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.

Inflammation of Unknown Origin: Evaluation and Prognosis of 57 Cases

“…The diagnoses were classified into five categories: (1) infections, (2) malignancies, (3) NIID, including connective tissue diseases, vasculitis, and granulomatous disorders, (4) miscellaneous causes, and (5) no diagnosis established. Only certain diagnoses meeting the consensual classification criteria were retained (i.e., European Alliance of Associations for Rheumatology (EULAR) criteria for active giant-cell arteritis [ 5 ], three-step criteria for microscopic polyangiitis [ 6 ], the American College of Rheumatology (ACR) criteria for Takayasu arteritis [ 7 ], ACR/EULAR classification criteria for IgG4-related disease [ 8 ], Fautrel classification criteria for adult-onset Still’s disease [ 9 ], modified Duke criteria [ 10 ], and the European Society of Cardiology [ 11 ] for infective endocarditis).…”

“…Takayasu arteritis [7], ACR/EULAR classification criteria for IgG4-related disease [8], Fautrel classification criteria for adult-onset Still's disease [9], modified Duke criteria [10], and the European Society of Cardiology [11] for infective endocarditis).…”

Adult-Onset Still’s Disease-like Syndrome following COVID-19 Vaccination: A Case Report and Review of the Literature

“…Although the etiopathogenesis of this disease is not clear, evidence has shown that various mechanisms contribute to the pathogenesis, including genetic susceptibility, triggering factors, particularly infections, cytokine storm syndrome, and activation of the innate and adaptive immune system, which leads to the release of several inflammatory cytokines, thus causing inflammation in various organ systems (Figure 1) [1,2]. Diagnosing this disease is clinically challenging, as clinical manifestations can mimic infections, autoimmune diseases, and malignancies, which must be ruled out prior to diagnosis [3,4]. During the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or coronavirus disease 2019 (COVID-19), people worldwide have been encouraged to perform social distancing, take precautions against infection, and receive COVID-19 vaccinations to prevent severe disease from infection.…”

“…Although the etiopathogenesis of this disease is not clear, evidence has shown that various mechanisms contribute to the pathogenesis, including genetic susceptibility, triggering factors, particularly infections, cytokine storm syndrome, and activation of the innate and adaptive immune system, which leads to the release of several inflammatory cytokines, thus causing inflammation in various organ systems ( Figure 1 ) [ 1 , 2 ]. Diagnosing this disease is clinically challenging, as clinical manifestations can mimic infections, autoimmune diseases, and malignancies, which must be ruled out prior to diagnosis [ 3 , 4 ].…”

Autoinflammation It Is!

“…The field of auto-inflammation has further extended to more complex polygenetic disorders. In this context, two diseases, namely adult-onset Still’s disease [ 3 ] and gouty arthritis [ 4 ], are focused on in this Special Issue. Both contributions show that in these clinically and mechanistically diverse diseases, the main symptoms are caused by a very similar cytokine signature referring to interleukin 1 as the main driver.…”