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

Francesca Minoia, Francesca Bovis, Sergio Davì, Antonella Insalaco, Kai Lehmberg, Susan Shenoi, Sheila Weitzman, Graciela Espada, Yi Jin Gao, Jordi Anton, Toshiyuki Kitoh, Ozgur Kasapcopur, Helga Sanner, Rosa Merino, Itziar Astigarraga, Maria Alessio, Michael Jeng, Vyacheslav Chasnyk, Kim E. Nichols, Zeng HuasongCaifeng Li, Concetta Micalizzi, Nicolino Ruperto, Alberto Martini, Randy Q. Cron, Angelo Ravelli, Anna Carin Horne, Mario Abinun, Amita Aggarwal, Jonathan Akikusa, Sulaiman Al-Mayouf, Maria Alessio, Jordi Anton, Maria Teresa Apaz, Itziar Astigarraga, Tadej Avcin, Nuray Aktay Ayaz, Patrizia Barone, Bianca Bica, Isabel Bolt, Fabrizia Corona, Sergio Davì, Antonella Insalaco, Loredana Lepore, Silvia Magni-Manzoni, Alberto Martini, Concetta Micalizzi, Francesca Minoia, Angelo Ravelli, Nicolino Ruperto

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective To develop and validate a diagnostic score that assists in discriminating primary hemophagocytic lymphohistiocytosis (pHLH) from macrophage activation syndrome (MAS) related to systemic juvenile idiopathic arthritis. Study design The clinical, laboratory, and histopathologic features of 362 patients with MAS and 258 patients with pHLH were collected in a multinational collaborative study. Eighty percent of the population was assessed to develop the score and the remaining 20% constituted the validation sample. Variables that entered the best fitted model of logistic regression were assigned a score, based on their statistical weight. The MAS/HLH (MH) score was made up with the individual scores of selected variables. The cutoff in the MH score that discriminated pHLH from MAS best was calculated by means of receiver operating characteristic curve analysis. Score performance was examined in both developmental and validation samples. Results Six variables composed the MH score: age at onset, neutrophil count, fibrinogen, splenomegaly, platelet count, and hemoglobin. The MH score ranged from 0 to 123, and its median value was 97 (1st-3rd quartile 75-123) and 12 (1st-3rd quartile 11-34) in pHLH and MAS, respectively. The probability of a diagnosis of pHLH ranged from 99% for a score of ≥123. A cutoff value of ≥60 revealed the best performance in discriminating pHLH from MAS. Conclusion The MH score is a powerful tool that may aid practitioners to identify patients who are more likely to have pHLH and, thus, could be prioritized for functional and genetic testing.
Original languageEnglish
Pages (from-to)72-78.e3
JournalJournal of Pediatrics
Volume189
DOIs
Publication statusPublished - Oct 1 2017

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Macrophage Activation Syndrome
Hemophagocytic Lymphohistiocytosis
Juvenile Arthritis
Splenomegaly
Genetic Testing
Platelet Count
Age of Onset
ROC Curve
Fibrinogen
Hemoglobins
Neutrophils
Logistic Models
Weights and Measures

Keywords

  • diagnostic score, hemophagocytic syndrome, macrophage activation syndrome, primary hemophagocytic lymphohistiocytosis

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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. / Minoia, Francesca; Bovis, Francesca; Davì, Sergio; Insalaco, Antonella; Lehmberg, Kai; Shenoi, Susan; Weitzman, Sheila; Espada, Graciela; Gao, Yi Jin; Anton, Jordi; Kitoh, Toshiyuki; Kasapcopur, Ozgur; Sanner, Helga; Merino, Rosa; Astigarraga, Itziar; Alessio, Maria; Jeng, Michael; Chasnyk, Vyacheslav; Nichols, Kim E.; Huasong, Zeng; Li, Caifeng; Micalizzi, Concetta; Ruperto, Nicolino; Martini, Alberto; Cron, Randy Q.; Ravelli, Angelo; Horne, Anna Carin; Abinun, Mario; Aggarwal, Amita; Akikusa, Jonathan; Al-Mayouf, Sulaiman; Alessio, Maria; Anton, Jordi; Apaz, Maria Teresa; Astigarraga, Itziar; Avcin, Tadej; Ayaz, Nuray Aktay; Barone, Patrizia; Bica, Bianca; Bolt, Isabel; Corona, Fabrizia; Davì, Sergio; Insalaco, Antonella; Lepore, Loredana; Magni-Manzoni, Silvia; Martini, Alberto; Micalizzi, Concetta; Minoia, Francesca; Ravelli, Angelo; Ruperto, Nicolino.

