Pediatric Rheumatology最新文献

{"title":"A20 haploinsufficiency in a neonate caused by a large deletion on chromosome 6q","authors":"Fan Zhang, Liang Zhang","doi":"10.1186/s12969-023-00947-z","DOIUrl":"https://doi.org/10.1186/s12969-023-00947-z","url":null,"abstract":"Haploinsufficiency of A20 (HA20) is a rare monogenic disease caused by heterozygous loss-of-function mutations in the tumor necrosis factor alpha-induced protein 3 (TNFAIP3) gene located on chromosome 6q23.3. The majority of disease-causing mutations in most cases of HA20 comprise single nucleotide variations, small insertions, or deletions in TNFAIP3, which result in a premature termination codon and subsequent disruption of its anti-inflammatory role. Large deletions have been reported sporadically. HA20 patients may present with a variety of autoinflammatory and autoimmune features during early childhood; however, cases with neonatal onset are rare. Here, we describe a Chinese neonate presenting with concomitant inflammatory and other syndromic manifestations caused by a 5.15 Mb interstitial deletion in chromosome 6; these deletions affect TNFAIP3. Taken together, the data extend the clinical and genetic spectra of HA20.","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"77 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139101948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Part 5: Allogeneic HSCT in refractory SJIA with lung disease; recent cases from centers in North America & Europe","authors":"Alexei A. Grom, Scott W. Canna, Rolla F. Abu-Arja, Rashmi Sinha, Luciana Peixoto, Elvira Cannizzaro, Shanmuganathan Chandrakasan, Kyla Driest, Rebecca Marsh, Bénédicte Neven, Karen Onel, Sampath Prahalad, Susan Prockop, Pierre Quartier, Johannes Roth, Grant Schulert, Juliana M.F. Silva, Donna Wall, Ulrike Zeilhofer","doi":"10.1186/s12969-023-00868-x","DOIUrl":"https://doi.org/10.1186/s12969-023-00868-x","url":null,"abstract":"It has been increasingly recognized that there is a subset of patients with refractory systemic JIA, who have failed all available medications and may benefit from HSCT. The increasing experience with HSCT in SJIA, suggests that despite the complicated post-HSCT course, short-term, the transplanted patients either achieved SJIA remission or reduced burden of disease. Longer follow-up, however, is needed to better define the long-term outcomes. The discussion at the NextGen 2022 conference was focused on the optimal timing for the procedure, the need for a good control of inflammatory SJIA activity prior to HSCT, and the role of the reduced intensity conditioning regimens as there was a remote concern that such regimens might increase the risk of SJIA relapse after the transplantation. There was unanimous agreement about the importance of long-term registries to address these questions.","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"15 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139101966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tocilizumab for treating mevalonate kinase deficiency and TNF receptor-associated periodic syndrome: a case series and literature review","authors":"Yandie Li, Meiping Lu","doi":"10.1186/s12969-023-00952-2","DOIUrl":"https://doi.org/10.1186/s12969-023-00952-2","url":null,"abstract":"Mevalonate kinase deficiency (MKD) and TNF receptor-associated periodic syndrome (TRAPS) are categorized as systemic autoinflammatory diseases (SAIDs), which are rare diseases characterized by early onset, severe conditions, and challenging diagnosis and treatment. Although different SAIDs have varying standard treatments, some SAIDs are poorly controlled after routine treatment, seriously affecting the growth and development of children and their quality of life. This study aims to provide more treatment strategies for SAIDs. We present two Chinese patients with MKD and TRAPS who were resistant to TNF- (tumor necrosis factor-) α blockade. After using etanercept, baricitinib, and glucocorticoid, patients with MKD and TRAPS still had periodic fever and rash. Due to the unavailability of IL-1 antagonists in the Chinese Mainland, we started administering intravenous tocilizumab (TCZ) at a dosage of 240 mg every three weeks. They had not experienced fever or rash after receiving one or two doses of TCZ. Before treatment with TCZ in the MKD patient, white blood cell (WBC) count, and TNF-α level were normal, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) increased significantly, and IL-6 increased slightly. After treatment with TCZ, ESR and CRP levels returned to normal; however, IL-6 increased occasionally. In the TRAPS