Parents and physicians should be on the lookout for subtle signs of lung disease in children with systemic juvenile idiopathic arthritis, a study has found.
The study results, “Emergent high fatality lung disease in systemic juvenile arthritis,” were published in the Annals of Rheumatic Diseases.
Systemic juvenile idiopathic arthritis (sJIA) is the most severe type of juvenile arthritis (JA) and is characterized by widespread tissue inflammation that affects not only patients’ joints, but also organs and glands.
“The usual pulmonary complications of sJIA are pleuritis and pleural effusion. However, in the last decade, pediatric rheumatologists have increasingly detected cases with types of LDs [lung diseases] rarely seen in sJIA previously, [including] pulmonary arterial hypertension (64%), interstitial LD (28%) and pulmonary alveolar proteinosis (PAP) (20%),” the researchers wrote.
Researchers from Stanford University and their collaborators carried out a retrospective study to analyze the clinical features of children with sJIA who developed parenchymal lung disease (LD) to look for potential risk factors and early signs of the disorder setting in.
The multi-center retrospective study involved 61 children with sJIA and parenchymal LD, who were identified through the Childhood Arthritis and Rheumatology Research Alliance (CARRA) network and the international pediatric rheumatology listserv (administered by McMaster University, Ontario). A larger group of 471 children with sJIA without LD was used as a reference for comparison.
Medical history, clinical and demographic data were assessed in all children at sJIA onset, at LD diagnosis and at defined time points (medical visits) before and after LD diagnosis.
Sixty one children developed lung disease (parenchymal and/or pulmonary hypertension). Of these, 46 had experienced treatment with blockers of cytokine IL-1 and/or IL-6 while 15 had not had prior exposure to these newer medications.
Results showed that LD was associated with poor survival, with only 42% of the children predicted to remain alive five years after being diagnosed.
In addition, they found that LD seemed to be linked to certain unusual characteristics, including having acute clubbing (enlargement of the fingers or toes, 61%), skin rashes (56%), abdominal pain (16%), or having frequent anaphylactic (allergic) reactions to certain medications such as tocilizumab (38%).
Further analyses also showed that children who developed parenchymal LD tended to have higher blood levels of ferritin (an indicator of inflammation) and lower levels of white blood cells (approximately less than 60% of what would be expected for their age) in the 6 months prior to being diagnosed with the disease.
“Increased ferritin and lymphopenia [low white blood cell counts] before LD diagnosis suggest a possibly extended incubation phase associated with smouldering inflammation and/or delayed recognition of LD,” the researchers wrote.
Tissue analyses performed in the 36 children who developed parenchymal LD demonstrated the most frequent disorders they developed were pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), which are rare disorders caused by the accumulation of surfactants and fatty molecules in the lungs.
The team found that, compared with large cohorts of sJIA, there was an increase in cases reporting macrophage activation syndrome (MAS) — a condition caused by the over-activation of a type of immune cells called macrophages — at onset of sJIA.
However, no direct relationship was found between MAS and LD features in these children.
Investigators also found that having Down syndrome and being very young when experiencing the first symptoms of sJIA (being younger than five years of age), increased the risks of LD in children with sJIA. Exposure to certain medications (e.g., interleukin-1 and interleukin-6 inhibitors) also seemed to be associated with certain characteristics of LD.
“[I]n children with risk factors, close attention to subtle pulmonary symptoms is advised, and approaches for early detection of altered pulmonary function, guided by a pulmonary specialist, should be considered. In light of high fatality, efforts to determine LD prevalence, uncover molecular mechanism(s), and devise treatment and prevention approaches are urgently needed,” the researchers wrote.