From the Guidelines
Adult-onset Still's disease is a rare inflammatory disorder characterized by high fevers, joint pain, and a distinctive salmon-colored rash, typically affecting adults between 16-35 years old, though it can occur at any age, with diagnosis and management now unified across all ages as "Still's disease". The condition is marked by systemic inflammation with elevated inflammatory markers, high ferritin levels, and neutrophilic leukocytosis 1. Patients often experience daily spiking fevers, typically exceeding 39°C (102.2°F), along with severe joint pain that may progress to arthritis. The characteristic evanescent rash appears during fever spikes, primarily on the trunk and extremities. Other symptoms include:
- Sore throat
- Lymphadenopathy
- Hepatosplenomegaly
- Occasionally serious complications like pericarditis or pleuritis The disease follows either a monocyclic pattern (single episode), polycyclic pattern (recurrent flares with remissions), or chronic pattern (persistent symptoms). Treatment should prioritize the use of IL-1 or IL-6 inhibitors as early as possible, due to their high efficacy in controlling the disease and limiting exposure to glucocorticoids (GCs), with anakinra appearing to have a reassuring safety profile 1. For mild cases, NSAIDs may be used, while corticosteroids like prednisone are considered for more severe symptoms, with the goal to minimize GC use and avoid dependence. Steroid-sparing agents such as methotrexate may also be added, although their efficacy in Still's disease is less clear compared to biologic agents. Diagnosis is challenging and requires excluding other conditions with similar presentations, typically made using operational definitions for fever, rash, joint involvement, and systemic inflammation, with the presence of arthritis not essential for diagnosis 1.
From the Research
Definition of Adult Still's Disease
Adult Still's disease (AOSD) is a rare systemic inflammatory disorder characterized by:
- Persistent high spiking fevers
- Evanescent rash
- Joint involvement, including arthralgia and arthritis 2, 3, 4, 5
- Multiorgan involvement may develop according to the hyper-inflammatory extent 4
Clinical Manifestations
The clinical presentation of AOSD is highly variable, accompanied by a broad spectrum of disease manifestations, including:
- Systemic manifestations, such as high spiking fever and evanescent rash
- Articular manifestations, such as arthralgia and arthritis
- Life-threatening complications, such as macrophage activation syndrome 3, 4
Pathogenesis
The pathogenesis of AOSD is not completely recognized, but:
- Pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, and IL-18, play a fundamental role in disease onset and progression 2, 3, 4, 5
- Macrophage activation, which results in T helper 1 (Th1) cell cytokine activation, is well established 4, 5
Diagnosis
The diagnosis of AOSD is difficult due to the ambiguity in presentation and lack of serologic markers, and is often reached by exclusion while investigating a patient with fever of unknown origin 3