Date: Monday, November 6, 2017
Session Title: Miscellaneous Rheumatic and Inflammatory Diseases Poster I
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Yamaguchi’s criteria for classification of adult-onset Still’s disease (AOSD) has been widely applied in clinic despite it was established decades ago. However, hyperferritinemia, which is a hallmark of AOSD, is not included in the criteria. Moreover, the criteria requires differential diagnosis of malignancy, infection, etc., which has been challenging. Heme oxygenase (HO)-1 is a stress-inducible heme degrading enzyme highly expressed in monocyte/macrophage, serum levels of which has been reported as a promising biomarker for AOSD. We here report data on the use of serum ferritin and HO-1 levels in an attempt to improve the classification of AOSD.
Methods: Under the Hypercytokinemia Study Group collaboration, we collected sera from a total of 145 AOSD cases. Three independent experts judged whether the patient is definite AOSD depending on clinical information. These “definite AOSD” patients were further divided into active, remission, and relapse groups, based on their clinical status. Other rheumatic diseases such as ANCA-associated vasculitis, and culture-positive sepsis were included as disease controls. Serum ferritin and HO-1 levels were measured in all of the collected samples by means of ELISA. An association among clinical symptoms, serum ferritin, and HO-1 was explored. Multivariate regression analysis was performed to identify the independent variables associated with definite AOSD diagnosis.
Results: Serum ferritin and HO-1 levels were significantly higher in active and relapsed AOSD cases compared to disease controls, and were reduced by the treatment. Although significant correlation between serum ferritin and HO-1 levels were observed, discrepancy was found in some cases such as patients with iron-deficient anemia (Figure). ROC analysis identified optimal levels of serum ferritin (> 833 ng/ml; sensitivity 77.5%, specificity 81.1%), and HO-1 (>96.4 ng/ml; sensitivity 92.5%, specificity 81.1%) that differentiate AOSD from disease controls. Multivariate analysis identified typical skin rash, lymphadenopathy/splenomegary, seronegative, high HO-1 as independent variables associated with AOSD diagnosis.
Conclusion: We confirmed that serum ferritin and HO-1 serve as biomarkers for AOSD. Including biomarkers in the Yamaguchi’s criteria may reduce hetrogeneity of the included patients, although further validation is necessary.
Figure: Comparison of serum ferritin and serum HO-1 in AOSD and disease-controls.
Horizontal and vertical dots indicate cut-off values determined from ROC analysis.
To cite this abstract in AMA style:Kirino Y, Kawaguchi Y, Tada Y, Tsukamoto H, Ota T, Iwamoto M, Takahashi H, Nagasawa K, Takei S, Horiuchi T, Ichida H, Minota S, Ueda A, Ohta A, Ishigatsubo Y. Use of Including Serum Ferritin and Heme Oxygenase 1 in the Yamaguchi’s Classification for Adult-Onset Still’s Disease: A Multicenter Retrospective Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/use-of-including-serum-ferritin-and-heme-oxygenase-1-in-the-yamaguchis-classification-for-adult-onset-stills-disease-a-multicenter-retrospective-study/. Accessed November 13, 2018.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/use-of-including-serum-ferritin-and-heme-oxygenase-1-in-the-yamaguchis-classification-for-adult-onset-stills-disease-a-multicenter-retrospective-study/