Lab findings include:
- Neutrophilic leukocytosis;
- Elevated sedimentation rate (ESR), CRP and platelets; hypoalbuminemia; and
- Negative antinuclear antibody and rheumatoid factor tests.
Patients with AOSD are at risk for macrophage activation syndrome (MAS), which clinicians can identify via fever hepatosplenomegaly, elevated liver function test results (LFTs) and pancytopenia.
“This is a big worry here,” Dr. Cush said. “A third of patients can die with a macrophage activation syndrome.”
Clues to MAS onset include a change in cell counts to rapid cytopenia, marked LFT elevations, hyperferritinemia and a rising C-reactive protein with a dropping ESR (normally, both remain very high).
Dr. Cush said the doctors most likely to correctly identify AOSD are not necessarily rheumatologists, but pediatric rheumatologists, infectious disease specialists and rheumatologists who know the criteria. The Cush Criteria for diagnosis require 10 points, with two points each for major criteria (e.g., quotidian fever; salmon-colored rash; simultaneously high white blood cell count and ESR, or CRP; seronegativity for RF and ANA; and carpal ankylosis), plus one point each for minor criteria (e.g., onset at younger than 35 years; polyarthritis; prodromal sore throat; increased hepatic enzymes; serositis; and cervical or tarsal ankyloses).
Treatment should start with steroids with or without NSAIDs, and sometimes methotrexate. Dr. Cush also noted more and more doctors are moving quickly to using an IL-1 or IL-6 inhibitor.
“The question remains, how to use these [inhibitors]? When to use these? And which do you use?” They’re both effective, he said, but there’s a potential advantage with anakinra and IL-1 inhibitors because they work fast.
If a clinician uses anakinra, they should give it at night, because endogenous circadian IL-1 spikes late at night, he said. Give steroids at doses of at least 40–80 mg per day in divided doses. Smaller doses don’t work, he said. If they do, “it’s not AOSD you’re treating.”
Although AOSD isn’t very common, Dr. Cush said, “You need to be prepared for how you’re going to diagnose and manage this, because it still is a challenge.”
Thomas R. Collins is a freelance writer living in South Florida.
References
- Hashem H, Kumar AR, Muller I, et al. Hematopoietic stem cell transplantation rescues the hematological, immunological and vascular phenotype in DADA2. Blood. 2017 Dec 14;130(24):2682–2688.
- Standing AS, Malinova D, Hong Y, et al. Autoinflammatory period fever, immunodeficiency and thrombocytopenia (PFIT) caused by mutation in actin-regulatory gene WDR1. J Exp Med. 2017 Jan;214(1):59–71.
