Life-threatening Macrophage Activation Syndrome Research Articles

Life threatening macrophage activation syndrome as the initial presentation of systemic lupus erythematosus: A case report and review of the literature

BackgroundMacrophage activation syndrome (MAS) is characterized by activation of hemophagocytic cells and is a very rare initial manifestation of systemic lupus erythematosus (SLE). Aim of the workTo describe the features of a challenging case of SLE initially presented with MAS. Case reportA previously healthy 20-year-old female was referred to the Rheumatology clinic with a 25-days’ history of persistent fever, general fatigue, and significant weight loss. Clinical examination revealed a high-grade fever (41 °C), significant hair loss and general malaise. Laboratory investigations revealed leucopenia (1.5 × 109/L), neutropenia (0.7 × 109/L), lymphopenia (0.6 × 109/L), normocytic normochromic anemia (9 g/dL), thrombocytopenia (95 × 109/L), elevated liver enzymes, hyperbilirubinemia (2.6 mg/dl); hypertriglyceridemia (306 mg/dL), hyperferritinemia (16000 ng/mL), elevated D-Dimer (4.7 mg/L), elevated lactate dehydrogenase (1379 U/L) and direct and indirect Coombs' tests were positive. Erythrocyte sedimentation rate was 28 mm/1st h. Immunological screening was positive for antinuclear antibody (ANA) and anti-double stranded deoxyribonucleic acid (anti-dsDNA). Serum C3 and C4 complement factors were low and C reactive protein was negative. Soluble CD25 was elevated (9800 pg/ml). Bone marrow biopsy showed hypocellular bone marrow with normal megakaryocytes and erythroid series with evidence of hemophagocytosis. A diagnosis of SLE initially presented with MAS was made. The patient received intravenous methylprednisolone for 5 consecutive days followed by prednisolone and cyclosporine A and intravenous immunoglobulin. The condition deteriorated with progressive coagulopathy, thrombocytopenia and hyperferritinemia. Subsequently, the conscious level of the patient deteriorated, multiorgan failure developed and the patient died. ConclusionMAS is a serious condition that may be the first presentation of SLE.

Aadult-onset Still's disease: new insights from the rheumatologists

Adult onset Still's disease (AOSD) is a rare polygenic autoinflammatory disease mainly manifesting as high-spiking fever, rash, arthritis/arthralgia, lymphadenopathy, and leukocytosis. More importantly, life threatening macrophage activation syndrome may occur in AOSD patients. Recently, with the development of research in pathogenesis and therapy strategies of biological agents and small molecule targeted drugs, we have new recognition of AOSD. In this commentary, we attempt to place this syndrome in perspective, including data in the past year on pathogenesis, clinical and laboratory features and therapy.

P27 Life-threatening macrophage activation syndrome with neurological involvement responding to very high dose IV anakinra

P27 Life-threatening macrophage activation syndrome with neurological involvement responding to very high dose IV anakinra

Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis is the most common chronic rheumatic disease of unknown aetiology in childhood and predominantly presents with peripheral arthritis. The disease is divided into several subgroups, according to demographic characteristics, clinical features, treatment modalities and disease prognosis. Systemic juvenile idiopathic arthritis, which is one of the most frequent disease subtypes, is characterized by recurrent fever and rash. Oligoarticular juvenile idiopathic arthritis, common among young female patients, is usually accompanied by anti-nuclear antibodie positivity and anterior uveitis. Seropositive polyarticular juvenile idiopathic arthritis, an analogue of adult rheumatoid arthritis, is seen in less than 10% of paediatric patients. Seronegative polyarticular juvenile idiopathic arthritis, an entity more specific for childhood, appears with widespread large- and small-joint involvement. Enthesitis-related arthritis is a separate disease subtype, characterized by enthesitis and asymmetric lower-extremity arthritis. This disease subtype represents the childhood form of adult spondyloarthropathies, with human leukocyte antigen-B27 positivity and uveitis but commonly without axial skeleton involvement. Juvenile psoriatic arthritis is characterized by a psoriatic rash, accompanied by arthritis, nail pitting and dactylitis. Disease complications can vary from growth retardation and osteoporosis secondary to treatment and disease activity, to life-threatening macrophage activation syndrome with multi-organ insufficiency. With the advent of new therapeutics over the past 15 years, there has been a marked improvement in juvenile idiopathic arthritis treatment and long-term outcome, without any sequelae. The treatment of juvenile idiopathic arthritis patients involves teamwork, including an experienced paediatric rheumatologist, an ophthalmologist, an orthopaedist, a paediatric psychiatrist and a physiotherapist. The primary goals of treatment are to eliminate active disease, to normalize joint function, to preserve normal growth and to prevent long-term joint damage. Timely and aggressive treatment is important to provide early disease control. The first-line treatment includes disease-modifying anti-rheumatic drugs (methotrexate, sulphasalazine, leflunomide) in combination with corticosteroids, used in different dosages and routes (oral, intravenous, intra-articular). Intra-articular application of steroids seems to be an effective treatment modality, especially in monoarthritis. Biological agents should be added in the treatment of unresponsive patients. Anti-tumour necrosis factor agents (etanercept, infliximab, adalimumab), anti-interleukin-1 agents (anakinra, canakinumab), anti- interleukin-6 agents (tocilizumab) and T-cell regulatory agents (abatacept) have been shown to be safe and effective in childhood patients. Recent studies reported sustained reduction in joint damage with even complete clinical improvement in paediatric patients, compared to previous data.

