Diagnostic and management of life-threatening Adult-Onset Still Disease: a French nationwide multicenter study and systematic literature review

Abstract

Background: Adult-onset Still disease (AOSD) is a rare systemic inflammatory disorder. A few patients develop organ complications that can be life-threatening. Our objectives were to describe the disease course and phenotype of life-threatening AOSD, including response to therapy and long-term outcome.

Methods: A multicenter case series of intensive care medicine (ICU) patients with life-threatening AOSD and a systematic literature review.

Results: Twenty patients were included. ICU admission mostly occurred at disease onset (90%). Disease manifestations included fever (100%), sore throat (65%), skin rash (65%), and arthromyalgia (55%). Serum ferritin was markedly high (median: 29,110 ng/mL). Acute respiratory failure, shock and multiple organ failure occurred in 15 (75%), 10 (50%), and 7 (35%) cases, respectively. Hemophagocytosis was demonstrated in eight cases. Two patients died. Treatment delay was significant. All patients received corticosteroids. Response rate was 50%. As second-line, intravenous immunoglobulins were ineffective. Anakinra was highly effective. After ICU discharge, most patients required additional treatment. Literature analysis included 79 cases of AOSD with organ manifestations, which mainly included reactive hemophagocytic syndrome (42%), acute respiratory failure (34%), and cardiac complications (23%). Response rate to corticosteroids was 68%. Response rates to IVIgs, cyclosporin, and anakinra were 50%, 80%, and 100%, respectively.

Conclusions: AOSD should be recognized as a rare cause of sepsis mimic in patients with fever of unknown origin admitted to the ICU. The diagnosis relies on a few simple clinical clues. Early intensive treatment may be discussed. IVIgs should be abandoned. Long-term prognosis is favorable.

Keywords: Adult onset Still disease; Anakinra; Cyclosporin; Differential diagnosis; ICU; Intravenous immunoglobulins; Reactive hemophagocytic syndrome; Shock.

Fig. 1

Phenotypic spectrum of life-threatening AOSD. a Venn diagram depicting the association and overlap of five key clinical features of AOSD with organ failure. b Evanescent skin rash in two patients with AOSD. c Kinetics of leukocytosis and ferritinemia. T0 before ICU admission, ICU first recorded value in the ICU

Fig. 2

Disease course prior to ICU admission and therapeutic delay. a Time from first symptoms (i.e. fever onset) to hospitalization and to ICU admission. b Treatment delay among 17 untreated patients upon ICU admission. c Antibiotic use per patient, prior to AOSD recognition

Fig. 3

Biological correlates of bone marrow hemophagocytosis. Fourteen patients have had bone marrow examination. Key biological parameters are compared according to the presence or absence of hemophagocytosis in the bone marrow. Histograms depict the median. *p < 0.05, Mann-Whitney test