P034 Macrophage activation syndrome in Juvenile Idiopathic Arthritis

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_5) ◽  
Author(s):  
Rahma Guedri ◽  
Glaimeriem ◽  
Zohra Fitouri ◽  
Saayda Ben Becher ◽  
Bechir Hamza
Keyword(s):  
Biological Treatment ◽  
Pediatric Rheumatology ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Systemic Jia ◽  
Rheumatology Unit ◽  
The Mean ◽  
And Biological Markers ◽  
Activation Syndrome

Abstract Objectives To describe the epidemiological, clinical-biological, and therapeutic characteristics of children with systemic JIA complicated with a macrophage activation syndrome (MAS). Methods It was a retrospective study, including children with JIA followed at the pediatric rheumatology unit of the children's hospital in Tunis for 22 years (January 1999 to December 2020), and presented MAS during their follow-up. Results We included 40 patients with JIA. Nineteen children (47.5%) presented MAS during the disease. They are 11 boys and 8 girls, with a sex ratio of 1.3. The mean age was 5.31 years (range: 0.66–10.83 years). The circumstances of the occurrence were variable. MAS was inaugural in 10 patients. Three of our patients presented MAS twice. MAS was definitive with clinical and biological markers in 12 cases and only biological in 7 cases. Seventeen of our patients were treated with intravenous Corticosteroids. Seven Childs among them received, in combination, Immunoglobulins (IG). We prescribed a biological treatment in 3 patients. We have mourned only one death. Conclusion MAS is a severe complication of JIA and is the leading cause of death.

scholarly journals Intravenous administration of anakinra in children with macrophage activation syndrome

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Omkar Phadke ◽  
Kelly Rouster-Stevens ◽  
Helen Giannopoulos ◽  
Shanmuganathan Chandrakasan ◽  
Sampath Prahalad
Keyword(s):  
Intravenous Administration ◽  
Lupus Erythematosus ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Therapeutic Option ◽  
Interleukin 1 ◽  
Neurological Dysfunction ◽  
Systemic Jia ◽  
Subcutaneous Edema ◽  
Activation Syndrome

Abstract Background Subcutaneous anakinra is an interleukin-1 inhibitor used to treat juvenile idiopathic arthritis. Recent reports suggest anakinra can be a valuable addition to the treatment of COVID-19 associated cytokine storm syndrome and the related multisystem inflammatory syndrome (MIS-C) in children. Herein, we describe our experience with intravenously administered anakinra. Findings 19 Patients (9 male) received intravenous (IV) anakinra for treatment of macrophage activation syndrome (MAS) secondary to systemic lupus erythematosus (SLE), systemic JIA (SJIA) or secondary hemophagocytic lymphohistiocytosis (sHLH). In most cases the general trend of the fibrinogen, ferritin, AST, and platelet count (Ravelli criteria) improved after initiation of IV anakinra. There were no reports of anaphylaxis or reactions associated with administration of IV anakinra. Conclusion Intravenous administration of anakinra is an important therapeutic option for critically ill patients with MAS/HLH. It is also beneficial for those with thrombocytopenia, subcutaneous edema, neurological dysfunction, or very young, hospitalized patients who need multiple painful subcutaneous injections.

Efficacy of moderately dosed etoposide in macrophage activation syndrome - hemophagocytic lymphohistiocytosis (MAS-HLH)

2021 ◽  
pp. jrheum.200941
Author(s):  
AnnaCarin Horne ◽  
Tatiana von Bahr Greenwood ◽  
Samuel C.C. Chiang ◽  
Marie Meeths ◽  
Caroline Björklund ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Nk Cell ◽  
Cell Activity ◽  
Neutropenic Sepsis ◽  
Lymphocyte Cytotoxicity ◽  
Activation Syndrome

