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Review
. 2021 Jun 15;10(12):2633.
doi: 10.3390/jcm10122633.

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

Stéphane Mitrovic  1   2   3 , Bruno Fautrel  1   2   4
Affiliations
Review

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

Stéphane Mitrovic et al. J Clin Med. .

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.

Keywords: adult-onset Still’s disease; autoinflammation; immunological disease continuum; innate immunity; neutrophil urticarial dermatosis; osteitis; phenotypes; psoriatic arthritis; spondyloarthritis; systemic-onset juvenile idiopathic arthritis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
AOSD phenotypes based on the evolution of symptoms over time.
Figure 2
Figure 2
Continuum between AOSD and other autoinflammatory disorders. Diseases of the immune system are classified according to whether the innate immune system (myeloid lineage) is mainly responsible for the disease (autoinflammation) or the adaptive immune system (lymphoid lineage, autoimmunity). A disease spectrum includes rare monogenic diseases at the polar ends of the spectrum, and polygenic diseases, involving both myeloid and lymphoid cells in pathogenesis, in the center. This diagram adds a third variable, environmental triggers, to further define the pathogenesis of these diseases. The figure does not include all immunological recognized diseases, because of their large number, but focuses on the continuum between AOSD and other polygenic autoinflammatory disorders (please note the overlap among certain conditions). It is adapted from [45,46,47]. AOSD and SJIA are currently considered to be the same disease occurring at different moments of life. ALPS, autoimmune lymphoproliferative syndrome; AOSD, adult-onset Still’s disease; APECED, autoimmune polyendocrinopathy—candidiasis—ectodermal—dystrophy syndrome; AS, ankylosing spondylitis; CAPS, cryopyrin-associated periodic syndrome; DAMPS, danger-associated molecular patterns; FMF, familial Mediterranean fever; HIDS, hyperimmunoglobulinaemia D with periodic fever syndrome; IPEX, immune dysregulation polyendocrinopathy enteropathy X-linked syndrome; NUD, neutrophilic urticarial dermatosis; PAMPS, pathogen-associated molecular patterns; PAPA, pyogenic arthritis-pyoderma gangrenosum-acne syndrome; PG, pyoderma gangrenosum; PsA, psoriatic arthritis; RA, rheumatoid arthritis; SAPHO, synovitis acnea pustulosis hyperostosis osteitis syndrome; SLE, systemic erythematosus lupus; SpA, spondyloarthritis (include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, seronegative arthritis associated with inflammatory bowel diseases and SAPHO syndrome); TRAPS, tumour necrosis factor receptor-associated periodic syndrome.
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