PATIENTS WITH RHEUMATOID ARTHRITIS AND THE CORRELATION WITH QUALITY OF LIFE

Introduction. Rheumatoid arthritis (RA) is accompanied by numerous comorbidities, among which depression and anxiety (D/A) occupy a significant place. Objective. To assess the prevalence of D/A in RA patients and their correlation with quality of life. Methods. The study included RA patients treated at the Rheumatology Clinic of the Military Medical Academy in the period from May to November 2016. Disease activity was assessed by the Disease Activity Score 28-SE (DAS28-SE). Depression/anxiety was determined using the Hospital Anxiety and Depression Scale (HADS Questionnaire) and EuroQoL Five-Dimensional Questionnaire (EQ5D3L Questionnaire) Question 5. Three questionnaires were used to assess quality of life: the general RAND36 (The RAND 36-item Health Survey 1.0) and the specific RAQL and EQ5D3L. Results. On the basis of the HADS Questionnaire, the prevalence of depression was 52% with the average HADS score value of 7.6±3.2, while the prevalence of anxiety was 32% with the mean HADS score value of 5.8±3.8. Question 5 of the EQ5D Questionnaire showed that the prevalence of D/A was 77.4%, of which 71.7% of patients had moderate D/A, while 5.7% of patients had severe D/A. Impairment in all the domains of quality of life was found in some patients, as assessed by all the three questionnaires. The RAQL Questionnaire showed moderate quality of life impairment, with the value of 15.5±7.9. The EQ-VAS value was 58.6±16.0, while the EQ5D index was 0.6±0.3. Univariate linear regression produced a statistically significant negative predictive value of quality of life for the presence of anxiety/depression. Multivariate linear regression showed a statistically significant independent negative predictive value of quality of life, as assessed by the RAQL Questionnaire (p=0.010) and the mental quality of life component of the RAND 36 Questionnaire (p=0.030) for the degree of depression. Conclusion. In RA patients, there is significant prevalence of D/A as well as impairment of quality of life in all domains. The tests performed have shown that quality of life has a statistically significant negative predictive value for the presence of D/A. in our study using all the three questionnaires. The quality of life of our patients was reduced in all domains of the EQ5D3L questionnaire as well as all physical and mental health domains of the RAND36 questionnaire. These results are in compliance with the results of a study conducted by West and Jonsson (23), who have demonstrated an


INTRODUCTION
Rheumatoid arthritis (RA) is a chronic disease characterized by persistent synovitis and systemic inflammation leading to joint destruction, functional disability and premature mortality. The disease is accompanied by numerous comorbidities that significantly impair quality of life. According to the results of the large multicenter COMORA (COMOrbidities in Rheumatoid Arthritis) study, which determined the prevalence of comorbidities in RA, depression was most common with 15%, followed by asthma with 6.6%, cardiovascular events (myocardial infarction, CVI) with 6%, solid tumors (except for basal cell carcinoma) with 4.5%, and COPD with 3.5% (1).
Despite the prevalence and significance, mental health has been rarely investigated in rheumatology studies and clinical practice. Reports show that mental health has been studied in less than 8% of published works dealing with rheumatoid arthritis, while quality of life is studied somewhat more frequently (in 19% of studies), mostly using the SF36 Questionnaire (2).
The prevalence of depression in RA ranges between 9.5% (3) and 41.5% (4), while the prevalence of anxiety ranges from 21% to 70% (5). Follow-up studies have indicated that the cumulative risk of the occurrence of depression after 9 years of RA is 40%. (6).
Depression and anxiety in RA are associated with a higher degree of disease activity, reduced quality of life, increased use of healthcare services, as well as reduced adherence to therapy. The correlation between depression and RA is multifactorial: it may be a result of social and economic factors, functional disability and/or inflammation. There are various reasons for the large variation in the prevalence. It is very difficult to distinguish between patients with depressive disorder and those with a normal reaction to the fact that they live with a chronic, functionally limiting condition. Further, numerous symptoms of depression, such as fatigue, poor sleep and loss of appetite, can be part of the clinical picture of rheumatoid arthritis itself. In addition to the foregoing, the prevalence is also affected by different methods used for diagnosing depression. A gold standard is a psychiatric interview and diagnosis through the Diagnostic and Statistical Manual (DSM) or International Classification of Diseases (ICD) criteria. However, alternative self-report questionnaires can also be useful due to their practicality in everyday work. Previous research has indicated that the recognition and appropriate treatment of D/A improve the 6 response to treatment and considerably reduce symptoms associated with RA, improving the functional status and quality of life (7). That is why the objective of our study was to assess the prevalence of D/A in our patients and the correlation with quality of life.

