Rheumatoid arthritis (RA) is a chronic, persistent autoimmune disease that causes severe joint tissue damage and irreversible disability. Cumulative evidence suggests that patients suffering from RA for long durations are at risk of functional damage to cardiovascular, kidney, lung, and other tissues. This seriously affects the quality of work and life of patients. To date, no clear etiology of RA has been found. Recent studies have revealed that the massive proliferation of synoviocytes and immune cells requires a large amount of energy supply. Rapid energy supply depends on the anaerobic glucose metabolic pathway in both RA animal models and clinical patients. Anaerobic glycolysis can increase intracellular lactic acid (LA) content. LA induces the overexpression of monocarboxylate transporters (MCTs) in cell membranes. MCTs rapidly transport LA from the intracellular to the intercellular or articular cavity. Hence, a relatively high accumulation of LA could be formed in the intercellular and articular cavities of inflammatory joints. Moreover, LA contributes to the migration and activation of immune cells. Immune cells proliferate and secrete interleukins (IL) including IL-1, IL-2, IL-13, IL-17, and other inflammatory factors. These inflammatory factors enhance the immune inflammatory response of the body and aggravate the condition of RA patients. In this paper, the effects of LA on RA pathogenesis will be summarized from the perspective of the production, transport, and metabolism of synoviocytes and immune cells. Additionally, the drugs involved in the production, transport, and metabolism of LA are highlighted.

Objective To explore the incidence and clinical significance of fatigue in early RA (duration ≤ 1 year). Methods A total of 472 cases of early RA and 80 healthy controls matched by sex and age were recruited. The SF-36 was used to assess fatigue in early RA. Results ①The incidence of fatigue in early RA was 63.00%, 44% of the patients with early RA had severe fatigue, and 32% had fatigue as the first symptom. ②There were significant differences in sex, education level, disability, sleep factors and depression between the fatigue and nonfatigue groups of early RA. The joint tenderness, tenderness index, HAQ, VAS and PGA in the early RA fatigue group were higher than those in the nonfatigue group. The level of IL-6 and DAS28 in the early RA fatigue group were significantly higher than those in the nonfatigue group, while the ESR and CRP, RF, and anti-CCP levels were not significantly different. ③Correlation analysis showed that fatigue severity was negatively correlated with education level in early RA and was positively correlated with the level of IL-6 and the DAS28. ④Logistic analysis showed that female sex, joint tenderness, VAS, HAQ and IL-6 levels were independent risk factors for early RA with fatigue. Conclusion These results suggest that severe fatigue occurs in early RA. Early RA with fatigue have more obvious joint pain, poorer quality of life and higher disease activity. Patients who need interventions for fatigue may be diagnosed with RA early in the course of the disease.