title: Macrophage activation syndrome complicating adult onset Still's disease: A single center case series and comparison with literature.
abstract: Macrophage activation syndrome (MAS) is a life-threatening condition that can complicate adult onset Still's disease (AOSD). Due to its rarity, there is no clear consensus concerning treatment recommendations and outcomes. We studied the clinical manifestations and outcomes of a relatively large cohort of patients with MAS and AOSD, and compared the data with the literature reports.
  
  
  
  We performed a retrospective review of 7 adult patients with MAS complicating AOSD at the Cleveland Clinic (CCF) over 7 years. All patients underwent bone marrow biopsies. Through MEDLINE and PubMed literature searches, we identified 48 cases of MAS/AOSD. We compared the data of the CCF and literature cohorts.
  
  
  
  We identified 7 patients with MAS complicating AOSD (6 females and 1 males) for our CCF cohort, with 4 cases simultaneously presenting with MAS and AOSD. The mean age at diagnosis of MAS was 41.9 ± 20.2 years and mean follow-up time was 18.6 ± 16.0 months. All patients had fever, arthralgias, and typical rash; 6 had leukocytosis, 4 had sore throat, and 3 had lymphadenopathy. These patients with AOSD also had MAS, with renal insufficiency and disseminated intravascular coagulation in 4, lung involvement in 3, and serositis and shock in 2. There was significant hepatic dysfunction in all patients and 6 had bi-cytopenias. At onset of MAS, all 7 patients had active AOSD. In addition to systemic glucocorticoids, 5 patients received anakinra, with 3 patients receiving combination therapy with cyclosporine. We also identified 48 cases (35 females and 13 males) for the literature cohort with the mean age at diagnosis of MAS of 40.2 ± 16.0 years and mean follow-up time of 17.5 ± 32.3 months. While the 2 cohorts were similar clinically, in the CCF cohort, more patients had renal insufficiency (p < 0.001), higher soluble IL-2 receptor level (p = 0.01), and lower ESR (p = 0.02) as compared with the literature cohort. All of our patients survived with a better outcome than the literature cohort.
  
  
  
  MAS can be a serious complication of active AOSD. Our study of a relatively large cohort in conjunction with literature suggests that prompt recognition and treatment with early addition of anakinra, systemic glucocorticoids, and cyclosporine as a triple regimen may improve clinical outcomes.
authors.affiliation: Department of Rheumatic and Immunological Diseases, Orthopedic and Rheumatologic Institute, Cleveland Clinic, Cleveland, OH 44106; Division of Rheumatology, Department of Internal Medicine, University of Kentucky, Kentucky Clinic, J507, 740 South Limestone St, Lexington, KY 40536-0284. Electronic address: ale259@uky.edu.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Lenert
authors.affiliation: Department of Rheumatic and Immunological Diseases, Orthopedic and Rheumatologic Institute, Cleveland Clinic, Cleveland, OH 44106; Division of Rheumatology, Allergy and Immunology, Department of Medicine, Stony Brook University Hospital, Stony Brook, NY.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Yao
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000627:therapeutic use; D004211:Disseminated Intravascular Coagulation / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D008107:Liver Diseases / Q000209:etiology / Q000503:physiopathology; D008171:Lung Diseases / Q000209:etiology / Q000503:physiopathology; D055501:Macrophage Activation Syndrome / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000209:etiology / Q000503:physiopathology; D012189:Retrospective Studies; D012700:Serositis / Q000209:etiology / Q000503:physiopathology; D012769:Shock / Q000209:etiology / Q000503:physiopathology; D016706:Still's Disease, Adult-Onset / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D016572:Cyclosporine
keywords: Adult onset Still’s disease; Anakinra; Cyclosporine; Hemophagocytosis; Macrophage activation syndrome; Treatment outcomes