Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

Sergio Davì; Francesca Minoia; Angela Pistorio; Annacarin Horne; Alessandro Consolaro; Silvia Rosina; Francesca Bovis; Rolando Cimaz; Maria Luz Gamir; Norman T. Ilowite; Isabelle Kone-Paut; Sheila Knupp Feitosa De Oliveira; Deborah McCurdy; Clovis Artur Silva; Flavio Sztajnbok; Elena Tsitsami; Erbil Unsal; Jennifer E. Weiss; Nico Wulffraat; Mario Abinun; Amita Aggarwal; Maria Teresa Apaz; Itziar Astigarraga; Fabrizia Corona; Ruben Cuttica; Gianfranco D'Angelo; Eli M. Eisenstein; Soad Hashad; Loredana Lepore; Velma Mulaosmanovic; Susan Nielsen; Sampath Prahalad; Donato Rigante; Valda Stanevicha; Gary Sterba; Gordana Susic; Syuji Takei; Ralf Trauzeddel; Mabruka Zletni; Nicolino Ruperto; Alberto Martini; Randy Q. Cron; Angelo Ravelli

doi:10.1002/art.38769

Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

Sergio Davì, Francesca Minoia, Angela Pistorio, Annacarin Horne, Alessandro Consolaro, Silvia Rosina, Francesca Bovis, Rolando Cimaz, Maria Luz Gamir, Norman T. Ilowite, Isabelle Kone-Paut, Sheila Knupp Feitosa De Oliveira, Deborah McCurdy, Clovis Artur Silva, Flavio Sztajnbok, Elena Tsitsami, Erbil Unsal, Jennifer E. Weiss, Nico Wulffraat, Mario AbinunAmita Aggarwal, Maria Teresa Apaz, Itziar Astigarraga, Fabrizia Corona, Ruben Cuttica, Gianfranco D'Angelo, Eli M. Eisenstein, Soad Hashad, Loredana Lepore, Velma Mulaosmanovic, Susan Nielsen, Sampath Prahalad, Donato Rigante, Valda Stanevicha, Gary Sterba, Gordana Susic, Syuji Takei, Ralf Trauzeddel, Mabruka Zletni, Nicolino Ruperto, Alberto Martini, Randy Q. Cron, Angelo Ravelli

Pediatrics

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

87 Scopus citations

Abstract

Results The study sample included 362 patients with systemic JIA and MAS, 404 patients with active systemic JIA without MAS, and 345 patients with systemic infection. The best capacity to differentiate MAS from systemic JIA without MAS was found when the preliminary MAS guidelines were applied. The 3/5-adapted HLH-2004 guidelines performed better than the 4/5-adapted guidelines in distinguishing MAS from active systemic JIA without MAS. The 3/5-adapted HLH-2004 guidelines and the preliminary MAS guidelines with the addition of ferritin levels ≥500 ng/ml discriminated best between MAS and systemic infections.

Conclusion The preliminary MAS guidelines showed the strongest ability to identify MAS in systemic JIA. The addition of hyperferritinemia enhanced their capacity to differentiate MAS from systemic infections. The HLH-2004 guidelines are likely not appropriate for identification of MAS in children with systemic JIA.

Objective To compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH-2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)-associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection.

Methods International pediatric rheumatologists and hemato-oncologists were asked to retrospectively collect clinical information from patients with systemic JIA-associated MAS and confusable conditions. The ability of the guidelines to differentiate MAS from the control diseases was evaluated by calculating the sensitivity and specificity of each set of guidelines and the kappa statistics for concordance with the physician's diagnosis. Owing to the fact that not all patients were assessed for hemophagocytosis on bone marrow aspirates and given the lack of data on natural killer cell activity and soluble CD25 levels, the HLH-2004 guidelines were adapted to enable the diagnosis of MAS when 3 of 5 of the remaining items (3/5-adapted) or 4 of 5 of the remaining items (4/5-adapted) were present.

