A new study suggests that serious lung complications may be more common in patients with systemic juvenile idiopathic arthritis (sJIA) than previously believed. These complications can go undiagnosed and may be fatal. But researchers stress that they affect a very small subset of patients and, if identified early, can be addressed.

The complications include three conditions in which inflammation is suspected of playing an important role: pulmonary artery hypertension (PAH), interstitial lung disease (ILD) and alveolar proteinosis (AP). Until 2008, there were only scattered reports of these diseases in sJIA, but more frequent reports have surfaced since then. This led researchers to question whether there is link between these lung problems and the use of certain biologics – such as anakinra (Kineret) and canakinumab (Ilaris) – which became more common around the same time.

The study, which was published online recently in Arthritis Care & Research, compared a group of 25 children with one or more of these lung complications to 389 sJIA patients without lung complications to see if they differed in important ways. The children in the second group came from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry database.

“We are looking at reports from physicians about these complications in these children. And the concern is [they] tend to be increasing in the past five to 10 years,” says study author Yukiko Kimura, MD, chief of pediatric rheumatology at the Joseph M. Sanzari Children’s Hospital at Hackensack University Medical Center in New Jersey. “It is something that we need to pay more attention to and be more concerned about.”

But Dr. Kimura also cautions that the incidence of these complications remains quite rare. She says that up to 10 percent of juvenile idiopathic arthritis patients have systemic JIA, which is very different from other types of JIA and is associated with a daily fever, rash and problems outside of the joints, including in different organs.

The comparison shows the patients who developed the three pulmonary complications had more severe disease symptoms than the patients who didn’t have lung complications, including enlarged liver or spleen, rash, fever and inflammation around the heart, lungs or abdomen. Further, of those with the lung complications:

• 92 percent had these systemic symptoms when the pulmonary issues were diagnosed.
• 80 percent had macrophage activation syndrome (MAS) – a potentially fatal complication that occurs when the immune system goes into overdrive to fight infection, but then doesn’t slow down when the infection is gone.
• 68 percent of these patients died an average of nine months after being diagnosed with the pulmonary complications.

Researchers say that not enough information is known to be able to say whether the lung complications were triggered by severity of the patients’ disease or whether they may have been influenced by certain medications. But 68 percent of the patients with pulmonary complications were on a biologic medication or had discontinued one within a month of being diagnosed, and 80 percent of the complications occurred after 2004.

“I can’t say that there is a definite relationship to taking any medication, but we do know that patients with systemic JIA were being treated with biologic agents much more frequently after 2004,” Dr. Kimura says.

Dr. Kimura says it is important to stress that these medications help sJIA patients tremendously. She cautions that patients should not stop taking them because of this report.

“It is important we are aware of and look at this issue very carefully. Parents should be cautioned not to stop these medicines just because they are hearing this information and are afraid,” she says. “Stopping these medications can cause sJIA patients to become very ill, including developing something like MAS which can be rapidly fatal. So it would be a big mistake to stop taking medications, and if there are concerns, they should talk to their doctor.”

Dr. Kimura says patients and their parents can keep an eye out for signs and symptoms of these rare complications, which include shortness of breath and difficulty breathing during exercise, especially if this is associated with hard-to-control fevers and a rash, as well as enlarged lymph nodes, an enlarged liver or spleen, or MAS. These symptoms should be reported to the pediatric rheumatologist.

Dr. Kimura says though this data is concerning, this report is helpful because it puts physicians who care for children with sJIA on alert, which in turn should translate to higher detection rates than in the past.

The other important message of this study, says Dr. Kimura, is that parents need to make sure their children are enrolled in registries – such as the CARRA registry – that are attempting to collect information to look for associations like this.

“That is the only way – by collecting information on all patients, whether they take biologics or not – that we will be able to accurately answer the question of whether the incidence of these complications is higher among patients taking certain medications or whether it is because these patients have more severe disease,” Dr. Kimura says.

Deborah McCurdy, MD, a professor of pediatrics and the director of pediatric rheumatology at Mattel Children’s Hospital UCLA, agrees that the CARRA registry is proving to be very helpful in understanding and treating patients with this disease.

“We’re just learning things that we probably weren’t able to realize before because we didn’t have large enough populations to understand all the complications of our diseases,” Dr. McCurdy says.

She also says it’s important to stress to parents that though this is rare, most pediatric rheumatologists are routinely screening for shortness of breath. Still, if you are concerned, she says to mention it to your child’s doctor. Pulmonary hypertension doesn’t develop overnight; it comes on gradually. 

“This is very rare. It’s so rare it isn’t worth losing sleep over,” Dr. McCurdy says. “But if they notice that all the time the child is breathing faster or getting out of breath more than they used to or having trouble climbing stairs or has a dry cough – those are things to mention at the next visit so they can be evaluated.”