Fever is a hallmark of AOSD. Typically, the fever is quotidian, with spikes to ≥39°C (often in the afternoon or evening) followed by return to normal temperature in the absence of antipyretic medications. Shaking chills and sweating can accompany these daily temperature swings, which can be as high as 4°C. Occasionally, the fever is double quotidian (two spikes daily). In a small percentage of patients, a low-grade baseline fever persists between spikes. Untreated, the fever of AOSD is relentless, frequently lasting weeks at a time. Constitutional symptoms of profound fatigue, weight loss, and anorexia are common.
The rash of AOSD is a salmon-colored, macular or maculopapular eruption (Plate 34). Occasionally, it has an urticarial appearance. The rash usually affects the trunk and the extremities and spares the face, palms, and soles. It is evanescent, often appearing during febrile episodes and then clearing when the temperature returns to normal. The rash of AOSD usually is asymptomatic, but it may be mildly pruritic. Scratching uninvolved skin can elicit the rash (Koebner phenomenon). Biopsy of involved skin reveals a neutrophilic infiltration of the dermis and perivascular spaces; these histologic findings are not specific for AOSD and can be seen with urticaria of any cause, cellulitis, and other conditions.
A sore throat due to nonsuppurative pharyngitis is often the earliest symptom of AOSD and may precede fever, rash, and arthralgias by days to weeks.
Marked polyarthralgias are common at the onset of AOSD and usually occur without clinically detectable joint inflammation. With time, however, synovitis can develop, particularly in large joints (the hips, knees, ankles, shoulders and wrists) and less often in the small joints of the hands and feet. Articular involvement can persist after resolution of fever and leads to a chronic, destructive arthritis in approximately 20% of patients with AOSD.
Lymphadenopathy (particularly of cervical nodes) and splenomegaly are present in approximately 50% of patients at the time of initial presentation. Fine-needle aspirates and excisional biopsies of affected nodes reveal reactive hyperplasia.
Most patients have myalgias, but weakness is uncommon. Serositis leading to symptomatic pleuritis or pericarditis occurs in a sizeable minority. Hepatomegaly is less common than elevations of the serum hepatic transaminases.
No laboratory finding, or combination of test results, is diagnostic for AOSD. However, several nonspecific laboratory abnormalities are characteristic of active AOSD. Most patients (>80%) have a leukocytosis that is neutrophil-predominant and often exceeds 15,000 cells/mcL. Virtually all patients have an elevated erythrocyte sedimentation rate and an elevated level of serum C-reactive protein. A modest normochromic normocytic anemia (“anemia of chronic disease”), low serum albumin, and mild elevations of serum hepatic transaminases are common. Only a minority of patients have thrombocytosis. Typically, the serum creatinine and urinalysis are normal. Tests for antinuclear antibodies and rheumatoid factor are negative in almost all cases. Serum complement levels are normal or elevated.
Most patients with AOSD (>90%) have elevated levels of serum ferritin, and very high levels (>10,000 mcg/L) occur in approximately 30%. The proportion of serum ferritin that is glycosylated is often lower (<20%) in AOSD than in other conditions associated with elevated levels of serum ferritin, but measurements of glycosylated ferritin are not routinely available in clinical practice.