In: Journal of Pediatrics, Vol. 189, 01.10.2017, p. 72-78.e3.

Research output: Contribution to journalArticle

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, AC, Abinun, M, Aggarwal, A, Akikusa, J, Al-Mayouf, S, Alessio, M, Anton, J, Apaz, MT, Astigarraga, I, Avcin, T, Ayaz, NA, Barone, P, Bica, B, Bolt, I, Corona, F, Davì, S, Insalaco, A, Lepore, L, Magni-Manzoni, S, Martini, A, Micalizzi, C, Minoia, F, Ravelli, A & Ruperto, N 2017, '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', Journal of Pediatrics, vol. 189, pp. 72-78.e3. https://doi.org/10.1016/j.jpeds.2017.06.005
Minoia, Francesca ; Bovis, Francesca ; Davì, Sergio ; Insalaco, Antonella ; Lehmberg, Kai ; Shenoi, Susan ; Weitzman, Sheila ; Espada, Graciela ; Gao, Yi Jin ; Anton, Jordi ; Kitoh, Toshiyuki ; Kasapcopur, Ozgur ; Sanner, Helga ; Merino, Rosa ; Astigarraga, Itziar ; Alessio, Maria ; Jeng, Michael ; Chasnyk, Vyacheslav ; Nichols, Kim E. ; Huasong, Zeng ; Li, Caifeng ; Micalizzi, Concetta ; Ruperto, Nicolino ; Martini, Alberto ; Cron, Randy Q. ; Ravelli, Angelo ; Horne, Anna Carin ; Abinun, Mario ; Aggarwal, Amita ; Akikusa, Jonathan ; Al-Mayouf, Sulaiman ; Alessio, Maria ; Anton, Jordi ; Apaz, Maria Teresa ; Astigarraga, Itziar ; Avcin, Tadej ; Ayaz, Nuray Aktay ; Barone, Patrizia ; Bica, Bianca ; Bolt, Isabel ; Corona, Fabrizia ; Davì, Sergio ; Insalaco, Antonella ; Lepore, Loredana ; Magni-Manzoni, Silvia ; Martini, Alberto ; Micalizzi, Concetta ; Minoia, Francesca ; Ravelli, Angelo ; Ruperto, Nicolino. / 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. In: Journal of Pediatrics. 2017 ; Vol. 189. pp. 72-78.e3.
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abstract = "Objective To develop and validate a diagnostic score that assists in discriminating primary hemophagocytic lymphohistiocytosis (pHLH) from macrophage activation syndrome (MAS) related to systemic juvenile idiopathic arthritis. Study design The clinical, laboratory, and histopathologic features of 362 patients with MAS and 258 patients with pHLH were collected in a multinational collaborative study. Eighty percent of the population was assessed to develop the score and the remaining 20{\%} constituted the validation sample. Variables that entered the best fitted model of logistic regression were assigned a score, based on their statistical weight. The MAS/HLH (MH) score was made up with the individual scores of selected variables. The cutoff in the MH score that discriminated pHLH from MAS best was calculated by means of receiver operating characteristic curve analysis. Score performance was examined in both developmental and validation samples. Results Six variables composed the MH score: age at onset, neutrophil count, fibrinogen, splenomegaly, platelet count, and hemoglobin. The MH score ranged from 0 to 123, and its median value was 97 (1st-3rd quartile 75-123) and 12 (1st-3rd quartile 11-34) in pHLH and MAS, respectively. The probability of a diagnosis of pHLH ranged from 99{\%} for a score of ≥123. A cutoff value of ≥60 revealed the best performance in discriminating pHLH from MAS. Conclusion The MH score is a powerful tool that may aid practitioners to identify patients who are more likely to have pHLH and, thus, could be prioritized for functional and genetic testing.",
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T1 - 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

AU - Minoia, Francesca

AU - Bovis, Francesca

AU - Davì, Sergio

AU - Insalaco, Antonella

AU - Lehmberg, Kai

AU - Shenoi, Susan

AU - Weitzman, Sheila

AU - Espada, Graciela

AU - Gao, Yi Jin

AU - Anton, Jordi

AU - Kitoh, Toshiyuki

AU - Kasapcopur, Ozgur

AU - Sanner, Helga

AU - Merino, Rosa

AU - Astigarraga, Itziar

AU - Alessio, Maria

AU - Jeng, Michael

AU - Chasnyk, Vyacheslav

AU - Nichols, Kim E.

