Background/Purpose:

Adult Onset Still’s Disease (AOSD) is a systemic inflammatory syndrome driven by interleukin (IL)-18. Since differential diagnosis between AOSD, sepsis and other inflammatory conditions can be difficult, we aimed to investigate IL-18 serum levels in AOSD and to assess whether this cytokine could be used as disease biomarker. 

Methods:

Patients with AOSD (Yamaguchy criteria) were evaluated. Disease activity was assessed with Pouchot’s and Rau’s criteria and patients were defined active if they had ≥4 criteria. Serum IL-18 levels were detected by ELISA (Immuno-Pharmacology Research, Italy) in patients with AOSD and sepsis (according to ACCP/SCCM Consensus Conference). Furthermore, patients with Rheumatoid Arthritis (RA), Sjögren Syndrome (SS), Systemic Lupus Erythematosus (SLE) and healthy subjects (NHS) served as controls. Area under the receiver operating curve (ROC-AUC) analysis was used to evaluate the diagnostic utility of the IL-18. 

Results:

Clinical and laboratory features of 50 AOSD patients are described in table.

AOSD patients		N=50
Male/Female		23/27
Age at onset [mean (range), years]		34 (17-64)
Symptoms	N	%
Fever	50	100.0
Arthralgia	39	78.0
Rash	38	76.0
Sore Throat	30	60.0
Lymphadenopathy	29	58.0
Arthritis	24	48.0
Hepatomegaly	19	38.0
Splenomegaly	19	38.0
Myalgia	15	30.0
Pleuritis	3	6.0
Pericarditis	2	4.0
Abdominal Pain	1	2.0
Laboratory features	mean	range
ESR (mm/h)	74.8	20 – 124
CRP (mg/dl)	84.8	3 – 354
WBC (cells/µl)	19004.7	8600 – 35900
Ferritin (ng/ml)	5582	69 – 32800
AST (UI/l)	67.4	8 – 404
ALT (UI/l)	91.6	4 – 535

Two patients experienced DIC, one with fatal outcome. Considering Pouchot’s and Rau’s criteria, active patients were 18/50 (36%) and 21/50 (42%), respectively. Mean ferritin was higher in active than non active patients (p=0.001). IL-18 was detected in 30 patients with AOSD, 7 with sepsis, 21 with RA, 21 with SS, 20 with SLE and 21 NHS. IL-18 significantly correlates with AOSD activity score (p<0.0001) and ferritin level (p=0.0127). Mean IL-18 was significantly higher in AOSD than in sepsis [1298.7 pg/ml (range 0–6015) vs 113.5 pg/ml (range 52–328), p=0.008]. The ROC-AUC analysis for IL-18 serum levels between AOSD and sepsis was 0.712 [cut-off=179 pg/ml, specificity (sp)=69.7%, sensitivity (se)=87.5%, likelihood (LR)=2.89]. IL-18 serum levels were significantly higher in active than non active patients and sepsis (p=0.0039 and p=0.007, respectively). The ROC-AUC analysis for IL-18 between active AOSD and sepsis was 0.845 (cut-off=223 pg/ml, sp=87.5%, se=80.9%, LR=6.48). The ROC-AUC analyses for IL-18 between AOSD patients and other groups (NHS, RA, SS, SLE) were respectively 0.853 / 0.720 / 0.750 / 0.791 (NHS: cut-off=293.7 pg/ml, sp=85.19%, se=85.71%, LR=5.79; RA: cut-off=335.5 pg/ml, sp=81.48%, se=52.38%, LR=2.83; SS: cut-off=424.3 pg/ml, sp=74.07%, se=66.67%, LR=2.57; SLE: cut-off =268.2 pg/ml, sp=85.19%, se=60%, LR=4.05). 

Conclusion:

The clinical and laboratory findings of our cohort overlap with the literature. Ferritin parallels disease activity, suggesting that the Rau’s criteria could be more accurate. AOSD prognosis is usually favourable but severe complications may occur. Finally, a significant difference in IL-18 serum levels between patients with AOSD and sepsis was observed, and IL-18 can represent a useful biomarker in the differential diagnosis between AOSD and other inflammatory conditions. Moreover, IL-18 serum levels reflects disease activity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-and-laboratory-findings-in-a-cohort-of-italian-patients-with-adult-onset-stills-disease-the-role-of-il-18-as-a-disease-biomarker/