Adult Still’s Disease

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 Presentationcont’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 TNFa’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.