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Macrophage activation syndrome

MedGen UID:
242753
•Concept ID:
C1096155
•
Disease or Syndrome
Synonyms: Macrophage Activation Syndrome; Syndrome, Macrophage Activation
SNOMED CT: Macrophage activation syndrome (430478003); Hemophagocytic lymphohistiocytosis with rheumatologic disease (430478003); Reactive hemophagocytic syndrome (430478003)
 
Monarch Initiative: MONDO:0015545
Orphanet: ORPHA158061

Definition

A rare hemophagocytic syndrome characterized by excessive activation and proliferation of macrophages and T cells occurring in the context of a variety of diseases, including infections, neoplasms, rheumatic disorders, and leading to sudden onset of persistent fever, lymphadenopathy, and hepatosplenomegaly. Complications include profound depression of one or more blood cell lines with coagulopathy and pancytopenia, and impaired liver and renal function. Bone marrow examination reveals numerous well differentiated macrophages actively phagocytosing hematopoietic elements. [from ORDO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMacrophage activation syndrome
Follow this link to review classifications for Macrophage activation syndrome in Orphanet.

Professional guidelines

PubMed

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Kawasaki Disease.
Gorelik M, Chung SA, Ardalan K, Binstadt BA, Friedman K, Hayward K, Imundo LF, Lapidus SK, Kim S, Son MB, Sule S, Tremoulet AH, Van Mater H, Yildirim-Toruner C, Langford CA, Maz M, Abril A, Guyatt G, Archer AM, Conn DL, Full KA, Grayson PC, Ibarra MF, Merkel PA, Rhee RL, Seo P, Stone JH, Sundel RP, Vitobaldi OI, Warner A, Byram K, Dua AB, Husainat N, James KE, Kalot M, Lin YC, Springer JM, Turgunbaev M, Villa-Forte A, Turner AS, Mustafa RA
Arthritis Care Res (Hoboken) 2022 Apr;74(4):538-548. Epub 2022 Mar 7 doi: 10.1002/acr.24838. PMID: 35257507
Consensus-Based Guidelines for the Recognition, Diagnosis, and Management of Hemophagocytic Lymphohistiocytosis in Critically Ill Children and Adults.
Hines MR, von Bahr Greenwood T, Beutel G, Beutel K, Hays JA, Horne A, Janka G, Jordan MB, van Laar JAM, Lachmann G, Lehmberg K, Machowicz R, Miettunen P, La Rosée P, Shakoory B, Zinter MS, Henter JI
Crit Care Med 2022 May 1;50(5):860-872. Epub 2021 Oct 5 doi: 10.1097/CCM.0000000000005361. PMID: 34605776
Adult-onset Still's disease in focus: Clinical manifestations, diagnosis, treatment, and unmet needs in the era of targeted therapies.
Efthimiou P, Kontzias A, Hur P, Rodha K, Ramakrishna GS, Nakasato P
Semin Arthritis Rheum 2021 Aug;51(4):858-874. Epub 2021 Jun 13 doi: 10.1016/j.semarthrit.2021.06.004. PMID: 34175791

