The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)

Bita Shakoory; Ashley Geerlinks; Marta Wilejto; Kate Kernan; Melissa Hines; Micol Romano; David Piskin; Angelo Ravelli; Rashmi Sinha; Daniel Aletaha; Carl Allen; Hamid Bassiri; Edward M. Behrens; Joseph Carcillo; Linda Carl; Winn Chatham; Jeffrey I. Cohen; Randy Q. Cron; Erik Drewniak; Alexei A. Grom; Lauren A. Henderson; Annacarin Horne; Michael B. Jordan; Kim E. Nichols; Grant Schulert; Sebastiaan Vastert; Erkan Demirkaya; Raphaela Goldbach-Mansky; Fabrizio De Benedetti; Rebecca A. Marsh; Scott W. Canna

doi:10.1136/ard-2023-224123

The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)

Bita Shakoory, Ashley Geerlinks, Marta Wilejto, Kate Kernan, Melissa Hines, Micol Romano, David Piskin, Angelo Ravelli, Rashmi Sinha, Daniel Aletaha, Carl Allen, Hamid Bassiri, Edward M. Behrens, Joseph Carcillo, Linda Carl, Winn Chatham, Jeffrey I. Cohen, Randy Q. Cron, Erik Drewniak, Alexei A. GromLauren A. Henderson, Annacarin Horne, Michael B. Jordan, Kim E. Nichols, Grant Schulert, Sebastiaan Vastert, Erkan Demirkaya, Raphaela Goldbach-Mansky^*, Fabrizio De Benedetti^*, Rebecca A. Marsh^*, Scott W. Canna^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

1 Citation (Scopus)

Abstract

Objective Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the early stages of diagnosis, treatment and monitoring of HLH/MAS. Methods A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision-making and optimising the initial care of patients with HLH/MAS. Results The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance. Conclusion These 2022 EULAR/American College of Rheumatology points to consider provide up-to-date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life-threatening immunopathology.

Original language	English
Pages (from-to)	1271-1285
Number of pages	15
Journal	Annals of the rheumatic diseases
Volume	82
Issue number	10
DOIs	https://doi.org/10.1136/ard-2023-224123
Publication status	Published - 1 Oct 2023

Keywords

arthritis, juvenile
cytokines
inflammation
Still's disease, adult-onset

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10.1136/ard-2023-224123

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Shakoory, B., Geerlinks, A., Wilejto, M., Kernan, K., Hines, M., Romano, M., Piskin, D., Ravelli, A., Sinha, R., Aletaha, D., Allen, C., Bassiri, H., Behrens, E. M., Carcillo, J., Carl, L., Chatham, W., Cohen, J. I., Cron, R. Q., Drewniak, E., ... Canna, S. W. (2023). The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Annals of the rheumatic diseases, 82(10), 1271-1285. https://doi.org/10.1136/ard-2023-224123

@article{e7be77bfde8c4762a54b2a388d5d9342,

title = "The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)",

abstract = "Objective Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the early stages of diagnosis, treatment and monitoring of HLH/MAS. Methods A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision-making and optimising the initial care of patients with HLH/MAS. Results The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance. Conclusion These 2022 EULAR/American College of Rheumatology points to consider provide up-to-date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life-threatening immunopathology.",

keywords = "arthritis, juvenile, cytokines, inflammation, Still's disease, adult-onset",

author = "Bita Shakoory and Ashley Geerlinks and Marta Wilejto and Kate Kernan and Melissa Hines and Micol Romano and David Piskin and Angelo Ravelli and Rashmi Sinha and Daniel Aletaha and Carl Allen and Hamid Bassiri and Behrens, {Edward M.} and Joseph Carcillo and Linda Carl and Winn Chatham and Cohen, {Jeffrey I.} and Cron, {Randy Q.} and Erik Drewniak and Grom, {Alexei A.} and Henderson, {Lauren A.} and Annacarin Horne and Jordan, {Michael B.} and Nichols, {Kim E.} and Grant Schulert and Sebastiaan Vastert and Erkan Demirkaya and Raphaela Goldbach-Mansky and {De Benedetti}, Fabrizio and Marsh, {Rebecca A.} and Canna, {Scott W.}",

