Dr. Ombrello noted that sJIA is phenotypically heterogeneous, genetically complex and appears to involve hyperactivation of the innate immune system. Severe complications of disease can include pericardial effusions, macrophage activation syndrome and interstitial lung disease. Although familial inheritance of the disease is not typical, the strongest genetic locus risk association is with HLA-DRB1.
Treatment of sJIA may include the use of non-steroidal anti-inflammatory drugs (NSAIDs); glucocorticoids; disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate; and biologics that—in particular—inhibit interleukin (IL) 1, such as anakinra, canakinumab and rilonacept, or IL-6, such as tocilizumab.
An intriguing question Dr. Ombrello posed was: Is there a therapeutic window of opportunity in sJIA? In 2020, Henderson et al. characterized T cells from patients with acute and chronic sJIA using flow cytometry, mass cytometry and RNA sequencing. Using these data, the researchers found evidence of an evolution of Th17 polarization in sJIA. This process, which begins in regulatory T cells and progresses to effector T cells, is consistent with a biphasic model of disease pathogenesis and indicates T cells may be a potential treatment target in sJIA.5
Dr. Ombrello noted that studies such as this one may provide clues to the best time to initiate treatment. The nature of that treatment may evolve as we better understand the pathogenesis of disease.
The Lungs
The final portion of the session was led by Grant Schulert, MD, PhD, assistant professor of pediatrics, Division of Rheumatology, Cincinnati Children’s Hospital, and focused on lung disease in sJIA. Dr. Schulert noted that most children with sJIA-associated lung disease do not have pulmonary involvement at presentation, but develop signs of disease in the first two years after diagnosis. Signs may include shortness of breath, chronic cough, concern for recurrent pneumonia and even clubbing of the fingers.
Of the 39 patients with suspected, probable or definite sJIA-associated lung disease at the Cincinnati Children’s Hospital, the majority of patients were female and 85% had a history of macrophage activation syndrome. Also, their total serum IL-18 was significantly higher than in patients with sJIA and no evidence of lung disease. Frequent radiographic findings on computed tomography (CT) chest scans included pleural, bronchial wall or peribronchovascular thickening and septal widening.6
Regarding disease management, Dr. Schulert described three core tenets of treatment:
- Controlling underlying sJIA disease activity;
- Targeting pulmonary inflammation; and
- Preventing lung infections.
To treat the underlying sJIA, it’s important to stop any ineffective biologic therapies and ensure no drug reactions occur that may include pulmonary side effects.
