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Review
. 2022 Mar 17:9:852220.
doi: 10.3389/fmed.2022.852220. eCollection 2022.

Insights Into the Concept of Rheumatoid Arthritis Flare

Emanuele Bozzalla-Cassione  1 , Silvia Grignaschi  1 , Blerina Xoxi  1 , Terenzj Luvaro  1 , Maria Immacolata Greco  1 , Iolanda Mazzucchelli  1 , Serena Bugatti  1 , Carlomaurizio Montecucco  1 , Antonio Manzo  1
Affiliations
Review

Insights Into the Concept of Rheumatoid Arthritis Flare

Emanuele Bozzalla-Cassione et al. Front Med (Lausanne). .

Abstract

Identification of a pathological change in the course of systemic chronic immune-inflammatory diseases is key to delivering effective treatment strategies. In this context, one of the most compelling issues is the concept of flare. The multifaceted expression of disease activity in rheumatoid arthritis (RA) makes it challenging to provide an omni-comprehensive definition of flare, encompassing the pathology's different objective and subjective domains. Our incomplete understanding of the pathophysiological mechanisms underlying this process contributes to the partial comprehension of its potential clinical expression. This review focuses on the proposed pathophysiological processes underlying disease recrudescence in RA and the variable definitions adopted to capture flare in clinical practice through its objective, subjective, and temporal domains. Overall, what emerges is a complex landscape far from being unraveled.

Keywords: clinical outcomes; composite disease activity indices; flare; pathophysiology; rheumatoid arthritis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Rheumatoid arthritis activity natural history. Rheumatoid arthritis's natural history starts with pre-arthritis, where immunological and inflammatory changes occur in the absence of overt clinical manifestations. Following this phase, the process can evolve in overt joint swelling and in the typical clinical manifestations of RA. Patients may then experience a persistent state of active disease, reach and maintain remission, or experience a flare where a stepwise process resembling onset may occur. The mechanisms supporting the homeostasis in the post-arthritis remissions phase and the biologic dynamics of flare have not been fully clarified yet. The green and red sections of the diagram represent phases characterized by the absence or the presence of joint clinical manifestations, respectively.
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