A comprehensive review on adult onset Still's disease

J Autoimmun. 2018 Sep;93:24-36. doi: 10.1016/j.jaut.2018.07.018. Epub 2018 Aug 1.

Abstract

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology usually affecting young adults; spiking fever, arthritis and evanescent rash are commonly observed during the disease. Other frequently observed clinical features include sore throat, hepatomegaly, splenomegaly, lymphadenopathy and serositis. Furthermore, AOSD patients may experience different life-threating complications. Macrophage activation syndrome (MAS) has been reported up to 15% of AOSD patients and it is considered to be the most severe complication of the disease being characterised by high mortality rate. During AOSD, laboratory tests reflect the systemic inflammatory process showing high levels of erythrocyte sedimentation rate and C-reactive protein. In addition, the ferritin levels are typically higher than those observed in other autoimmune, inflammatory, infectious, or neoplastic diseases. Analysing AOSD disease course, 3 different clinical patterns of AOSD have been identified: i. monocyclic pattern, characterised by a systemic single episode; ii. polycyclic pattern, characterised by multiple, ≤ 1 year lasting, flares, alternating with remissions; iii. chronic pattern, related to a persistently active disease with associated polyarthritis. At present, AOSD therapeutic strategy is aimed at targeting pro-inflammatory signs and symptoms, preventing organ damage and life-threating complications and minimising adverse effects of treatment. However, the treatment of AOSD remains largely empirical, lacking controlled clinical trials. High dosages of corticosteroids are usually the first line therapy when the systemic symptoms predominate. Despite this treatment, a large percentage of patients experiences several flares with an evolution toward the chronic disease course and up to 16% of patients die during the follow up, due to AOSD-related complications. On these bases, in the last years, biological agents have been successfully used in refractory cases. Finally, multiple recent lines of evidence have suggested new insights in AOSD pathogenesis unmasking further therapeutic targets. In fact, small molecules, used in experimental MAS models, might represent new therapeutic options.

Keywords: Adult onset Still's disease; Ferritin; Macrophage activation syndrome; Pathogenesis.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity
  • Adrenal Cortex Hormones / therapeutic use
  • Age of Onset
  • Animals
  • Arthritis / complications
  • Arthritis / diagnosis
  • Arthritis / drug therapy
  • Arthritis / immunology*
  • Biomarkers / blood
  • Blood Sedimentation
  • C-Reactive Protein / metabolism
  • Disease Models, Animal
  • Ferritins / blood
  • Humans
  • Immunity, Innate
  • Macrophage Activation Syndrome / diagnosis
  • Macrophage Activation Syndrome / drug therapy
  • Macrophage Activation Syndrome / etiology
  • Macrophage Activation Syndrome / immunology*
  • Methotrexate / therapeutic use
  • Still's Disease, Adult-Onset / complications
  • Still's Disease, Adult-Onset / diagnosis
  • Still's Disease, Adult-Onset / drug therapy
  • Still's Disease, Adult-Onset / immunology*
  • Survival Analysis
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Biomarkers
  • C-Reactive Protein
  • Ferritins
  • Methotrexate