Clinical Phenotypes of Adult-Onset Still’s Disease: New Insights from Pathophysiology and Literature Findings

Abstract

Adult-onset Still’s disease (AOSD) is a non-familial, polygenic systemic autoinflammatory disorder. It is traditionally characterized by four cardinal manifestations—spiking fever, an evanescent salmon-pink maculopapular rash, arthralgia or arthritis and a white-blood-cell count (WBC) ≥ 10,000/mm3, mainly neutrophilic polymorphonuclear cells (PMNs)—but many other manifestations and complications can be associated, making clinical expression very heterogeneous and diagnosis sometimes difficult. The AOSD course can be diverse and is currently impossible to predict. Several clinical phenotypes have been described, either on the basis of the evolution of symptoms over time (monocyclic, polycyclic and chronic evolution) or according to dominant clinical evolution (systemic and arthritis subtypes). However, these patterns are mainly based on case series and not on robust epidemiological studies. Furthermore, they have mainly been established a long time ago, before the era of the biological treatments. Thus, based on our personal experience and on recent advances in the understanding of disease pathogenesis, it appears interesting to reshuffle AOSD phenotypes, emphasizing the continuum between AOSD profiles and other systemic autoinflammatory disorders, eventually proposing a research agenda.