Case Of Macrophage Activation Syndrome Research Articles

A Case of Macrophage Activation Syndrome With Elderly Onset Still’s Disease Under Tocilizumab Treatment

A Case of Macrophage Activation Syndrome With Elderly Onset Still’s Disease Under Tocilizumab Treatment

Efficacy and safety of canakinumab in systemic juvenile idiopathic arthritis, the first Chinese experience

BackgroundSystemic juvenile idiopathic arthritis (sJIA) is a severe form of juvenile arthritis that is characterized by chronic joint inflammation and systemic symptoms such as fever, rash, and organ involvement. Anti-IL-6 receptor monoclonal antibody tocilizumab is an effective treatment. However, some patients still experience persisting or recurrent symptoms and the real-world effectiveness of canakinumab in Chinese patients with sJIA has never been reported. Therefore, this study aimed to assess the efficacy and safety of canakinumab in Chinese patients with sJIA using real-world data.MethodsWe conducted a retrospective study on children with active sJIA. Clinical features, laboratory data, corticosteroid dosage, and adverse events (AEs) were collected at baseline and at 4, 8, 12, and 24 weeks after initiating canakinumab treatment.ResultsSeven female and four male patients were included in the study. All patients had previously been treated with tocilizumab and were administered canakinumab for 12.4 ± 3.4 months. Notably, significant improvements were observed in both clinical signs and symptoms as well as laboratory indicators. Four children under corticosteroid treatment were able to successfully discontinue their corticosteroid therapy: one at week 4, two at week 12, and one at week 24. Notably, there was a significant reduction in the number of tender and swollen joints (P = 0.0059) as well as the systemic juvenile arthritis disease activity score (P < 0.0001). The most common AE was infection, but no patients experienced serious AEs. No cases of macrophage activation syndrome or death were reported during the follow-up period.ConclusionsCanakinumab was found to be potentially efficacious and safe in Chinese patients with sJIA. No new AEs were observed with canakinumab treatment.

A MASsive attack: a pediatric case of macrophage activation syndrome complicated by DIC as an onset of systemic juvenile idiopathic arthritis successfully treated with anakinra and review of the literature.

Macrophage activation syndrome (MAS) is one of the most severe complications of systemic juvenile idiopathic arthritis (sJIA). Around 10% of patients with sJIA exhibit systemic symptoms accompanied by macrophage activation syndrome (MAS), but it may occur subclinically in another 30-40%. In this article, we present a case of a 3-year-old girl diagnosed with sever MAS as an onset of sJIA complicated by disseminated intravascular coagulation (DIC). First symptoms of sJIA were observed about 5months before setting the diagnose, and it was resembling urticaria. A comprehensive allergological diagnostics were conducted, but no cause for the skin changes was identified. A few weeks before admission to the hospital, the girl was presented with a high fever. During the hospital stay, viral, bacterial, and fungal infections were ruled out. However, the findings indicated significantly elevated markers of inflammation (ferritin, CRP, ESR) in the conducted tests. Meanwhile, swelling of the feet and ankle joints was also observed. Based on Ravelli criteria, we set the diagnosis of MAS in a course of sJIA. We implemented treatment with steroid pulses, followed by cyclosporine; however, her clinical condition did not improve. Despite intensive treatment, skin petechiae were observed twice, and laboratory tests revealed a very high INR along with an extremely low level of fibrinogen. The patient required multiple plasma transfusions and clotting factor administrations. Due to the severe condition of the girl, we initiated biological treatment with anakinra, after which the child's condition gradually improved. In this case, we want to present how dynamic and life-threatening the course of MAS can be. In the discussion, we are also comparing our approach and the applied treatment with the currently available knowledge.

A Case of Macrophage Activation Syndrome (MAS) and Atypical HUS in Newely Diagnosed SLE

A Case of Macrophage Activation Syndrome (MAS) and Atypical HUS in Newely Diagnosed SLE

Macrophagic Activation Syndrome Revealing Hodgkin Lymphoma: Case Report

Macrophage Activation Syndrome (MAS), or Haemophagocytosis Syndrome, is a clinical-biological entity characterized by the proliferation and non-specific activation of macrophages of the reticulo-histiocytic system, with phagocytosis of the blood elements formed. This syndrome can be primary in children or secondary to various conditions at any age. Its association with Hodgkin's lymphoma is exceptional. We report here a case of MAS that revealed Hodgkin's lymphoma in a 5-year-old child. And we underline the interest of an urgent diagnosis and a fast care because risk of evolution towards a fatal multivisceral failure.