note = "Funding Information: CA participated in a DSMB for Sobi and OPNA. HB received consulting fees from FirstThought, Guidepoint and Kriya Therapeutics. EMB received research support from AB2Bio and consulting fees from Sobi and Genzyme. SWC received research support from Novartis and AB2Bio, has performed consulting for Simcha and Apollo therapeutics and received travel support from Sobi. RQC has received research support from Sobi, consulting fees from Sironax, speakers{\textquoteright} bureau payments from Sobi and Lilly, participated on the DSMB for Sobi, Pfizer and AbbVie. RG-M has received reseach support from IFM, Lilly, Sobi and Regeneron, and participates on a DSMB for AstraZeneca. AG has received research support from Sobi, Novartis and Novimmune, royalties from UpToDate, consulting fees from Ethos, payments from Novartis for educational materials. LAH has received research support from BMS and Sobi, consulting fees from Sobi, Pfizer and Adaptive Biotechnologies. MH has received research support from Incyte. AH has received honoraria from Sobi and Novartis. RAM has received honoraria for PracticePoint Communications, and participates on the DSMB for Horizon. KEN has received research support from Incyte and owns stock in Incyte. AR has received honoraria from AbbVie, Alexion, Novartis, Pfizer, Reckitt, Benckiser and Sobi. GS has received consulting fees from Sobi and Novartis. SV has received research support from Sobi, consulting fees from Sobi and Novartis. Funding Information: The task force is grateful to the librarian Darren Hamilton (London Health Sciences Center, London, Ontario, Canada) for his contribution to the systematic literature search, Brian Feldman and Joan Moore for their support in conducting the Delphi process and EULAR and the ACR for financial and logistical support. This project is part of a series of 'points to consider' consensus efforts (overseen by EDe and RG-M) to standardise the diagnosis and care of patients within major groups of known autoinflammatory diseases including (1) the IL-1 mediated diseases CAPS, TRAPS, MKD and DIRA; (2) the autoinflammatory interferonopathies chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), STING-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Gouti{\`e}res syndrome and (3) the early diagnosis and management of inflammatory conditions with the potential progression to HLH/MAS. This research was supported in part by the intramural research programme of the National Institute for Allergy and Infectious Diseases. We are grateful for the invaluable financial and organisational support from the Autoinflammatory Alliance and the Systemic JIA Foundation, who substantially contributed to an international meeting and workgroup organisation in August 2019 that developed the outline of the points to consider project. The funds for that meeting came largely from patient fundraisers, online fundraising and the work of countless volunteers who made this project possible. Funding Information: This work was funded by European Alliance of Associations for Rheumatology/American College of Rheumatology (CLI120). KK was supported by K12HD047349. SWC was supported by R01HD098428. Publisher Copyright: {\textcopyright} 2023 BMJ Publishing Group. All rights reserved.",

year = "2023",

month = oct,

day = "1",

doi = "10.1136/ard-2023-224123",

language = "English",

volume = "82",

pages = "1271--1285",

journal = "Annals of the rheumatic diseases",

issn = "0003-4967",

publisher = "BMJ Publishing Group",

number = "10",

}

Shakoory, B, Geerlinks, A, Wilejto, M, Kernan, K, Hines, M, Romano, M, Piskin, D, Ravelli, A, Sinha, R, Aletaha, D, Allen, C, Bassiri, H, Behrens, EM, Carcillo, J, Carl, L, Chatham, W, Cohen, JI, Cron, RQ, Drewniak, E, Grom, AA, Henderson, LA, Horne, A, Jordan, MB, Nichols, KE, Schulert, G, Vastert, S, Demirkaya, E, Goldbach-Mansky, R, De Benedetti, F, Marsh, RA & Canna, SW 2023, 'The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)', Annals of the rheumatic diseases, vol. 82, no. 10, pp. 1271-1285. https://doi.org/10.1136/ard-2023-224123

The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). / Shakoory, Bita; Geerlinks, Ashley; Wilejto, Marta et al.
In: Annals of the rheumatic diseases, Vol. 82, No. 10, 01.10.2023, p. 1271-1285.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)

AU - Shakoory, Bita

AU - Geerlinks, Ashley

AU - Wilejto, Marta

AU - Kernan, Kate

AU - Hines, Melissa

AU - Romano, Micol

AU - Piskin, David

AU - Ravelli, Angelo

AU - Sinha, Rashmi

AU - Aletaha, Daniel

AU - Allen, Carl

AU - Bassiri, Hamid

AU - Behrens, Edward M.

AU - Carcillo, Joseph

AU - Carl, Linda

AU - Chatham, Winn

AU - Cohen, Jeffrey I.

