Background/Purpose:

Systemic Juvenile Idiopathic Arthritis (sJIA) is characterized by fevers, rash and arthritis, for which IL1 and IL6 inhibitors appear to be effective.  Pulmonary artery hypertension (PAH), interstitial lung disease (ILD) and alveolar proteinosis (AP) have been recently reported in sJIA patients with increased frequency and is associated with mortality. The purpose of our study was to identify and characterize these cases and compare them to a larger cohort of sJIA patients.

Methods:

A retrospective review of sJIA patients who developed PAH, ILD and/or AP solicited through an electronic listserv was performed.  Demographic, sJIA and pulmonary disease characteristics and medication exposure information were collected. These features were compared to a cohort of sJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) pediatric rheumatic diseases registry.

Results:

Patients (N=25) were significantly more likely (p<0.05) than the CARRA registry cohort (N=389) to be female and have more systemic features. They were also significantly more likely to have been exposed to the following: an IL-1 inhibitor, tocilizumab, infliximab, corticosteroids, intravenous immunoglobulin, cyclosporine and cyclophosphamide.  Eighty% were diagnosed after 2004. Twenty (80%) patients had MAS during their disease course and 16 (64%) had suspected/confirmed MAS at pulmonary diagnosis. Sixteen patients had PAH, 7 AP and 8 ILD. Dyspnea on exertion and shortness of breath were the most common symptoms. One patient was diagnosed at autopsy and did not have any known prior pulmonary symptoms.  Pulmonary disease characteristics are shown in the Table. Seventeen (68%) patients were taking or recently (<1 month) discontinued a biologic agent at pulmonary symptom onset, and 12 (48%) were taking anti-IL1 therapy (primarily anakinra). Seventeen (68%) patients died at a mean of 10.2 months from pulmonary diagnosis.

Clinical features at pulmonary disease diagnosis

Total N: 25
Age at start of pulmonary symptoms (years)*	11.7 ± 5.2 (3.5-18.8)
Disease duration at pulmonary diagnosis (months [mos])*	50.6 ± 44.6 (8-160)
Time between pulmonary symptoms to diagnosis (mos)*	3.1 ± 3.2 (0-10)
Time between pulmonary diagnosis to death (mos) (N=17)*	10.2 ± 13 (0-44)
Disease features at pulmonary disease diagnosis	N (%)
sJIA manifestations
Any systemic manifestation**	23 (92)
MAS (suspected or confirmed)	16 (64)
Pericarditis/serositis	11 (44)
Thrombotic thrombocytopenic purpura	1 (4)
Arthritis	16 (64)
Pulmonary symptoms
Shortness of breath	16 (64)
Dyspnea on exertion	18 (72)
Cough	11 (44)
Clubbing	10 (40)
Chest pain	5 (20)
Pulmonary diagnosis
Pulmonary artery hypertension	16 (64)
Alveolar proteinosis	7 (28)
Interstitial lung disease	7 (28)

* Mean ± SD (range)

**Includes patients with one or more of the following: fever, rash, lymphadenopathy, hepatomegaly, splenomegaly

Conclusion:

Despite recent advances in therapy, sJIA remains a disease with significant morbidity and mortality.  This is the first time that a large cohort of sJIA patients who developed PAH, AP and ILD has been described.  These are important, largely fatal and under-recognized complications of sJIA which are likely to be the result of severe uncontrolled systemic disease activity and inflammation, but may be influenced by exposure to certain medications.  Further prospective studies are needed to determine the factors associated with the development of these complications.  Increased awareness regarding these complications in sJIA is needed, and screening for these complications should be considered in sJIA patients with significant and persistent systemic disease activity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/potentially-fatal-pulmonary-complications-in-systemic-juvenile-idiopathic-arthritis/