A Case of Macrophage Activation Syndrome During the Treatment of Adult-onset Still's Disease With Tocilizumab.

Macrophage activation syndrome (MAS) is a fatal complication of adult-onset Still's disease (AOSD). Although anti-cytokine agents have been recommended for refractory AOSD or complicated with MAS, MAS cases have been rarely reported during anti-cytokine treatment. Herein, we describe the first AOSD case complicated with MAS during the treatment with tocilizumab in Korea. Two years after tocilizumab maintenance therapy, high fever and hypertransaminasemia recurred. MAS was diagnosed based on hyperferritinemia, elevated soluble IL-2 receptor levels, and the presence of hemophagocytic histiocytes in the bone marrow. However, she had normal white blood cell counts and acute phase reactant levels. High-dose glucocorticoid and anakinra therapies were not effective, but her disease improved with etoposide. This case shows that tocilizumab may not prevent MAS development and can modify clinical features making it challenging to diagnose. Cytotoxic therapy such as etoposide may be required in MAS cases that develop during anti-cytokine therapy.

Macrophage Activated Syndrome associated with Adult Onset Still Disease

Haemophagocytic lymphohistiocytosis (HLH) is an underrecognized hyperinflammatory condition with a high mortality, characterized by inappropriate survival of histiocytes and cytotoxic T cells (CTLs), leading to a cytokine storm, haemophagocytosis and multi-organ damage (1). The currently accepted terminology includes two forms of HLH: the primary or familial HLH (fHLH) and the secondary HLH (sHLH) (2). The sHLH associated with rheumatic conditions is known as macrophage activation syndrome (MAS). MAS can develop at any time during the evolution of the rheumatic diseases: at the beginning, during flare of the disease or during intercurrent infections – mostly with viral trigger. We present a case of MAS in an patient with adult-onset Still Disease. It is of great importance to be recognized in early stages, because if promptly treated it might respond well to combination therapy of glucocorticoids and IL1- blockers.

СИНДРОМ АКТИВАЦИИ МАКРОФАГОВ ПРИ РЕВМАТИЧЕСКИХ ЗАБОЛЕВАНИЯХ У ДЕТЕЙ: РЕТРОСПЕКТИВНОЕ ИССЛЕДОВАНИЕ

Macrophage activation syndrome (MAS) is a rare life-threatening complication of rheumatic diseases (RD) that requires early recognition and adequate immediate treatment. Objective of the study: to identify the features of onset of RD in patients who developed MAS, the clinical and laboratory characteristics of the MAS, possible trigger factors and the timing of development. Materials and methods of research: 57 patients (20 boys and 37 girls) with RD who developed MAS were included in a retrospective continuous non-randomized study: 36 (63%) with systemic juvenile idiopathic arthritis (sJIA), 19 (33%) with Systemic lupus erythematosus (SLE), 1 (2%) – with juvenile dermatomyositis (JDM), one (2%) – with overlapping syndrome. Results: in the structure of patients with sJIA, patients with a history of MAS accounted for 28%, among patients with SLE – 7,6%. The median age at the time of sJIA debut in the study group was 2,6 years [1,5; 5,75], patients with SLE – 11,8 years [8,6; 13,95]. The ratio of boys and girls in the study group was 1:1,85. 70 MAS episodes were recorded: 48 – with sJIA, 20 – with SLE, one episode each for JDM and crossover syndrome. A single episode of MAS at the onset had 22% of patients with sJIA, 47% – with SLE, MAS during the course of the disease – 55% and 47%, repeated episodes of MAS – 25% and 5% of patients, respectively. Clinical manifestations of MAS included fever in 91% of children, hepatomegaly in 54%, pericarditis in 51%, skin lesions in 68%, CNS damage in 44%, lung damage in 33%, hyperferritinemia in 96%, thrombocytopenia – in 79%, increased aminotransferases – in 89%, hypertriglyceridemia – in 53%. Patients with sJIA and MAS had statistically significantly earlier onset (p=0,047), a greater number of systemic manifestations (p=0,012), a typical exanthema (p&lt;0,0001), and a smaller number of active joints (p=0,041). 83% of them had episodes of MAS before the initiation of therapy with biological disease-modifying antirheumatic drugs (bDMARDs). There was no statistically significant relationship between the development of MAS with the use of bDMARDs with a clear positive relationship with the violation of the therapy regimen. 19% of patients with sJIA and MAS had a history of infusion reaction to tocilizumab, 8% later had interstitial lung damage. Patients with SLE and MAS at the onset were statistically significantly more likely to have serositis (p=0,0028), ulcers of the oral mucosa (p&lt;0,0001), neuropsychiatric disorders (p=0,0024), positive Coombs' test (p=0,026). All patients received glucocorticoid therapy; experience with the use of GIBP in the study group was limited. Conclusion: MAS in children develops more often with sJIA; the dominant provoking factor is the activity of the underlying disease. The overwhelming majority of patients developed MAS during the course of the disease, less often at the onset. Patients with a history of MAS with sJIA are characterized by an earlier age of onset, a predominance of systemic manifestations, the need for early administration of bDMARDs therapy, and a tendency to infusion reaction to tocilizumab. Against the background of bDMARDs, a subclinical course of MAS with the absence of fever is possible. The risk of developing MAS along with SLE is higher in patients with onset of serositis, ulcers of the oral mucosa, neuropsychiatric disorders, and a positive Coombs' test. MAS cases were detected with high SLE activity at the onset, violation of the treatment protocol.

