EULAR/PReS Still's Disease Management Recommendations Save

This joint task force has reviewed the literature and established four overarching principles, and 14 specific recommendations for the management of sJIA and AOSD. Notably this task force has stated that these are one disease, to be designated by one name, Still’s disease. The primary targets of treatment are clinically inactive disease (CID) and remission, maintained for at least 6 months. 

These guidelines reinforce similar ACR guidelines stating the optimal strategy requires early use of interleukin (IL-1 or IL-6 inhibitors associated to short duration glucocorticoid (GC).  Moreover they stress the importance of identifying and treating macrophage activation syndrome (MAS) and severe lung disease associated with Still’s disease. 

These first consensus recommendations for the diagnosis and management of children and adults with Still’s disease.

Overarching Principles

• sJIA and AOSD are the same disease, that should be designated by the same unique name, Still’s disease (formerly called sJIA/AOSD). 
• Treatment targets and the therapeutic strategy should be based on shared decision making between the parents/patients and the treating team.    
• T2T by regularly assessing disease activity and adapting therapy accordingly is important. The ultimate goal is drug-free remission. 
• MAS should be detected promptly and treated rapidly.

Recommendations

1. To facilitate rapid diagnosis and initiate early treatment, operational definitions should be used to identify patients with Still’s disease, namely high spiking fevers, evanescent rash, etc. Fever is typically spiking with temperature ≥39°C (102.2°F) for at least 7 days
2. Marked elevation of serum IL-18 and/or S100 proteins (eg, calprotectin) strongly supports the diagnosis, and therefore should be measured if available
3. Alternative diagnoses such as malignancies, infectious diseases, other immune-mediated inflammatory diseases and monogenic autoinflammatory disorders should be carefully considered
4. CID is defined as absence of Still’s disease-related symptoms and normal ESR or CRP. Remission is defined as a period of at least 6 months with CID
5. In order to achieve the ultimate goal (drug-free remission), the following intermediate targets are recommended:

   • At day 7, resolution of fever and reduction of CRP by >50%,

   • At week 4, no fever, reduction of active (or swollen) joint count by >50%, normal CRP and physician and patient/parent global assessment less than 20 on a 0–100 VAS,

   • At month 3, CID with glucocorticoids less than 0.1 or 0.2 mg/kg/day,

   • At month 6, CID without glucocorticoids.

6. To avoid prolonged systemic GC use for achieving and maintaining the target, the use of IL-1 and IL-6 inhibitors should be prioritised due to high evidence of efficacy.

7. An IL-1 or an IL-6 inhibitor should be initiated as early as possible when the diagnosis is established.

8. Maintenance of CID for 3 to 6 months without glucocorticoids should be achieved before initiating bDMARD tapering.

9. Severe/life-threatening complications, including MAS or lung disease, may develop at any point during the disease course. Patients should be actively screened and monitored.

10. MAS should be considered in patients with persistent fever, splenomegaly, elevated or rising serum ferritin, inappropriately low cell counts, abnormal LFT, intravascular activation of coagulation, elevated or rising serum triglycerides

11. MAS treatment must include high dose glucocorticoids. In addition, treatments including anakinra, ciclosporin and/or IFNγ inhibitors should be considered as part of initial therapy.

12. Lung disease should be actively screened by search for clinical symptoms (eg, clubbing, persistent cough, shortness of breath) and pulmonary function tests (pulse oximetry, DLCO measurement), and investigated by high resolution CT scan in any patients with clinical symptoms.

13. Based on the available data, the presence of risk factors for Still’s lung disease or the development of Still’s lung disease should not be considered as a contraindication to IL-1 or IL-6 inhibitors

14. Difficult-to-treat patients, those with severe MAS and those with lung disease should be managed in collaboration with Still’s disease expert centres.