Pulmonary hypertension and other potentially fatal pulmonary complications in systemic juvenile idiopathic arthritis

Yukiko Kimura, Jennifer E. Weiss, Kathryn L. Haroldson, Tzielan Lee, Marilynn Punaro, Sheila Oliveira, Egla Rabinovich, Meredith Riebschleger, Jordi Antõn, Peter R. Blier, Valeria Gerloni, Melissa M. Hazen, Elizabeth Kessler, Karen Onel, Murray H. Passo, Robert M. Rennebohm, Carol A. Wallace, Patricia Woo, Nico Wulffraat

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Abstract

Objective Systemic juvenile idiopathic arthritis (JIA) is characterized by fevers, rash, and arthritis, for which interleukin-1 (IL-1) and IL-6 inhibitors appear to be effective treatments. Pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and alveolar proteinosis (AP) have recently been reported with increased frequency in systemic JIA patients. Our aim was to characterize and compare systemic JIA patients with these complications to a larger cohort of systemic JIA patients. Methods Systemic JIA patients who developed PAH, ILD, and/or AP were identified through an electronic Listserv and their demographic, systemic JIA, and pulmonary disease characteristics as well as their medication exposure information were collected. Patients with these features were compared to a cohort of systemic JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. Results The patients (n = 25) were significantly (P < 0.05) more likely than the CARRA registry cohort (n = 389) to be female; have more systemic features; and have been exposed to an IL-1 inhibitor, tocilizumab, corticosteroids, intravenous immunoglobulin, cyclosporine, and cyclophosphamide. Twenty patients (80%) were diagnosed with pulmonary disease after 2004. Twenty patients (80%) had macrophage activation syndrome (MAS) during their disease course and 15 patients (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 had AP, and 7 had ILD. Seventeen patients (68%) were taking or recently discontinued (<1 month) a biologic agent at pulmonary symptom onset; 12 patients (48%) were taking anti-IL-1 therapy (primarily anakinra). Seventeen patients (68%) died at a mean of 10.2 months from the diagnosis of pulmonary complications. Conclusion PAH, AP, and ILD are underrecognized complications of systemic JIA that are frequently fatal. These complications may be the result of severe uncontrolled systemic disease activity and may be influenced by medication exposure.

Original languageEnglish (US)
Pages (from-to)745-752
Number of pages8
JournalArthritis Care and Research
Volume65
Issue number5
DOIs
StatePublished - May 2013

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Juvenile Arthritis
Pulmonary Hypertension
Lung
Interstitial Lung Diseases
Macrophage Activation Syndrome
Interleukin-1
Arthritis
Rheumatology
Lung Diseases
Registries
Interleukin 1 Receptor Antagonist Protein
Intravenous Immunoglobulins
Biological Factors
Exanthema
Research
Cyclophosphamide
Cyclosporine
Interleukin-6
Adrenal Cortex Hormones

ASJC Scopus subject areas

  • Rheumatology

Cite this

Kimura, Y., Weiss, J. E., Haroldson, K. L., Lee, T., Punaro, M., Oliveira, S., ... Wulffraat, N. (2013). Pulmonary hypertension and other potentially fatal pulmonary complications in systemic juvenile idiopathic arthritis. Arthritis Care and Research, 65(5), 745-752. https://doi.org/10.1002/acr.21889

Pulmonary hypertension and other potentially fatal pulmonary complications in systemic juvenile idiopathic arthritis. / Kimura, Yukiko; Weiss, Jennifer E.; Haroldson, Kathryn L.; Lee, Tzielan; Punaro, Marilynn; Oliveira, Sheila; Rabinovich, Egla; Riebschleger, Meredith; Antõn, Jordi; Blier, Peter R.; Gerloni, Valeria; Hazen, Melissa M.; Kessler, Elizabeth; Onel, Karen; Passo, Murray H.; Rennebohm, Robert M.; Wallace, Carol A.; Woo, Patricia; Wulffraat, Nico.

In: Arthritis Care and Research, Vol. 65, No. 5, 05.2013, p. 745-752.