Macrophage activation syndrome triggered by systemic lupus erythematosus flare: successful treatment with a combination of dexamethasone sodium phosphate, intravenous immunoglobulin, and cyclosporine: a case report

BackgroundMacrophage activation syndrome is classified as a secondary form of hemophagocytic lymphohistiocytosis. It is a hyperinflammatory complication observed to be comorbid with a variety of autoimmune diseases, including adult-onset Still’s disease and systemic juvenile idiopathic arthritis. Macrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus, which, if untreated, can be fatal, though determining the optimum treatment strategy is still a challenge.Case presentationHerein, we report a case of macrophage activation syndrome in a 33-year-old Egyptian female as an unusual complication of a systemic lupus erythematosus flare in adult patients. Our patient was initially treated with a combination of intravenous methylprednisolone pulse therapy and intravenous immunoglobulin therapy, which was followed by a course of oral prednisolone and oral cyclosporine with little response. Switching from oral prednisone to intravenous dexamethasone sodium phosphate showed a more favorable clinical and biochemical response.ConclusionMacrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus. Our case demonstrates that dexamethasone sodium phosphate can be a successful alternative treatment for patients with systemic lupus erythematosus complicated by macrophage activation syndrome in whom the response to pulse methylprednisolone was inadequate to manage their illness, proving to be remarkably effective in a relatively short time frame.

Canakinumab in systemic juvenile idiopathic arthritis: real-world data from a retrospective Italian cohort.

The objective of this study was to use real-world data to evaluate the effectiveness and safety of canakinumab in Italian patients with systemic JIA (sJIA). A retrospective multicentre study of children with sJIA was performed. Clinical features, laboratory parameters and adverse events were collected at baseline, and 6 and 12 months after starting canakinumab. The primary outcome measure of effectiveness was clinically inactive disease (CID) off glucocorticoids (GCs) treatment at 6 months. A total of 80 children from 15 Italian centres were analysed. Of the 12 patients who started canakinumab in CID while receiving anakinra, all maintained CID. Of the 68 with active disease at baseline, 57.4% achieved CID off GCs at 6 months and 63.8% at 12 months. In univariate analysis, the variables significantly related to non-response were number of active joints (NAJs) ≥5, history of macrophage activation syndrome (MAS) and disease duration. Multivariate analysis confirmed the association between non-response and NAJs ≥5 [odds ratio (OR) 6.37 (95% CI: 1.69, 24.02), P = 0.006] and between non-response and history of MAS [OR 3.53 (95% CI: 1.06, 11.70), P = 0.039]. No serious adverse events were recorded in this series. There were two cases of MAS during canakinumab, leading to a rate of 2.9 episodes per 100 patient years. We have confirmed, using real-world data, the efficacy of canakinumab in sJIA in a multicentric cohort. History of MAS and higher NAJ were associated with lower probability of achieving CID.

