Macrophage activation syndrome in systemic lupus erythematosus and Still’s disease: distinct phenotypes shaped by the underlying diseases

{"OBJECTIVES:":[0],"Macrophage":[1],"activation":[2],"syndrome":[3],"(MAS)":[4],"is":[5],"a":[6,47,150],"severe":[7],"complication":[8],"of":[9,26,44,49,80,145,153],"Still's":[10],"disease":[11],"(SD-MAS),":[12],"but":[13,219],"may":[14,243],"also,":[15],"albeit":[16],"rarely,":[17],"complicate":[18],"systemic":[19],"lupus":[20],"erythematosus":[21],"(SLE-MAS).":[22],"The":[23,91],"clinical":[24],"profile":[25],"SLE-MAS":[27,50,92,131,168,194,209,241],"compared":[28,96,196],"with":[29,46,97,111,149,169,213],"SD-MAS":[30,52,109,212],"remains":[31],"unclear,":[32],"as":[33],"do":[34],"the":[35,78,81,112,193,227],"optimal":[36],"treatment":[37],"strategies.":[38],"METHODS:":[39],"A":[40],"retrospective":[41],"multicenter":[42],"cohort":[43],"adults":[45],"history":[48],"or":[51],"was":[53,70,94,164],"gathered":[54],"from":[55,77,211,253],"nine":[56],"tertiary":[57],"referral":[58],"centers.":[59],"MAS":[60,175],"clinical/laboratory":[61],"features,":[62],"treatments":[63],"and":[64,123,187,204,216,224,246],"outcomes":[65],"were":[66],"compared;":[67],"\\"inaugural":[68],"MAS\\"":[69],"defined":[71],"if":[72],"occurring":[73],"within":[74],"6":[75],"months":[76],"onset":[79],"underlying":[82],"disease.":[83],"exploratory":[84],"multivariable":[85],"profiling":[86],"assessed":[87],"for":[88],"disease-specific":[89],"features.":[90],"group":[93],"also":[95],"large":[98],"historical":[99,198],"SLE":[100,199],"cohorts":[101,200],"to":[102,197,231],"identify":[103],"candidate":[104],"risk":[105],"signals.":[106],"RESULTS:":[107],"While":[108],"aligned":[110],"prototypical":[113],"hyperinflammatory":[114],"pattern":[115],"(more":[116],"marked":[117],"hyperferritinemia,":[118],"very":[119],"high":[120],"CRP,":[121],"organomegaly":[122,215],"liver":[124,141,217],"injury;":[125],"100%":[126],"meeting":[127,133],"2016":[128],"ACR/EULAR/PRINTO":[129],"criteria),":[130],"(92%":[132],"criteria)":[134],"more":[135,220],"often":[136],"featured":[137],"CNS":[138,181,222],"dysfunction,":[139],"less":[140,183,214],"injury,":[142],"greater":[143],"degree":[144],"cytopenias":[146],"including":[147],"anemia,":[148],"strong":[151],"signal":[152],"autoimmune":[154,179],"hemolysis":[155],"(73%":[156],"direct":[157],"Coombs":[158],"[DCT]":[159],"positivity).":[160],"Therapeutically,":[161],"IL-1":[162],"antagonism":[163],"used":[165],"in":[166],"7":[167],"mixed":[170],"results":[171],"without":[172],"any":[173],"rapid":[174],"resolution.":[176],"Mucocutaneous":[177],"disease,":[178],"hemolysis,":[180],"involvement,":[182,226],"pronounced":[184,221],"female":[185],"preponderance":[186],"much":[188],"higher":[189],"DCT":[190],"positivity":[191],"dominated":[192],"phenotype":[195],"comprising":[201],"1000,":[202],"2228,":[203],"2055":[205],"cases":[206],"each.":[207],"CONCLUSIONS:":[208],"diverged":[210],"injury":[218],"involvement":[223],"hematological":[225],"latter":[228],"strongly":[229],"linked":[230],"red":[232],"blood":[233],"cell":[234],"directed":[235],"autoantibodies.":[236],"These":[237],"findings":[238],"indicate":[239],"that":[240],"pathogenesis":[242],"be":[244],"divergent":[245],"require":[247],"distinct":[248],"therapeutic":[249],"approaches":[250],"beyond":[251],"extrapolation":[252],"SD-MAS.":[254]}

