1. Adult Still’s Disease Grant Paulsen AM Report May 22, 2009

2. What is it? Inflammatory disease with symptoms of Daily fevers Arthritis Rash (evanescent) Still’s Disease first described in 1896; now called systemic onset juvenile inflammatory arthritis Formerly know as JRA (juvenile rheumatoid arthritis) ‘Adult’ Still’s describes adult patients with similar features to the childhood disease, but don’t meet RA criteria for adult RA.

3. Basics Etiology Basically no one knows. Possibly due to viral or bacterial trigger. No confirmed genetic link, familial cases are rare. Epidemiology Approx 0.16 cases per 100,000 Equal male:female ratio Bimodal peaks of incidence Age 15-25 & age 36-46

4. Diagnostic Criteria In the past there have been up to 7 (yep, seven) sets of diagnostic criteria. Yamaguchi Criteria (need 5, with at least 2 major) Major Fever - at least 39.0 for at least 1 week Arthralgias/Arthritis - 2 weeks, or more Rash – salmon-colored, nonpruritic or maculopap, often during febrile episodes. Minor Sore Throat LAD Hepatomegaly or Splenomegaly Abnormal LFT’s – Commonly, elevated AST, ALT, LDH Negative ANA, and RF

5. Details Fever Daily, often with dramatic temp swings Rash Often involves trunk and extremities, but can go to face, palms, soles Koebner Phenomenon – Rash after stroking the skin Frequently mis-diagnosed as drug rash Path – Perivascular inflammation (non-specific) Arthralgia/Arthritis Often start as mild monoarticular to oligoarticular Progress to severe, destructive polyarthritis over months  May lead to fusion of wrist joints Most frequent joints – knees, wrists, ankles, elbows, PIP, shoulders Pharyngitis Severe, non-suppurative

6. Clinical Presentation cont’d Liver Disease Elevated AST, ALT LAD & Splenomegaly Often cervical, and often takes people down the lymphoma path Cardiopulmonary Pericarditis Pleural effusions Pulmonary infiltrates – transient, non-infectious. Severe ILD – rare, but has been reported Heme Reactive Hemophagocytic Syndrome (Macrophage activation) DIC MAHA – including TTP/HUS Alopecia

7. Lab Abnormalities Lots of ‘characteristic’ abnormalities, but none are truly specific Elevated CRP, ESR Leukocytosis – often >15,000 Anemia – normochromic, normocytic Thrombocytosis – reactive Elevated AST, ALT – mild all the way to fulminant necrosis Elevated Ferritin – often >3000, which is rare in the other Rheum diseases Bone Marrow – hyperplasia of granulocyte precursors, hypercellularity, histiocytosis, hemophagocytosis

8. Radiographic X-Rays Wrist films – narrowing of carpo-metacarpal and intercarpal joint spaces, leading to ankylosis Late finding

9. Stop. Too many details What to remember Think about Still’s after you’ve chased the common sites of infection/fever Start thinking about it when you see Daily fevers associated with rash/joint pain High CRP, ESR; but negative ANA, RF Very high ferritin levels Sore Throat – non-exudative

10. Course Monophasic Lasts <1 year and resolves completely Intermittent Have flares with complete remission between episodes Flares are often less severe Chronic Persistently active, often going to destructive arthritis May ultimately need total joint arthroplasty

11. Treatment NSAIDs first Use standing doses (Ibuprofen 800 QID) Monitor for reactive hemophagocytic syndrome Steroids next If present with debilitating symptoms, internal organ involvement, persistent high fever, start with steroids. Pred 0.5-1.0mg/kg/day Methylpred pulse if severe/life-threatening symptoms Biologics (newer, but not yet standard of care) TNF-alpha inhibitors – infliximab, etanercept, adlimumab Rituximab – Often used after TNF  ’s fail Anakinra (IL-1 antagonist) – currently last line, due to insufficient data

12. Treatment DMARDs Methotrexate Cyclosporine Hydroxychloroquine Cyclophosphamide Azathioprine IVIG

13. References www.utdol.com. Arlet JB. Huong DL. Et al. Reactive haemophagocytic syndrome in adult-onset Still’s disease: a report of six patients and a review of the literature. Ann Rheum Dis 2006;65;1956-1601. Mert A. Ozaras R. et al. Fever of unknown origin: a review of 20 patients with Adult-onset Still’s disease. Clin Rheumatol 2003;22:89-93. Zeng T. Zou YQ. et al. Clinical features and prognosis of Adult-onset Still’s disease: 61 cases from China. J Rheum 2009;36:1-6.