IL-18 testing in the diagnosis and management of Still’s disease: Game-changer or Red Herring?

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The content discusses IL-18 testing in the diagnosis and management of Still's disease and its differentiation from other conditions.
It outlines a clinical conundrum involving a young patient with fever, rash, and anemia, exploring potential diagnoses including viral infection and Kawasaki disease.
It covers the management of Still's disease, including initial response to treatment and the need for further workup and therapy adjustments based on IL-18 levels and other factors.
It addresses the concept of remission and the use of medications like ruxolitinib and canakinumab, along with Still's MRD biomarkers for monitoring disease activity.

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1. IL-18 testing in the diagnosis and management of Still’s disease: Game-changer or Red Herring? A manufactured conflict moderated by Scott Canna, MD 13 November 2024 Rheumatology

2. Disclosures • Industry funded research • Site PI (completed): Novartis, AB2Bio • In-kind support: Simcha • Advisor/Consultant • AB2Bio, Apollo, Sobi, Bristol-Myers Squibb • Educational Speaker • PracticePoint CME, Sobi, Johnson & Johnson, Bristol-Myers Squibb • Advisory Committee/Board: none • Stock/ownership: none • Relevant patents: none

4. A common clinical conundrum 6 mos prev healthy male - Born FT, no preg/perinatal issues - Presented to ED for fever x 3d, rash prior but not present in ED - Noted to have anemia (Hgb 9), ANC 730, Plt 65 🡪 dx’d virus/viral suppression and DC’d - 10 days later at Pediatrician for repeat labs - No more fevers. Modest cough (parents say has been there a while) - ANC 790, Hgb stable, Plt 150 - A few days after some vaccinations 🡪 Fever 39 - ED: ANC 260, Hgb 8.5, Plt 138, LDH 742, Uric Acid normal. - Admission: Blood Cx neg, peripheral smear without blasts, a few atypical lymphs - CRP 3.2 mg/dL - AST 243, ALT 347, normal bilirubin - Spleen tip palpable🡪 sl enlarged on US - Ferritin 3537, Fibrinogen 105, TG 398 - Multiple consults: Exam o/w normal. Echo normal (no other KD stigmata). No arthritis. No uveitis. - Febrile one night – resident reported a red hive-like rash

8. Presentation continued EBV/CMV/Adeno/HHV 6 - PCR neg Perforin/GranyzmeB: elevated by % & MCF CD107a mobilization: normal Rapid WES sent: TAT ~ 2 weeks Remains stable

9. FUO with HLH • Prolonged viral syndrome • Still’s • Atypical KD • Autoinflammatory To ‘Roid Or Not To ‘Roid • Occult leukemia • Neuroblastoma • Cutaneous T-cell lymphoma Bone Marrow Biopsy Pan-Scan Further workup Empiric Treatment

10. FUO with HLH • Prolonged viral syndrome • Atypical KD • Autoinflammatory • Still’s • Monogenic IL-18opathies To ‘Roid Or Not To ‘Roid • Occult leukemia • Neuroblastoma • Cutaneous T-cell lymphoma Bone Marrow Biopsy Pan-Scan Further workup Treatment IL-18* > 20,000 – 40,000 Genetic workup if indicated Treatment 🡪 DC

11. OK, so it’s IL-18 = 128,000 Still’s pg/mL CXCL9 = 14,000 pg/mL sIL-2Ra = 2300 pg/mL Anakinra 4mg/kg GC 2mg/kg Good initial response! • Fevers • CBC • ferritin Recheck IL-18 in …?

12. Flare upon GC wean Recheck IL-18 to determine: Fever, ferritin, LFTs don’t tolerate < 0.5 mg/kg/day prednisolone • canakinumab up to 8mg/kg/dose q4week Need for sJIA-LD workup? Change in therapy? Prognosis?

13. Remission on medication Still’s MRD biomarkers • LDH/aldolase • D-dimer • Ferritin • sIL-2Ra • CXCL9 • S100A8/A9 • S100A12 • IL-18 Does great on ruxolitinib (10mg/m2/dose) and canakinumab (4mg/kg/month) - Normal CBC diff, ferritin X 18 month