Understanding the Continuum Between sJIA and AOSD
Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD) have long been considered separate conditions, primarily distinguished by an arbitrary age cutoff of 16 years. However, growing evidence suggests these two entities may in fact represent a single disease occurring at different ages.
The data extracted from extensive systematic reviews and meta-analyses reveal a remarkable similarity in the clinical and biological manifestations, as well as the complications, between sJIA and AOSD. The pooled prevalence of key features like fever, rash, arthralgia/arthritis, and elevated inflammatory markers were nearly identical across the two conditions. The few observed differences, such as higher frequency of myalgia, sore throat, and weight loss in AOSD, can be attributed to reporting bias and differences in how these symptoms are ascertained in children versus adults.
Importantly, the systematic reviews also found no significant distinction in the prevalence of life-threatening complications like macrophage activation syndrome (MAS) between sJIA and AOSD. This further supports the notion of a continuum between the two diseases.
The strong similarities in clinical presentation, laboratory findings, and disease course provide a robust rationale for considering sJIA and AOSD as a single disease entity, to be designated by a unified name – Still’s disease. This recommendation aligns with the views of many experts who have long advocated for this change, as it would facilitate more cohesive diagnosis, management, and research across all ages.
Streamlining Diagnosis with Operational Definitions
To enable rapid diagnosis and prompt initiation of treatment, the task force proposed a set of operational definitions for the key manifestations of Still’s disease:
- Fever: Spiking temperature ≥39°C (102.2°F) for at least 7 days
- Rash: Transient, often coinciding with fever spikes, typically salmon-pink but may present as urticarial
- Musculoskeletal involvement: Arthralgia/myalgia, with arthritis not being mandatory for diagnosis
These definitions, along with the recognition that no single symptom or lab finding is entirely specific, can help clinicians identify Still’s disease even in the early stages when the full clinical picture may not yet be apparent.
While classification criteria sets like Yamaguchi have been used in both children and adults, the task force emphasizes the need for a common set of diagnostic/classification criteria encompassing the full age spectrum. This would further streamline identification and management of Still’s disease patients.
Targeting Clinical Inactivity and Remission
The ultimate goal in Still’s disease management is to achieve drug-free remission. To guide clinicians toward this outcome, the task force defined two key treatment targets:
- Clinically Inactive Disease (CID): Absence of Still’s disease-related symptoms and normal erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP).
- Remission: CID maintained for at least 6 months, irrespective of treatment status.
A stepwise “treat-to-target” approach is recommended, with intermediate targets defined at day 7, week 4, and months 3 and 6 to monitor progress and guide therapeutic adjustments. This structured management strategy aims to optimize outcomes while minimizing glucocorticoid exposure.
Prioritizing IL-1 and IL-6 Inhibitors
The advent of interleukin-1 (IL-1) and interleukin-6 (IL-6) inhibitors has dramatically improved the treatment landscape for Still’s disease. These targeted therapies have shown superior efficacy compared to conventional glucocorticoids, with the added benefit of limiting long-term steroid-related toxicities.
The task force strongly recommends the early initiation of IL-1 or IL-6 inhibitors as soon as the diagnosis of Still’s disease is established. The evidence suggests these biologic agents should be prioritized over prolonged glucocorticoid use, as they can help achieve the treatment targets more effectively and safely.
However, for patients with severe presentations or impending MAS, high-dose glucocorticoids may still be warranted initially, with the IL-1/IL-6 inhibitors introduced shortly thereafter.
Managing Macrophage Activation Syndrome (MAS)
MAS is a feared, life-threatening complication of Still’s disease that requires prompt recognition and aggressive treatment. The task force emphasizes the need for vigilant monitoring, with regular screening of key laboratory parameters like ferritin, cell counts, liver enzymes, and coagulation factors.
In addition to high-dose glucocorticoids, the treatment of MAS may also involve IL-1 inhibitors, cyclosporine, and interferon-gamma inhibitors. Newer biomarkers like interleukin-18, CXCL9, and activated T-cell populations show promise in improving the early diagnosis of MAS, which is crucial for improving outcomes.
Addressing Severe Phenotypes and Lung Disease
A small subset of Still’s disease patients may develop refractory or difficult-to-treat phenotypes, as well as the emerging complication of Still’s disease-related lung disease. For these complex cases, the task force recommends management in collaboration with expert centers that can provide specialized care and access to innovative therapies.
T-cell-directed immunosuppressants may be considered for patients with severe lung involvement, although more research is needed to establish the optimal treatment approach.
Toward Harmonized Care and Research
The EULAR/PReS recommendations represent a significant milestone in unifying the diagnosis and management of Still’s disease across pediatric and adult rheumatology. By recognizing sJIA and AOSD as a single disease continuum, these guidelines lay the groundwork for more cohesive clinical practice, collaborative research, and ultimately, improved outcomes for patients of all ages.
The proposed operational definitions, treatment targets, and prioritization of targeted therapies provide a practical framework for clinicians to deliver evidence-based, patient-centered care. Ongoing efforts to validate novel biomarkers and establish common disease activity measures will further enhance the management of this rare, complex condition.
As these recommendations are implemented across European and global rheumatology communities, we can expect to see greater alignment in diagnostic approaches, more efficient clinical trials, and ultimately, better quality of life for individuals affected by Still’s disease.