patient, ESR, CRP, WBC, IL-6, and TNF-α levels were increased significantly. After TCZ treatment, ESR, CRP, WBC, IL-6, and TNF-α levels returned to normal. The two patients were treated with TCZ for more than six months and achieved clinical and serological remission. Furthermore, they had no adverse reactions after injection of TCZ. In the absence of IL-1 antagonists in mainland China, tocilizumab emerges as an alternative drug in SAIDs that are resistant to TNF-α blockade.","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"66 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139102055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 4th NextGen therapies for SJIA and MAS: part 2 phenotypes of refractory SJIA and the landscape for clinical trials in refractory SJIA","authors":"Grant Schulert, Sebastiaan J. Vastert, Alexei A. Grom","doi":"10.1186/s12969-023-00865-0","DOIUrl":"https://doi.org/10.1186/s12969-023-00865-0","url":null,"abstract":"Although the introduction of the IL-1 and IL-6 inhibiting biologics in 2012 has revolutionized the treatment and markedly improved outcomes for many patients with SJIA, about 20% of these patients continue to have active disease, have markedly decreased quality of life and high disease activity as well as treatment-related morbidity and mortality. There is a clear need to define these disease states, and then use these definitions as the basis for further studies into the prevalence, clinical features, and pathophysiologic mechanisms. While such patients are most likely to benefit from novel therapies, they are very difficult to enroll in the ongoing clinical trials given the unique features of their disease and large numbers of background medications. The discussions at the NextGen 2022 conference focused on strategies to overcome these obstacles and accelerate studies in refractory SJIA.","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"200 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139102119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 4th NextGen therapies of SJIA and MAS, part 4: it is time for IL-18 based trials in systemic juvenile idiopathic arthritis?","authors":"Scott W. Canna, Fabrizio De Benedetti","doi":"10.1186/s12969-023-00867-y","DOIUrl":"https://doi.org/10.1186/s12969-023-00867-y","url":null,"abstract":"Since IL-18 has recently emerged as a biomarker associated with refractory disease course in SJIA, the focus of the discussion was the feasibility of the biomarker-driven drug development to SJIA. Overall, there was broad agreement on the conclusion that IL-18 is a uniquely specific biomarker for many of the subsets of SJIA most in need of new therapies, and it may define a class of diseases mediated by IL-18 excess. The consensus was that leveraging IL-18 remains our most promising “lead” for use in refractory SJIA as it may mechanistically explain the disease pathophysiology and lead to more targeted therapies.","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"13 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139101924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mental comorbidities in adolescents and young adults with juvenile idiopathic arthritis: an analysis of German nationwide health insurance data","authors":"Florian Milatz, Katinka Albrecht, Kirsten Minden, Ursula Marschall, Jens Klotsche, Johanna Callhoff","doi":"10.1186/s12969-023-00948-y","DOIUrl":"https://doi.org/10.1186/s12969-023-00948-y","url":null,"abstract":"Studies on prevalence rates of mental comorbidities in patients with juvenile idiopathic arthritis (JIA) have reported varying results and provided limited information on related drugs. The purpose of this study was to determine the prevalence of selected mental health diagnoses and the range of associated drug prescriptions among adolescents and young adults (AYA) with JIA compared with general population controls. Nationwide statutory health insurance data of the years 2020 and 2021 were used. Individuals aged 12 to 20 years with an ICD-10-GM diagnosis of JIA in ≥ 2quarters, treated with disease-modifying antirheumatic drugs and/or glucocorticoids were included. The frequency of selected mental health diagnoses (depression, anxiety, emotional and adjustment disorders) was determined and compared with age- and sex-matched controls. Antirheumatic, psychopharmacologic, psychiatric, and psychotherapeutic therapies were identified by Anatomical Therapeutic Chemical (ATC) codes and specialty numbers. Based on data from 628 AYA with JIA and 6270 controls, 15.3% vs. 8.2% had a diagnosed mental health condition, with 68% vs. 65% receiving