Let’s Discuss Part 2: More Insights from the ACR Convergence 2025 Review Course

For treatment, Dr. Gaffo noted that the Gout Education Society’s website, gouteducation.org, has excellent resources for patients and caregivers who are dealing with this chronic disease that is clearly impacted by diet and lifestyle. For pharmacologic treatment, treat-to-target remains the most evidence-based approach, and clinicians should seek to help patients get to and maintain a serum uric acid level of <6 mg/dL. Allopurinol remains the first-line urate-lowering therapy and, in a study from O’Dell et al., allopurinol was noninferior to febuxostat in controlling flares, and similar outcomes were noted in participants with stage 3 chronic kidney disease.³ Flare prophylaxis also remains a necessary part of management when initiating urate lowering therapy, and the ACR recommends colchicine as first-line prophylaxis when starting urate-lowering therapy for gout, with continuation for three to six months to minimize flare risk.⁴

For severe cases of chronic tophaceous gout, pegloticase can be employed, and it is ideal to prescribe either methotrexate or mycophenolate mofetil along with this therapy to increase response rates and reduce the risk of infusion reactions. Based on work showing that sodium-glucose cotransporter-2 inhibitors promote uricosuria and lower serum urate concentrations, Dr. Gaffo predicted that these medications may be recommended in the future for patients with gout, particularly for those with comorbid diabetes, renal disease or cardiovascular disease.⁵

Macrophage Activation Syndrome

Dr. Schulert

The penultimate speaker, Grant Schulert, MD, PhD, associate professor of pediatrics in the Division of Rheumatology, Cincinnati Children’s Hospital Medical Center and the Department of Pediatrics, University of Cincinnati College of Medicine, Ohio, discussed macrophage activation syndrome (MAS). Dr. Schulert provided an extremely helpful discussion of the different terminology employed by rheumatologists and oncologists around this topic. MAS, hemophagocytic lymphohistiocytosis, cytokine storm and cytokine release syndrome (CRS) are overlapping but distinct hyperinflammatory syndromes, each defined by specific clinical contexts and triggers.

HLH is a life-threatening syndrome of uncontrolled immune activation, characterized by fever, cytopenias, hepatosplenomegaly, hyperferritinemia and multiorgan dysfunction. It is classified as primary (genetic, often in children) or secondary (acquired, triggered by infection, malignancy or autoimmune disease), and when HLH is associated with rheumatic disease, it is termed MAS. MAS is, therefore, a subtype of secondary HLH, most commonly seen in systemic juvenile idiopathic arthritis, adult-onset Still’s disease (AOSD) or SLE, and shares clinical features with HLH but is specifically linked to autoimmune triggers.

Cytokine storm is a broader umbrella term describing any syndrome with excessive cytokine release, systemic inflammation and organ dysfunction, including HLH, MAS and CRS. It is defined by elevated circulating cytokines, acute systemic symptoms and secondary organ dysfunction beyond a normal immune response. CRS refers specifically to cytokine storm syndromes triggered by immunotherapies, such as CAR T–cell therapy, and it presents with fever, hypotension, hypoxemia and multiorgan dysfunction; it is most often seen in the context of hematologic malignancy treatment.