Begin – are you treating “systemic” or “articular” (arthritis) Still’s disease? Most Still’s patients have a dominance of one or the other. With certainty, the right therapy for the right symptoms can be chosen.

1. Systemic disease: key symptoms/findings include high daily fevers (>102oF), rashes, pleuritis or pericarditis, enlarged liver/spleen/lymph nodes, wt. loss
   • Labs: active disease is indicated by very high ESR, CRP, WBC, ferritin levels, aldolase, increased LFTs; with anemia (low Hgb/Hct), low albumin
2. Articular disease: key symptoms are multiple painful, swollen joints (usually hands, wrists, knees, ankles, feet, shoulders), often with fatigue & stiffness
   • Labs: active disease usually has normal WBC, mild anemia, increased ESR or CRP, negative tests for ANA & RF. (Normal: ferritin, albumin, LFTs)

Sequential Drug Use – The goal is to rapidly control of pain and inflammation – this is starts with using “1st Line Therapy”.

• 1st Line Therapy: start with drugs that act quickly (hours, days). The potential down side of fast-acting drugs may be long-term side effects; this is the case with NSAIDs and steroids; see Best Drugs Table below. With time 1st line drugs are replaced by more long-lasting therapies – “2nd Line Therapy”.
• 2nd Line Therapy: these drugs are referred to as Disease Modifying Anti-Rheumatic Drugs (DMARDs). DMARDs may be oral pills or injectables and are typically a) slow-acting (weeks to months), b) given chronically (often called “steroid-sparing drugs”), and c) are  given to change the underlying disease. “Biologic” DMARDs (injectable or parenteral) are similar to your body’s proteins, and are used to specifically regulate an overactive immune system.

When Not Responding?  While most patients respond well to the treatments noted below, some patients may have an incomplete or no response, or become unresponsive to a drug that once worked well. Three key questions need to be answered when the patient is not responding (or refractory): (1) Is this the right diagnosis?  (2) Is this Systemic or Articular disease?  (3)  I there another problem (new diagnosis/complication or medication side effect developing)? Off-Label Use: When poorly responsive or refractory to standard DMARD or biologic therapy, numerous options can be considered. All of these are considered “off-label”, as these treatment options are not FDA approved for use in Still’s disease.  Nearly all treatments used in Still’s disease are “off-label” because Still’s is a very rare, for which there are few studies that might lead to FDA approved drugs. Only tocilizumab & canakinumab are FDA approved for use in children (sJIA) and only canakinumab is FDA approved for adult-onset Still’s disease (AOSD). MAS (Macrophage Activation Syndrome): MAS is a severe complication of “systemic” Still’s disease, where uncontrolled, hyper-inflammation can lead to organ damage.  MAS is associated with a 10-35% risk of death. MAS should be considered with very high fever, hypotension, altered mental status, very high levels of CRP, liver enzymes, and ferritin (often >10,000), along with a sudden drop in blood counts (leukopenia, lymphopenia, thrombocytopenia). Drugs used to treat MAS include high dose steroids, inhibitors of IL-1 or IL-6, emapalumab, cyclosporine, etoposide or JAK inhibitors.    TREATMENT OPTIONS IN STILL’S DISEASE