related drugs and/or psychotherapy. In both groups, depression diagnosis became more common in older teenagers, whereas emotional disorders declined. Females with and without JIA were more likely to have a mental health diagnosis than males. Among AYA with any psychiatric diagnosis, 5.2% (JIA) vs. 7.0% (controls) received psycholeptics, and 25% vs. 27.3% psychoanaleptics. Selected mental health conditions among 12-20-year-old JIA patients are diagnosed more frequently compared to general population. They tend to occur more frequently among females and later in childhood. They are treated similarly among AYA regardless of the presence of JIA.","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"66 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139101964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proceedings from the 4th NextGen Therapies for SJIA and MAS virtual symposium held February 13–14, 2022","authors":"Rashmi Sinha, Fabrizio De Benedetti, Alexei A. Grom","doi":"10.1186/s12969-023-00863-2","DOIUrl":"https://doi.org/10.1186/s12969-023-00863-2","url":null,"abstract":"<p>Refractory Systemic Juvenile Idiopathic Arthritis (SJIA) remains a major source of morbidity and mortality in children with pediatric rheumatic disease [1, 2]. Although several potential therapeutic targets have been recently identified, only few patients have been enrolled in ongoing clinical trials. The 4<sup>th</sup>\u0000<b>“</b>NextGen Therapies for SJIA and MAS” virtual symposium organized by the “SJIA Foundation” and held February 13–14, 2022<b>,</b> brought together SJIA families, leading researchers, clinicians and representatives from Pharma and FDA with the main goals to identify barriers to clinical research in this area and develop new strategies to advance it.</p><p>Systemic Idiopathic Arthritis (SJIA; estimated U.S. prevalence of 1:10,000 children) is the most severe subtype of chronic childhood arthropathy, notable for marked systemic immune activation with features of autoinflammation, and development of severe joint damage [2,3,4,5,6]. The licensing of IL-1 and IL-6-blocking monoclonal antibodies in 2012 resulted in superior control of SJIA-associated arthritis and systemic manifestations [7,8,9,10,11]. However, despite the use of these biologic disease modifying antirheumatic medications (b-DMARDs) about 15% of patients with SJIA develop macrophage activation syndrome (MAS<u>)</u>, i.e. potentially fatal episodes of systemic hyperinflammation that are associated with hemophagocytosis [5, 6, 12, 13]. Furthermore, since the licensing of these b-DMARDs, children with SJIA (~ 5% in 2020) have increasingly been diagnosed with life-threatening chronic parenchymal lung disease (SJIA-LD) [14,15,16]. This has prompted speculations that drugs blocking IL-1 and/or IL-6 might contribute to the development of SJIA-LD [16]. Given high mortality and frequent need for hospitalization, there is an urgent need for life-saving treatments for SJIA-LD and MAS.</p><p>Translational research identified IFN-γ as the pivotal cytokine in MAS [6, 17,18,19] and Phase II clinical trials are in progress [20]. In contrast, the nature of the SJIA-associated lung disease remains elusive, and potential therapeutic targets in this disease still need to be defined. The typical histopathology of SJIA-LD includes (a) extensive lymphoplasmacytic inflammatory infiltrates in the lung interstitial tissue; (b) organizing pneumonia; (c) pleural and interlobular septal collagenous fibrosis; (d) vasculopathy associated with muscular mural thickening of the pulmonary arteries; and (e) alveolar inflammation with accumulation of foamy <i>alveolar macrophages</i> with some features of pulmonary alveolar proteinosis (PAP) [15, 16]. Features of PAP typically result from dysfunction of <i>alveolar macrophages</i> leading to accumulation of pulmonary surfactant in alveolar space, and it has been suggested that there may be acquired <i>alveolar macrophages</i> dysfunction in SJIA-LD.