Recent clinical studies

Etiology

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Kawasaki Disease.
Gorelik M, Chung SA, Ardalan K, Binstadt BA, Friedman K, Hayward K, Imundo LF, Lapidus SK, Kim S, Son MB, Sule S, Tremoulet AH, Van Mater H, Yildirim-Toruner C, Langford CA, Maz M, Abril A, Guyatt G, Archer AM, Conn DL, Full KA, Grayson PC, Ibarra MF, Merkel PA, Rhee RL, Seo P, Stone JH, Sundel RP, Vitobaldi OI, Warner A, Byram K, Dua AB, Husainat N, James KE, Kalot M, Lin YC, Springer JM, Turgunbaev M, Villa-Forte A, Turner AS, Mustafa RA
Arthritis Care Res (Hoboken) 2022 Apr;74(4):538-548. Epub 2022 Mar 7 doi: 10.1002/acr.24838. PMID: 35257507
Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages.
Emile JF, Abla O, Fraitag S, Horne A, Haroche J, Donadieu J, Requena-Caballero L, Jordan MB, Abdel-Wahab O, Allen CE, Charlotte F, Diamond EL, Egeler RM, Fischer A, Herrera JG, Henter JI, Janku F, Merad M, Picarsic J, Rodriguez-Galindo C, Rollins BJ, Tazi A, Vassallo R, Weiss LM; Histiocyte Society
Blood 2016 Jun 2;127(22):2672-81. Epub 2016 Mar 10 doi: 10.1182/blood-2016-01-690636. PMID: 26966089Free PMC Article
2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.
Ravelli A, Minoia F, Davì S, Horne A, Bovis F, Pistorio A, Aricò M, Avcin T, Behrens EM, De Benedetti F, Filipovic L, Grom AA, Henter JI, Ilowite NT, Jordan MB, Khubchandani R, Kitoh T, Lehmberg K, Lovell DJ, Miettunen P, Nichols KE, Ozen S, Pachlopnik Schmid J, Ramanan AV, Russo R, Schneider R, Sterba G, Uziel Y, Wallace C, Wouters C, Wulffraat N, Demirkaya E, Brunner HI, Martini A, Ruperto N, Cron RQ; Paediatric Rheumatology International Trials Organisation; Childhood Arthritis and Rheumatology Research Alliance; Pediatric Rheumatology Collaborative Study Group; Histiocyte Society
Arthritis Rheumatol 2016 Mar;68(3):566-76. Epub 2016 Feb 9 doi: 10.1002/art.39332. PMID: 26314788
Macrophage Activation Syndrome.
Ravelli A, Davì S, Minoia F, Martini A, Cron RQ
Hematol Oncol Clin North Am 2015 Oct;29(5):927-41. Epub 2015 Aug 25 doi: 10.1016/j.hoc.2015.06.010. PMID: 26461152
Treatment of Epstein Barr virus-induced haemophagocytic lymphohistiocytosis with rituximab-containing chemo-immunotherapeutic regimens.
Chellapandian D, Das R, Zelley K, Wiener SJ, Zhao H, Teachey DT, Nichols KE; EBV-HLH Rituximab Study Group
Br J Haematol 2013 Aug;162(3):376-82. Epub 2013 May 21 doi: 10.1111/bjh.12386. PMID: 23692048Free PMC Article

Diagnosis

Subtypes and Mimics of Sepsis.
Kellum JA, Formeck CL, Kernan KF, Gómez H, Carcillo JA
Crit Care Clin 2022 Apr;38(2):195-211. doi: 10.1016/j.ccc.2021.11.013. PMID: 35369943
Consensus-Based Guidelines for the Recognition, Diagnosis, and Management of Hemophagocytic Lymphohistiocytosis in Critically Ill Children and Adults.
Hines MR, von Bahr Greenwood T, Beutel G, Beutel K, Hays JA, Horne A, Janka G, Jordan MB, van Laar JAM, Lachmann G, Lehmberg K, Machowicz R, Miettunen P, La Rosée P, Shakoory B, Zinter MS, Henter JI
Crit Care Med 2022 May 1;50(5):860-872. Epub 2021 Oct 5 doi: 10.1097/CCM.0000000000005361. PMID: 34605776
Update οn the diagnosis and management of systemic lupus erythematosus.
Fanouriakis A, Tziolos N, Bertsias G, Boumpas DT
Ann Rheum Dis 2021 Jan;80(1):14-25. Epub 2020 Oct 13 doi: 10.1136/annrheumdis-2020-218272. PMID: 33051219
Hemophagocytic lymphohistiocytosis: An update on pathogenesis, diagnosis, and therapy.
Griffin G, Shenoi S, Hughes GC
Best Pract Res Clin Rheumatol 2020 Aug;34(4):101515. Epub 2020 May 7 doi: 10.1016/j.berh.2020.101515. PMID: 32387063
Macrophage Activation Syndrome.
Ravelli A, Davì S, Minoia F, Martini A, Cron RQ
Hematol Oncol Clin North Am 2015 Oct;29(5):927-41. Epub 2015 Aug 25 doi: 10.1016/j.hoc.2015.06.010. PMID: 26461152

