<p class="first" id="d931841e83">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.
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