Secondary Macrophage Activation Syndrome Research Articles

EBV-triggered secondary macrophage activation syndrome in the backdrop of lupus in an adult.

Macrophage activating syndrome (MAS) is a potentially life-threatening condition falling under the spectrum of secondary hemophagocytic lymphohistiocytosis, in the backdrop of rheumatological conditions. In this case of a middle-aged man, we see how an initial Epstein Barr virus infection triggered a chain of events, which after serial monitoring of labs was promptly diagnosed as MAS and treated appropriately, resulting in overall clinical improvement of the patient.

Adult-onset Still’s disease with secondary macrophage activation syndrome: a case report

We describe a case of adult-onset Still’s disease (AOSD) with secondary macrophage activation syndrome. AOSD is a rare disease with unknown origin. Rarely it’s complicated by secondary macrophage activation syndrome, which is a life-threatening disorder. Because the diagnosis of AOSD is essential for exclusion and complications are life-threatening, it is mandatory for a prompt and extensive diagnostic workup and treatment.

Systemic Juvenile Idiopathic Arthritis and Secondary Macrophage Activation Syndrome in Latvia from 2009 to 2020: A Nationwide Retrospective Study.

Background and Objectives: Systemic juvenile idiopathic arthritis (sJIA) is a distinctive JIA subtype with mostly nonspecific systemic clinical features, which can be a diagnostic challenge. This study aimed to analyze our experience with sJIA in Latvia for twelve years: assessing clinical and epidemiological characteristics, the efficacy of therapy, and disease outcomes, including the development of macrophage activation syndrome (MAS). Materials and methods: This is a descriptive study in which we conducted a retrospective case review of all patients with sJIA diagnosis admitted to the only pediatric tertiary centre in Latvia during the period 2009-2020. Results: sJIA was diagnosed in 35 patients with a mean annual incidence rate of 0.85 patients per 100,000 children. Major clinical signs at the first visit were: fever, rash, arthritis, and lymphadenopathy. Almost half of the patients, 48.5%, had a monocyclic disease course, and only 20% of patients had persistent disease. MAS developed in 28.6% of patients. Biological therapy was administered to 48.6% of patients, mostly by tocilizumab, which induced remission in 75% after one year, and in 81.2% after two years without any serious therapy-related complications. In our study, none of the patients had interstitial lung disease, drug reaction with eosinophilia and systemic symptoms (DRESS)-like syndrome, or fatal disease. Conclusions: The incidence and clinical characteristics of sJIA correlate with the literature findings, although MAS was more common than described in other studies. There is a tendency for the persistent disease to decrease with the use of biological therapy. Tocilizumab is an efficient choice of treatment with a good safety profile.

O08 A case of juvenile systemic lupus erythematosus with pyrexia of unknown origin

Case report - IntroductionAn 18-year-old young man with diagnosis of Juvenile SLE with lupus nephritis maintained in remission on Mycophenolate Mofetil (MMF), presented with high-grade fever without focus close to his 18th birthday. History or examination did not point to any focus of infection, but blood tests showed systemic inflammation. Extensive investigations, including extended infection screen and bone marrow aspiration, were negative. His blood tests were suggestive of macrophage activation syndrome with no clinical or laboratory evidence of flare of lupus. MRI scan revealed extensive para-aortic lymphadenopathy and a diagnosis of classical Hodgkin's lymphoma confirmed on lymph node biopsy.Case report - Case descriptionInterestingly he first presented with fever and cervical lymphadenopathy at 13 years of age to local hospital, when a biopsy had revealed lymphoma but the diagnosis was changed to SLE following review at tertiary hospital. He was started on steroids and low-dose methotrexate. He later developed facial swelling, abdominal distension and groin swelling, following which he was referred to tertiary renal centre. His examination revealed scarring malar rash, anaemia, ankle and scrotal oedema, ascites and pleural effusion. His investigations showed anaemia, thrombocytopaenia, ESR over 100mm/hour, hypoalbuminaemia, low complement levels, positive ANA and double-stranded DNA. He had nephrotic range proteinuria and renal biopsy showed Class V lupus nephritis. He was treated with intravenous and later weaning dose of oral steroids and started on MMF. He remained in remission on a stable dose of MMF, except for brief flare of proteinuria, which settled with short course of oral steroids.A few months before his eighteenth birthday, he presented to local hospital with recurrent episodes of high-grade fever with no clear focus. He was twice managed with broad spectrum antibiotics, despite negative septic screen and an extended infection screen including viral PCRs and IGRA for tuberculosis. He had no focal symptoms or symptoms to suggest flare of underlying lupus, but had loss of appetite and loss of weight. He developed splenomegaly with increasing inflammatory markers and fall in all cell lines of full blood count with deranged coagulation. He satisfied the clinical and laboratory criteria of the preliminary Diagnostic Guidelines for Macrophage Activation Syndrome in JSLE (2009), following which he was commenced on three days of IV methylprednisolone following normal bone marrow aspirate. However, fever recurred after initial response and MRI scan revealed mediastinal and para-aortic lymphadenopathy, and a diagnosis of classical Hodgkin's lymphoma was confirmed on lymph node biopsy.Case report - DiscussionThis young man initially presented with fever and cervical lymphadenopathy, when a diagnosis of lymphoma was made. Yet, following review of the biopsy at the local tertiary centre and the abnormal immunological profile, a diagnosis of lupus was made. He then developed nephrotic syndrome, when a diagnosis of lupus nephritis was confirmed on biopsy. Other clinical and laboratory profile (raised ESR, hypocomplementeamia, serositis and haematological parameters) corroborated the diagnosis. He responded well to steroids and immunosuppression, when he presented with fever again. He had no evidence of flare of underlying lupus or any infection, but blood tests and splenomegaly pointed to macrophage activation syndrome (MAS). A negative bone marrow examination suggested that pancytopaenia was unlikely to be due to bone marrow infiltration, which is why he was treated with steroids. Yet, when fever recurred, MRI was arranged to investigate further, which eventually led to revelation of lymphadenopathy and biopsy, which eventually led to the right diagnosis. Another dilemma was if his MAS was to respond to steroids, whether we should change his baseline immunosuppression which had worked well so far for him and if we chose to, what would be the best agent.Case report - Key learning points1. Although extremely uncommon, children and young people with rheumatic diseases can develop malignancy, which may be unrelated to the primary condition or the therapeutic agents used. Unexplained symptoms in the absence of flare of underlying condition and with infections ruled out, warrant extension of investigations to rule out an underlying malignancy.2. Diagnosis of secondary MAS in a rheumatological condition without any evidence of flare of the underlying condition should be viewed as suspicious and warrants more investigations to rule out other causes.3. In patients who develop MAS, there are very few agents which work for both lupus and MAS, choosing an agent which treats both conditions is challenging.