Original language	English (US)
Pages (from-to)	2871-2880
Number of pages	10
Journal	Arthritis and Rheumatology
Volume	66
Issue number	10
DOIs	https://doi.org/10.1002/art.38769
State	Published - Oct 1 2014

ASJC Scopus subject areas

Immunology and Allergy
Rheumatology
Immunology

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Davì, S., Minoia, F., Pistorio, A., Horne, A., Consolaro, A., Rosina, S., Bovis, F., Cimaz, R., Gamir, M. L., Ilowite, N. T., Kone-Paut, I., Feitosa De Oliveira, S. K., McCurdy, D., Silva, C. A., Sztajnbok, F., Tsitsami, E., Unsal, E., Weiss, J. E., Wulffraat, N., ... Ravelli, A. (2014). Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Arthritis and Rheumatology, 66(10), 2871-2880. https://doi.org/10.1002/art.38769

Davì, S, Minoia, F, Pistorio, A, Horne, A, Consolaro, A, Rosina, S, Bovis, F, Cimaz, R, Gamir, ML, Ilowite, NT, Kone-Paut, I, Feitosa De Oliveira, SK, 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 2014, 'Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis', Arthritis and Rheumatology, vol. 66, no. 10, pp. 2871-2880. https://doi.org/10.1002/art.38769

@article{c0b8071a15834a5cb03473e54dc27766,

title = "Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis",

abstract = "Results The study sample included 362 patients with systemic JIA and MAS, 404 patients with active systemic JIA without MAS, and 345 patients with systemic infection. The best capacity to differentiate MAS from systemic JIA without MAS was found when the preliminary MAS guidelines were applied. The 3/5-adapted HLH-2004 guidelines performed better than the 4/5-adapted guidelines in distinguishing MAS from active systemic JIA without MAS. The 3/5-adapted HLH-2004 guidelines and the preliminary MAS guidelines with the addition of ferritin levels ≥500 ng/ml discriminated best between MAS and systemic infections.Conclusion The preliminary MAS guidelines showed the strongest ability to identify MAS in systemic JIA. The addition of hyperferritinemia enhanced their capacity to differentiate MAS from systemic infections. The HLH-2004 guidelines are likely not appropriate for identification of MAS in children with systemic JIA.Objective To compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH-2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)-associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection.Methods International pediatric rheumatologists and hemato-oncologists were asked to retrospectively collect clinical information from patients with systemic JIA-associated MAS and confusable conditions. The ability of the guidelines to differentiate MAS from the control diseases was evaluated by calculating the sensitivity and specificity of each set of guidelines and the kappa statistics for concordance with the physician's diagnosis. Owing to the fact that not all patients were assessed for hemophagocytosis on bone marrow aspirates and given the lack of data on natural killer cell activity and soluble CD25 levels, the HLH-2004 guidelines were adapted to enable the diagnosis of MAS when 3 of 5 of the remaining items (3/5-adapted) or 4 of 5 of the remaining items (4/5-adapted) were present.",

author = "Sergio Dav{\`i} and Francesca Minoia and Angela Pistorio and Annacarin Horne and Alessandro Consolaro and Silvia Rosina and Francesca Bovis and Rolando Cimaz and Gamir, {Maria Luz} and Ilowite, {Norman T.} and Isabelle Kone-Paut and {Feitosa De Oliveira}, {Sheila Knupp} and Deborah McCurdy and Silva, {Clovis Artur} and Flavio Sztajnbok and Elena Tsitsami and Erbil Unsal and Weiss, {Jennifer E.} and Nico Wulffraat and Mario Abinun and Amita Aggarwal and Apaz, {Maria Teresa} and Itziar Astigarraga and Fabrizia Corona and Ruben Cuttica and Gianfranco D'Angelo and Eisenstein, {Eli M.} and Soad Hashad and Loredana Lepore and Velma Mulaosmanovic and Susan Nielsen and Sampath Prahalad and Donato Rigante and Valda Stanevicha and Gary Sterba and Gordana Susic and Syuji Takei and Ralf Trauzeddel and Mabruka Zletni and Nicolino Ruperto and Alberto Martini and Cron, {Randy Q.} and Angelo Ravelli",

note = "Publisher Copyright: Copyright {\textcopyright} 2014 by the American College of Rheumatology.",

year = "2014",

month = oct,

day = "1",

doi = "10.1002/art.38769",

language = "English (US)",

volume = "66",

pages = "2871--2880",

journal = "Arthritis and Rheumatology",

issn = "2326-5191",

publisher = "John Wiley and Sons Ltd",

number = "10",

}

TY - JOUR

T1 - Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

AU - Davì, Sergio

AU - Minoia, Francesca

AU - Pistorio, Angela

AU - Horne, Annacarin

AU - Consolaro, Alessandro

AU - Rosina, Silvia

AU - Bovis, Francesca

AU - Cimaz, Rolando

AU - Gamir, Maria Luz

AU - Ilowite, Norman T.