AU - Huasong, Zeng

AU - Li, Caifeng

AU - Micalizzi, Concetta

AU - Ruperto, Nicolino

AU - Martini, Alberto

AU - Cron, Randy Q.

AU - Ravelli, Angelo

AU - Horne, Anna Carin

AU - Abinun, Mario

AU - Aggarwal, Amita

AU - Akikusa, Jonathan

AU - Al-Mayouf, Sulaiman

AU - Alessio, Maria

AU - Anton, Jordi

AU - Apaz, Maria Teresa

AU - Astigarraga, Itziar

AU - Avcin, Tadej

AU - Ayaz, Nuray Aktay

AU - Barone, Patrizia

AU - Bica, Bianca

AU - Bolt, Isabel

AU - Corona, Fabrizia

AU - Davì, Sergio

AU - Insalaco, Antonella

AU - Lepore, Loredana

AU - Magni-Manzoni, Silvia

AU - Martini, Alberto

AU - Micalizzi, Concetta

AU - Minoia, Francesca

AU - Ravelli, Angelo

AU - Ruperto, Nicolino

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Objective To develop and validate a diagnostic score that assists in discriminating primary hemophagocytic lymphohistiocytosis (pHLH) from macrophage activation syndrome (MAS) related to systemic juvenile idiopathic arthritis. Study design The clinical, laboratory, and histopathologic features of 362 patients with MAS and 258 patients with pHLH were collected in a multinational collaborative study. Eighty percent of the population was assessed to develop the score and the remaining 20% constituted the validation sample. Variables that entered the best fitted model of logistic regression were assigned a score, based on their statistical weight. The MAS/HLH (MH) score was made up with the individual scores of selected variables. The cutoff in the MH score that discriminated pHLH from MAS best was calculated by means of receiver operating characteristic curve analysis. Score performance was examined in both developmental and validation samples. Results Six variables composed the MH score: age at onset, neutrophil count, fibrinogen, splenomegaly, platelet count, and hemoglobin. The MH score ranged from 0 to 123, and its median value was 97 (1st-3rd quartile 75-123) and 12 (1st-3rd quartile 11-34) in pHLH and MAS, respectively. The probability of a diagnosis of pHLH ranged from 99% for a score of ≥123. A cutoff value of ≥60 revealed the best performance in discriminating pHLH from MAS. Conclusion The MH score is a powerful tool that may aid practitioners to identify patients who are more likely to have pHLH and, thus, could be prioritized for functional and genetic testing.

AB - Objective To develop and validate a diagnostic score that assists in discriminating primary hemophagocytic lymphohistiocytosis (pHLH) from macrophage activation syndrome (MAS) related to systemic juvenile idiopathic arthritis. Study design The clinical, laboratory, and histopathologic features of 362 patients with MAS and 258 patients with pHLH were collected in a multinational collaborative study. Eighty percent of the population was assessed to develop the score and the remaining 20% constituted the validation sample. Variables that entered the best fitted model of logistic regression were assigned a score, based on their statistical weight. The MAS/HLH (MH) score was made up with the individual scores of selected variables. The cutoff in the MH score that discriminated pHLH from MAS best was calculated by means of receiver operating characteristic curve analysis. Score performance was examined in both developmental and validation samples. Results Six variables composed the MH score: age at onset, neutrophil count, fibrinogen, splenomegaly, platelet count, and hemoglobin. The MH score ranged from 0 to 123, and its median value was 97 (1st-3rd quartile 75-123) and 12 (1st-3rd quartile 11-34) in pHLH and MAS, respectively. The probability of a diagnosis of pHLH ranged from 99% for a score of ≥123. A cutoff value of ≥60 revealed the best performance in discriminating pHLH from MAS. Conclusion The MH score is a powerful tool that may aid practitioners to identify patients who are more likely to have pHLH and, thus, could be prioritized for functional and genetic testing.

KW - diagnostic score, hemophagocytic syndrome, macrophage activation syndrome, primary hemophagocytic lymphohistiocytosis

U2 - 10.1016/j.jpeds.2017.06.005

DO - 10.1016/j.jpeds.2017.06.005

M3 - Article

VL - 189

SP - 72-78.e3

JO - Journal of Pediatrics

JF - Journal of Pediatrics

SN - 0022-3476

ER -