Consensus-Based Guidelines for the Recognition, Diagnosis, and Management of Hemophagocytic Lymphohistiocytosis in Critically Ill Children and Adults.

Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome that often requires critical care support and remains difficult to diagnose. These guidelines are meant to aid in the early recognition, diagnosis, supportive care, and treatment of patients with hemophagocytic lymphohistiocytosis in ICUs. The literature searches were performed with PubMed (MEDLINE). Keywords and medical subject headings terms for literature search included "macrophage activation syndrome," hemophagocytic lymphohistiocytosis," and "hemophagocytic syndrome." The Histiocyte Society developed these consensus recommendations on the basis of published reports and expert opinions with level of evidence provided for each recommendation. They were endorsed by the Society of Critical Care Medicine. Testing for hemophagocytic lymphohistiocytosis should be initiated promptly in all patients admitted to ICUs with an unexplained or disproportionate inflammatory response, especially those with rapid clinical deterioration. Meeting five or more of eight hemophagocytic lymphohistiocytosis 2004 diagnostic criteria serves as a valuable diagnostic tool for hemophagocytic lymphohistiocytosis. Early aggressive critical care interventions are often required to manage the multisystem organ failure associated with hemophagocytic lymphohistiocytosis. Thorough investigation of the underlying triggers of hemophagocytic lymphohistiocytosis, including infections, malignancies, and autoimmune/autoinflammatory diseases, is essential. Early steroid treatment is indicated for patients with familial hemophagocytic lymphohistiocytosis and is often valuable in patients with acquired hemophagocytic lymphohistiocytosis (i.e., secondary hemophagocytic lymphohistiocytosis) without previous therapy, including macrophage activation syndrome (hemophagocytic lymphohistiocytosis secondary to autoimmune/autoinflammatory disease) without persistent or relapsing disease. Steroid treatment should not be delayed, particularly if organ dysfunction is present. In patients with macrophage activation syndrome, whose disease does not sufficiently respond, interleukin-1 inhibition and/or cyclosporine A is recommended. In familial hemophagocytic lymphohistiocytosis and severe, persistent, or relapsing secondary macrophage activation syndrome, the addition of prompt individualized, age-adjusted etoposide treatment is recommended. Further studies are needed to determine optimal treatment for patients with hemophagocytic lymphohistiocytosis in ICUs, including the use of novel and adjunct therapies.

Complications after CD19+ CAR T-Cell Therapy.

