Macrophage activation syndrome (MAS) is an acute, potentially fatal complication of pediatric rheumatic disorders, which is seen most commonly in systemic juvenile idiopathic arthritis (sJIA).

Because MAS is a serious condition that can follow a rapidly fatal course, its prompt recognition and an immediate therapeutic intervention are critical. However, diagnosis of MAS can be difficult and hard to distinguish from “confusable” conditions such as sJIA flare and sepsis-like syndromes.

Aims of the project

The project is aimed to develop a new set of classification criteria for MAS occurring in the context of sJIA, based on the combination of expert consensus and analysis of real patient data. Well validated and widely agreed upon criteria for MAS will be useful to enable timely diagnosis and correct classification of patients, to assist in the evaluation of different therapeutic approaches, and to facilitate communication among specialists in different fields who are interested in reactive hemophagocytic syndromes.

Project steps

The project is meant to be conducted through the following 4 steps: 1) a Delphi survey among international pediatric rheumatologists; 2) a large-scale data collection of patients with sJIA-associated MAS and patients with conditions potentially confusable with MAS (sJIA flare and sepsis-like syndromes); 3) a consensus conference of physicians with specific expertise in MAS; 4) a prospective validation of the new criteria.

The first and the second phases of the project have already been completed and the results of the Delphi survey have been published.

Toward the analysis of data obtained from the data-collection phase we evaluated the ability of each clinical, laboratory, and histopathologic feature to discriminate patients with MAS from patients with “confusable” conditions. Altogether, these analyses suggested a core set of criteria and the combinations of features with the greatest classifcation accuracy for MAS.

Objectives to be accomplished

Consensus conference.The third step of the project consists in a consensus conference, among pediatric rheumatologists and pediatric hemato-oncologists with specific expertise in MAS, which will be held in Genoa on 21-22 march 2014.The overall goal of the meeting will be to decide upon the classification criteria for MAS using a combination of statistical and consensus formation techniques.

Prospective validation of the new classification criteria.Prospective validation of the criteria set promulgated by the consensus conference will be conducted by asking international pediatric rheumatologists to test the criteria in their patients with MAS complicating sJIA.

Minoia F, Bovis F, Davì S, Horne A, Fischbach M, Frosch M, Huber A, Jelusic M, Sawhney S, McCurdy DK, Silva CA, Rigante D, Unsal E, Ruperto N, Martini A, Cron RQ, Ravelli A; Pediatric Rheumatology International Trials Organization (PRINTO), the Childhood Arthritis & Rheumatology Research Alliance, the Pediatric Rheumatology Collaborative Study Group and the Histiocyte Society.
Development and initial validation of the MS score for diagnosis of macrophage activation syndrome in systemic juvenile idiopathic arthritis.
Ann Rheum Dis 2019 Oct;78(10):1357-1362
Year: 2019 -

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Minoia F, Bovis F, Davì S, Insalaco A, Lehmberg K, Shenoi S, Weitzman S, Espada G, Gao YJ, Anton J, Kitoh T, Kasapcopur O, Sanner H, Merino R, Astigarraga I, Alessio M, Jeng M, Chasnyk V, Nichols KE, Huasong Z, Li C, Micalizzi C, Ruperto N, Martini A, Cron RQ, Ravelli A, Horne A; Pediatric Rheumatology International Trials Organization (PRINTO), the Childhood Arthritis and Rheumatology Research Alliance, the Pediatric Rheumatology Collaborative Study Group, and the Histiocyte Society.
Development and Initial Validation of the Macrophage Activation Syndrome/Primary Hemophagocytic Lymphohistiocytosis Score, a Diagnostic Tool that Differentiates Primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome.
J Pediatr 2017;189:72-78
Year: 2017 -

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Grom AA, Ilowite NT, Pascual V, Brunner HI, Martini A, Lovell DJ, Ruperto N, Leon K, Lheritier K, Abrams K for the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG).
Canakinumab in Systemic Juvenile Idiopathic Arthritis: Impact on the Rate and Clinical Presentation of Macrophage Activation Syndrome.
Arthritis Rheum 2016;68(1):218-28
Year: 2016 -

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Ravelli A, Minoia F, Davì S, Horne A, Bovis F, Pistorio A, Aricò M, Avcin T, Behrens EM, De Benedetti F, Filipovich L, Grom AA, Henter J, Ilowite NT, Jordan MB, Khubchandani R, Kitoh T, Lehmberg K, Lovell DJ, Miettunen P, Nichols KE, Ozen S, Pachlopnick-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 for the Pediatric Rheumatology International Trials Organization (PRINTO); the Childhood Arthritis & Rheumatology Research Alliance (CARRA); the Pediatric Rheumatology Collaborative Study Group (PRCSG); the Histiocyte Society.
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.
Ann Rheum Dis 2016;75:481–489.
Year: 2016 -

