Features of the course of ankylosing spondylitis depending on the psychosocial status and duration of the disease

Introduction

In modern rheumatology, the study of the psychological factor significance in the occurrence of autoimmune pathologies and their course occupies an important place. Nowadays, it has been established that in patients suffering from various rheumatological diseases, the frequency of psychoemotional disorders significantly exceeds the similar frequency in the general population [1][2]. The results of recent studies demonstrate that patients with ankylosing spondylitis (AS) are characterized by a high frequency of depression and anxiety, which is associated with the severity of pain syndrome and later age of diagnosis [3][4].

The constant presence of pain, characteristic of AS patients, contributes to a change in their psychoemotional state, which is clinically manifested by anxiety, depression, apathy, fatigue, increased excitability, irritability, forming anxiety-depressive spectrum disorders (ADSDs), the presence of which leads to the progression of patients’ social maladaptation [5][6].

In the academic studies devoted to the problem of AS progression, a significant place is given to the role of functional disorders and deterioration of life quality (LQ) indicators with an increase in the activity of inflammation and an increase in the duration of AS [7][8]. However, the low LQ of patients with AS is due not only to functional changes but also to psychosocial maladaptation, including the development of ADSD [9]. It is proved that the negative psycho-emotional state of patients affects their adherence to treatment. High levels of anxiety and depression, in turn, are an additional factor in their low mental, physical, and social activity [10].

Taking into account the above-mentioned information, it is important to note that the purpose of this particular research was to study the effect of psychosocial indicators and duration of the disease on LQ, ADSD, and clinical and laboratory activity in patients with AS.

Materials and methods

The study involved 112 patients with AS, aged from 25 to 58 (43.7±7.9 years), 71 men and 41 women; the average duration of the disease was 9.5±4.4 years; 35 (31.2%) of them had higher education (HE) (17 women, 18 men); urban population prevailed – 70.5% (43 men and 36 women). 59 (52.7%) patients suffered from disabilities: group III – 41 (69.5%), group II – 18 (30.5%); functional disorders corresponding to FC III prevailed – 65.2% of cases, therefore. By social status, the examined patients were distributed as follows: 32.1% – employees, 46.4% – workers, 21.5% – did not have a permanent place of work or temporarily did not work. While assessing the marital status, it was found that married persons prevailed (51.7%); as for the remaining – 4.5% were widow(er)s, 17.8% were divorced, 26% were not married. The diagnosis of AS was established in accordance with the modified New York criteria (ACR, 1984); the degree of activity of the pathological process was assessed taking into account the Bath AS disease activity index (BASDAI) in accordance with the EULAR criteria.

The criteria for the study inclusion were as follows: informed consent of the patient, verified diagnosis of AS, duration of AS for more than three years, absence of diagnosed disorders of the central nervous system that could lead to ADSDs. The exclusion criteria were: duration of AS less than 3 years, age over 60 years, presence of organic brain damage, manifestations of anxiety depression detected before the diagnosis of AS.

The pain syndrome, the duration of morning stiffness, and the patient's own health indicator (POHI) were evaluated by the visual analog scale (VAS) by the patients themselves. Quantitative indicators of pain syndrome were studied in accordance with the McGill Pain Questionnaire (MGBO). Laboratory parameters were also examined: CRP, ESR, levels of calcium, uric acid (UA), fibrinogen, and ceruloplasmin (CP) in blood serum.

The patients’ LQ was assessed by means of using the Medical Outcomes Study Short Form (SF-36) questionnaire, reflecting 8 concepts (scales) of health: physical functioning (PF), the impact of physical condition on daily activities (role-physical functioning – RP), pain intensity (body pain – BP), general health (GH), vital activity (vitality – VT), social functioning (SF), role-based functioning due to emotional state (role–emotional – RE), mental health (MH). In general, the SF-36 questionnaire allows evaluating two components of health: the total physical component (PSH) and the psychological one (MSH). The results of each of the 8 scales are expressed in points from 0 to 100. At the same time, the higher the value of the indicator, the better the condition on the selected scale [7].

