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16-06-2021 | Rheumatology | News | Article

Biomarkers may distinguish hyperinflammatory syndromes in children

medwireNews: Two studies have identified serum biomarkers that could be used to differentiate between hyperinflammatory syndromes in children.

“Combatting cytokine storm syndromes is an increasingly frequent challenge faced by paediatric rheumatologists,” says Lauren Henderson (Boston Children's Hospital, Massachusetts, USA) in a comment accompanying the studies published in The Lancet Rheumatology.

She explains that although conditions such as macrophage activation syndrome (MAS), primary hemophagocytic lymphohistiocytosis (HLH), and secondary HLH “share clinical features, they require different treatments,” and “additional diagnostic tools are needed to guide clinical decision making.”

In the first study, the researchers analyzed serum samples from children with systemic juvenile idiopathic arthritis (JIA)-associated MAS (n=11), primary HLH (n=10), or secondary HLH (n=12), to determine whether biomarkers differed across these groups.

Christoph Kessel (University Children’s Hospital Muenster, Germany) and team found “distinct serum biomarker profiles” in patients with primary or secondary HLH versus systemic JIA-associated MAS, and six individual markers were taken forward for validation in an independent cohort of 79 patients.

The two biomarkers that best differentiated these conditions were S100A12 and interleukin (IL)-18. Specifically, S100A12 correctly distinguished patients with systemic JIA-associated MAS from those with primary HLH on 94% of occasions (cutoff=535 ng/mL), and from those with secondary HLH on 85% of occasions (cutoff=635 ng/mL). IL-18 differentiated between these conditions on 82% and 79% of occasions, respectively, with corresponding cutoffs of 1157 pg/mL and 1022 pg/mL.

“These findings can support an early differential diagnosis between systemic JIA-MAS and HLH and thus can help to guide treatment decisions,” write the researchers.

In the second study, Grant Schulert (Cincinnati Children’s Hospital Medical Center, Ohio, USA) and colleagues evaluated whether inflammatory biomarkers could distinguish between multisystem inflammatory syndrome in children (MIS-C), a complication typically occurring after SARS-CoV-2 infection, and other cytokine storm syndromes.

They found that median CXCL9 levels were significantly higher among 11 children with MIS-C compared with nine with Kawasaki disease, at 1730 versus 278 pg/mL, while the CXCL9 elevations in the MIS-C group were “comparable” to those seen in nine patients with systemic JIA-associated MAS.

This protein was also associated with MIS-C severity; patients with high CXCL9 levels (>739 pg/mL) were more likely than those with low levels (≤739 pg/mL) to have shock (90 vs 40%), acute kidney injury (60 vs 0%), myocardial dysfunction (50 vs 20%), or altered mental status (40 vs 0%).

Schulert et al report that patients with MIS-C had “similar” levels of S100A8/A9, S100A12, and IL-18 to those with Kawasaki disease, but these markers “performed well” in differentiating Kawasaki disease from systemic JIA, with sensitivity and specificity values of 100% when respective cutoffs of 29,577 ng/mL, 1984 ng/mL, and 2632 pg/mL were used.

These findings support the use of “clinical biomarkers to distinguish hyperinflammatory diseases from each other and to determine clinical severity for MIS-C,” write the researchers, noting that “[s]uch biomarkers will be essential as the COVID-19 pandemic continues and seroconversion is likely to increase, and history of exposure and serology will become less reliable in diagnosing MIS-C.”

In the accompanying commentary, Henderson says that the results of this study “are interesting,” but they “will need to be replicated in a larger multicentre cohort.”

She believes that IL-18 and S100A12 “have the potential to be important tools in the paediatric rheumatologist’s arsenal for combatting cytokine storm syndromes,” but notes that “measurements are unavailable locally at most centres and must be sent to specialty laboratories, often with slow turnaround time.”

Therefore, “further efforts are needed to maximise these biomarkers so that they can be deployed to the front lines and improve patient outcomes,” she concludes.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

16 June 2021: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.

Lancet Rheumatol 2021; doi:10.1016/S2665-9913(21)00115-6
Lancet Rheumatol 2021; doi:10.1016/S2665-9913(21)00139-9
Lancet Rheumatol 2021; doi:10.1016/S2665-9913(21)00180-6

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