Efficacy and safety of canakinumab in systemic juvenile idiopathic arthritis: 48-week results from an open-label phase III study in Japanese patients

Objectives To assess the efficacy and safety of canakinumab in Japanese patients with systemic juvenile idiopathic arthritis (sJIA). Methods This was an open-label, single-arm active treatment study. sJIA patients, aged ≥2 to <20 years, were administered canakinumab 4 mg/kg every 4 weeks for ≤48 weeks. The co-primary endpoints were the proportion of patients who achieved an adapted American College of Rheumatology pediatric (ACR pedi) 30 criteria at week 8, and the proportion of patients who successfully tapered corticosteroids at week 28. Herein, the efficacy and safety results up to 48 weeks are reported. Results Of the 19 patients enrolled, 15 (78.9%) had previously used tocilizumab. All patients achieved ACR pedi 30 at week 8 and 73.7% (14/19) successfully tapered corticosteroids at week 28. At week 48, ACR pedi 50/70/90/100 responses were achieved by 100.0%/100.0%/87.5%/68.8% of patients. The most common adverse events (AEs) were infections (271.6 patient-years), 42.1% (8/19) patients had serious AEs. Two potential cases of macrophage activation syndrome were identified. No deaths were reported. Conclusion Canakinumab was efficacious in Japanese patients with sJIA and was associated with substantial corticosteroid dose reduction in the majority of patients. The safety profile of canakinumab was consistent with that observed from previous studies. ClinicalTrials.gov (identifier NCT02396212).

Lessons from dermatology about inflammatory responses in Covid-19.

SummaryThe SARS‐Cov‐2 is a single‐stranded RNA virus composed of 16 non‐structural proteins (NSP 1‐16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid‐19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid‐19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a ‘cytokine storm’. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D‐dimer, lactic dehydrogenase, reactive‐C‐protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug‐related intertriginous and flexural exanthema. This review describes the complexity of Covid‐19, its pathophysiological and clinical aspects.

Lisocabtagene Maraleucel (liso-cel) for Treatment of Second-Line Transplant Noneligible (TNE) Relapsed/Refractory (R/R) Aggressive Non-Hodgkin Lymphoma (NHL): Initial Results from the PILOT Study

Lisocabtagene Maraleucel (liso-cel) for Treatment of Second-Line Transplant Noneligible (TNE) Relapsed/Refractory (R/R) Aggressive Non-Hodgkin Lymphoma (NHL): Initial Results from the PILOT Study

Multicenter Study of Ruxolitinibcombined DEP Regimen As a Salvage Therapy for Refractory/Relapsed Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a refractory immune disorder with a significant risk of death.Current therapies have improved the survival of HLH patients; however, approximately 30% patients do not respond to current therapies. At present, there is nounanimously recommended salvage HLH treatment regimen, and there are a few case reports or clinical reports with small sample sizes concerning salvage therapy after first line treatment failure. Therefore, alternative therapies for relapsed/refractory HLH is needed. Previous studies have found that ruxolitinib can improve the inflammatory status well, but the remission depth is not sufficient. This prospective study aimed to investigate the efficacy of ruxolitinib combined with our previous DEP (doxorubicin-etoposide-methylprednisolone) regimen(DEP-Ru) as a salvage therapy for refractory/relapsed(R/R)HLH.All patients who did not achieve at least partial response 2 weeks after initial standard HLH therapy or relapsed after remission with HLH-94 regimen were enrolled in this study between June 2018 and June 2019. Response to salvage therapy was assessed every 2 weeks after initiation of DEP-Ru therapy and patients were followed until death or until July 2019. Fifty-four R/R HLH patients were enrolled, including 28 cases of Epstein-Barr virus-associated HLH(EBV-HLH), 5 cases of macrophage activation syndrome (MAS), 3 cases of lymphoma-associated HLH, and 6 cases of familial HLH, 1case of pregnancy, 1 case of drug, and 2 cases of infection. There were 8 cases with unknown underlying diseases. One case was lost to follow-up, Eight cases (15.1%) achieved complete response and 31 cases (58.5%) achieved partial response. The overall response was 73.6% (39/53).Thirty two of the 54 patients survived to subsequent chemotherapy or allogenic hematopoietic stem cell transplantation. Our study suggests that DEP-Ru regimen compared with DEP regimen had similar efficacy, and no serious complications such as gastrointestinal bleeding occurred in DEP regimen. DEP-Ru has higher efficacy for MAS and HLH with unknown reason , while EBV-HLH and lymphoma-associated HLH have lower efficacy. DEP-Ru regimen is an effective salvage regimen for R/R HLH, which can prolong patient survival and bridge the gap between HLH and its underlying diseases. This study was registered in the Clinical Trail (ClinicalTrails.gov Identifier: NCT03533790). Disclosures No relevant conflicts of interest to declare.