AU - Cron, Randy Q.

AU - Drewniak, Erik

AU - Grom, Alexei A.

AU - Henderson, Lauren A.

AU - Horne, Annacarin

AU - Jordan, Michael B.

AU - Nichols, Kim E.

AU - Schulert, Grant

AU - Vastert, Sebastiaan

AU - Demirkaya, Erkan

AU - Goldbach-Mansky, Raphaela

AU - De Benedetti, Fabrizio

AU - Marsh, Rebecca A.

AU - Canna, Scott W.

N1 - Funding Information: CA participated in a DSMB for Sobi and OPNA. HB received consulting fees from FirstThought, Guidepoint and Kriya Therapeutics. EMB received research support from AB2Bio and consulting fees from Sobi and Genzyme. SWC received research support from Novartis and AB2Bio, has performed consulting for Simcha and Apollo therapeutics and received travel support from Sobi. RQC has received research support from Sobi, consulting fees from Sironax, speakers’ bureau payments from Sobi and Lilly, participated on the DSMB for Sobi, Pfizer and AbbVie. RG-M has received reseach support from IFM, Lilly, Sobi and Regeneron, and participates on a DSMB for AstraZeneca. AG has received research support from Sobi, Novartis and Novimmune, royalties from UpToDate, consulting fees from Ethos, payments from Novartis for educational materials. LAH has received research support from BMS and Sobi, consulting fees from Sobi, Pfizer and Adaptive Biotechnologies. MH has received research support from Incyte. AH has received honoraria from Sobi and Novartis. RAM has received honoraria for PracticePoint Communications, and participates on the DSMB for Horizon. KEN has received research support from Incyte and owns stock in Incyte. AR has received honoraria from AbbVie, Alexion, Novartis, Pfizer, Reckitt, Benckiser and Sobi. GS has received consulting fees from Sobi and Novartis. SV has received research support from Sobi, consulting fees from Sobi and Novartis. Funding Information: The task force is grateful to the librarian Darren Hamilton (London Health Sciences Center, London, Ontario, Canada) for his contribution to the systematic literature search, Brian Feldman and Joan Moore for their support in conducting the Delphi process and EULAR and the ACR for financial and logistical support. This project is part of a series of 'points to consider' consensus efforts (overseen by EDe and RG-M) to standardise the diagnosis and care of patients within major groups of known autoinflammatory diseases including (1) the IL-1 mediated diseases CAPS, TRAPS, MKD and DIRA; (2) the autoinflammatory interferonopathies chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), STING-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome and (3) the early diagnosis and management of inflammatory conditions with the potential progression to HLH/MAS. This research was supported in part by the intramural research programme of the National Institute for Allergy and Infectious Diseases. We are grateful for the invaluable financial and organisational support from the Autoinflammatory Alliance and the Systemic JIA Foundation, who substantially contributed to an international meeting and workgroup organisation in August 2019 that developed the outline of the points to consider project. The funds for that meeting came largely from patient fundraisers, online fundraising and the work of countless volunteers who made this project possible. Funding Information: This work was funded by European Alliance of Associations for Rheumatology/American College of Rheumatology (CLI120). KK was supported by K12HD047349. SWC was supported by R01HD098428. Publisher Copyright: © 2023 BMJ Publishing Group. All rights reserved.

PY - 2023/10/1

Y1 - 2023/10/1

N2 - Objective Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the early stages of diagnosis, treatment and monitoring of HLH/MAS. Methods A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision-making and optimising the initial care of patients with HLH/MAS. Results The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance. Conclusion These 2022 EULAR/American College of Rheumatology points to consider provide up-to-date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life-threatening immunopathology.

AB - Objective Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the early stages of diagnosis, treatment and monitoring of HLH/MAS. Methods A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision-making and optimising the initial care of patients with HLH/MAS. Results The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance. Conclusion These 2022 EULAR/American College of Rheumatology points to consider provide up-to-date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life-threatening immunopathology.

KW - arthritis, juvenile

KW - cytokines

KW - inflammation

KW - Still's disease, adult-onset

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U2 - 10.1136/ard-2023-224123

DO - 10.1136/ard-2023-224123

M3 - Article

C2 - 37487610

AN - SCOPUS:85166762187

SN - 0003-4967

VL - 82

SP - 1271

EP - 1285

JO - Annals of the rheumatic diseases

JF - Annals of the rheumatic diseases

IS - 10

ER -

The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)

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