In order to identify ADSDs in patients, a questionnaire was organized. In order to assess the level of anxiety, the Taylor Manifest Anxiety Scale (TMAS) with a Russian-language adaptation of Nemchinov was used therefore. The questionnaire includes 50 questions to which the patient had to answer (“yes” or “no”). The result is estimated in points, which the patient gains by answering the relevant questions positively or negatively. The interpretation of the results follows the principle: 0–5 points indicate a low level of anxiety of the patient; 5–15 points indicate an average with a tendency to a low level of anxiety; 15–25 points on average with a tendency to a high level of anxiety; 20–40 points are an indicator of a high level of anxiety; 40–50 points reflect a very high level of anxiety. The Spielberger anxiety self-assessment scale was also used, according to which the anxiety level of less than 30 points was regarded as low one, 30–45 – as moderate one, more than 45 – as high one. In order to identify symptoms of depression, the Hamilton Depression Scale (HDS) was used, according to which, while summing up the scores obtained, the result of 16-18 in the young and 18–20 in the elderly indicates the presence of a non-psychotic depressive state.

The presence and severity of autonomic disorders were investigated by testing according to the methods “Vane-patient” (VP) and “Vane-doctor” (VD), where possible autonomic dysfunction (AD) was more than 15 points for VP, and the confirmed AD – was more than 25 points for VD.

Statistical analysis of the obtained results was carried out using the Statistica 10.0 statistical software package (Statsoft, USA). Under normal distribution, the data were given in the form of mean±standard deviation (m±σ), in other cases in the form of Me (LQ-UQ), where Me is the median, LQ is the lower quartile, UQ is the upper quartile. The nonparametric U Mann-Whitney criterion was used to compare quantitative features between groups. For the analysis of qualitative data, the analysis of conjugacy tables using the χ² criterion was used. The differences were considered statistically significant at p<0.05.

Results

When assessing the severity of pain syndrome and morning stiffness in patients who participated in the study, the following data were obtained: pain in the spine – 64.7 ±17.2 mm, morning stiffness – 68.0 (51.0; 78.5) mm, POHI – 31.5 (20.0; 44.0) mm. Quantitative indicators of pain syndrome according to MGBO were as follows: the number of sensory and affective class descriptors 6.0 (5.0; 6.0) and 4.0 (4.0; 5.0), the evaluative component of pain – 3.0 (2.0; 3.0), the number index of the selected descriptors (NISD) – 11.5 (10.0; 12.0) points, the rank pain index (RPI) – 24.3±5.9 points.

Low activity of the inflammatory process was found in 31 patients, moderate – in 53, and high – in 28. The BASDAI index averaged 3.9 (3.3; 4.2); in 35% of patients, it was higher than 4, and in 3.6%, it was higher than 7. The BASFI index was 4.1 (3.6; 4.7); in 51.8% of cases it was above 4, and in 1.8% it was below 2.5. The average value of ESR was 27 (22.5; 30.0) mm/h, the level of CRP was 12.0 (7.8; 24.0) mg/l; in 73 (65.2%) it was above 10 mg/l, and in 5.3% – above 50 mg/l. The blood calcium level was 2.32±0.11 mmol/l, UA – 354.2±87.2 mmol/l; fibrinogen – 4.55 (3.5; 5.37) g/l; CP – 24.2 (22.5; 27.6) mg/dl.

The LQ indicators (SF-36 questionnaire) registered in the surveyed were as follows: PF – 35 (25; 40) points; RP – 25 (0; 25) points; BP – 32 (22; 41) points; GH – 46 (30; 55) points; VT – 37.5 (30; 45) points; SF – 50 (50; 62.5) points; RE – 66.6 (33.3; 66.6) points; MH – 40 (40; 56) points. The results obtained are generally assessed as low, both in terms of the total PSH, which amounted to 30.4 (27.2; 35.6), and in terms of the overall MSH, which amounted to 41.4 (37.2; 44.3) points in the surveyed. The low level of PSH in the examined patients depended mainly on the RP – 25 (0; 25) points, reflecting the influence of the patient's physical condition on his/her daily activity, and also, to a certain extent, was due to the intensity of the pain syndrome. Speaking about the psychological component, it should be noted that some indicators were at an average level. However, the low vital activity of patients and reduced mental health indicators affected the overall score of psychological health of patients with AS.

