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Juvenile idiopathic arthritis - from macrophage to mortality

Berthold, Elisabet LU (2022) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Studies of the immunopathogenesis in JIA has mainly focused on the adaptive immune system, while less is known of the role of the monocytes. JIA is considered a chronic disease, although only about 50% of participants in long-term follow-up studies have active disease as adults. The treatment arsenal for JIA has expanded during the last three decades, but if this has improved the long-term outcome is not known.

When a diagnosis of JIA is confirmed almost all children and parents ask the same important questions: “Why did I/my child get this disease?”, “What will happen to me now?” and “Will I ever get well?”. The overall aim of this thesis has... (More)
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Studies of the immunopathogenesis in JIA has mainly focused on the adaptive immune system, while less is known of the role of the monocytes. JIA is considered a chronic disease, although only about 50% of participants in long-term follow-up studies have active disease as adults. The treatment arsenal for JIA has expanded during the last three decades, but if this has improved the long-term outcome is not known.

When a diagnosis of JIA is confirmed almost all children and parents ask the same important questions: “Why did I/my child get this disease?”, “What will happen to me now?” and “Will I ever get well?”. The overall aim of this thesis has been to study different aspects of these questions – from the pathophysiological role of monocytes and their function in blood and the synovial environment, to incidence, outcome measures with short- and long-term perspectives, risk of depression and anxiety, and mortality.

Children with active oligoarticular JIA display monocytes of a mixed pro- and anti-inflammatory polarization pattern in the synovial environment, with reduced capacity to phagocytize, unique for this JIA subtype. This supports the hypothesis that oligoarticular JIA should not be considered as a pediatric version of adult rheumatic arthritides.
The mean annual incidence rate in Skåne (the southernmost region of Sweden) 1980 – 2010 was 9.9/100,000 children < 16 years, with significantly increasing numbers during the period. The mortality was interpreted as low, fewer patients were diagnosed with JIA-associated uveitis and the need of joint corrective surgery was decreased compared to previously published data. However, children with JIA diagnosed since the introduction of biologic immunomodulatory treatment still experienced disease activity more than 50% of the follow-up years. No increased risk for diagnosis with depression or anxiety was found in JIA patients and they were also not diagnosed at an earlier age than age- and sex-matched controls.

In conclusion, the long-term outcome of JIA has improved and the risk for depression and anxiety is not found to be increased in JIA. There are however still challenges with active disease more than half of the time in spite of state-of-the-art treatment. Follow-up in adulthood is needed to answer the question of how many JIA patients that still needs healthcare as adults. (Less)
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author
supervisor
opponent
  • Professor Rygg, Marite, Norwegian University of Science and Technology, Trondheim, Norway
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Juvenile idiopathic arthritis, Epidemiology, outcome evaluation, Monocytes, Inflammation, Depression and Anxiety
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2022:56
pages
92 pages
publisher
Lund University, Faculty of Medicine
defense location
Reumatologiska klinikens föreläsningssal, Lottasalen, Universitetssjukhuset i Lund. Join by Zoom: https://lu-se.zoom.us/j/67302589343
defense date
2022-04-29 09:00:00
ISSN
1652-8220
ISBN
978-91-8021-217-5
language
English
LU publication?
yes
id
53a3f1c1-2e56-42b2-9201-82784ebbde03
date added to LUP
2022-04-06 13:37:06
date last changed
2022-04-11 14:53:26
@phdthesis{53a3f1c1-2e56-42b2-9201-82784ebbde03,
  abstract     = {{Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Studies of the immunopathogenesis in JIA has mainly focused on the adaptive immune system, while less is known of the role of the monocytes. JIA is considered a chronic disease, although only about 50% of participants in long-term follow-up studies have active disease as adults. The treatment arsenal for JIA has expanded during the last three decades, but if this has improved the long-term outcome is not known.<br/><br/>When a diagnosis of JIA is confirmed almost all children and parents ask the same important questions: “Why did I/my child get this disease?”, “What will happen to me now?” and “Will I ever get well?”. The overall aim of this thesis has been to study different aspects of these questions – from the pathophysiological role of monocytes and their function in blood and the synovial environment, to incidence, outcome measures with short- and long-term perspectives, risk of depression and anxiety, and mortality.<br/><br/>Children with active oligoarticular JIA display monocytes of a mixed pro- and anti-inflammatory polarization pattern in the synovial environment, with reduced capacity to phagocytize, unique for this JIA subtype. This supports the hypothesis that oligoarticular JIA should not be considered as a pediatric version of adult rheumatic arthritides.<br/>The mean annual incidence rate in Skåne (the southernmost region of Sweden) 1980 – 2010 was 9.9/100,000 children &lt; 16 years, with significantly increasing numbers during the period. The mortality was interpreted as low, fewer patients were diagnosed with JIA-associated uveitis and the need of joint corrective surgery was decreased compared to previously published data. However, children with JIA diagnosed since the introduction of biologic immunomodulatory treatment still experienced disease activity more than 50% of the follow-up years. No increased risk for diagnosis with depression or anxiety was found in JIA patients and they were also not diagnosed at an earlier age than age- and sex-matched controls.<br/><br/>In conclusion, the long-term outcome of JIA has improved and the risk for depression and anxiety is not found to be increased in JIA. There are however still challenges with active disease more than half of the time in spite of state-of-the-art treatment. Follow-up in adulthood is needed to answer the question of how many JIA patients that still needs healthcare as adults.}},
  author       = {{Berthold, Elisabet}},
  isbn         = {{978-91-8021-217-5}},
  issn         = {{1652-8220}},
  keywords     = {{Juvenile idiopathic arthritis; Epidemiology; outcome evaluation; Monocytes; Inflammation; Depression and Anxiety}},
  language     = {{eng}},
  number       = {{2022:56}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Juvenile idiopathic arthritis - from macrophage to mortality}},
  url          = {{https://lup.lub.lu.se/search/files/116369789/JIA_from_macrophage_to_mortality.pdf}},
  year         = {{2022}},
}