mycophenolic-acid and Macrophage-Activation-Syndrome

Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is-by and large-a systemic disease, occasionally it can be organ-dominant, posing diagnostic challenges. To date, diagnosis of SLE remains clinical with a few cases being negative for serologic tests. Diagnostic criteria are not available and classification criteria are often used for diagnosis, yet with significant caveats. Newer sets of criteria (European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019) enable earlier and more accurate classification of SLE. Several disease endotypes have been recognised over the years. There is increased recognition of milder cases at presentation, but almost half of them progress overtime to more severe disease. Approximately 70% of patients follow a relapsing-remitting course, the remaining divided equally between a prolonged remission and a persistently active disease. Treatment goals include long-term patient survival, prevention of flares and organ damage, and optimisation of health-related quality of life. For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses. Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance. New disease-modifying conventional and biologic agents-used alone, in combination or sequentially-have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use.

Topics: Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal, Humanized; Autoantibodies; Azathioprine; Calcineurin Inhibitors; Cardiovascular Diseases; Cyclophosphamide; Disease Management; Female; Glucocorticoids; Heart Valve Diseases; Humans; Hydroxychloroquine; Hypertension, Pulmonary; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Lupus Vasculitis, Central Nervous System; Macrophage Activation Syndrome; Methotrexate; Mycophenolic Acid; Myocarditis; Outcome Assessment, Health Care; Pericarditis; Phenotype; Pregnancy; Pregnancy Complications; Prognosis; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Recurrence; Rituximab; Severity of Illness Index; Survival Rate; Uterine Cervical Neoplasms

Macrophage activation syndrome (MAS) is a severe and under-recognized complication of rheumatologic diseases. We describe a patient who presented with rapidly progressive, refractory MAS found to have anti-MDA5 antibody Juvenile Dermatomyositis (JDM) as her underlying rheumatologic diagnosis.. We describe a 14-year-old female who at the time of admission had a history of daily fevers for 6 weeks and an unintentional sixteen-pound weight loss. Review of systems was significant for cough, shortness of breath, chest pain, headaches, sore throat, muscle aches, rash, nausea, and loss of appetite. An extensive initial workup revealed findings consistent with an autoimmune process. While awaiting results of her workup she had clinical decompensation with multi-organ system involvement including pancytopenias, interstitial lung disease, hepatitis, cardiac involvement, gastrointestinal distension and pain, feeding intolerance, extensive mucocutaneous candidiasis, and neuropsychiatric decline. Due to her decompensation, significant interstitial lung disease, and likely underlying rheumatologic condition she was started on high dose pulse steroids and mycophenolate. An MRI was performed due to her transaminitis and shoulder pain revealing significant myositis. Intravenous immunoglobulin was then initiated. The myositis antibody panel sent early in her workup was significant for anti-MDA5 and anti-SSA-52 antibodies. Despite high dose pulse steroids, mycophenolate, and IVIG, her disease progressed requiring escalating therapies. Ultimately, she responded with resolution of her MAS as well as significant and steady improvement in her feeding intolerance, interstitial lung disease, cardiac dysfunction, myositis, arthritis, and cutaneous findings.. JDM in the pediatric patient is rare, as is MAS. In patients with complex rheumatologic conditions and lack of response to treatment, it is important to continually assess the patient's clinical status with MAS in mind, as this may change the treatment approach. Without proper recognition of this complication, patients can have a significant delay in diagnosis leading to life-threatening consequences.

Topics: Adolescent; Autoantibodies; Clinical Deterioration; Dermatomyositis; Dose-Response Relationship, Immunologic; Female; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Interferon-Induced Helicase, IFIH1; Macrophage Activation Syndrome; Magnetic Resonance Imaging; Multiple Organ Failure; Mycophenolic Acid; Pulse Therapy, Drug; Treatment Outcome

This report highlights the importance of tailored treatment strategies in severe systemic lupus erythematosus (SLE) flares driving the life-threatening condition, macrophage activation syndrome (MAS). We report the case of a 42-year-old woman with active systemic lupus erythematosus (SLE) who was diagnosed with MAS within 3 days of onset of lethargy, rash, joint pain and significant cytopenias. This early diagnosis meant that her condition was managed with less intensive immunosuppression with only modest doses of steroids and mycophenolate mofetil.

Topics: Adult; Diagnosis, Differential; Drug Therapy, Combination; Enzyme Inhibitors; Female; Glucocorticoids; Humans; Lupus Erythematosus, Systemic; Macrophage Activation Syndrome; Mycophenolic Acid; Prednisolone

Topics: Adult; Cyclophosphamide; Cyclosporine; Female; Fever; Glucocorticoids; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Macrophage Activation Syndrome; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Thrombocytopenia; Treatment Outcome

To describe patient demographics, interventions, and outcomes in hospitalized children with macrophage activation syndrome (MAS) complicating systemic lupus erythematosus (SLE) or juvenile idiopathic arthritis (JIA).. We performed a retrospective cohort study using data recorded in the Pediatric Health Information System (PHIS) database from October 1, 2006 to September 30, 2010. Participants had International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for MAS and either SLE or JIA. The primary outcome was hospital mortality (for the index admission). Secondary outcomes included intensive care unit (ICU) admission, critical care interventions, and medication use.. A total of 121 children at 28 children's hospitals met the inclusion criteria, including 19 children with SLE and 102 children with JIA. The index admission mortality rate was 7% (8 of 121 patients). ICU admission (33%), mechanical ventilation (26%), and inotrope/vasopressor therapy (26%) were common. Compared to children with JIA, those with SLE had a similar mortality rate (6% versus 11%, respectively; exact P = 0.6). More patients with SLE than those with JIA received ICU care (63% versus 27%; P = 0.002), received mechanical ventilation (53% versus 21%; P = 0.003), and had cardiovascular dysfunction (47% versus 23% received inotrope/vasopressor therapy; P = 0.02). Children with SLE and those with JIA received cyclosporine at similar rates, but more children with SLE received cyclophosphamide and mycophenolate mofetil, and more children with JIA received interleukin-1 antagonists.. Organ system dysfunction is common in children with rheumatic diseases complicated by MAS, and more organ system support is required in children with underlying SLE than in children with JIA. Current treatment of pediatric MAS varies based on the underlying rheumatic disease.

Topics: Adolescent; Arthritis, Juvenile; Child; Child, Preschool; Cohort Studies; Cyclophosphamide; Cyclosporine; Female; Hospital Mortality; Humans; Infant; Infant, Newborn; Inpatients; Intensive Care Units, Pediatric; Interleukin-1; Lupus Erythematosus, Systemic; Macrophage Activation Syndrome; Male; Mycophenolic Acid; Retrospective Studies; Treatment Outcome