The ADSD signs corresponding to clinical manifestations of anxiety depression (F41.2) were detected in the majority of patients – 67 people (42 men, 25 women), which accounted for 59.2% of men and 61% of women out of the total number of patients. Thus, the gender trait had no significance in the development of ADSD in patients with AS. In this subgroup, the following results were obtained in terms of the severity of ADSD: the level of depression according to HDS was 17 (14; 19) points, which, in general, taking into account the age of the subjects, corresponds to a non-psychotic depressive state; the revealed increased anxiety on the Spielberger scale was RA 32 (29; 37), PA was 40 (35; 44) points, as well as the Taylor scale – 27 (19; 36) points generally correspond to a moderately high level of anxiety in the group of examined AS with ADSD.

More than a third of patients with ADSD (38.8%) had HE, which amounted to 26 people, including 14 men and 12 women, which as a percentage of the total number of all the examined people was 33.3% men and 48% women. Patients with AS without signs of ADSD (45 patients: 29 men and 16 women) mostly had secondary specialized education (SSE). There were 9 of them (4 men and 5 women), which accounted for 13.8% of the total number of surveyed men and 31.2% of women. Thus, HE was statistically significantly more often (χ²=4.56, p=0.033) observed in patients with AS with ADSD. In % ratio, ADSDs were registered in men with HE more often than in men with SSE (p=0.066).

When comparing patients with AS duration up to 10 years (67 patients) and more than 10 years (45 people), it was found that the incidence of ADSD in these subgroups did not have significant differences (χ²=0.6, p=0.44), 37 and 30 patients, respectively. Thus, the duration of the AS course did not affect the development of ADSD.

In 74 (66%) patients, signs of autonomic dysfunction according to the VP scale were detected, and confirmed AD (according to VD) was established in 66 (59%) cases. At the same time, the indicators were: VP – 18.0 (14.0; 22.0) points and VD 27.0 (23.0; 32.0) points.

A study of patients' LQ was conducted depending on one of the most significant social indicators – the level of education. It was found that the LQ indicators in patients with HE (group 2) were significantly worse than in patients with AS with SSE (group 1). The data are presented in Table 1. Statistically significant lower physical condition data for RP (p=0.012) were found in patients of group 2, and it was also revealed that a significant part of the indicators of the psycho-emotional block, namely, VT, SF, and MN were also reduced (all p<0.05) when compared with the data obtained in the 1st group. In general, persons with HE showed a tendency to lower (p=0.099) total health indicators PSH 30.2±4.8 than patients with SSE – 32.4±6.8, and significantly (p=0.016) lower MSH indicators, 38.1±8.7 and 41.5±5.9, respectively.

Statistically significant higher rates of spinal pain (p=0.03) and morning stiffness (p=0.037) according to VAS were also recorded in people with HE. However, quantitative indicators of PS (MGBO) did not differ in groups depending on the studied social factor. Indicators of inflammatory activity (ESR, CRP), the level of UA, SP, and fibrinogen also did not depend on the level of education.

The indicators of anxiety, depression, and the severity of autonomic disorders in patients with AS were studied, depending on the level of education. In group 2, a significantly higher severity of anxiety and depression was revealed (Table 2). This is natural, given the fact that in group 1, signs of ADSD were detected in 53.2%, and in group 2 in 74.3% of patients. There were no significant differences in the indicators of autonomic dysfunction in the groups.

Additionally, the psychological status of patients with AS (LQ, severity of ADSD signs) was assessed depending on the marital status of patients and the presence or absence of their employment. There were no significant differences when comparing the LQ indicators (SF-36) of patients who were married with the results obtained in patients who were divorced and had never been married. There was also no association between ADSD and the marital status of patients. When assessing the quality of life of patients with work – 88 people (employees and workers) and temporarily unemployed persons – 24 people, no significant differences were obtained in the total physical and psychological components of health. There were also no differences in the severity of anxiety and depression (HDS, TMAS, Spielberger scale), depending on the presence or absence of employment of the surveyed.

