Can a rheumatoid arthritis (RA) flare be associated with fever?

From the Guidelines

Yes, a rheumatoid arthritis (RA) flare can be associated with fever, although the provided evidence does not directly address RA, it discusses adult onset Still's disease (AOSD), which shares some similarities with RA in terms of symptoms like fever and arthritis. The study 1 highlights that fever is a common manifestation in AOSD, with an overall incidence of 95.7% across five large retrospective studies, suggesting that systemic symptoms like fever can be significant in autoimmune diseases.

Key Points to Consider:

• Fever in the context of autoimmune diseases like AOSD can be high-spiking, exceeding 39°C, and is often transient and quotidian or double quotidian in pattern.
• While the evidence provided focuses on AOSD, the principle that autoimmune diseases can present with fever is relevant, and fever can indeed be a symptom associated with RA flares, given the shared underlying inflammatory processes.
• Management of fever in RA flares may involve the use of acetaminophen or NSAIDs to reduce both fever and pain, but persistent or high fever, especially with other concerning symptoms, warrants medical attention.
• The pattern of arthritis in AOSD is typically symmetric, with most patients developing polyarthritis and joint pain associated with fever spikes, which can inform the understanding of similar symptoms in RA.
• It's crucial to differentiate between the symptoms of AOSD and RA, as the study notes that carpal and pericapitate abnormalities are more typical in AOSD, offering a means to clinically differentiate the two entities.

From the FDA Drug Label

General disorders and administration site conditions: Pyrexia The FDA drug label mentions pyrexia, which is a medical term for fever. Although it does not directly state that a rheumatoid arthritis (RA) flare is associated with fever, the presence of pyrexia as an adverse reaction in the postmarketing experience section suggests that fever can be associated with RA. However, it is essential to note that this information is not explicitly linked to RA flares in the provided drug label 2.

From the Research

Rheumatoid Arthritis Flare and Fever Association

• Rheumatoid arthritis (RA) flares can be associated with various symptoms, including fever, as indicated by a study published in 1998 3.
• The study suggests that fever can be an initial symptom of a rheumatic disease or a disease flare, and its pathogenesis is linked to endogenous pyrogens such as IL-1, IL-6, and Tumor necrosis factor.
• However, the association between RA flares and fever is not explicitly explored in the other studies provided, which focus on the frequency, management, and definition of RA flares 4, 5, 6, 7.
• It is worth noting that while fever is mentioned as a potential symptom of RA flares, the primary focus of the studies is on the characteristics, antecedents, and sequelae of flares, rather than their specific association with fever.

Characteristics of RA Flares

• RA flares are common and can be characterized by increases in tender/swollen joint counts, symptoms, or lower flare severity, as identified in a study published in 2019 4.
• The study also found that pain flares can occur independently of inflammatory flares, and that each type of flare is associated with increased disability.
• Another study published in 2014 found that RA flares can last for varying durations, with 30% of patients experiencing flares that last for 2 weeks or more, and 57% experiencing flares that last for less than 1 week 5.

Management and Definition of RA Flares

• The management of RA flares can involve changes in medication, nonpharmacologic strategies, or a combination of both, as reported in a study published in 2014 5.
• A more recent study published in 2024 aimed to develop and validate definitions for disease flares in RA based on the Simplified and Clinical Disease Activity Indices (SDAI, CDAI) 7.
• The study proposed definitions for absolute changes in SDAI and CDAI that can be used to identify flares, which may be useful for guiding decision making in clinical practice and designing clinical trials.