20-06: Adult Still Disease

Still disease is a systemic form of juvenile chronic arthritis in which high spiking fevers are much more prominent, especially at the outset, than arthritis. This rare syndrome also occurs in adults. Most adults are in their 20s or 30s; onset after age 60 is rare. The fever is dramatic, often with daily spikes to 40°C, associated with sweats and chills, and then plunging to normal or several degrees below normal in the absence of antipyretics. Many patients initially complain of sore throat. An evanescent salmon-colored nonpruritic rash, chiefly on the chest and abdomen, is a characteristic feature. The rash can easily be missed since it often appears only with the fever spike. Many patients also have lymphadenopathy and pericardial effusions. Joint symptoms are mild or absent in the beginning, but a destructive arthritis, especially of the wrists, may develop months later. Anemia and leukocytosis, with white blood counts sometimes exceeding 40,000/mcL, are the rule. Serum ferritin levels are often strikingly elevated (greater than 3000 mg/mL or 6741 pmol/L). (Other conditions, including viral infections, malignancy, and multiple blood transfusions, can also cause extreme elevations in ferritin levels.) A low percentage (less than 20%) of serum ferritin that is glycosylated may be even more specific for adult Still disease. The diagnosis of adult Still disease is suggested by the quotidian fever pattern, sore throat, and the classic rash but requires exclusion of other causes of fever. About half of the patients respond to NSAIDs, and half require prednisone, sometimes in doses greater than 60 mg/day orally. Targeting IL-1 with anakinra or canakinumab or IL-6 with tocilizumab can be effective for patients with refractory disease. The course of adult Still disease can be monophasic, intermittent, or chronic. Intermittent adult Still disease must be distinguished from other causes of periodic fever syndromes, including familial Mediterranean fever, TNF receptor-1 associated periodic syndrome (TRAPs), and Schnitzler syndrome (intermittent bone pain, urticarial rash, and fever associated with a monoclonal gammopathy). Macrophage activation syndrome is a life-threatening complication of adult Still disease and manifests as fever; splenomegaly; cytopenias; hypertriglyceridemia; hypofibrinogenemia; marked elevation of serum ferritin; elevated soluble CD25; depressed natural killer cell activity; and hemophagocytosis in bone marrow, spleen, and lymph nodes.