Therapy

Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome.
Hines MR, Knight TE, McNerney KO, Leick MB, Jain T, Ahmed S, Frigault MJ, Hill JA, Jain MD, Johnson WT, Lin Y, Mahadeo KM, Maron GM, Marsh RA, Neelapu SS, Nikiforow S, Ombrello AK, Shah NN, Talleur AC, Turicek D, Vatsayan A, Wong SW, Maus MV, Komanduri KV, Berliner N, Henter JI, Perales MA, Frey NV, Teachey DT, Frank MJ, Shah NN
Transplant Cell Ther 2023 Jul;29(7):438.e1-438.e16. Epub 2023 Mar 9 doi: 10.1016/j.jtct.2023.03.006. PMID: 36906275Free PMC Article
2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Kawasaki Disease.
Gorelik M, Chung SA, Ardalan K, Binstadt BA, Friedman K, Hayward K, Imundo LF, Lapidus SK, Kim S, Son MB, Sule S, Tremoulet AH, Van Mater H, Yildirim-Toruner C, Langford CA, Maz M, Abril A, Guyatt G, Archer AM, Conn DL, Full KA, Grayson PC, Ibarra MF, Merkel PA, Rhee RL, Seo P, Stone JH, Sundel RP, Vitobaldi OI, Warner A, Byram K, Dua AB, Husainat N, James KE, Kalot M, Lin YC, Springer JM, Turgunbaev M, Villa-Forte A, Turner AS, Mustafa RA
Arthritis Care Res (Hoboken) 2022 Apr;74(4):538-548. Epub 2022 Mar 7 doi: 10.1002/acr.24838. PMID: 35257507
Update οn the diagnosis and management of systemic lupus erythematosus.
Fanouriakis A, Tziolos N, Bertsias G, Boumpas DT
Ann Rheum Dis 2021 Jan;80(1):14-25. Epub 2020 Oct 13 doi: 10.1136/annrheumdis-2020-218272. PMID: 33051219
A comprehensive review on adult onset Still's disease.
Giacomelli R, Ruscitti P, Shoenfeld Y
J Autoimmun 2018 Sep;93:24-36. Epub 2018 Aug 1 doi: 10.1016/j.jaut.2018.07.018. PMID: 30077425
Systemic Juvenile Idiopathic Arthritis.
Lee JJY, Schneider R
Pediatr Clin North Am 2018 Aug;65(4):691-709. doi: 10.1016/j.pcl.2018.04.005. PMID: 30031494

Prognosis

Recent advances and evolving concepts in Still's disease.
Ruscitti P, Cantarini L, Nigrovic PA, McGonagle D, Giacomelli R
Nat Rev Rheumatol 2024 Feb;20(2):116-132. Epub 2024 Jan 11 doi: 10.1038/s41584-023-01065-6. PMID: 38212542
Update οn the diagnosis and management of systemic lupus erythematosus.
Fanouriakis A, Tziolos N, Bertsias G, Boumpas DT
Ann Rheum Dis 2021 Jan;80(1):14-25. Epub 2020 Oct 13 doi: 10.1136/annrheumdis-2020-218272. PMID: 33051219
A comprehensive review on adult onset Still's disease.
Giacomelli R, Ruscitti P, Shoenfeld Y
J Autoimmun 2018 Sep;93:24-36. Epub 2018 Aug 1 doi: 10.1016/j.jaut.2018.07.018. PMID: 30077425
Adult-onset Still's disease.
Gerfaud-Valentin M, Jamilloux Y, Iwaz J, Sève P
Autoimmun Rev 2014 Jul;13(7):708-22. Epub 2014 Mar 19 doi: 10.1016/j.autrev.2014.01.058. PMID: 24657513
Treatment of Epstein Barr virus-induced haemophagocytic lymphohistiocytosis with rituximab-containing chemo-immunotherapeutic regimens.
Chellapandian D, Das R, Zelley K, Wiener SJ, Zhao H, Teachey DT, Nichols KE; EBV-HLH Rituximab Study Group
Br J Haematol 2013 Aug;162(3):376-82. Epub 2013 May 21 doi: 10.1111/bjh.12386. PMID: 23692048Free PMC Article