Severe macrophage activation syndrome. Is there a causative role for a homozygous A91V mutation in the perforin gene?

A 16 year old lebanese girl with consanguinous parents presented with a severe “abdominal” sepsis supposedly resulting from an infected vaginal tampon (ESBL E.coli). She had been healthy before. She developed severe hepatic functional disorder, infarction of the spleen, cardiovascular and renal insufficiency, as well as anemia and thrombocytopenia. Macrophage activation syndrome was diagnosed subsequently and systemic glucocorticoid treatment initiated. The girl recovered clinically. Of note, she developed severe cushingoid syndrome. Due to limited compliance she discontinued all anti-inflammatory medication (nsaids, gc and ciclosporin) 4 weeks later. The following 18 months inflammatory parameters were persistantly elevated (ESR>100mm/h). Familial mediteranean fever was excluded. Genetic analysis revealed a homozygous perforin I gene mutation 91 (GCG) -> Valin (GTG)/.pAla91Val-/A91V in exon 2. Familial hemophagocytic lymphohistiocytosis type II was discussed as a potential diagnosis. Perforin expression was diminshed to about 50% in NK-cells, however functional NK-cell cytotoxicity was in the lower normal range, considered not impaired. On the basis of these findings, we want to discuss the role of the homozygous A91V perforin mutation for the initiation or perpetuation of a life-threatening macrophage activation syndrome, in addition to the further management of the patient.

Successful treatment of macrophage activation syndrome complicating adult Still disease with anakinra

A previously healthy 20-year-old man presented with adult Still disease (ASD). He developed life-threatening macrophage activation syndrome (MAS), which was refractory to standard immunosuppression but responded dramatically to the IL-1 receptor antagonist anakinra. Subsequent immunological investigations included assessment of the perforin expression of natural killer (NK) cells and CD8+ T cells, which confirmed MAS.

Plasmaféresis en el síndrome de activación macrofágica y fracaso multiorgánico como primera manifestación de una dermatomiositis juvenil

The use of extracorporeal techniques for the treatment of paediatric diseases has expanded dramatically in the past decade. Plasmapheresis, a technique for exchanging plasma components with albumin or plasma, has been used in some rheumatologic conditions. We report the clinical course of a 7 years old boy with clinical and biological features of macrophage activation syndrome and multiorgan failure, at the time of presentation of severe juvenile dermatomyositis, and non responsive to corticosteroids, cyclosporine and immunoglobulin. After 4 days in the paediatric intensive care unit, plasmapheresis was used as rescue therapy. Repeated therapeutic plasmapheresis was effective for improving the multiorgan failure and laboratory abnormalities. The patient was discharged on the 21st hospital day with good functional condition. Plasmapheresis should be considered as rescue treatment in patients with life threatening macrophage activation syndrome and systemic onset of juvenile dermatomyositis.

Systemic onset juvenile idiopathic arthritis with macrophage activation syndrome misdiagnosed as Kawasaki disease: case report and literature review

Patients with systemic onset juvenile idiopathic arthritis (SoJIA) are rarely known to develop coronary artery dilatation. The American heart association (AHA) statement on evaluation of suspected Kawasaki disease (KD) would lead some SoJIA patients (particularly in the early stages of the disease) to be inaccurately classified as KD. In addition to the institution of inappropriate therapy with IVIG, misdiagnosis as KD can delay definitive treatment for these SoJIA patients who probably have a worse predicted outcome. We present a 6-year-old male patient with SoJIA who was initially classified as incomplete KD. The child developed life-threatening macrophage activation syndrome (MAS). Previous literature regarding coronary dilatation in SoJIA is also reviewed.