Usefulness of Interleukin-18 as a Diagnostic Biomarker to Differentiate Adult-Onset Still’s Disease With/Without Macrophage Activation Syndrome From Other Secondary Hemophagocytic Lymphohistiocytosis in Adults

Shiga, Toshihiko; Nozaki, Yuji; Tomita, Daisuke; Kishimoto, Kazuya; Hirooka, Yasuaki; Kinoshita, Koji; Funauchi, Masanori; Matsumura, Itaru

doi:10.3389/fimmu.2021.750114

Cited by 27 publications

(24 citation statements)

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“…We reported that the serum IL-18 levels were significantly higher in patients with AOSD (with or without MAS) compared to patients with HLH secondary to other causes, including SLE ( 27 ), and we also observed that a serum IL-18 level >18,550 pg/mL could be used to distinguish between AOSD and HLH with 90.3% sensitivity and 93.5% specificity. Our patient’s remarkably high serum IL-18 level (161,221 pg/mL) was suggestive of AOSD.…”

Section: Discussionmentioning

confidence: 53%

Case Report: A Rare Case of Elderly-Onset Adult-Onset Still’s Disease in a Patient With Systemic Lupus Erythematosus

et al. 2022

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The rare systemic inflammatory disorder ‘adult-onset Still’s disease (AOSD)’ is characterized by recurrent fever, evanescent rash, arthralgia, and leukocytosis with neutrophilia. The Yamaguchi criteria are widely used to diagnose AOSD; these criteria can be used for diagnosis after a wide range of infectious, rheumatic, and neoplastic diseases have been excluded. AOSD generally does not overlap with other rheumatic diseases. We present the rare case of an 80-year-old Japanese woman who presented with arthralgia, fever, and skin rash during treatment for systemic lupus erythematosus (SLE), which was finally diagnosed as an overlap of AOSD. Blood tests revealed leukocytosis with neutrophilia, high C-reactive protein (CRP), and liver dysfunction. Her anti-ds-DNA antibody titer and serum complement titer were at the same level as before and remained stable. We suspected AOSD based on the high serum ferritin level but hesitated to diagnose AOSD because of the patient’s SLE history. We measured serum interleukin (IL)-18; it was extremely high at 161,221 pg/mL, which was strongly suggestive of AOSD. We thus diagnosed AOSD complicated during the course of treatment for SLE. The patient’s arthralgia and high CRP level persisted after we increased her oral prednisolone dose and added oral methotrexate, but her symptoms eventually improved with the addition of intravenous tocilizumab. We note that the presence of autoantibodies or other rheumatic diseases cannot be absolutely ruled out in the diagnosis of AOSD. Although high serum IL-18 levels are not specific for AOSD, the measurement of serum IL-18 may aid in the diagnosis of AOSD in similar rare cases.

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Section: Discussionmentioning

confidence: 53%

Case Report: A Rare Case of Elderly-Onset Adult-Onset Still’s Disease in a Patient With Systemic Lupus Erythematosus

et al. 2022

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“…The 28-day mortalities were 0%, 4.5 ± 4.4%, 4.0 ± 3.9%, and 17.9 ± 3.6% for EBV-HLH patients in the LLQ, LUQ, RUQ, and RLQ (p = 0.034), and the 5-year OS rates were 94.1 ± 5.7%, 81.1 ± 8.6%, 70.4 ± 9.5%, and 74.7 ± 7.1% (p = 0.24), respectively. differentiating HLH from infections or other inflammatory entities (13)(14)(15)(16). The present study shows that different subtypes of HLH present distinct cytokine patterns.…”

Section: Distinct Features Of Hlh Patients In a Four-quadrant Modelmentioning

confidence: 50%

“…HLH is a rapidly fatal disease caused by an immune dysregulation characterized by hypercytokinemia and overactivation of T cells and macrophages. Many inflammatory cytokines including IFN-γ, IL-6, IL-10, IL-12, IL-18, TNF-α, and CXCL9 are elevated in patients with HLH, and the cytokine patterns are helpful in differentiating HLH from infections or other inflammatory entities ( 13 – 16 ). The present study shows that different subtypes of HLH present distinct cytokine patterns.…”

Section: Discussionmentioning

confidence: 99%

Simple Evaluation of Clinical Situation and Subtypes of Pediatric Hemophagocytic Lymphohistiocytosis by Cytokine Patterns

Luo

Song

et al. 2022

Front. Immunol.

