Macrophage activation syndrome in juvenile systemic lupus erythematosus

A multinational multicenter study of thirty-eight patients

Alessandro Parodi, Sergio Davì, Alejandra Beatriz Pringe, Angela Pistorio, Nicolino Ruperto, Silvia Magni-Manzoni, Paivi Miettunen, Brigitte Bader-Meunier, Graciela Espada, Gary Sterba, Seza Ozen, Dowain Wright, Claudia Saad Magalhães, Raju Khubchandani, Hartmut Michels, Patricia Woo, Antonio Iglesias, Dinara Guseinova, Claudia Bracaglia, Kristen Hayward & 7 others Carine Wouters, Alexei Grom, Marina Vivarelli, Alberto Fischer, Luciana Breda, Alberto Martini, Angelo Ravelli

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Objective. To describe the clinical and laboratory features of macrophage activation syndrome as a complication of juvenile systemic lupus erythematosus (SLE). Methods. Cases of juvenile SLE - associated macrophage activation syndrome were provided by investigators belonging to 3 pediatric rheumatology networks or were found in the literature. Patients who had evidence of macrophage hemophagocytosis on bone marrow aspiration were considered to have definite macrophage activation syndrome, and those who did not have such evidence were considered to have probable macrophage activation syndrome. Clinical and laboratory findings in patients with macrophage activation syndrome were contrasted with those of 2 control groups composed of patients with active juvenile SLE without macrophage activation syndrome. The ability of each feature to discriminate macrophage activation syndrome from active disease was evaluated by calculating sensitivity, specificity, and area under the receiver operating characteristic curve. Results. The study included 38 patients (20 with definite macrophage activation syndrome and 18 with probable macrophage activation syndrome). Patients with definite and probable macrophage activation syndrome were comparable with regard to all clinical and laboratory features of the syndrome, except for a greater frequency of lymphadenopathy, leukopenia, and thrombocytopenia in patients with definite macrophage activation syndrome. Overall, clinical features had better specificity than sensitivity, except for fever, which was highly sensitive but had low specificity. Among laboratory features, the best sensitivity and specificity was achieved using hyperferritinemia, followed by increased levels of lactate dehydrogenase, hypertriglyceridemia, and hypofibrinogenemia. Based on the results of statistical analysis, preliminary diagnostic guidelines for macrophage activation syndrome in juvenile SLE were developed. Conclusion. Our findings indicate that the occurrence of unexplained fever and cytopenia, when associated with hyperferritinemia, in a patient with juvenile SLE should raise the suspicion of macrophage activation syndrome. We propose preliminary guidelines for this syndrome in juvenile SLE to facilitate timely diagnosis and correct classification of patients.

Original languageEnglish
Pages (from-to)3388-3399
Number of pages12
JournalArthritis and Rheumatism
Volume60
Issue number11
DOIs
Publication statusPublished - Nov 2009

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Macrophage Activation Syndrome
Systemic Lupus Erythematosus
Multicenter Studies
Sensitivity and Specificity
Fever
Guidelines
Hypertriglyceridemia
Leukopenia
Rheumatology

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Macrophage activation syndrome in juvenile systemic lupus erythematosus : A multinational multicenter study of thirty-eight patients. / Parodi, Alessandro; Davì, Sergio; Pringe, Alejandra Beatriz; Pistorio, Angela; Ruperto, Nicolino; Magni-Manzoni, Silvia; Miettunen, Paivi; Bader-Meunier, Brigitte; Espada, Graciela; Sterba, Gary; Ozen, Seza; Wright, Dowain; Magalhães, Claudia Saad; Khubchandani, Raju; Michels, Hartmut; Woo, Patricia; Iglesias, Antonio; Guseinova, Dinara; Bracaglia, Claudia; Hayward, Kristen; Wouters, Carine; Grom, Alexei; Vivarelli, Marina; Fischer, Alberto; Breda, Luciana; Martini, Alberto; Ravelli, Angelo.

In: Arthritis and Rheumatism, Vol. 60, No. 11, 11.2009, p. 3388-3399.