Clinical prediction guides

Efficacy and safety of emapalumab in macrophage activation syndrome.
De Benedetti F, Grom AA, Brogan PA, Bracaglia C, Pardeo M, Marucci G, Eleftheriou D, Papadopoulou C, Schulert GS, Quartier P, Antón J, Laveille C, Frederiksen R, Asnaghi V, Ballabio M, Jacqmin P, de Min C
Ann Rheum Dis 2023 Jun;82(6):857-865. Epub 2023 Mar 31 doi: 10.1136/ard-2022-223739. PMID: 37001971Free PMC Article
Adult-onset Still's disease in focus: Clinical manifestations, diagnosis, treatment, and unmet needs in the era of targeted therapies.
Efthimiou P, Kontzias A, Hur P, Rodha K, Ramakrishna GS, Nakasato P
Semin Arthritis Rheum 2021 Aug;51(4):858-874. Epub 2021 Jun 13 doi: 10.1016/j.semarthrit.2021.06.004. PMID: 34175791
Macrophage Activation-Like Syndrome: A Distinct Entity Leading to Early Death in Sepsis.
Karakike E, Giamarellos-Bourboulis EJ
Front Immunol 2019;10:55. Epub 2019 Jan 31 doi: 10.3389/fimmu.2019.00055. PMID: 30766533Free PMC Article
A comprehensive review on adult onset Still's disease.
Giacomelli R, Ruscitti P, Shoenfeld Y
J Autoimmun 2018 Sep;93:24-36. Epub 2018 Aug 1 doi: 10.1016/j.jaut.2018.07.018. PMID: 30077425
Macrophage activation syndrome in the era of biologic therapy.
Grom AA, Horne A, De Benedetti F
Nat Rev Rheumatol 2016 May;12(5):259-68. Epub 2016 Mar 24 doi: 10.1038/nrrheum.2015.179. PMID: 27009539Free PMC Article

Recent systematic reviews

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 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; HLH/MAS task force
Ann Rheum Dis 2023 Oct;82(10):1271-1285. Epub 2023 Jul 24 doi: 10.1136/ard-2023-224123. PMID: 37487610Free PMC Article
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 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
Arthritis Rheumatol 2023 Oct;75(10):1714-1732. Epub 2023 Jul 24 doi: 10.1002/art.42636. PMID: 37486733Free PMC Article
Systematic Review of Safety and Efficacy of IL-1-Targeted Biologics in Treating Immune-Mediated Disorders.
Arnold DD, Yalamanoglu A, Boyman O
Front Immunol 2022;13:888392. Epub 2022 Jul 6 doi: 10.3389/fimmu.2022.888392. PMID: 35874710Free PMC Article
2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.
Onel KB, Horton DB, Lovell DJ, Shenoi S, Cuello CA, Angeles-Han ST, Becker ML, Cron RQ, Feldman BM, Ferguson PJ, Gewanter H, Guzman J, Kimura Y, Lee T, Murphy K, Nigrovic PA, Ombrello MJ, Rabinovich CE, Tesher M, Twilt M, Klein-Gitelman M, Barbar-Smiley F, Cooper AM, Edelheit B, Gillispie-Taylor M, Hays K, Mannion ML, Peterson R, Flanagan E, Saad N, Sullivan N, Szymanski AM, Trachtman R, Turgunbaev M, Veiga K, Turner AS, Reston JT
Arthritis Rheumatol 2022 Apr;74(4):553-569. Epub 2022 Mar 1 doi: 10.1002/art.42037. PMID: 35233993Free PMC Article
2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.
Onel KB, Horton DB, Lovell DJ, Shenoi S, Cuello CA, Angeles-Han ST, Becker ML, Cron RQ, Feldman BM, Ferguson PJ, Gewanter H, Guzman J, Kimura Y, Lee T, Murphy K, Nigrovic PA, Ombrello MJ, Rabinovich CE, Tesher M, Twilt M, Klein-Gitelman M, Barbar-Smiley F, Cooper AM, Edelheit B, Gillispie-Taylor M, Hays K, Mannion ML, Peterson R, Flanagan E, Saad N, Sullivan N, Szymanski AM, Trachtman R, Turgunbaev M, Veiga K, Turner AS, Reston JT
Arthritis Care Res (Hoboken) 2022 Apr;74(4):521-537. Epub 2022 Mar 1 doi: 10.1002/acr.24853. PMID: 35233986Free PMC Article

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