45. A rare case of macrophage activation syndrome (MAS) associated with hypomyopathic dermatomyositis

45. A rare case of macrophage activation syndrome (MAS) associated with hypomyopathic dermatomyositis

Three cases of macrophage activation syndrome in children with juvenile idiopathic arthritis

Three cases of macrophage activation syndrome in children with juvenile idiopathic arthritis

Macrophage activation syndrome, an important differential diagnosis for septic shock.

Macrophage activation syndrome (MAS) is a rare and life threatening complication of rheumatic diseases. It is seen most frequently in association with systemic onset juvenile idiopathic arthritis and less commonly in other rheumatic diseases of childhood including systemic lupus erythematosus. Recognition of MAS in patients with rheumatic diseases is often challenging as it may mimic the clinical features of the underlying disease. Sometimes MAS can be the mode of initial presentation adding to the diagnostic complexity. We describe two cases of MAS in association with systemic onset juvenile idiopathic arthritis who presented with a clinical picture suggestive of septic shock. The Internal Review Board at Shands Children's Hospital and the University of Florida waived the need for approval for these case reports.

A Rare Case of Macrophage Activation Syndrome in a Neonate

Macrophage activation syndrome is excessive proliferation of macrophages associated with hemophagocytosis in bone marrow. It is characterized by fever >38.5oC for ≥7 days, splenomegaly, cytopenias (≥2 lineages), hypertriglyceridemia/ hypofibrinogenemia & hemophagocytosis. MAS occurying in neonatal period is very rare & only 2 sporadic case reports are available.We report a case of a neonate with MAS who presented with unremitting fever, hepatosplenomegaly, cytopenia, hyperferritinemia, with bone marrow suggestive of Hemophagocytosis.

Macrophage activation syndrome with acute hepatitis E during tocilizumab treatment for rheumatoid arthritis

Tocilizumab is a humanized antibody against the membrane and soluble receptors for interleukin-6. Tocilizumab is among the disease-modifying antirheumatic drugs (DMARDs) used to treat moderate-to-severe active rheumatoid arthritis (RA) refractory to conventional DMARDs. We report a case of macrophage activation syndrome that complicated acute hepatitis E and started within 24hours after the fourth tocilizumab infusion in a patient with RA.

Higher-dose canakinumab therapy for refractory macrophage activation syndrome in children with systemic juvenile idiopathic arthritis: two case reports

Macrophage activation syndrome (MAS) is a life-threatening, potentially fatal complication of systemic juvenile idiopathic arthritis (sJIA) appears in non-remitted fever, cytopenia, coagulopathy, liver and CNS dysfunctions. Triggers of MAS could be disease activity, infections and medications. Known IL-1 is the key cytokine in pathogenesis of MAS and SJIA, and disease flare associated with increased amounts of different cytokines, especially IL-1β. Many cases of MAS are medically-refractory to traditional doses of cytokine inhibition and may require increased dosing of biologic cytokine blockade. Interleukin-1 (IL-1) is typically a key cytokine in the pathogenesis of sJIA and associated MAS. When MAS occurs in the setting of sJIA treated with IL-1 inhibitors, then increased dosing of IL-1 blockers may be beneficial. This has been shown for anakinra, an IL-1 receptor antagonist, but this drug is currently not available worldwide. Another IL-1 blocker, canakinumbab (CKB), is a monoclonal antibody that blocks IL-1β, but does not also block IL-1α like anakinra. Herein, we describe 2 sJIA patients who developed MAS on standard doses of CKB (4 mg/kg). Both patients received an increased dose of CKB: 150 mg (7.5 and 12.5 mg/kg, respectively) with rapid and complete resolution of MAS. Later the CKB doses was tapered to normal regimen. No side effects or adverse events were noticed during usage of increased CKB doses. Increased dosing of CKB should be considered for CKB-treated sJIA patients who develop MAS on standard dosing.