Still disease

**Definition and variants** - Still disease originally described systemic-onset JIA (sJIA), the subtype of JIA with prominent systemic features. It makes up about 10-15% of JIA cases. - Adult-onset Still disease (AOSD) is a closely related, rare inflammatory disorder. It is a diagnosis of exclusion, with a bimodal age distribution (about 15-25 and 35-45 years).

**Pathophysiology** - It is considered an autoinflammatory (innate immune) disorder rather than a classic autoimmune one. Autoantibodies are typically absent. - Overproduction of IL-1β, IL-6, IL-18, and TNF-α drives systemic inflammation. IL-18 and IFN-γ pathways are linked to MAS.

**Clinical features** - High quotidian (daily) spiking fevers, often over 39°C, that return to normal or below baseline between spikes. They commonly peak in the evening. - Evanescent salmon-pink, macular or maculopapular rash on the trunk and proximal limbs. It appears with fever and fades as the fever drops. It may show Koebner phenomenon. - Arthritis or arthralgia, most often in the wrists, knees, and ankles. It may be absent early in the course. - Other features: lymphadenopathy, hepatosplenomegaly, serositis (pericarditis, pleuritis), myalgias, sore throat (especially in AOSD), and weight loss.

**Laboratory findings** - Markedly elevated ESR and CRP. - Neutrophilic leukocytosis, thrombocytosis, and anemia of chronic disease. - **Very high serum ferritin** (often >1000 ng/mL). A low glycosylated ferritin fraction (<20%) supports the diagnosis in AOSD. - Elevated LFTs. - RF and ANA are typically negative.

**Diagnosis** - sJIA (ILAR): arthritis for at least 6 weeks in a child under 16, with quotidian fever for at least 2 weeks plus one of the following: evanescent erythematous rash, lymphadenopathy, hepatosplenomegaly, or serositis. - AOSD uses the Yamaguchi criteria. Major criteria are fever of at least 39°C for 1 week or longer, arthralgia for 2 weeks or longer, the typical rash, and leukocytosis of at least 10,000 with at least 80% neutrophils. Minor criteria include sore throat, lymphadenopathy or splenomegaly, abnormal LFTs, and negative RF/ANA. - Infection, malignancy (especially lymphoma), and other rheumatic disease must be excluded first.

**Complications** - **Macrophage activation syndrome (MAS)** is a secondary hemophagocytic lymphohistiocytosis and the most feared complication. Look for a sudden drop in ESR and platelets despite worsening illness, a rapidly falling or very high ferritin, cytopenias, coagulopathy (low fibrinogen), hypertriglyceridemia, and elevated LFTs. Bone marrow shows hemophagocytosis. Treat with high-dose steroids, anakinra, and cyclosporine. - Others: pericardial tamponade, destructive arthritis, growth impairment, and amyloidosis (rare).

**Treatment** - NSAIDs and glucocorticoids. - Biologics targeting IL-1 (anakinra, canakinumab) or IL-6 (tocilizumab). These are increasingly used first line in sJIA. - Methotrexate for refractory articular disease.

**High-yield buzzwords** - Quotidian fever - Salmon-colored evanescent rash - Markedly elevated ferritin - RF/ANA negative - MAS complication - Treated with anakinra, canakinumab, or tocilizumab

**Differentials to keep in mind** - Kawasaki disease: fever for 5 or more days, conjunctivitis, and coronary aneurysms. - Acute rheumatic fever: migratory arthritis and a preceding group A strep infection. - SLE. - Leukemia or lymphoma. - Infection (e.g., endocarditis, EBV).