Research output: Contribution to journalArticle

Parodi, A, Davì, S, Pringe, AB, Pistorio, A, Ruperto, N, Magni-Manzoni, S, Miettunen, P, Bader-Meunier, B, Espada, G, Sterba, G, Ozen, S, Wright, D, Magalhães, CS, Khubchandani, R, Michels, H, Woo, P, Iglesias, A, Guseinova, D, Bracaglia, C, Hayward, K, Wouters, C, Grom, A, Vivarelli, M, Fischer, A, Breda, L, Martini, A & Ravelli, A 2009, 'Macrophage activation syndrome in juvenile systemic lupus erythematosus: A multinational multicenter study of thirty-eight patients', Arthritis and Rheumatism, vol. 60, no. 11, pp. 3388-3399. https://doi.org/10.1002/art.24883
Parodi, Alessandro ; Davì, Sergio ; Pringe, Alejandra Beatriz ; Pistorio, Angela ; Ruperto, Nicolino ; Magni-Manzoni, Silvia ; Miettunen, Paivi ; Bader-Meunier, Brigitte ; Espada, Graciela ; Sterba, Gary ; Ozen, Seza ; Wright, Dowain ; Magalhães, Claudia Saad ; Khubchandani, Raju ; Michels, Hartmut ; Woo, Patricia ; Iglesias, Antonio ; Guseinova, Dinara ; Bracaglia, Claudia ; Hayward, Kristen ; Wouters, Carine ; Grom, Alexei ; Vivarelli, Marina ; Fischer, Alberto ; Breda, Luciana ; Martini, Alberto ; Ravelli, Angelo. / Macrophage activation syndrome in juvenile systemic lupus erythematosus : A multinational multicenter study of thirty-eight patients. In: Arthritis and Rheumatism. 2009 ; Vol. 60, No. 11. pp. 3388-3399.
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T1 - Macrophage activation syndrome in juvenile systemic lupus erythematosus

T2 - A multinational multicenter study of thirty-eight patients

AU - Parodi, Alessandro

AU - Davì, Sergio

AU - Pringe, Alejandra Beatriz

AU - Pistorio, Angela

AU - Ruperto, Nicolino

AU - Magni-Manzoni, Silvia

AU - Miettunen, Paivi

AU - Bader-Meunier, Brigitte

AU - Espada, Graciela

AU - Sterba, Gary

AU - Ozen, Seza

AU - Wright, Dowain

AU - Magalhães, Claudia Saad

AU - Khubchandani, Raju

AU - Michels, Hartmut

AU - Woo, Patricia

AU - Iglesias, Antonio

AU - Guseinova, Dinara

AU - Bracaglia, Claudia

AU - Hayward, Kristen

AU - Wouters, Carine

AU - Grom, Alexei

AU - Vivarelli, Marina

AU - Fischer, Alberto

AU - Breda, Luciana

AU - Martini, Alberto

AU - Ravelli, Angelo

PY - 2009/11

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N2 - Objective. To describe the clinical and laboratory features of macrophage activation syndrome as a complication of juvenile systemic lupus erythematosus (SLE). Methods. Cases of juvenile SLE - associated macrophage activation syndrome were provided by investigators belonging to 3 pediatric rheumatology networks or were found in the literature. Patients who had evidence of macrophage hemophagocytosis on bone marrow aspiration were considered to have definite macrophage activation syndrome, and those who did not have such evidence were considered to have probable macrophage activation syndrome. Clinical and laboratory findings in patients with macrophage activation syndrome were contrasted with those of 2 control groups composed of patients with active juvenile SLE without macrophage activation syndrome. The ability of each feature to discriminate macrophage activation syndrome from active disease was evaluated by calculating sensitivity, specificity, and area under the receiver operating characteristic curve. Results. The study included 38 patients (20 with definite macrophage activation syndrome and 18 with probable macrophage activation syndrome). Patients with definite and probable macrophage activation syndrome were comparable with regard to all clinical and laboratory features of the syndrome, except for a greater frequency of lymphadenopathy, leukopenia, and thrombocytopenia in patients with definite macrophage activation syndrome. Overall, clinical features had better specificity than sensitivity, except for fever, which was highly sensitive but had low specificity. Among laboratory features, the best sensitivity and specificity was achieved using hyperferritinemia, followed by increased levels of lactate dehydrogenase, hypertriglyceridemia, and hypofibrinogenemia. Based on the results of statistical analysis, preliminary diagnostic guidelines for macrophage activation syndrome in juvenile SLE were developed. Conclusion. Our findings indicate that the occurrence of unexplained fever and cytopenia, when associated with hyperferritinemia, in a patient with juvenile SLE should raise the suspicion of macrophage activation syndrome. We propose preliminary guidelines for this syndrome in juvenile SLE to facilitate timely diagnosis and correct classification of patients.

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