Pulmonology
Common reported clinical features were minimal respiratory symptoms and
clubbing 6,10. Saper et al specifically describe
clubbing as acute and erythematous 9.
In contrast to the minimal
respiratory symptoms previously reported, the majority of our patients
did have chronic cough. Clubbing was the second most common finding in
our patients. Other respiratory symptoms of sJIA-LD reported included
tachypnea and decreased exercise tolerance 14.
Similarly, other respiratory signs within our cohort included tachypnea,
crackles, retractions, failure to thrive, and respiratory failure.
6-minute walk tests and spirometry were used to quantify patients’
pulmonary function, but results were limited for several reasons. First,
only 2 patients were over 5 years old on age of presentation of sJIA-LD
diagnosis and eligible for spirometry. Second, the joint symptoms of
sJIA limited patients’ ability to complete the 6-minute walk test,
confounding the interpretation of results. Although pulmonary function
testing was limited in our patients, abnormal spirometry can be a
presenting sign of developing lung pathology in patients with juvenile
arthritis. A study completed in India demonstrated that children with
juvenile idiopathic arthritis, even without respiratory symptoms,
significantly more likely to show a restrictive pattern on spirometry15. There is an ongoing need to identify appropriate
measures of pulmonary function to evaluate and monitor patients with
sJIA-LD as these patients are typically too young to perform spirometry
and too large for infant pulmonary testing.
The most common radiographic findings in our cohort are consistent with
those previously reported, specifically peripheral opacities, septal
thickening, and ground glass opacities 6, 9. In four
patients, subsequent CT imaging was useful in monitoring response to
treatment and helped to guide management of disease. While
high-resolution computed tomography (HRCT) remains the gold standard
imaging method for evaluating sJIA-LD 16, a recent
study found that lung ultrasound findings correlated well with HRCT
findings 17. In the future, lung ultrasound may
provide a useful, lower cost, radiation free imaging modality for
monitoring sJIA-LD.
Lung biopsy has also been recommended as part of the diagnostic workup
of patients with sJIA-LD, as pathological results may inform and guide
clinical management 18. For example, pathologic
findings can be helpful in establishing a diagnosis, justifying empiric
therapy, and narrowing treatment modality in specific cases. Prior
common findings on histopathology included pulmonary alveolar
proteinosis, endogenous lipoid pneumonia, and vasculopathy6,9. Two of the three lung biopsies completed for our
patients clearly demonstrated proteinaceous material consistent with
pulmonary alveolar proteinosis, while the third had findings consistent
with pulmonary alveolar proteinosis on BAL. In addition, all 3 had
evidence of either lipoid pneumonia, cholesterol clefts, or lipid laden
macrophages.
In a few of the cases of sJIA-LD, inhaled therapies such as inhaled
corticosteroids and bronchodilators were attempted for symptomatic
relief. These were primarily in patients with evidence of bronchodilator
responsiveness either by physician assessment or parental report. In one
severe case of sJIA-LD in our cohort, anti-inflammatory oral
azithromycin was attempted prior to discussion of bone marrow
transplantation. Oral azithromycin has been used in treatment for
general childhood interstitial lung disease to suppress inflammation;
one study hypothesized that the benefits seen in treating lymphocytic
airway inflammation in patients following lung transplant could also
benefit patients with sJIA-LD, who often have lymphoplasmacytic
infiltrates on biopsy 19. Bone marrow transplant was
offered to families of two of our patients with severe refractory
sJIA-LD; one successfully completed bone marrow transplant. In that
patient, there was improvement of clinical symptoms and reversal of
mixed obstructive and restrictive lung disease with normalization of
spirometry (FEV1, FVC, FEV1/FVC) and air trapping on plethysmography
after bone marrow transplantation.