Background/Purpose:

Systemic onset Juvenile Idiopathic Arthritis (sJIA) is a disease characterized by systemic inflammation in addition to arthritis and it’s diagnosis currently still depends on the clinical ILAR classification criteria of 2003, with arthritis as a required criterium. A significant portion of patients however exhibit inflammatory symptoms weeks, sometimes even months before showing signs of any joint involvement, making the diagnosis of sJIA challenging for the treating clinician due to the broad differential diagnosis of systemic inflammation. Recent insights in the underlying auto-inflammatory disease mechanisms in sJIA have proposed several candidate biomarkers aiding in the diagnostic process, including interleukin-18 (IL-18), a member of the IL-1 family. Here, we compare peripheral blood serum levels of IL-18 in sJIA at disease onset with several important differential diagnoses.

Here, we tested the value of IL-18 as a diagnostic biomarker aiding in diagnosing sJIA and differentiating sJIA from children with systemic infection (INF), acute lymphatic leukaemia (ALL) and auto-immune conditions like vasculitis.

Methods: A cohort was assembled retrospectively consisting of patients with sJIA at disease onset (n=39, presenting initially with and without arthritis, ultimately diagnosed according to ILAR criteria), oligo- and polyarticular JIA(n=28), ALL(n=18), various auto-immune diseases including vasculitis (n=14) and healthy controls(HC, n=30). Clinical and laboratory data were extracted from patient files. Peripheral blood serum IL-18 measurements were performed using a multiplex immunoassay based on Luminex technology.

Results: Of all sJIA patients(n=39), 97.1% experienced fever on the day of sampling. A cutaneous rash was seen in 82.9% of patients and 40% of patients suffered from lymphadenopathy at disease onset. 68.6% of patients showed overt arthritis (median joint count 1.5, IQR 0-3) and 77.1% suffered from arthralgia (median joint count 2, IQR 1-4). At time of sampling, 57.1% of patients were being treated with NSAID.

IL-18 values (pg/ml, median, IQR) were evidently elevated in sJIA (5465, 1962-13428) and differed significantly from the levels measured in the other disease groups (oligo JIA (274, 172-378), poly JIA (177, 121-342), ALL (542, 315-869), other auto-immune diseases including vasculitis (64, 36-131)) and healthy controls (228, 175-327). The IL-18 levels in the serum of children with systemic infections are currently being measured.

We evaluated different cut-off values for IL-18 using an ROC curve. A value of 1500pg/ml performed best, with a specificity of 0.976 and a sensitivity of 0.800.

Conclusion: Here we show the potential value of IL-18 as a diagnostic biomarker for sJIA in the process of differential diagnosis. When sJIA is suspected in a patient with symptoms of systemic inflammation with or without arthritis, an IL-18 level of 1500 or higher seems clearly suggestive of sJIA. In patients with suspected sJIA but IL-18 levels below 1500, we recommend additional diagnostic modalities, including for example PET scan or bone marrow biopsy where indicated, to rule out other diagnoses like childhood malignancy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-18-as-a-diagnostic-biomarker-differentiating-systemic-jia-from-acute-leukaemia-severe-bacterial-infections-and-other-auto-immune-disorders/