Objective Macrophage activation syndrome (MAS) constitutes one subtype of the hyperinflammatory syndrome hemophagocytic lymphohistiocytosis (HLH), and the term MAS-HLH was recently proposed for HLH with underlying autoimmune/autoinflammatory conditions. The mortality of MAS-HLH has been estimated to 5-10%. Here we report our experiences with moderately dosed etoposide in severe MAS-HLH, administered with the objective to effectively reduce severe hyperinflammatory activity with limited side effects. Methods In addition to conventional anti-inflammatory treatment, moderately dosed etoposide was administered to seven children affected by rapidly progressing MAS-HLH with central nervous system (n=5) and/or pulmonary (n=5) involvement. Three had underlying systemic onset juvenile idiopathic arthritis (sJIA), two atypical sJIA (no arthritis at diagnosis), and two systemic lupus erythematosus. We performed lymphocyte cytotoxicity analyses in all seven and genetic analyses in six. Results All children promptly responded to moderately dosed etoposide (50-100 mg/m2 once weekly), added to conventional MAS-HLH treatment which was considered insufficient. The mean accumulated etoposide dose was 671 mg/m2 (range 300-1,050 mg/m2), as compared to 1,500 mg/m2 recommended the first 8 weeks of the HLH-94/HLH-2004 protocols. One child developed neutropenic fever and another neutropenic sepsis (neutrophils 0.3x109/L at therapy onset). Five/seven children had low percentages (<5%) circulating NK-cells prior to or in association with diagnosis; NK-cell activity was pathologically low in two/five children studied. Disease-causing variants in HLH-associated genes were not found. All children were alive at latest follow-up (2-9 years after onset); neurological symptoms had normalized in four/five affected children. Conclusion Moderately dosed etoposide may be beneficial in severe and/or refractory MAS-HLH.

2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis

2016 ◽  
Vol 75 (3) ◽  
pp. 481-489 ◽  
Author(s):  
Angelo Ravelli ◽  
Francesca Minoia ◽  
Sergio Davì ◽  
AnnaCarin Horne ◽  
Francesca Bovis ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Consensus Conference ◽  
Classification Criteria ◽  
Systemic Jia ◽  
Patient Profiles ◽  
Activation Syndrome

To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA—associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ=0.76). We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies.

Association ofIRF5Polymorphisms with Susceptibility to Macrophage Activation Syndrome in Patients with Juvenile Idiopathic Arthritis

2011 ◽  
Vol 38 (4) ◽  
pp. 769-774 ◽  
Author(s):  
MASAKATSU YANAGIMACHI ◽  
TAKUYA NARUTO ◽  
TAKAKO MIYAMAE ◽  
TAKUMA HARA ◽  
MASAKO KIKUCHI ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Proinflammatory Cytokines ◽  
Lupus Erythematosus ◽  
Gene Polymorphisms ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Nucleotide Polymorphisms ◽  
Systemic Jia ◽  
Increased Risk ◽  
Activation Syndrome

Objective.Systemic-onset juvenile idiopathic arthritis (systemic JIA) and macrophage activation syndrome (MAS), the most devastating complication of systemic JIA, are characterized by abnormal levels of proinflammatory cytokines. Interferon regulatory factor 5 (IRF5) is a member of the IRF family of transcription factors, and acts as a master transcription factor in the activation of genes encoding proinflammatory cytokines. Polymorphisms in theIRF5gene have been associated with susceptibility to autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Our aim was to assess associations ofIRF5gene polymorphisms with susceptibility to systemic JIA and MAS.Methods.ThreeIRF5single-nucleotide polymorphisms (rs729302, rs2004640, and rs2280714) were genotyped using TaqMan assays in 81 patients with systemic JIA (33 with MAS, 48 without) and 190 controls.Results.There were no associations of theIRF5gene polymorphisms or haplotypes under study with susceptibility to systemic JIA. There was a significant association of the rs2004640 T allele with MAS susceptibility (OR 4.11; 95% CI 1.84, 9.16; p = 0.001). TheIRF5haplotype (rs729302 A, rs2004640 T, and rs2280714 T), which was reported as conferring an increased risk of SLE, was significantly associated with MAS susceptibility in patients with systemic JIA (OR 4.61; 95% CI 1.73, 12.3; p < 0.001).Conclusion.IRF5gene polymorphism is a genetic factor influencing susceptibility to MAS in patients with systemic JIA, and IRF5 contributes to the pathogenesis of MAS in these patients.

scholarly journals Effective Therapy of Tocilizumab on Systemic Juvenile Idiopathic Arthritis Associated Refractory Macrophage Activation Syndrome

2021 ◽  
Author(s):  
Jianqiang Wu ◽  
Li Sun ◽  
Xuemei Tang ◽  
Qi Zheng ◽  
Li Guo ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Statistical Significance ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Gastrointestinal Symptoms ◽  
Lactic Dehydrogenase ◽  
Reactive Protein ◽  
Activation Syndrome