METHODS
The study included RA patients who were treated at the Rheumatology  To assess the activity of RA, the Disease Activity Score 28 (DAS 28-SE) was determined for all patients based on the total number of tender and swollen joints, the patient's assessment of disease activity on the VAS scale and erythrocyte sedimentation rate (ESR) (mm/h). The assessment of the patient's functional ability was performed using the HAQ DI (Health Assessment Questionnaire), which contains a total of 20 questions scored from 0 to 3 (0 = without difficulties, 3 = I cannot do it).
The following tests were performed when it comes to inflammation markers: erythrocyte sedimentation rate by Westergreenum (SE) and C-reactive protein (CRP) using the nephelometric method. Depression and/or anxiety were diagnosed using two questionnaires: Hospital Anxiety and Depression Scale (HADS) and Question 5 of the EuroQoL five-dimensional questionnaire (EQ-5D-3L). The HADS (8) questionnaire contains 14 questions (7 for depression and 7 for anxiety). The patient assesses the degree of agreement using the Likert scale, from 0 to 3. The total score for each scale is from 0 to 21. A score exceeding 11 indicates the presence of depression/anxiety; 8-10 indicates borderline cases, and 0-7 is a normal finding. The EQ-5D-3L (9) questionnaire contains five questions regarding various dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Three questionnaires were used for the assessment of quality of life: general -the RAND 36-item Health Survey 1.0 (RAND36), specific -the Rheumatoid Arthritis Quality of Life (RAQL) and EQ5D3L. The RAND contains 36 questions scored in 8 domains (physical functioning, social functioning, limitations due to physical problems, limitations due to emotional problems, mental health, vitality, pain and general health perception).
Each subscale is ranked from 0 to 100, where a higher score indicates better quality of life.
The RAND can be converted into two composite scores: physical health composite score (PCS) and mental health composite score (MCS) (10). The RAQL contains 30 questions regarding the mental and physical domains, which are answered with yes and no (1/0). The total score is 30, and lower score indicates better quality of life (11). The EQ5D3L comprises two partsa descriptive system and a visual analog scale (VAS). The EQ-5D-

RESULTS
The study included 53 patients with rheumatoid arthritis of an average age of    Table 3.  Table 4. An analysis of the quality of life and anxiety/depression degree ratio has produced a statistically significant negative predictive value of quality of life, as assessed by the RAQL and RAND36 questionnaires with the presence of anxiety/depression.

DISCUSSION
Rheumatoid arthritis (RA) is a chronic inflammatory disease accompanied by numerous comorbidities, among which depression and anxiety occupy a significant place.
The results of our study based on the HADS questionnaire show that 52% of patients have some depression symptoms. This result is in compliance with the previous studies in which the same questionnaire was used and which showed that more than 50% of RA patients had depressive disorders (4). In other studies, the prevalence of depression in RA patients was 14-46% depending on measuring instruments (12,13). In our study, it was found using Question 5 of the EQ5D3L questionnaire that even 77.4% of patients had D/A. When it comes to anxiety, our research using the HADS questionnaire (HADS score >8) showed that 32% of patients were anxious. Using the same questionnaire and HADS score >8, Yokogawa and associates found that 29.3% of patients were anxious (18).
El-Miedany and El-Rasheed found that the prevalence of anxiety in RA was 70% (19), A large number of previous studies have demonstrated that a particular level of functional limitation determined using the HAQ is a strong predictor of depression in RA patients (22). Our study has not demonstrated a correlation between functional limitation and the degree of depression and/or anxiety as the average HAQ score value in our patients was 0.77±0.77, which is significantly lower than the average HAQ score in patients for whom a correlation with D/A has been found.
It is known that the quality of life of RA patients is considerably reduced, which we also obtained in our study using all the three questionnaires.  (26), high disease activity (27), and reduced quality of life. Our study has demonstrated a significant correlation between quality of life and the degree of depression and/or anxiety. Multivariate regression analysis has shown that the quality of life assessed using the RAQL questionnaire as well as the MCS score of the RAND 36 questionnaire is an independent predictor of the degree of depression. This is also in compliance with the studies of Covic and associates (28), who have discovered that physical limitations affect the patient's emotional condition, primarily depression. Numerous cross-sectional and longitudinal studies have demonstrated significant association of somatic symptoms with the occurrence of depression/anxiety. (29,30).

CONCLUSION
In RA patients, there is a high prevalence of depression/anxiety as well as considerable impairment of quality of life. The degree of quality of life impairment is an independent negative predictor for the degree of depression. The correlation between psychological disorders and somatic symptoms is actually bidirectional, indicating the need for discovering and treating psychological disorders simultaneously with somatic symptoms. Routine detection and treatment of depression and anxiety should be part of a future strategy to improve the overall treatment of rheumatoid arthritis (31), which requires a multidisciplinary approach in RA treatment. (32).