SAN DIEGO — A growing body of knowledge of autoinflammatory conditions may aid clinicians in managing these diseases, according to findings presented at the 2019 Congress of Clinical Rheumatology West.
Peter A. Nigrovic, MD, director of the Center for Adults with Pediatric Rheumatic Illness at Boston Children’s Hospital, and associate professor of medicine at Harvard Medical School, offered what he called a “theoretical introduction” to these conditions.
“It has gotten very frightening in the last few years,” he said. “A few years ago, we knew of three or four diseases that were in the category of autoinflammatory conditions. Now there are close to 40.”
The fear factor is that each of these diseases has demonstrated significant complexity in terms of pathogenesis and treatment. “How are we going to have a handle on this kind of complexity?” Nigrovic said. “That is why I will focus on the big picture.”
A growing body of knowledge of autoinflammatory conditions may aid clinicians in managing these diseases, according to findings.
Nigrovic suggested that it may be easiest to think of the autoinflammatory conditions as a spectrum of diseases with some shared features, including rash, fever, symptomatic inflammation and a multisystemic presentation. Within that spectrum are diseases that occur in the inflammasomes; those that are interferon-related; those with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) activation; those with cytokine dysregulation; and those with a deficiency in adenosine deaminase 2 deficiency (ADA2).
Throughout the presentation, Nigrovic mentioned several increasingly common autoinflammatory conditions that fall into these categories. One such condition is Familial Mediterranean Fever, which recent research has shown to be based in the neutrophils.
Familial Hibernian Fever is an example of a condition that impacts innate, rather than adaptive, immunity. “Autoinflammatory diseases are diseases that arise without a specific antigen,” he said. “There is some kind of dysfunction in the inflammatory cascade.”
Neonatal onset multisystem inflammatory disease has implications in the inflammasome, whereas periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) is marked by clockwork fevers that last 3 to 6 days and occur every month. “Understanding the pathways of these diseases gives you options for treatment” Nigrovic said. “In the case of PFAPA, a single dose of steroids at the beginning of disease can abort the flare.”
With this in mind, Nigrovic offered “four easy steps” for rheumatologists to use in managing autoinflammatory conditions.
“Step one is to suspect one,” he said, noting that these patients often have unexplained fevers and persistent or recurrent inflammation, rash, arthralgia, possible vasculitis, basal ganglia calcifications or colitis.
“Step two is pattern recognition,” Nigrovic said. Each group of conditions — those that occur in the inflammasomes, those that are interferon-related or have NF-KB involvement, etc. — each have their own markers with which rheumatologists could become familiar.
The third step is to test. “We should exclude cancer and infection, first,” Nigrovic said. “Now, we have so-called periodic fever panels. You can measure some 200 genes and see what you get.”
If testing fails to provide any clear indication of the disease, Nigrovic suggested referring the patient to the NIH or other clinicians who have specific expertise in autoinflammatory conditions.
“Step four: try things,” he said. “Colchicine is good for Familial Mediterranean Fever. Anakinra can be useful for florid bacterial sepsis. JAK inhibitors may be useful in interferonopathies.” – by Rob Volansky
Nigrovic, PA. Autoinflammatory syndromes. Presented at: Congress of Clinical Rheumatology West. Sept. 25-29, 2019; San Diego.
Disclosure: Nigrovic reports consulting for Novartis, Pfizer, Quench Bio, Simcere and Sobi; receiving research grants from Genentech, Novartis, Pfizer, and Sobi; receiving royalties from UptoDate; and salary support from the Childhood Arthritis & Rheumatology Research Alliance.