Abstract

A case and in-depth background information will be presented on Adult onset Still's Disease (ASD). ASD is an autoinflammatory disease with an estimated prevalence of 1 – 34 cases per 1 million persons and incidence varying from 0.16 to 0.4 cases per 100.000 persons (1). The most common symptoms are the classical triad of quotidian fever, evanescent salmon colored maculopapular rash and oligo-/polyarticular arthralgia or (possible destructive) arthritis. Accompanying symptoms in ASD patients may be myalgia, a non-suppurative pharyngitis, pericarditis, lymphadenopathy and hepatosplenomegaly.

Several diagnostic criteria have been proposed for ASD but up to now the Yamaguchi and Fautrel criteria have shown the best diagnostic properties for ASD in patients (2;3). According to these criteria the presence of a variety of major and/or minor criteria is required in absence of other clinical conditions explaining the symptoms for ASD diagnosis. Therefore, ASD is a diagnosis of exclusion and has a broad differential diagnosis including infections, (hematological) malignancies, rheumatoid arthritis and other rheumatic and autoinflammatory disorders.

The clinical manifestations may be variable as in some ASD patients clinical manifestations will resolve within a year and other patients will have a more intermittent or chronic pattern of the disease. Although rare, some patients will develop severe complications including hepatic failure, posterior reversible leukoencephalopathy syndrome (PRES), aseptic meningitis or encephalitis, seizures, myocarditis, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation or thrombotic thrombocytopenic purpura-hemolytic uremic disease syndrome (TTP-HUS). The combination of pancytopenia, markedly increased ferritin levels and the presence of (one of) the abovementioned life threatening complications should raise suspicion for a rare condition called Macrophage Activation Syndrome (MAS), also called Hemophagocytic Lymphohistiocytosis (HLH) or Reactive Hemophagocytic Syndrome (RHS) which has been associated with ASD.

MAS is a condition characterized by dysregulated immune system due to lack of negative feedback of Natural Killer cells and T helper cells, leading to an excessive immune response of activated macrophages secreting enormous amounts of cytokines, ultimately causing severe tissue damage. Untreated MAS patients may develop multiorgan failure.

In the last decades several treatment options have been introduced for ASD patients. Patients with mild to moderate disease can be treated with non-steroidal antiinflamatory drugs (NSAIDs) and/or corticosteroids. In cases with persistent arthritis, disease modifying antirheumatic drugs (DMARDs) like methotrexate (MTX) can be initiated. In refractory cases biological treatment with TNF inhibitors, IL-6 inhibition (tocilizumab) or IL-1-receptor antagonists (anakinra) can be considered. Patients with severe/life threatening disease manifestations may require stronger immunosuppressive therapy, eg. methylprednisolone pulses, rituximab, cyclosporine, IVIG or canakinumab. In general prognosis is good for ASD patients, although some patients can suffer from a more severe, potentially life threatening, disease.