Research output: Contribution to journalArticle

Kimura, Y, Weiss, JE, Haroldson, KL, Lee, T, Punaro, M, Oliveira, S, Rabinovich, E, Riebschleger, M, Antõn, J, Blier, PR, Gerloni, V, Hazen, MM, Kessler, E, Onel, K, Passo, MH, Rennebohm, RM, Wallace, CA, Woo, P & Wulffraat, N 2013, 'Pulmonary hypertension and other potentially fatal pulmonary complications in systemic juvenile idiopathic arthritis', Arthritis Care and Research, vol. 65, no. 5, pp. 745-752. https://doi.org/10.1002/acr.21889
Kimura, Yukiko ; Weiss, Jennifer E. ; Haroldson, Kathryn L. ; Lee, Tzielan ; Punaro, Marilynn ; Oliveira, Sheila ; Rabinovich, Egla ; Riebschleger, Meredith ; Antõn, Jordi ; Blier, Peter R. ; Gerloni, Valeria ; Hazen, Melissa M. ; Kessler, Elizabeth ; Onel, Karen ; Passo, Murray H. ; Rennebohm, Robert M. ; Wallace, Carol A. ; Woo, Patricia ; Wulffraat, Nico. / Pulmonary hypertension and other potentially fatal pulmonary complications in systemic juvenile idiopathic arthritis. In: Arthritis Care and Research. 2013 ; Vol. 65, No. 5. pp. 745-752.
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abstract = "Objective Systemic juvenile idiopathic arthritis (JIA) is characterized by fevers, rash, and arthritis, for which interleukin-1 (IL-1) and IL-6 inhibitors appear to be effective treatments. Pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and alveolar proteinosis (AP) have recently been reported with increased frequency in systemic JIA patients. Our aim was to characterize and compare systemic JIA patients with these complications to a larger cohort of systemic JIA patients. Methods Systemic JIA patients who developed PAH, ILD, and/or AP were identified through an electronic Listserv and their demographic, systemic JIA, and pulmonary disease characteristics as well as their medication exposure information were collected. Patients with these features were compared to a cohort of systemic JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. Results The patients (n = 25) were significantly (P < 0.05) more likely than the CARRA registry cohort (n = 389) to be female; have more systemic features; and have been exposed to an IL-1 inhibitor, tocilizumab, corticosteroids, intravenous immunoglobulin, cyclosporine, and cyclophosphamide. Twenty patients (80{\%}) were diagnosed with pulmonary disease after 2004. Twenty patients (80{\%}) had macrophage activation syndrome (MAS) during their disease course and 15 patients (60{\%}) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 had AP, and 7 had ILD. Seventeen patients (68{\%}) were taking or recently discontinued (<1 month) a biologic agent at pulmonary symptom onset; 12 patients (48{\%}) were taking anti-IL-1 therapy (primarily anakinra). Seventeen patients (68{\%}) died at a mean of 10.2 months from the diagnosis of pulmonary complications. Conclusion PAH, AP, and ILD are underrecognized complications of systemic JIA that are frequently fatal. These complications may be the result of severe uncontrolled systemic disease activity and may be influenced by medication exposure.",
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T1 - Pulmonary hypertension and other potentially fatal pulmonary complications in systemic juvenile idiopathic arthritis

AU - Kimura, Yukiko

AU - Weiss, Jennifer E.

AU - Haroldson, Kathryn L.

AU - Lee, Tzielan

AU - Punaro, Marilynn

AU - Oliveira, Sheila

AU - Rabinovich, Egla

AU - Riebschleger, Meredith

AU - Antõn, Jordi

AU - Blier, Peter R.

AU - Gerloni, Valeria

AU - Hazen, Melissa M.

AU - Kessler, Elizabeth

AU - Onel, Karen

AU - Passo, Murray H.

AU - Rennebohm, Robert M.

AU - Wallace, Carol A.

AU - Woo, Patricia

AU - Wulffraat, Nico

PY - 2013/5

Y1 - 2013/5

N2 - Objective Systemic juvenile idiopathic arthritis (JIA) is characterized by fevers, rash, and arthritis, for which interleukin-1 (IL-1) and IL-6 inhibitors appear to be effective treatments. Pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and alveolar proteinosis (AP) have recently been reported with increased frequency in systemic JIA patients. Our aim was to characterize and compare systemic JIA patients with these complications to a larger cohort of systemic JIA patients. Methods Systemic JIA patients who developed PAH, ILD, and/or AP were identified through an electronic Listserv and their demographic, systemic JIA, and pulmonary disease characteristics as well as their medication exposure information were collected. Patients with these features were compared to a cohort of systemic JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. Results The patients (n = 25) were significantly (P < 0.05) more likely than the CARRA registry cohort (n = 389) to be female; have more systemic features; and have been exposed to an IL-1 inhibitor, tocilizumab, corticosteroids, intravenous immunoglobulin, cyclosporine, and cyclophosphamide. Twenty patients (80%) were diagnosed with pulmonary disease after 2004. Twenty patients (80%) had macrophage activation syndrome (MAS) during their disease course and 15 patients (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 had AP, and 7 had ILD. Seventeen patients (68%) were taking or recently discontinued (<1 month) a biologic agent at pulmonary symptom onset; 12 patients (48%) were taking anti-IL-1 therapy (primarily anakinra). Seventeen patients (68%) died at a mean of 10.2 months from the diagnosis of pulmonary complications. Conclusion PAH, AP, and ILD are underrecognized complications of systemic JIA that are frequently fatal. These complications may be the result of severe uncontrolled systemic disease activity and may be influenced by medication exposure.

AB - Objective Systemic juvenile idiopathic arthritis (JIA) is characterized by fevers, rash, and arthritis, for which interleukin-1 (IL-1) and IL-6 inhibitors appear to be effective treatments. Pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and alveolar proteinosis (AP) have recently been reported with increased frequency in systemic JIA patients. Our aim was to characterize and compare systemic JIA patients with these complications to a larger cohort of systemic JIA patients. Methods Systemic JIA patients who developed PAH, ILD, and/or AP were identified through an electronic Listserv and their demographic, systemic JIA, and pulmonary disease characteristics as well as their medication exposure information were collected. Patients with these features were compared to a cohort of systemic JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. Results The patients (n = 25) were significantly (P < 0.05) more likely than the CARRA registry cohort (n = 389) to be female; have more systemic features; and have been exposed to an IL-1 inhibitor, tocilizumab, corticosteroids, intravenous immunoglobulin, cyclosporine, and cyclophosphamide. Twenty patients (80%) were diagnosed with pulmonary disease after 2004. Twenty patients (80%) had macrophage activation syndrome (MAS) during their disease course and 15 patients (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 had AP, and 7 had ILD. Seventeen patients (68%) were taking or recently discontinued (<1 month) a biologic agent at pulmonary symptom onset; 12 patients (48%) were taking anti-IL-1 therapy (primarily anakinra). Seventeen patients (68%) died at a mean of 10.2 months from the diagnosis of pulmonary complications. Conclusion PAH, AP, and ILD are underrecognized complications of systemic JIA that are frequently fatal. These complications may be the result of severe uncontrolled systemic disease activity and may be influenced by medication exposure.

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