Adult Onset Still Disease

A rare systemic autoinflammatory disorder characterised by the classical triad of high spiking quotidian fever, evanescent salmon coloured rash and arthritis, occurring predominantly in young adults, with a pathophysiology driven by innate immune activation rather than the autoantibody mediated processes typical of classical connective tissue disease.

Pathophysiology

Massive activation of the innate immune system drives overproduction of proinflammatory cytokines, particularly interleukin 1, interleukin 6 and interleukin 18, producing the systemic inflammatory phenotype and, in severe cases, a cytokine storm indistinguishable clinically from macrophage activation syndrome, a recognised and life threatening complication.

The absence of specific autoantibodies places this disease within the autoinflammatory rather than classical autoimmune spectrum, and this distinction informs the choice of biologic therapy.

High spiking quotidian or double quotidian fever, typically reaching thirty nine degrees Celsius or higher once or twice daily with return to baseline between spikes, is the defining and near universal feature.

The evanescent salmon pink macular or maculopapular rash characteristically appears with the fever spikes, affecting the trunk and proximal limbs, and is often transient enough to be missed unless specifically sought during a febrile episode.

Arthralgia and arthritis affect the wrists, knees and ankles most commonly, ranging from mild transient joint pain to a chronic destructive polyarthritis in a subset of patients, with ankylosis of the carpal bones a recognised late complication in chronic disease.

Sore throat, often severe and occurring early in the illness, is a frequent and sometimes misleading feature prompting initial investigation for infective pharyngitis.

Lymphadenopathy, hepatosplenomegaly and serositis (pleuritis, pericarditis) occur in a substantial proportion, alongside myalgia that accompanies the fever spikes.

Macrophage activation syndrome, a severe complication marked by persistent high fever, cytopenias, hepatic dysfunction, coagulopathy and markedly elevated ferritin, represents a medical emergency requiring urgent recognition and aggressive treatment.

Adult onset Still disease is a diagnosis of exclusion, made clinically using established criteria (such as the Yamaguchi criteria) combining major features (fever, arthralgia, typical rash, leucocytosis with neutrophilia) and minor features (sore throat, lymphadenopathy or splenomegaly, abnormal liver function, negative antinuclear antibody and rheumatoid factor) after excluding infection, malignancy and other connective tissue disease.

Markedly elevated ferritin is characteristic and, when very high, supportive of the diagnosis, though non specific alone. A low glycosylated ferritin fraction (below twenty percent) adds specificity when available.

Inflammatory markers (erythrocyte sedimentation rate, C reactive protein) are typically very high, with leucocytosis and neutrophilia on full blood count.

Blood cultures, viral serology and other infective screening are essential to exclude sepsis and infection before attributing fever to this diagnosis, and imaging or biopsy to exclude lymphoma or other malignancy is warranted where the clinical picture is atypical or fails to respond as expected.

Antinuclear antibody and rheumatoid factor are typically negative, supporting the diagnosis and helping distinguish from classical connective tissue disease.

Monitor closely for evolving macrophage activation syndrome with serial ferritin, full blood count, liver function, fibrinogen and triglycerides, since a sudden deterioration in the clinical picture with falling blood counts and rising ferritin warrants urgent reassessment.

Nonsteroidal anti inflammatory drugs may control mild disease, though most patients require corticosteroids at moderate to high dose for initial control of significant systemic symptoms.

Interleukin 1 inhibition (anakinra) is highly effective and increasingly used as first line steroid sparing therapy given the central role of this cytokine in disease pathogenesis, with canakinumab as an alternative interleukin 1 pathway agent.

Interleukin 6 inhibition (tocilizumab) is an effective alternative, particularly for patients with a predominantly arthritic phenotype.

Methotrexate is used as a conventional steroid sparing agent, particularly for the chronic articular pattern of disease.

Macrophage activation syndrome requires urgent, aggressive treatment with high dose corticosteroids, often combined with anakinra, ciclosporin or etoposide based regimens under close specialist supervision, given the substantial associated mortality if treatment is delayed.

Long term monitoring for disease pattern evolution (systemic predominant versus chronic articular predominant, the latter carrying a worse joint outcome) guides ongoing treatment adjustment, with tapering of immunosuppression attempted once sustained remission is achieved.