Fatigue is a vague subjective symptom that is one of the most common symptoms encountered in primary care. Fatigue can accompany many different diseases, which range from organic to psychological and can affect the quality of life.[11, 12, 21] As in Western countries, GERD is increasing in Asia and Korea.[22, 23] Theoretically, GERD can cause fatigue and daytime sleepiness via sleep disturbance due to acid regurgitation. We examined whether there is a connection between GERD and fatigue.
The study results showed that fatigue and erosive esophagitis were not correlated with the MFI-K total score or the general or physical fatigue, mental fatigue, reduced activity, or motivation subscales. Daytime sleepiness was not associated with erosive esophagitis. These findings are inconsistent with epidemiology studies that reported that people who experience nighttime heartburn have sleep disorders that alter daytime performance.[14, 24-27] One systematic review found GERD was associated with sleep disturbance, and this association appeared to be bidirectional. Although not all sleep disturbances due to acid regurgitation cause daytime sleepiness, night sleep disturbance could cause daytime sleepiness. However, the ESS score was not higher in endoscopy-proved erosive esophagitis in this study. This suggests that acid contact and regurgitation alone cannot cause daytime sleepiness and that a variety of other factors, including psychological causes, cause daytime sleepiness. Similarly, fatigue may also represent a psychophysiological symptom complex. A few studies have found relations between reflux esophagitis and fatigue, while just one study found no correlation of fatigue with active reflux esophagitis or peptic ulcer. Those authors emphasized that psychosocial stress affects reflux esophagitis and is correlated with the severity of reflux esophagitis. That earlier study used the FSS, a one-dimensional instrument of fatigue. We used the MFI-K, a more complex multidimensional measure of fatigue, to find a more detailed link between fatigue and erosive esophagitis, but found no correlation.
Fatigue and depression are highly correlated. Symptoms and prevalence of depression increase significantly in individuals with high fatigue. In particular, the association between fatigue and depression is completely independent of the overlapping symptoms. While many factors play a role in the development of depression and fatigue, both are associated with increased activation of inflammation in the immune system.[29, 30] Most of the GERD studies involving anxiety and depression focused on patient symptoms and, in almost all studies, anxiety and depression seemed to affect GERD symptoms bidirectionally.[8, 31-33] In our subgroup analysis of GERD symptoms, depression and anxiety were strongly associated with symptoms, similar to other studies. In contrast to the comparison of the groups with or without endoscopy-proven erosive esophagitis, GERD symptoms such as heartburn and regurgitation were correlated with fatigue in the MFI-K total and subscale scores. The ESS score was also much higher in the GERD symptom group. These findings indicate that the presence of symptoms is related more to fatigue and daytime sleepiness than to the endoscopic findings.
GERD can be classified into erosive (ERD), non-erosive (NERD), and asymptomatic erosive esophagitis. Asymptomatic erosive esophagitis has a reported prevalence of 20~45%.[4-6, 34] The overall prevalence of NERD and asymptomatic erosive esophagitis was 15.3% and 17.5%, respectively. Interestingly, 84.5% of those with ERD had no symptoms, probably because only typical symptoms such as heartburn or degeneration are considered GERD symptoms and most patients had relatively mild erosive esophagitis, such as LA grades A and B. In the present study, fatigue and depression were common in the NERD group. Daytime sleepiness also tended to increase in the NERD group, but the difference was not significant. These findings suggest that organic causes, visceral sensitivity, esophageal motility, and psychological factors can affect NERD, as proposed in other studies.[35, 36] Furthermore, fatigue was correlated with depression, anxiety, and daytime sleepiness regardless of the presence of erosive esophagitis. In mild erosive esophagitis, psychological factors can cause fatigue and daytime sleepiness, rather than organic factors, such as acid regurgitation.
Although some studies have reported that fatigue is not related to age, in general, fatigue is more common in adults than in children and adolescents, and it has been reported that the frequency of fatigue increases from middle-aged to old age. In this study, age was not associated with fatigue, which may be due to the relatively small number of elderly subjects. Few studies have analyzed gender and fatigue in Koreans. In some meta-analysis studies, women reported that the prevalence of chronic fatigue syndrome was approximately 1.5 to 3 times higher than that of men. This study also found that women had a higher degree of fatigue than men.[38, 39]
This study had several limitations. First, only a relatively small number of the study participants with erosive esophagitis had LA class C (n=12) or D (n=1) reflux esophagitis. Therefore, it is necessary to investigate relationships between fatigue, anxiety, and depression in patients with LA-C or LA-D reflux esophagitis. Second, few variables related to socioeconomic status, such as household income and marital status, which may affect patient fatigue, depression, and anxiety, were included. Third, it is important to confirm NERD by 24hr pH-monitoring, but in this study, the presence or absence of esophagitis was determined by endoscopic findings. Finally, diet have a significant impact on reflux symptoms, but we did not survey the diet of the subjects in this study.
Nevertheless, this study has strengths. First, it is the first study to use the MFI-K, a multidimensional scaling tool for fatigue validated by the author, to examine the relationship between GERD and fatigue. Second, all subjects underwent endoscopy by well-trained endoscopists and the findings were reviewed by expert endoscopists.