency in artists, and exposure to toxins, such as those found in painting materials, and smoking have been discussed as contributing factors7,8,9. Would a chronic inflammatory pediatric rheumatic disease possibly influence artistic work? Juvenile idiopathic arthritis (JIA) and other chronic rheumatologic conditions with childhood onset have a significant effect on health-related quality of life and physical function, imposing a societal and psychological burden, especially in the prebiologic era10. Art therapy has been shown to be beneficial in adults and children with chronic diseases by reducing stress and pain and enabling the expression of the cognitive and emotional ideas of the patients11,12,13,14,15. To our knowledge and in contrast to the many artists with adult-onset autoimmune rheumatic conditions, there are only 2 famous artists with known chronic pediatric rheumatic diseases: Antoni Gaudi, the unique Catalan architect, and Maud Lewis, one of Canada’s best known and most loved folk art painters. The medical literature discussing Gaudi’s articular symptoms is scarce and we are not aware of any publication on Lewis’s medical history16,17,18. Dufy experienced an episode of self-limited arthritis in childhood, but he remained …

Risk of Serious Infections Associated with Biologic Agents in Juvenile Idiopathic Arthritis: A Systematic Review and Meta-Analyses

Objective To assess whether treatment with biologic response modifying agents during clinical trial study periods increases the risk of serious infections in children with juvenile idiopathic arthritis (JIA). Study design A systematic literature review using Medline, Embase, Cochrane library, and the clinical trial registry was performed up to July 2017. Random effects meta‐analyses were used to compare rates of serious infections in children with JIA given biologic agents compared with controls, and the pooled relative risk calculated. Subanalyses were performed for different biologic agent classes. Results In total, 19 trials accounting for 21 individual studies were included (11 for tumor necrosis factor‐alpha inhibitors [n = 814 patients], 3 for interleukin‐6 inhibitors [n = 318], 6 for interleukin‐1 inhibitors [n = 353], and 1 for selective T‐lymphocyte costimulation modulators [n = 122]). Patients (68% female) had a mean age of 10.8 years. Seventeen serious infections were reported among 810 children receiving biologic agents and 15 among 797 controls. The most frequent infections were bronchopulmonary and varicella. No statistically significant difference in risk of serious infections was found between children receiving biologic agents compared with control groups (pooled relative risk = 1.13; 95% CI [0.63, 2.03]) during the trial study periods. The risk remained nonsignificant when evaluating the different classes of biologic agents separately. However, the analyses were underpowered to detect differences in the risk of serious infections overall or differences between classes of biologic agents. Conclusions In this systematic review and meta‐analyses, serious infections were uncommon and not significantly increased among patients with JIA receiving biologic agents compared with controls. However, the analyses were underpowered and study periods were relatively short. Ongoing careful monitoring for serious infections remains necessary for all patients with JIA, and particularly those receiving biologic agents.

Response to: ’A20 haploinsufficiency (HA20): clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease' by Aeschlimann et al

We thank Dr Berteau et al 1 for sharing their experience of a family diagnosed with HA20 based on a Behcet-like disease phenotype and an autosomal-dominant inheritance pattern. The presentation and disease course described in the mother and her two children support the findings described in our cohort2 and in a recent large cohort of Japanese patients with HA20.3 An interesting …

A Toddler Presenting with Pulmonary Renal Syndrome

Pulmonary renal syndrome refers to an association of pulmonary and glomerular disease and includes disorders, such as the ANCA-associated vasculitides, anti-glomerular basement membrane antibody disease, systemic lupus erythematosus, and IgA vasculitis (Henoch-Schönlein purpura). We present the medical history of a 26-month-old boy with an extensive purpuric rash, involving the limbs, trunk, and face, who developed clinically significant pulmonary hemorrhage and renal involvement. Rapid recognition of this rare but potentially life-threatening condition is crucial. In this report, we discuss the differential diagnosis, diagnostic studies, and treatment options to consider when facing a young child presenting with a pulmonary renal syndrome.