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Clin Exp Rheumatol. 2018 Nov-Dec;36(6 Suppl 115):74-79. Epub 2018 Nov 14.

Association between fever pattern and clinical manifestations of adult-onset Still's disease: unbiased analysis using hierarchical clustering.

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Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Korea.
Data Science for Knowledge Creation Research Centre, Seoul National University, Korea.
Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Korea.



To perform unbiased analysis of fever patterns and to investigate their association with clinical manifestations and outcome of patients with adult-onset Still's disease (AOSD).


AOSD patients who were treated as in-patients from 2004 through 2015 were grouped according to 24-hour body temperature (BT) by hierarchical clustering using a Euclidean distance metric with complete linkage. The clinical and laboratory characteristics of the groups were then examined.


Hierarchical clustering partitioned 70 AOSD patients into three distinct groups. Group 1 (n=14) had the highest mean BT (38.1± 0.4°C) and the widest variation in BT (2.7±0.9°C). Group 2 (n=35) had a lower mean BT (37.4±0.3°C) and a smaller variation (2.1±0.7°C). Group 3 (n=21) had the lowest mean BT (36.7±0.3°C) and the smallest variation (1.5±0.6°C). Clinical features and extent of organ involvement did not differ significantly between groups. However, Group 1 had lower platelet counts and higher lactate dehydrogenase, ferritin levels, and prothrombin time than the other groups. In addition, Group 1 exhibited higher risk of having a macrophage activation syndrome (MAS) and tended to require more intense treatment with corticosteroids and immunosuppressant to achieve clinical remission as compared to other groups.


Hierarchical clustering identified three distinct fever patterns in patients with AOSD. Higher BT was associated with wider variations in diurnal temperature, higher risk of developing MAS, more intense treatment, and longer time to clinical remission, suggesting that fever pattern is a prognostic factor for AOSD.

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