**4. Discussions**

Comparably to the literature, where ME/CFS is said to be more commonly seen in women than men [31,32], in our study the tendency was similar (67% women, 33% men). The average age in our study was 49 years in persons diagnosed with ME/CFS (without

and with comorbidities), which is more than stated in the literature, where the average age of onset is considered to be approximately 33 years [10].

According to the literature, in many cases ME/CFS follows a period of an acute infection [33–36], emotionally stressful incidents [37,38], or physical stressors. In one study the most common insidious event was considered an infection (64%) and stressful incidents (39%) [39], whereas our patients diagnosed with ME/CFS subjectively identified emotional (24%) or physical (22%) stress and to a lesser extent chronic diseases (16%)—to be possible triggers for their symptoms.

As regards the core symptoms of ME/CFS, there has been an ongoing discussion whether the diagnostic criteria identify the most prevalent symptoms and which criteria system would be the most suitable one. In our study the most prevalent symptoms apart from fatigue in the ME/CFS group were myalgia, headache, arthralgia, difficulty concentrating and neck stiffness. However, the symptoms that might be helpful in differentiating between ME/CFS and non-ME/CFS patients were fatigue, myalgia, arthralgia and sleep disturbances, which in our study were more commonly found in ME/CFS patients. Sleep disturbances were a common finding in our study (53%), which is less than in other research, where it has been found as common as in 79% of the subjects [40] showing a positive correlation regarding sleep problems and symptoms of ME/CFS [41]. As neurological and psychiatric comorbidities were excluded in our study, the identification and treatment of sleep disturbances might sugges<sup>t</sup> a decrease in symptom severity. As it is stated in the literature [42], treatment of comorbidities might give promising results in attenuating the symptom severity. Although we did not make any follow-up of symptoms in this study, that would be a subject of interest in the future to evaluate the symptoms and investigate whether it is the most persistent symptom at follow-ups as stated in the literature [40] and whether treating these sleep disturbances could make any change in the current symptoms.

Some researchers have investigated the changes in the circadian rhythm in patients with fibromyalgia [43] and ME/CFS [44], showing that bright light during mornings has a tendency to improve function and pain sensitivity in fibromyalgia patients but has no effect in ME/CFS patients. In our study we concluded that ME/CFS patients report having fatigue as a rather steady symptom throughout the day (65%), but if there was a fluctuation in the severity during the day, then fatigue is more prevalent in the morning (16%), which corresponds to the information in other publications [45].

Our findings sugges<sup>t</sup> that there is a rather limited association of fatigue and a positive family history. In most cases our respondents could not report any similar symptoms in their first-degree relatives in contrary to the other studies, where a positive family history showed a contribution to the predisposition of ME/CFS [46–48].

Whether the duration of the disease affects the outcome is still a debate in the literature. Some state that the duration of the illness might rather increase the ability to cope with the symptoms, in that way leading to less symptom prevalence [49], although others have found that those who have had ME/CFS for a longer period of time tend to have a more severe pattern of the disease [50,51]. Still other authors present with a finding that the duration of the illness does not predict the outcome [52]. In our study we found that there is a negative correlation regarding the age and current symptoms identified by the patients in the ME/CFS group without comorbidities, indicating that more symptoms are identified by younger patients. This caused us to think that younger patients might not ye<sup>t</sup> have identified the coping mechanisms that help minimizing their symptoms. As to the effect of fatigue on work status in our study, 53% have reduced their workload or become professionally disabled, comparing to 65.1% [53] or 47% [39] in other latest studies and 40% presented in a systematic review of studies published from 1988 and 2001 [54]. In the current study those who were having the disease for 2 years or longer were more prone to change their workload and/or become professionally disabled, although follow-up surveillance would be needed to observe this tendency. Our findings regarding the effect of ME/CFS on the employment status are comparable to a study by Tiersky et al. [55], where the authors concluded that in most of the cases the patients are functionally affected

and unemployed not only at the time of the diagnosis, but also on follow-ups. In our study 82% had reduced their workload or become unemployed in both of the ME/CFS groups. The authors of this study agree to the fact presented in previous research that the symptom severity decreases over time [4,39] as patients might be able to better manage their illness. It is substantiated by the fact that there was a negative correlation between the duration of fatigue, as well as age and an increase in VAS score in the ME/CFS group without comorbidities, showing no correlation in the non-ME/CFS group.

Although no treatment is found for ME/CFS, there are various strategies the patients use to decrease the severity of the symptoms. Interestingly, patients with ME/CFS were more prone to find a solution for their symptoms comparing to the non-ME/CFS group. According to the literature, the best way to decrease the symptom severity is to treat pain and sleep problems, because they might also be leading to a more severe pattern of other symptoms [4]. As it is seen in this study, nonsteroidal anti-inflammatory drugs are one of the most used pharmacological drugs and are considered effective in 90% of users in both of the ME/CFS groups. None of the patients reported taking supplements or undergoing cognitive behavioural therapy, which might be due to the fact that patients and their caregivers might not be informed about variable strategies to manage the disease.