Authors

Institutions

Publication Details

Journal
Lara D. Veeken
Published
2026-09-11
DOI
https://doi.org/10.1093/rheumatology/keag490
Primary Topic
Autoimmune and Inflammatory Disorders Research
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
article

Macrophage activation syndrome in systemic lupus erythematosus and Still’s disease: distinct phenotypes shaped by the underlying diseases

Sinisa Savic, Micaela Fredi, Antonio Tonutti, Franco Franceschini et al.
Lara D. Veeken
Autoimmune and Inflammatory Disorders Research
article

Macrophage activation syndrome in systemic lupus erythematosus and Still’s disease: distinct phenotypes shaped by the underlying diseases

Sinisa Savic, Micaela Fredi, Antonio Tonutti, Franco Franceschini, Aamir Aslam, Francesca Crisafulli, Francesco Caso, Ala Altaie, Addolorata Corrado, Francesca Trunfio, Maria Gerosa, Maria De Santis, Tom Macleod, Vishal Kakkar, Letizia Pia Di Corcia, Kerem Abacar, Edward Vital, Md Yuzaiful Md Yusof, Antonio Vitale, Dina Youssef, Andrew Barr, Roberto Giacomelli, Dennis McGonagle, Piero Ruscitti, Micol Frassi, Ilaria Cavazzana, Carlo Selmi
article en

Abstract

OBJECTIVES: Macrophage activation syndrome (MAS) is a severe complication of Still's disease (SD-MAS), but may also, albeit rarely, complicate systemic lupus erythematosus (SLE-MAS). The clinical profile of SLE-MAS compared with SD-MAS remains unclear, as do the optimal treatment strategies. METHODS: A retrospective multicenter cohort of adults with a history of SLE-MAS or SD-MAS was gathered from nine tertiary referral centers. MAS clinical/laboratory features, treatments and outcomes were compared; "inaugural MAS" was defined if occurring within 6 months from the onset of the underlying disease. exploratory multivariable profiling assessed for disease-specific features. The SLE-MAS group was also compared with large historical SLE cohorts to identify candidate risk signals. RESULTS: While SD-MAS aligned with the prototypical hyperinflammatory pattern (more marked hyperferritinemia, very high CRP, organomegaly and liver injury; 100% meeting 2016 ACR/EULAR/PRINTO criteria), SLE-MAS (92% meeting criteria) more often featured CNS dysfunction, less liver injury, greater degree of cytopenias including anemia, with a strong signal of autoimmune hemolysis (73% direct Coombs [DCT] positivity). Therapeutically, IL-1 antagonism was used in 7 SLE-MAS with mixed results without any rapid MAS resolution. Mucocutaneous disease, autoimmune hemolysis, CNS involvement, less pronounced female preponderance and much higher DCT positivity dominated the SLE-MAS phenotype compared to historical SLE cohorts comprising 1000, 2228, and 2055 cases each. CONCLUSIONS: SLE-MAS diverged from SD-MAS with less organomegaly and liver injury but more pronounced CNS involvement and hematological involvement, the latter strongly linked to red blood cell directed autoantibodies. These findings indicate that SLE-MAS pathogenesis may be divergent and require distinct therapeutic approaches beyond extrapolation from SD-MAS.

Lara D. Veeken
University of Siena (IT), University of Foggia (IT), University of Leeds (GB), Humanitas University (IT), Università Campus Bio-Medico (IT), University of Milan (IT), University of L'Aquila (IT), Leeds Teaching Hospitals NHS Trust (GB), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Istituto Ortopedico Gaetano Pini (IT), NIHR Leeds Musculoskeletal Biomedical Research Unit (GB), Federico II University Hospital (IT), Azienda Ospedaliera Universitaria Senese (IT), IRCCS Humanitas Research Hospital (IT), Bradford Teaching Hospitals NHS Foundation Trust (GB), University of Naples Federico II (IT), University of Brescia (IT)
Good health and well-being
Openalex Percentile: Top 11%
Autoimmune and Inflammatory Disorders Research
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.