Correlation of C-Reactive Protein With Severe Fatigue in Patients With Myasthenia Gravis

Most patients with myasthenia gravis (MG) suffer from fatigue, which can be defined as a subjective lack of energy and difficulty in initiating or sustaining voluntary activities. This is conceptually different from muscle weakness or muscle fatigability. Fatigue is one of the most reported symptoms in MG and has been hypothesized to be an innate mechanism to minimize muscle activity in order to protect muscles from (further) damage. The exact pathophysiology of fatigue remains unclear, and it is very likely a multifactorial phenomenon. The aim of this study was to provide a better understanding on the pathophysiology of fatigue in MG.

We analyzed 38 serum biomarkers including various cytokines and myokines in a cohort of 116 anti-acetylcholine receptor-positive patients with MG. A multivariate linear regression analysis for each biomarker was performed in search for a correlation with fatigue. The following preselected covariates were included in the primary analysis: sex, age, disease severity, depression and anxiety scores, nonsteroid immune suppressive medication, and cumulative prednisone dosage in the past 6 months.

Severe fatigue was present in 64% of patients. Results show a robust correlation between fatigue and C-reactive protein (CRP) in the primary analysis. This correlation persisted when additionally adjusting for BMI, strenuous physical activities, and hemoglobulin levels.

Our findings suggest that chronic low-grade inflammation, mediated by CRP, contributes to the pathogenesis of fatigue in MG. This aligns with the hypothesis that local peripheral inflammatory processes induce systemic inflammatory cascades responsible for fatigue.