Simple SummaryCD19+ Chimeric antigen receptor (CAR) T-cells are used against CD19+ hematologic malignancies, such as high-grade B-cell lymphoma and acute lymphoblastic leukemia. Since this is a relatively new treatment approach, not all potential side effects are well described, and the underlying pathobiology is often not well defined. Here, we summarize current data on the incidence and the current management of CD19+ CAR T-cell complications. We discuss frequently occurring toxicities and we highlight evidence for the occurrence of rarer side effects affecting different organ systems. In addition, we highlight new findings that shed light on the pathophysiology of CAR T-cell-related complications.Clinical trials demonstrated that CD19+ chimeric antigen receptor (CAR) T-cells can be highly effective against a number of malignancies. However, the complete risk profile of CAR T-cells could not be defined in the initial trials. Currently, there is emerging evidence derived from post approval studies in CD19+ CAR T-cells demonstrating both short-term and medium-term effects, which were unknown at the time of regulatory approval. Here, we review the incidence and the current management of CD19+ CAR T-cell complications. We highlight frequently occurring events, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cardiotoxicity, pulmonary toxicity, metabolic complications, secondary macrophage-activation syndrome, and prolonged cytopenia. Furthermore, we present evidence supporting the hypothesis that CAR T-cell-mediated toxicities can involve any other organ system and we discuss the potential risk of long-term complications. Finally, we discuss recent pre-clinical and clinical data shedding new light on the pathophysiology of CAR T-cell-related complications.

European evidence-based recommendations for diagnosis and treatment of childhood-onset systemic lupus erythematosus: the SHARE initiative

Childhood-onset systemic lupus erythematosus (cSLE) is a rare, multisystem and potentially life-threatening autoimmune disorder with significant associated morbidity. Evidence-based guidelines are sparse and management is often based on clinical expertise....

Leishmaniose viscérale sans splénomégalie. À propos d’un cas chez un nourrisson

Pediatric visceral leishmaniasis is caused by Leishmania infantum, a dog parasite transmitted to humans by the bite of the female phlebotomine sand fly. The well-known clinical triad is fever, pallor, and splenomegaly. A secondary macrophage activation syndrome (MAS) can complicate this infection, which is lethal when not treated. When MAS is observed without any explanation, a visceral leishmaniasis is highly recommended. We report a case of visceral leishmaniasis in a 21-month-old child complicated by a macrophage activation syndrome without splenomegaly. No immunodeficiency was diagnosed that could explain this unusual clinical condition. To our knowledge, this is the first case of visceral leishmaniasis without splenomegaly reported to date.

AB0921 Secondary Macrophage Activation Syndrome: Report of 13 Clinical Cases and the Difference between the 4 Groups of Diseases

BackgroundThe secondary macrophage activation syndrome (SMAS) is a group of diseases that include the: Autoimmune (AI), Hemato-Oncological (HO), Infectious (Inf) and Oncological (Onco). We make a review of the the...

P57 Etoposide in secondary macrophage activation syndrome in children

P57 Etoposide in secondary macrophage activation syndrome in children

Distinct cytokine profiles of systemic-onset juvenile idiopathic arthritis-associated macrophage activation syndrome with particular emphasis on the role of interleukin-18 in its pathogenesis

To compare the pro-inflammatory cytokine profiles and the cytokine kinetics in patients with secondary macrophage activation syndrome (MAS) due to systemic-onset juvenile idiopathic arthritis (s-JIA) and in both active and inactive disease states of s-JIA (but no MAS), with those demonstrated in EBV-induced haemophagocytic lymphohistiocytosis (HLH) and Kawasaki disease (KD), and to investigate the significance of IL-18 in the pathogenesis of s-JIA. Five patients with MAS complicating s-JIA (MAS/s-JIA), 10 with HLH due to EBV infection (EBV-HLH), 22 with KD and 28 healthy controls were analysed. Cytokine concentrations (IL-18, IL-6, neopterin and TNF-alpha receptor Types I and II) were quantified in serum by ELISA. Results were compared with clinical features of MAS/s-JIA, including ferritin concentrations. Serum IL-18 concentrations in MAS/s-JIA patients were significantly higher than those in EBV-HLH or KD patients (P < 0.05). Serum IL-6 concentrations in KD patients were significantly higher than those in EBV-HLH or MAS/s-JIA patients. Serum neopterin concentrations in EBV-HLH patients were significantly higher than those in MAS/s-JIA or KD patients. Serum IL-18 correlated positively with the following measurements of disease activity: CRP, ferritin, lactate dehydrogenase and other cytokines (P < 0.05). Serum concentrations of IL-18 in s-JIA patients remained elevated in the inactive phase of disease, whereas clinical parameters and other cytokines normalized. IL-18 may be an important mediator in s-JIA. Although serum Il-18 concentrations correlated with markers of the disease activity, IL-18 concentrations remained elevated even when other markers of disease activity normalized. Serum IL-18 concentration may be a promising indicator of the disease activity. The cytokine release pattern in MAS/HLH is different among patients with different aetiologies. Monitoring the cytokine profile, including IL-18, may be useful for differentiation of MAS/HLH and evaluation of disease activity in s-JIA.