Sarcopenia in Autoimmune and Rheumatic Diseases: A Comprehensive Review

Sarcopenia refers to a decrease in skeletal muscle mass and function. Because sarcopenia affects mortality, and causes significant disability, the clinical importance of sarcopenia is emerging. At first, sarcopenia was recognized as an age-related disease but, recently, it has been reported to be prevalent also in younger patients with autoimmune diseases. Specifically, the association of sarcopenia and autoimmune diseases such as rheumatoid arthritis has been studied in detail. Although the pathogenesis of sarcopenia in autoimmune diseases has not been elucidated, chronic inflammation is believed to contribute to sarcopenia, and moreover the pathogenesis seems to be different depending on the respective underlying disease. The definition of sarcopenia differs among studies, which limits direct comparisons. Therefore, in this review, we cover various definitions of sarcopenia used in previous studies and highlight the prevalence of sarcopenia in diverse autoimmune diseases including rheumatoid arthritis, spondyloarthritis, systemic sclerosis, inflammatory bowel disease, and autoimmune diabetes. In addition, we cover the pathogenesis and treatment of sarcopenia in autoimmune and rheumatic diseases. This review provides a comprehensive understanding of sarcopenia in various autoimmune diseases and highlights the need for a consistent definition of sarcopenia.


Sarcopenia in Autoimmune and Rheumatic Diseases: A Comprehensive Review
. Study findings of rheumatoid arthritis and sarcopenia Table S2. Study findings of rheumatic diseases other than rheumatoid arthritis and sarcopenia Table S3. Study findings of inflammatory bowel disease and sarcopenia

Author
Study Findings Definition of Sarcopenia Vulnerability Dao et al. [1] Female early RA patients in Vietnam had lower appendicular LM. FFMI (Hull et al. [2]) Doğan et al. [3] Female RA patients had lower SMI and higher sarcopenia prevalence. SMI (Janssen et al. [4]) Santo et al. [5] According to meta-analysis, rheumatoid cachexia is a common comorbidity in RA whose prevalence is 15-32%. -Munro et al. [6] RA patients had lower upper arm muscle mass. -Kasher et al. [7] Female RA patients in Kazakhstan had lower MMI. -Associated factors Dao et al. [1] Disease activity, functional status, RF seropositivity was associated with abnormal body composition in female RA patients.

FFMI (Hull et al. [2])
Giles et al. [8] CRP levels, RF seropositivity, joint deformity, functional limitation was associated with abnormal body composition in RA patients. SMI (Janssen et al. [4]) Ngeuleu et al. [9] Bone erosion, normal/over fat BMI were associated to sarcopenia but disease activity and functional status were not associated in RA patients. In AiA rats, formoterol administration decreased severity of disease and skeletal muscle loss. It was associated with decreased inflammation, myostatin, the p-NF-κB(p65)/TNF pathway, IGFBP-3 and increased Akt and myogenin. -

Yamada et al. [24]
According to an animal study of AiA rats, antioxidant treatment could prevent skeletal muscle dysfunction in RA patients. -

Himori et al. [25]
According to an animal study of AiA rats, neuromuscular electrical stimulation could prevent skeletal muscle dysfunction in RA patients. -

Fenton et al. [26]
In mice models of chronic polyarthritis, GC increased muscle wasting but reduced bone loss. -Yamada et al. [27] GC use could promote sarcopenia in RA patients.

Mechanism
Roubenoff et al. [29] Loss of body cell mass, high TNF-α and IL-1 were observed and cytokine production was associated with resting energy expenditure in RA patients. - Little et al. [30] In AiA rabbits, reduction of muscle mass and diameter seem to be related with increased IL-1β, NF-κB, p38 MAPK signaling and seem to trigger anabolic compensation of increased myonuclei, Pax7, MyoD, myogenin and reduced pSTAT3, myostatin.