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BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by immune dysregulation. Early initiation of treatment is imperative for saving lives. However, a laboratory approach that could be used to quickly evaluate the HLH subtype and clinical situation is lacking. Our previous studies indicated that cytokines such as interferon (IFN)-γ and interleukin (IL)-10 were helpful for the early diagnosis of HLH and were associated with disease severity. The purpose of this study is to clarify the different cytokine patterns of various subtypes of pediatric HLH and to investigate the role of cytokines in a simple evaluation of disease feature.Patients and MethodsWe enrolled 256 pediatric patients with newly diagnosed HLH. The clinical features and laboratory findings were collected and compared among different subtypes of HLH. A model integrating cytokines was established to stratify HLH patients into different clinical groups.ResultsTwenty-seven patients were diagnosed with primary HLH (pHLH), 179 with EBV-HLH, and 50 with other causes. The IL-6, IL-10, and IFN-γ levels and the ratios of IL-10 to IFN-γ were different among EBV-HLH, other infection-associated HLH, malignancy-associated HLH, familial HLH, and X-linked lymphoproliferative disease. Patients with the ratio of IL-10 to IFN-γ >1.33 and the concentration of IFN-γ ≤225 pg/ml were considered to have pHLH, with a sensitivity of 73% and a specificity of 84%. A four-quadrant model based on the two cutoff values was established to stratify the patients into different clinical situations. The HLH subtypes, cytokine levels, treatment regimens, treatment response, and outcomes were different among the four quadrants, with the 8-week mortality from 2.9 ± 2.9% to 21.4 ± 5.5% and the 5-year overall survival from 93.9 ± 4.2% to 52.6 ± 7.1%.ConclusionsDifferent subtypes of HLH present distinct cytokine patterns. IFN-γ and the ratio of IL-10 to IFN-γ are helpful tools to differentiate HLH subtypes. A four-quadrant model based on these two parameters is a useful tool for a simple evaluation of the HLH situation.

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“…Javaux et al have published different parameters that are useful for distinguishing HLH and AOSD flare, including lower fibrinogen, leukocyte and platelet counts, but no difference in GF fraction [ 7 ]. Another study showed that interleukin (IL)-18 levels have high accuracy for the differential diagnosis of AOSD and HLH but IL-18 is rarely available routinely [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…Unlike GF, total serum ferritin (TSF) has been repeatedly reported as a hallmark of AOSD, mostly for extreme values [ 16 , 17 , 18 ]. However, TSF lacks sensitivity and specificity [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Glycosylated Ferritin in Adult-Onset Still’s Disease and Differential Diagnoses

Guerber

Garneret

Jammal

et al. 2022

JCM

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Glycosylated ferritin (GF) has been reported as a good diagnostic biomarker for adult-onset Still’s disease (AOSD), but only a few studies have validated its performance. We performed a retrospective study of all adult patients with at least one GF measurement over a 2-year period in one hospital laboratory. The diagnosis of AOSD was based on the expert opinion of the treating physician and validated by two independent investigators. Patients’ characteristics, disease activity, and outcome were recorded and compared. Twenty-eight AOSD and 203 controls were identified. Compared to controls, the mean GF was significantly lower (22.3% vs. 39.3, p < 0.001) in AOSD patients. GF had a high diagnostic accuracy for AOSD, independent of disease activity or total serum ferritin (AUC: 0.674 to 0.915). The GF optimal cut-off value for AOSD diagnosis was 16%, yielding a specificity of 89% and a sensitivity of 63%. We propose a modified diagnostic score for AOSD, based on Fautrel’s criteria but with a GF threshold of 16% that provides greater specificity and increases the positive predictive value by nearly 5 points. GF is useful for ruling out differential diagnoses and as an appropriate classification criterion for use in AOSD clinical trials.

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Usefulness of Interleukin-18 as a Diagnostic Biomarker to Differentiate Adult-Onset Still’s Disease With/Without Macrophage Activation Syndrome From Other Secondary Hemophagocytic Lymphohistiocytosis in Adults

Cited by 27 publications

References 50 publications

Case Report: A Rare Case of Elderly-Onset Adult-Onset Still’s Disease in a Patient With Systemic Lupus Erythematosus

Case Report: A Rare Case of Elderly-Onset Adult-Onset Still’s Disease in a Patient With Systemic Lupus Erythematosus

Simple Evaluation of Clinical Situation and Subtypes of Pediatric Hemophagocytic Lymphohistiocytosis by Cytokine Patterns

Evaluation of Glycosylated Ferritin in Adult-Onset Still’s Disease and Differential Diagnoses

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