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

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

    S
    @SJIA_Foundation
    8 Followers
    7 months ago 318

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    Key Insights

    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
    1/13
    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
    2/13
    IL-18 
testing
    3/13
    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
    4/13
    IL-18 testing in the diagnosis and management of Still’s disease:
Game-changer or Red Herring? - Page 5
    5/13
    Which is the Still’s 
Rash?
    6/13
    Still’ s
FMF
TRA
PS HID S
Kawasa
ki
CAP S
???
Stre p
    7/13
    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
    8/13
    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
    9/13
    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
    10/13
    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 
…?
    11/13
    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?
    12/13
    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
    13/13

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

    • 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
    • 3. IL-18 testing
    • 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
    • 6. Which is the Still’s Rash?
    • 7. Still’ s FMF TRA PS HID S Kawasa ki CAP S ??? Stre p
    • 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


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