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Ravelli A, Minoia F, Davì S, Horne A, Bovis F, Pistorio A, Aricò M, Avcin T, Behrens EM, De Benedetti F, Filipovic A, 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, on behalf of the Pediatric Rheumatology International Trials Organization, the Childhood Arthritis & Rheumatology Research Alliance, the Pediatric Rheumatology Collaborative Study Group and the Histiocyte Society
Expert consensus on dynamics of laboratory tests for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis
RDM open 2016 Jan 19;2(1)
Year: 2016 -

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Ravelli A, Minoia F, Davì S, Horne A, Bovis F, Pistorio A, Aricò M, Avcin T, Behrens EM, De Benedetti F, Filipovich L, Grom AA, Henter J, Ilowite NT, Jordan MB, Khubchandani R, Kitoh T, Lehmberg K, Lovell DJ, Miettunen P, Nichols KE, Ozen S, Pachlopnick-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 for the Pediatric Rheumatology International Trials Organization (PRINTO); the Childhood Arthritis & Rheumatology Research Alliance (CARRA); the Pediatric Rheumatology Collaborative Study Group (PRCSG); the Histiocyte Society.
Development and initial validation of classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.
Arthritis Rheum 2016;68(3):566-76
Year: 2016 -

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Minoia F, Davì S, Horne A, Bovis F, Demirkaya E, Akikusa J, Ayaz NA, Al-Mayouf SM, Barone P, Bica B, Bolt I, Breda L, De Cunto C, Enciso S, Gallizzi R, Griffin T, Hennon T, Horneff G, Jeng M, Kapovic AM, Lipton JM, Magni Manzoni S, Rumba-Rozenfelde I, Magalhaes CS, Sewairi WM, Stine KC, Vougiouka O, Weaver LK, Davidsone Z, De Inocencio J, Ioseliani M, Lattanzi B, Tezer H, Buoncompagni A, Picco P, Ruperto N, Martini A, Cron RQ, Ravelli A; Pediatric Rheumatology International Trials Organization; Childhood Arthritis and Rheumatology Research Alliance; Pediatric Rheumatology Collaborative Study Group; and the Histiocyte Society.
Dissecting the Heterogeneity of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis.
J Rheumatol 2015;42(6):994-1001.
Year: 2015 -

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Davì S, Minoia F, Pistorio A, Horne AC, Consolaro A, Rosina S, Bovis F, Cimaz R, Gamir ML, Ilowite N, Kone-Paut I, de Oliveira SKF, McCurdy D, Silva CA, Sztajnbok F, Tsitsami E, Unsal E, Weiss JE, Wulffraat N, Abinun M, Aggarwal A, Apaz MT, Astigarraga I, Corona F, Cuttica R, D'Angelo G, Eisenstein EM, Hashad S, Lepore L, Mulaosmanovic V, Nielsen S, Prahalad S, Rigante D, Stanevicha V, Sterba G, Susic G, Takei S, Trauzeddel R, Zletni M, Ruperto N, Martini A, Cron RQ, Ravelli A on behalf of the Pediatric Rheumatology International Trials Organization (PRINTO); the Childhood Arthritis & Rheumatology Research Alliance; the Pediatric Rheumatology Collaborative Study Group and the Histiocyte Society
Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis
Arthritis Rheum 2014;66(10):2871-2880
Year: 2014 -

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Minoia F, Davì S, Horne A, Demirkaya E, Bovis F, Li C, Lehmberg K, Weitzman S, Insalaco A, Wouters C, Shenoi S, Espada G, Ozen S, Anton J, Khubchandani R, Russo R, Pal P, Kasapcopur O, Miettunen P, Maritsi D, Merino R, Shakoory B, Alessio M, Chasnyk V, Sanner H, Gao YJ, Huasong Z, Kitoh T, Avcin T, Fischbach M, Frosch M, Grom A, Huber A, Jelusic M, Sawhney S, Uziel Y, Ruperto N, Martini A, Cron RQ, Ravelli A on behalf of the Pediatric Rheumatology International Trials Organization (PRINTO); the Childhood Arthritis and Rheumatology Research Alliance; the Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Histiocyte Society.
Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients.
Arthritis Rheum 2014; Nov.66(11):3160-9
Year: 2014 -

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