EULAR/PReS recommendations for the diagnosis and management of Still's disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still's disease

Abstract

Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are considered the same disease, but a common approach for diagnosis and management is still missing.

Methods: In May 2022, EULAR and PReS endorsed a proposal for a joint task force (TF) to develop recommendations for the diagnosis and management of sJIA and AOSD. The TF agreed during a first meeting to address four topics: similarity between sJIA and AOSD, diagnostic biomarkers, therapeutic targets and strategies and complications including macrophage activation syndrome (MAS). Systematic literature reviews were conducted accordingly.

Results: The TF based their recommendations on four overarching principles, highlighting notably that sJIA and AOSD are one disease, to be designated by one name, Still's disease.Fourteen specific recommendations were issued. Two therapeutic targets were defined: clinically inactive disease (CID) and remission, that is, CID maintained for at least 6 months. The optimal therapeutic strategy relies on early use of interleukin (IL-1 or IL-6 inhibitors associated to short duration glucocorticoid (GC). MAS treatment should rely on high-dose GCs, IL-1 inhibitors, ciclosporin and interferon-γ inhibitors. A specific concern rose recently with cases of severe lung disease in children with Still's disease, for which T cell directed immunosuppressant are suggested. The recommendations emphasised the key role of expert centres for difficult-to-treat patients. All overarching principles and recommendations were agreed by over 80% of the TF experts with a high level of agreement.

Conclusion: These recommendations are the first consensus for the diagnosis and management of children and adults with Still's disease.

Keywords: Still's disease, adult-onset; arthritis, juvenile; biological therapy; inflammation; macrophage activation syndrome.

Figure 1. Treatment algorithm to manage people with Still’s disease footnotes. ¹High disease activity includes: high spiking fever, wide-spread polyarthritis, high levels of pain (VAS >6–7/10), pericarditis, impending MAS (elevated LFT and/or high serum ferritin levels). ²High-dose GC is equal to or greater than 1 mg/kg/day of prednisone equivalent in adults and 2 mg/kg/day in children. Low-dose GC is equal to or lower than 0.1 mg/kg/day of prednisone equivalent in adults and 0.2 mg/kg/day in children. ³Anakinra would be the preferred choice for a patient with impending MAS. High-dose anakinra (> 4 mg/kg/day in children or 100 mg twice a day in adults) are often used in these circumstances. ⁴GC tapering should be started as soon as the first intermediate target (see RS5) is reached (no fever and decrease by 50% of active joints). ⁵Difficult-to-treat Still’s disease requires discussion in multidisciplinary round of a ERN reference centre. ⁶Experimental therapy may include JAK inhibitors, emapalumab, bispecific antibody to IL-1/IL-18. The choice among these possible therapies is driven by the features of the disease (eg, chronic relapsing MAS, severe and persistent joint involvement, lung disease) in consultation with ERN experts. ⁷Remission defined as CID maintained for 6 months or more. ⁸ Tapering of IL-1i, IL-6Ri or experimental therapy is usually based on progressive injection spacing. ⁹Patient education and counselling aims to learn to the patients the signs and symptoms that could indicate Still’s disease relapse and the ways to reach the medical team to manage it. CID, clinically inactive disease; GC, glucocorticoid, IL, interleukin; LFT, liver function test; MAS, macrophage activation syndrome.