Systemic juvenile idiopathic arthritis and macrophage activation syndrome: update on pathogenesis and treatment

Yasin, Shima; Schulert, Grant S.

doi:10.1097/bor.0000000000000526

Cited by 55 publications

(42 citation statements)

References 45 publications

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“…In particular, MAS is a common manifestation of gain‐of‐function mutations in NLRC4, a protein that activates the inflammasome. XIAP deficiency and MAS due to NLRC4 mutations and sJIA are characterized by high levels of IL‐18, which serves as a useful biomarker for these disorders …”

Section: Other Primary Immune Regulatory Disordersmentioning

confidence: 99%

“…55 Although HLH typically presents in an infant or young child with biomarker for these disorders. 58,59 Patients with periodic fever syndromes or inflammasomopathies (periodic fever syndromes) such as familial Mediterranean fever (FMF), 60 tumor necrosis factor receptor-associated periodic syndrome (TRAPS), 61 Although varying degrees of lymphoproliferation are common in primary immune regulatory disorders, in the majority it is benign lymphoproliferation. However, similar to other known classic immune defects with autoimmunity such as Wiskott-Aldrich syndrome and ALPS, a small but significant proportion of patients with primary immune regulatory disorders have an increased incidence of lymphoma/leukemia.…”

Section: Immune Defects With Increased Susceptibility To Lymphoid Malmentioning

confidence: 99%

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Primary immune regulatory disorders for the pediatric hematologist and oncologist: A case‐based review

Chandrakasan

Chandra

Saldaña

et al. 2019

Pediatric Blood & Cancer

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An array of monogenic immune defects marked by autoimmunity, lymphoproliferation, and hyperinflammation rather than infections have been described. Primary immune regulatory disorders pose a challenge to pediatric hematologists and oncologists. This paper focuses on primary immune regulatory disorders including autoimmune lymphoproliferative syndrome (ALPS) and ALPS‐like syndromes, immunodysregulation, polyendocrinopathy, enteropathy, X‐linked (IPEX) and IPEX‐like disorders, common variable immunodeficiency (CVID), CVID‐like, and late‐onset combined immunodeficiency (CID) disorders. Hyperinflammatory disorders and those associated with increased susceptibility to lymphoid malignancies are also discussed. Using a case‐based approach, a review of clinical pearls germane to the clinical and laboratory evaluation as well as the treatment of these disorders is provided.

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Section: Other Primary Immune Regulatory Disordersmentioning

confidence: 99%

Section: Immune Defects With Increased Susceptibility To Lymphoid Malmentioning

confidence: 99%

Primary immune regulatory disorders for the pediatric hematologist and oncologist: A case‐based review

Chandrakasan

Chandra

Saldaña

et al. 2019

Pediatric Blood & Cancer

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“…Systemic juvenile idiopathic arthritis (SoJIA), and later onset chronic infantile neurologic, cutaneous, and arthritis (CINCA) syndrome were once suspected. Different from the clinical manifestations of this patient, chilblains and intracranial calci cation are not present in SoJIA or CINCA; leukocytosis, destructive arthritis, or macrophage activation syndrome (MAS) are noted in SoJIA [4][5][6]; visual impairment, sensor neural deafness or progressive chronic meningitis have been commonly reported in CINCA [5]. Chronic kidney disease due to amyloidosis has been rarely reported in SoJIA, which is common in CINCA (Table 2) [8].…”

Section: Discussionmentioning

confidence: 63%

Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect

Xia

Yang

2020

Preprint

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Introduction: Aicardi-Goutières (AGS) is a rare immune dysregulated disease due to mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or IFIH1. Clinical features include basal ganglia calcifications, white matter abnormalities, and cerebral atrophy. Severe systemic inflammation and chronic kidney disease (CKD) are extremely rare in AGS. Herein, we report a patient presenting with systemic inflammation and CKD to broaden the clinical phenotype spectrum of the RNASEH2B defect. Methods: All testing and molecular genetic analysis were performed after obtaining the informed consent of the parents. Demographic, clinical, and laboratory findings were abstracted from outpatient and inpatient encounters. Cerebral magnetic resonance imaging (MRI), computed tomography (CT) scans, and renal biopsy histopathology reports were reviewed and summarized. Whole exome sequencing (WES) was performed on peripheral blood cells. After exposure to cGAMP in vitro for 24 hours, mRNA expression of twelve IFN-stimulated cytokine genes in PBMCs was assessed. Serum cytokine levels were detected by Milliplex. Results: A 11-year-old girl presented with recurrent aseptic fever, arthritis, chilblains, failure to thrive, mild hearing loss, and neurological manifestations. Laboratory and immunologic findings demonstrated lymphopenia, low complement levels, positive autoantibodies, elevated levels of acute-phase reactants and inflammatory cytokines. Cerebral imaging showed cerebral atrophy, white matter abnormalities, and intracranial calcification. Renal biopsy showed glomerular sclerosis in three of fourteen glomeruli, infiltration of lymphocytes and other mononuclear cells. WES revealed a homozygous and heterozygous mutations in RNASEH2B . Over-expression of IFN-stimulated cytokine genes was observed, including IFI44, IFI27, IFIT1, IFIT2, IFIT3, ISG15, OAS1, and SIGLEC1. Conclusions: To date, only two cases with AGS have been reported to have renal disease. Here, we describe a patient with both homozygous and heterozygous variants in RNASEH2B, presenting with neurological manifestations, persistently systemic autoinflammation, and CKD. CKD has never been reported in patients with AGS due to the RNASEH2B defect .

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“…Clinically overt MAS develops in systemic‐onset juvenile idiopathic arthritis in 10% of cases and has been claimed to be sub‐clinically present in 30%‐40% . MAS or secondary HLH may also complicate other immunological conditions and the most important are systemic lupus erythematosus and Kawasaki disease . Again, MAS may be the first presentation of these underlying immunological disorders.…”

Section: Resultsmentioning

confidence: 99%

An overview of how on‐call consultant paediatricians can recognise and manage severe primary immunodeficiencies

et al. 2019

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Severe primary paediatric immunodeficiency syndromes are rare and potentially fatal unless suspected, diagnosed and treated early. We provide clinical guidance and support for on‐call consultant paediatricians working in secondary level hospitals on how to recognise and manage children with these conditions. Our paper addresses four conditions that risk the most severe outcomes if they are not adequately cared for during on‐call periods, such as weekends: severe combined immunodeficiency, haemophagocytic lymphohistiocytosis, severe congenital neutropaenia and chronic granulomatous disease. Conclusion On‐call paediatricians are provided with advice on handling the most severe primary immunodeficiencies.

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Systemic juvenile idiopathic arthritis and macrophage activation syndrome: update on pathogenesis and treatment

Abstract: Collectively, these research advances have significant implications regarding the classification and diagnosis of SJIA and MAS, and support a next generation of biologic treatments including kinase inhibitors and targeted interleukin-18 or IFNγ blockade.

Cited by 55 publications

References 45 publications

Primary immune regulatory disorders for the pediatric hematologist and oncologist: A case‐based review

Primary immune regulatory disorders for the pediatric hematologist and oncologist: A case‐based review

Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect

An overview of how on‐call consultant paediatricians can recognise and manage severe primary immunodeficiencies

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