AU - Kone-Paut, Isabelle

AU - Feitosa De Oliveira, Sheila Knupp

AU - McCurdy, Deborah

AU - Silva, Clovis Artur

AU - Sztajnbok, Flavio

AU - Tsitsami, Elena

AU - Unsal, Erbil

AU - Weiss, Jennifer E.

AU - Wulffraat, Nico

AU - Abinun, Mario

AU - Aggarwal, Amita

AU - Apaz, Maria Teresa

AU - Astigarraga, Itziar

AU - Corona, Fabrizia

AU - Cuttica, Ruben

AU - D'Angelo, Gianfranco

AU - Eisenstein, Eli M.

AU - Hashad, Soad

AU - Lepore, Loredana

AU - Mulaosmanovic, Velma

AU - Nielsen, Susan

AU - Prahalad, Sampath

AU - Rigante, Donato

AU - Stanevicha, Valda

AU - Sterba, Gary

AU - Susic, Gordana

AU - Takei, Syuji

AU - Trauzeddel, Ralf

AU - Zletni, Mabruka

AU - Ruperto, Nicolino

AU - Martini, Alberto

AU - Cron, Randy Q.

AU - Ravelli, Angelo

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Results The study sample included 362 patients with systemic JIA and MAS, 404 patients with active systemic JIA without MAS, and 345 patients with systemic infection. The best capacity to differentiate MAS from systemic JIA without MAS was found when the preliminary MAS guidelines were applied. The 3/5-adapted HLH-2004 guidelines performed better than the 4/5-adapted guidelines in distinguishing MAS from active systemic JIA without MAS. The 3/5-adapted HLH-2004 guidelines and the preliminary MAS guidelines with the addition of ferritin levels ≥500 ng/ml discriminated best between MAS and systemic infections.Conclusion The preliminary MAS guidelines showed the strongest ability to identify MAS in systemic JIA. The addition of hyperferritinemia enhanced their capacity to differentiate MAS from systemic infections. The HLH-2004 guidelines are likely not appropriate for identification of MAS in children with systemic JIA.Objective To compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH-2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)-associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection.Methods International pediatric rheumatologists and hemato-oncologists were asked to retrospectively collect clinical information from patients with systemic JIA-associated MAS and confusable conditions. The ability of the guidelines to differentiate MAS from the control diseases was evaluated by calculating the sensitivity and specificity of each set of guidelines and the kappa statistics for concordance with the physician's diagnosis. Owing to the fact that not all patients were assessed for hemophagocytosis on bone marrow aspirates and given the lack of data on natural killer cell activity and soluble CD25 levels, the HLH-2004 guidelines were adapted to enable the diagnosis of MAS when 3 of 5 of the remaining items (3/5-adapted) or 4 of 5 of the remaining items (4/5-adapted) were present.

AB - Results The study sample included 362 patients with systemic JIA and MAS, 404 patients with active systemic JIA without MAS, and 345 patients with systemic infection. The best capacity to differentiate MAS from systemic JIA without MAS was found when the preliminary MAS guidelines were applied. The 3/5-adapted HLH-2004 guidelines performed better than the 4/5-adapted guidelines in distinguishing MAS from active systemic JIA without MAS. The 3/5-adapted HLH-2004 guidelines and the preliminary MAS guidelines with the addition of ferritin levels ≥500 ng/ml discriminated best between MAS and systemic infections.Conclusion The preliminary MAS guidelines showed the strongest ability to identify MAS in systemic JIA. The addition of hyperferritinemia enhanced their capacity to differentiate MAS from systemic infections. The HLH-2004 guidelines are likely not appropriate for identification of MAS in children with systemic JIA.Objective To compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH-2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)-associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection.Methods International pediatric rheumatologists and hemato-oncologists were asked to retrospectively collect clinical information from patients with systemic JIA-associated MAS and confusable conditions. The ability of the guidelines to differentiate MAS from the control diseases was evaluated by calculating the sensitivity and specificity of each set of guidelines and the kappa statistics for concordance with the physician's diagnosis. Owing to the fact that not all patients were assessed for hemophagocytosis on bone marrow aspirates and given the lack of data on natural killer cell activity and soluble CD25 levels, the HLH-2004 guidelines were adapted to enable the diagnosis of MAS when 3 of 5 of the remaining items (3/5-adapted) or 4 of 5 of the remaining items (4/5-adapted) were present.

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Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

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