October 14, 2020
2 min read
Nigrovic P. What’s New with sJIA and Adult Stills Disease? Presented at: Congress of Clinical Rheumatology-West annual symposium; October 8-11, 2020 (virtual meeting).
Nigrovic reports associations with Genentech, Novartis and Sobi.
Advances in understanding of systemic juvenile idiopathic arthritis and adult-onset Still’s disease have elucidated the impact of biologic therapies on these conditions, according to a presenter at the 2020 Congress of Clinical Rheumatology-West.
Peter Nigrovic, MD, attending physician in the rheumatology program at Boston Children’s Hospital and associate professor of rheumatology at Harvard Medical School, ran down diagnostic criteria for sJIA and adult-onset Still’s disease, addressed the topic of potentially fatal macrophage activation syndrome (MAS) and provided an overview of therapeutic options.
The three “cardinal” features of sJIA include fever, rash and arthritis. That said, while fever is “uniform,” between 70% and 90% of patients have rash and 80% to 90% have arthritis.
Other markers can include anemia, low platelet counts and elevated C-reactive protein (CRP), ferritin and D-dimers, according to Nigrovic. “The fever spikes once or twice a day” in unambiguous cases, he said, adding that temperature can also dip below normal.
Age of onset of sJIA is commonly between 4 and 6 years, with a roughly 50-50 male-to-female incidence ratio. “It may slightly skew to the female side,” Nigrovic said.
Disease course can be monophasic, intermittent or persistent, with intermittent as the least common, followed by monophasic and persistent as the most common.
However, identifying clinical features that predict persistent disease has proven elusive to the clinical community, according to Nigrovic. “It is impossible to look at a child on the first day of making the diagnosis and know who is going to have persistent disease,” he said, noting that the natural history of sJIA is “quite problematic” for many physicians.
This is of particular concern because sJIA carries a mortality rate ranging from 2% to 8%.
“As with any disease that can appear at different ages, early disease is more severe than later disease,” he said. Severe disease is marked by MAS or serositis, which drives up mortality rates, according to Nigrovic.
Turning to adult-onset Still’s disease, Nigrovic noted that this disease looks “identical” to sJIA, at least with regard to the frequency of fever, rash and arthritis as signature features. “The course can be monophasic, intermittent or persistent,” he said.
Regarding biomarkers, interleukin (IL)-1, IL-6 and IL-18 are generally elevated in adult-onset Still’s disease. “Patients with higher levels of IL-6 have more arthritis but no MAS,” he said. “Patients with higher levels of IL-18 have more MAS but lower levels of arthritis.”
While the root cause of every MAS event remains uncertain, Nigrovic suggested that viral infection such as herpes zoster may trigger this outcome, along with certain medications. Persistent rather than spiking fever can be seen in patients who experience MAS, along with falling erythrocyte sedimentation rate (ESR), elevated D-dimers, ferritins and triglycerides. Anemia and thrombocytopenia may also be observed in these patients. “Ferritin is really the best marker that we have on a day to day basis,” he said.
This understanding of MAS pathogenesis has helped clinicians learn how to “shut down” the process, according to Nigrovic.
Blockade of both IL-1 with canakinumab (Ilaris, Novartis) and IL-6 with tocilizumab (Actemra, Genentech) have been “transformative” to the field, according to Nigrovic. “Early data shows IL-1 blockade with anakinra (Kineret, Sobi) may be effective in reducing MAS. It is really quite safe.”