CRP and sCD25 help distinguish between adult‐onset Still's disease and HLH

Author:

Beckett Madelaine1ORCID,Spaner Caroline1ORCID,Goubran Mariam1ORCID,Wade John2,Avina‐Zubieta Juan Antonio2ORCID,Setiadi Audi34ORCID,Tucker Lori5ORCID,Shojania Kam2ORCID,Au Sheila6,Mattman Andre47ORCID,Lee Agnes Y. Y.8ORCID,Fajgenbaum David C.9ORCID,Chen Luke Y. C.810ORCID

Affiliation:

1. Department of Medicine University of British Columbia Vancouver British Columbia Canada

2. Division of Rheumatology, Department of Medicine University of British Columbia Vancouver Canada

3. Department of Pathology and Laboratory Medicine University of British Columbia Vancouver Canada

4. Division of Hematopathology British Columbia Children's Hospital Vancouver Canada

5. Division of Pediatric Rheumatology, Department of Pediatrics, BC Children's Hospital University of British Columbia Vancouver Canada

6. Department of Dermatology and Skin Science University of British Columbia Vancouver Canada

7. Department of Pathology and Laboratory Medicine St. Paul's Hospital Vancouver Canada

8. Division of Hematology, Department of Medicine University of British Columbia Vancouver Canada

9. Center for Cytokine Storm Treatment & Laboratory University of Pennsylvania Philadelphia Pennsylvania USA

10. Division of Hematology, Department of Medicine Dalhousie University Halifax Nova Scotia Canada

Abstract

AbstractObjectiveAdult‐onset Still's disease (AOSD) and secondary hemophagocytic lymphohistiocytosis (sHLH) are both hyperferritinemic cytokine storm syndromes that can be difficult to distinguish from each other in hospitalized patients. The objective of this study was to compare the inflammatory markers ferritin, D‐dimer, C‐reactive protein (CRP), and soluble CD25 (sCD25) in patients with AOSD and sHLH. These four markers were chosen as they are widely available and represent different aspects of inflammatory diseases: macrophage activation (ferritin); endothelialopathy (D‐dimer); interleukin‐1/interleukin‐6/tumour necrosis factor elevation (CRP) and T cell activation (sCD25).MethodsThis was a single‐center retrospective study. Patients diagnosed by the Hematology service at Vancouver General Hospital for AOSD or sHLH from 2009 to 2023 were included.ResultsThere were 16 AOSD and 44 sHLH patients identified. Ferritin was lower in AOSD than HLH (median 11 360 μg/L vs. 29 020 μg/L, p = .01) while D‐dimer was not significantly different (median 5310 mg/L FEU vs. 7000 mg/L FEU, p = .3). CRP was higher (median 168 mg/L vs. 71 mg/L, p <.01) and sCD25 was lower (median 2220 vs. 7280 U/mL, p = .004) in AOSD compared to HLH. The combined ROC curve using CRP >130 mg/L and sCD25< 3900 U/mL to distinguish AOSD from HLH had an area under the curve (AUC) of 0.94 (95% confidence interval 0.93–0.97) with sensitivity 91% and specificity 93%.ConclusionsThese findings suggest that simple, widely available laboratory tests such as CRP and sCD25 can help clinicians distinguish AOSD from HLH in acutely ill adults with extreme hyperferritinemia. Larger studies examining a wider range of clinically available inflammatory biomarkers in a more diverse set of cytokine storm syndromes are warranted.

Publisher

Wiley

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