Abstract Objectives To evaluate the safety and efficacy of tocilizumab (TCZ) on refractory macrophage activation syndrome (rMAS) associated with systemic juvenile idiopathic arthritis (sJIA-rMAS). Methods We retrospectively reviewed the charts of 14 patients diagnosed with sJIA-rMAS, who were treated with TCZ after failing conventional therapies at three hospital centers from Jan 2016 to Dec 2020. Demographic, clinical, and laboratory characteristics were recorded at the onset of MAS, before TCZ (pre-TCZ) and 14 days after TCZ (post-TCZ). Results The clinical manifestation of sJIA-rMAS included fever (100%), skin rashes (35.7%), lymphadenomegaly (42.9%), hepatomegaly (57.1%), splenomegaly (7.1%), gastrointestinal symptoms (28.6%), arthritis (14.3%), myalgia (28.6%) and polyserositis (14.3%). After TCZ treatment, fever (100%, 14/14), gastrointestinal symptoms (100%, 4/4) and myalgia (100%, 4/4) were significantly improved after one week (p&lt; 0.05). Skin rashes, lymphadenomegaly and arthritis also improved in many patients but these parameters did not reach statistical significance. In post-TCZ group, decreases in levels of c-reactive protein, erythrocyte sedimentation rate and serum ferritin of sJIA-rMAS were observed compared with pre-TCZ (p&lt; 0.05). Although not statistically significant, post-TCZ group showed normalization of white blood cell, platelet count, alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and triglyceride levels compared with pre-TCZ. No disease relapse or fatality was recorded during the follow-up (25 months, range 3–60 months). Conclusions TCZ is safe and effective for the treatment of sJIA-rMAS after failure of conventional therapies.

P043 Predictors of mortality in childhood-onset Systemic Lupus Erythematosus

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_5) ◽  
Author(s):  
O Gacem ◽  
Z Zeroual ◽  
Z Arrada ◽  
Moussa Achir ◽  
M S Ladj
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Interquartile Range ◽  
Systemic Lupus ◽  
Pediatric Systemic Lupus Erythematosus ◽  
The Mean ◽  
Activation Syndrome

Abstract Background Pediatric Systemic Lupus Erythematosus (pSLE) is a severe autoimmune disease due to its serious multi-visceral disorders, its morbidity causing deleterious and sometimes permanent effects. The objective is to determine the prognostic predictive factors of death in pSLE. Methods This was a prospective, descriptive, multicentre study, including patients less than16 years of age with SLE according to the criteria SLE of the American College of Rheumatology over a period of 36 months (2015–2018) carried out in the CHU Nefissa Hamoud in Algiers. The number of deaths during this follow-up period was determined and compared with surviving patients in several parameters (demographic, clinical, laboratory, therapeutic and disease activity). Disease activity was estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the use of which has been validated in children and damage and sequelae were appreciated by the Systemic Lupus International Collaborating Clinics (SLICC). Means, percentages and χ2 tests were specified. The multivariate analysis of logistic regression was used to determine prognostic factors associated with the outcome variable. P values &lt;0.05 were considered statistically significant. Results 83 patients were collected and divided into two groups: deceased and survivors in which different parameters were compared and analyzed. Results: Female: male ratio 1: 4.9, mean age at diagnosis 11.3 ± 3.62. Clinical involvements at diagnosis were: cutaneous (100%), hematological (79.5%), articular (65, 1%), renal (44, 6%), neurological (41%), hepato-digestive (41%), cardiac (27, 7%), pleuropulmonary (19, 3%) and ocular involvement (7, 2%). The mean of SLEDAI was 22.11 ± 11.87 [interquartile range 2–53]. The prevalence of death was 11% of cases with an average age of death of 11 years [interquartile range 5–15 years]. The comparison of the two groups demonstrated a significant association between death and the following parameters: renal and neurological damage respectively: ((P = 0.03), (P = 0.02)), macrophage activation syndrome (MAS) (P = 0.0002), infections (P = 0.027), disease activity (P = 0.006) and damage score (P = 0.001). The mean SLEDAI activity in deceased patients was 32 ± 11.9 [interquartile range 17–53], compared with surviving patients which was 20.9 ± 11.4 [interquartile range 2–51]. Multivariate analysis with logistic regression revealed two major predictors of death, namely neurological involvement (odds ratio = 6,093 95% confidence interval ((1,1 8 0 ∼ 31 446)) and macrophage activation syndrome. Adherence to treatment was a protective factor: ([0.016 (0.001–0.353)]. Conclusion These results showed that pediatric systemic lupus erythematosus exhibits an aggressive and severe phenotype with an unpredictable course. Studies are needed in children in order to specify and develop prognostic predictive factors and to identify patients at high risk of early mortality in order to design early and effective care of this vulnerable entity of lupus disease. Keywords Child, Systemic Lupus Erythematosus, mortality

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