A. Introduction

1. Systemic Onset form of Juvenile Chronic (Rheumatoid) Arthritis
   1. Severe Disease with acutely disabling symptoms
   2. ~10% of all cases of JCA are Still's Type
   3. M:F ~1:1
   4. Overall long-term prognosis is good
2. Adult Onset [1,2,3]
   1. 75% of adult patients with Still's develop disease between ages 15-35
   2. Older patients have been described
   3. Age <16 years implies Juvenile Form
   4. Adult form generally good prognosis despite pain and disability [4]
3. No specific Diagnostic Tests are available for this disease

B. Presentation

1. Major Symptom Criteria
   1. Macular erythematous (pink) rash, centripetal, may be fleeting; often with fever onset
   2. Intermittent fever >39.4° ± rigors
   3. Arthritis - usually involves multiple joints; may not be present initially
2. Other Common Symptoms and Signs
   1. Serositis - Pleurisy and/or Pericarditis ± effusion
   2. Hepatosplenomegaly
   3. Lymphadenopathy
   4. Malaise, Fatigue, Weight Loss
3. Laboratory
   1. Leukocytosis - may be quite marked (up to 20-50K/µL); may have leukemoid reactions
   2. Anemia - usually chronic disease type; autoimmune hemolysis may be present
   3. Erythrocyte Sedimentation Rate (ESR) - often > 100mm/hr
   4. Ferritin Levels >5000 during flares are not uncommon
   5. Most patients are HLA-DR5+
   6. ANA and RF are usually negative or very low titer
   7. Blood cultures must be obtained to rule out infection [3]

C. Differential Diagnosis [5]

1. Infections
   1. Bacteremia
   2. Endocarditis
   3. Mycobacteria
   4. Infections with lymphadenopathy
   5. Fungal Infections including coccidiomycosis
2. Neoplasia
   1. Leukemia
   2. Lymphoma
   3. Neuroblastoma
   4. Renal Cell Carcinoma
3. Kawasaki Disease
4. Hyper-IgD syndrome
5. Period Fever Syndrome
6. Hemophagocytic syndrome
7. Aphthous stomatitis

D. Treatment

1. Similar to that of Rheumatoid Arthritis
2. Nonsteroidal Antiinflammatory Drugs (NSAIDs) [2]
   1. May be particularly helpful for fever
   2. Some improvement with arthritis
   3. Indomethacin (Indocin®) may be particularly effective
3. Glucocorticoids
   1. Required for severe symptoms including cardiac and pulmonary
   2. Recommend prednisone 1-2mg/kg/day with taper
   3. Combination with methotrexate recommended for chronic disease maintenance
4. Other Agents
   1. Hydroxychloroqine (Plaquenil®) is the safest agent and should be used initially
   2. Methotrexate (Rheumatrex®) - resistant cases or as glucocorticoid-sparing agent [3]
   3. Azathioprine (Imuran®) can also be effective
5. Flares
   1. Assess for other causes of inflammation including infection (blood cultures)
   2. Stress-dose hydrocortisone should be given to any patients on chronic glucocorticoids
   3. Patients on chronic immunosuppressive agents should be evaluated for infections, other causes of disease flare

References

1. Ohta A, Yamaguchi M, Kaneoka H, et al. 1987. J Rheumatol. 14:1139
2. Jha AK, Collard HR, Tierney LM. 2002. NEJM. 346(23):1813 (Case Discussion)
3. Sawalha AH, Saint S, Ike RW, Bronze MS. 2005. NEJM. 353(14):1503 (Case Discussion)
4. Sampalis JS, Esdaile JM, Medsger TA Jr, et al. 1995. Am J Med. 98(4):384
5. Woo P and Wedderburn LR. 1998. Lancet. 351(9107):969