Abstract

Frailty is a syndrome characterized by the decline in the physiologic reserve and function of several systems, leading to increased vulnerability and adverse health outcomes. While common in the elderly, recent studies have underlined the higher prevalence of frailty in chronic diseases, independent of age. The pathophysiological mechanisms that contribute to frailty have not been completely understood, although significant progresses have recently been made. In this context, chronic inflammation is likely to play a pivotal role, both directly and indirectly through other systems, such as the musculoskeletal, endocrine, and neurological systems. Rheumatic diseases are characterized by chronic inflammation and accumulation of deficits during time. Therefore, studies have recently started to explore the link between frailty and rheumatic diseases, and in this review, we report what has been described so far. Frailty is dynamic and potentially reversible with 8.3%–17.9% of older adults spontaneously improving their frailty status over time. Muscle strength is likely the most significant influencing factor which could be improved with training thus pointing at the need to maintain physical activity. Not surprisingly, frailty is more prevalent in patients affected by rheumatic diseases than in healthy controls, regardless of age and is associated with high disease activity to affect the clinical outcomes, largely due to chronic inflammation. More importantly, the treatment of the underlying condition may prevent frailty. Scales to assess frailty in patients affected by rheumatic diseases have been proposed, but larger casuistries are needed to validate disease-specific indexes, which could allow more accurate prognostic estimates than demographic and disease-related variables alone. Frail patients can be more vulnerable and more difficult to treat, due to the risk of side effects, therefore frailty should be taken into account in clinical decisions. Clinical trials addressing frailty could identify patients who are less likely to tolerate potentially toxic medications and might benefit from more conservative regimens. In conclusion, the implementation of the concept of frailty in rheumatology will allow a better understanding of the patient global health, a finest risk stratification and a more individualized management strategy.

Highlights

  • Life expectancy has markedly increased worldwide during the last decades, mainly due to medicine progresses [1]

  • Age was non-linearly correlated to frail state, and the association between frail status and unfavorable outcomes persisted after adjustment for age [140, 141, 143, 150, 158, 164]

  • Some analyses have been performed in young populations, as it was in a Rheumatoid arthritis (RA) cohort [141] and in Systemic lupus erythematosus (SLE) patients [150] and frailty was associated with high disease activity, implying a key role of inflammation

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Summary

Frailty in Rheumatic Diseases

Reviewed by: Ana-Maria Orbai, Johns Hopkins University, United States Marco Infante, University of Miami, United States. The pathophysiological mechanisms that contribute to frailty have not been completely understood, significant progresses have recently been made. In this context, chronic inflammation is likely to play a pivotal role, both directly and indirectly through other systems, such as the musculoskeletal, endocrine, and neurological systems. Studies have recently started to explore the link between frailty and rheumatic diseases, and in this review, we report what has been described so far. Frailty is more prevalent in patients affected by rheumatic diseases than in healthy controls, regardless of age and is associated with high disease activity to affect the clinical outcomes, largely due to chronic inflammation.

INTRODUCTION
FRAILTY MEASUREMENT
INFLAMMATION AND FRAILTY
TISSUE CHANGES AND FRAILTY
FRAILTY IN RHEUMATIC DISEASES
CHS CHS GFI
Rheumatoid Arthritis
Systemic Lupus Erythematosus
Systemic Sclerosis
NATURAL HISTORY AND MANAGEMENT OF FRAILTY
DISCUSSION
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