</p><p>Recent studies suggested potential risk factors for SJIA-LD: (a) SJIA onset under age 2 years wi","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"29 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139101969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 4th NextGen Therapies for SJIA and MAS: part 1 the elephant in the room: diagnostic/classification criteria for systemic juvenile idiopathic arthritis and adult-onset still’s disease","authors":"Peter A. Nigrovic, Fabrizio de Benedetti, Yukiko Kimura, Daniel J. Lovell, Sebastiaan J. Vastert","doi":"10.1186/s12969-023-00864-1","DOIUrl":"https://doi.org/10.1186/s12969-023-00864-1","url":null,"abstract":"Currently, the criteria used to classify patients with SJIA are different from those used for AOSD. However, it has been recognized that the existing terms are too narrow, subdividing the Still’s population unnecessarily between pediatric-onset and adult-onset disease and excluding an appreciable group of children in whom overt arthritis is delayed or absent. Government regulators and insurers rely upon the guidance of subject experts to provide disease definitions, and when these definitions are flawed, to provide new and better ones. The classification session at the NextGen 2022 conference helped to serve this purpose, establishing the need for a revised definitional system that transcends the fault lines that remain in existing definitions.","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"135 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139102147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Juvenile idiopathic recurrent parotitis (JIRP) treated with short course steroids, a case series study and one decade follow up for potential autoimmune disorder","authors":"Farhad Salehzadeh, Rasol Molatefi, Ali Mardi, Negin Nahanmoghaddam","doi":"10.1186/s12969-023-00946-0","DOIUrl":"https://doi.org/10.1186/s12969-023-00946-0","url":null,"abstract":"Juvenile idiopathic recurrent parotitis (JIRP) in children is a condition characterized with recurrent episodes of idiopathic parotid gland inflammation. Since there are no definitive guidelines for diagnosis and management of this condition, we present a consecutive case series of patients with more than one decade follow up and their dramatic response to short course treatment by prednisolone. We conducted this study by retrospectively reviewed medical charts of children who were diagnosed with JIRP, from 1 January 2002 to 29 February 2023. We performed usual serological tests to exclude some possible background. We administered short course prednisolone on first day of episode as divided dosage (0.5 mg /kg). In this case series of 10 patients (70%) were male, median age of onset was 5 years, duration of episodes 5 days, and the mean course of disease were 3.8 years. The average follows up of patients was near 10 years. In comparison with their natural course of disease all patients showed a dramatic response to treatment on the first day of administration of prednisolone (P Value 0.005). For ten years follow up there was not any additional accompanying autoimmune disorder. Short course prednisolone on first day of each episode and its dramatic and meaningful response in our patients, introduce a new, effective, fast, and inexpensive regimen of therapy in patients with JIRP.","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"76 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139095823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A rare manifestation of STING-associated vasculopathy with onset in infancy: a case report","authors":"Sophia Weidler, Sarah Koss, Christine Wolf, Nadja Lucas, Jürgen Brunner, Min Ae Lee-Kirsch","doi":"10.1186/s12969-023-00934-4","DOIUrl":"https://doi.org/10.1186/s12969-023-00934-4","url":null,"abstract":"STING-associated vasculopathy with onset in infancy (SAVI) is a rare type I interferonopathy caused by heterozygous variants in the STING gene. In SAVI, STING variants confer a gain-of-function which causes overactivation of type I interferon (IFN) signaling leading to autoinflammation and various degrees of immunodeficiency and autoimmunity. We report the case of a 5 year old child and his mother, both of whom presented with systemic inflammatory symptoms yet widely varying organ involvement, disease course and therapeutic response. Genetic testing revealed a heterozygous STING variant, R281Q, in the child and his mother that had previously been associated with SAVI. However, in contrast to previously reported SAVI cases due to the R281Q variant, our patients showed an atypical course of disease with alopecia totalis in the child and a complete lack of lung involvement in the mother. Our findings demonstrate the phenotypic breadth of clinical SAVI manifestations. Given the therapeutic benefit of treatment with JAK inhibitors, early genetic testing for SAVI should be considered in patients with unclear systemic inflammation involving cutaneous, pulmonary, or musculoskeletal symptoms, and signs of immunodeficiency and autoimmunity.","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"15 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139095916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}