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.