The next stage in the study was to study the characteristics of the studied indicators of LQ, clinical and laboratory activity, and the severity of ADSD signs, depending on the prescription of AS. As a result, when comparing patients of two subgroups (duration of AS of up to 10 years and more than 10 years) significant differences in some indicators of LQ according to SF-36 were revealed. Namely, statistically significant lower indicators of vital activity and social functioning were registered in patients with AS for more than 10 years, which affected the level of the general psychological component of health in this category of patients. The data are presented in Table 3.

A significantly (p=0.011) higher level of depression according to HDS was detected in patients with AS prescription for more than 10 years. Also, in this category of patients, there was a tendency to increase anxiety indicators, more significantly related to the personal sphere (p=0.18). The data are presented in Table 4.

The AS pain syndrome indicators did not depend on the duration of AS (up to 10 years and more than 10 years) (p>0.05 for all the patients). However, there were differences in some indicators of clinical and laboratory activity. The data are presented in Table 5. Statistically significant higher indicators of the clinical activity of the disease, pain and stiffness according to VAS, and a low indicator of POHI, obtained in a subgroup of patients with AS prescription of more than 10 years, confirm that the long-term presence of pain syndrome and insufficient adaptation to the disease enhance the personal perception of pain. A significant decrease in the level of CP and an increase in MC indicators observed in patients with a disease duration of more than 10 years compared with patients with a shorter duration of AS indicate depletion of antioxidant potential and progression of inflammatory activity, which is confirmed by a statistically significant increase in fibrinogen levels (p=0.018) and a tendency to increase ESR and CRP in patients with more long-term disease.

Discussion

According to this study, the majority of patients with AS (59.8%) showed signs of ADSD. The data obtained are similar to the results of other studies, where the frequency of ADSD varies from 24% to 65% [11][12]. It should be noted that the gender trait did not affect the development of ADSD, which corresponds to the data obtained by other authors [13]. Also, the psychological status of patients (LQ, severity of signs of ADSD) did not depend on their marital status and employment. However, it was found that in people with HE, ADSD occurred significantly more often (χ²=4.56, p=0.033) than in patients with SSE. Also noteworthy is the fact that male patients with HE had a tendency to suffer from ADSD more frequently. At the same time, in the group of patients with HE, as a whole, a statistically significantly higher level of anxiety and depression was observed.

Chronic pain syndrome, inherent in patients with AS, has a common neurochemical substrate with depressive disorders – serotonergic and noradrenergic insufficiency, which ultimately leads to the formation of a stereotype of pain behavior, the strengthening of inadequate emotional, vegetative, and behavioral reactions of patients directly dependent on high levels of stress, which exacerbate the negativity of thinking and trigger a vicious circle of chronic stress. All of the above contributes to the chronization of pain and significantly affects the reduction of LQ in patients [14][15][16].

In this particular study, when studying the indicators of LQ according to the SF-36 questionnaire, it was found that in people with HE, daily activities were more dependent on physical condition than in patients with SSE. Also, in this category of patients, lower vital activity, the ability to adapt social functioning and an indicator of mental health were revealed, which in general affected the overall indicators of physical and psychological health. The study of the effect of AS duration on LQ allowed the authors of this study to establish a link between an increase in AS duration and a decrease in the overall psychological component of health.

The authors also obtained results that allow talking about the effect of the duration of the disease on the growth of inflammatory activity of AS (ESR, CRP, fibrinogen) associated with depletion of antioxidant defense factors, in particular, an increase in the level of MC and a decrease in CP. This corresponds to the data of other researchers presented in the academic literature [17][18].

Conclusion

Male patients with a higher level of education have a greater tendency to suffer from ADSD. This category of patients with AS is characterized by lower indicators of LQ, mainly psychological health. Increasing the prescription of AS disease does not affect the development of ADSD. With the duration of AS for more than 10 years, the indicators of the psycho-emotional and physical components of LQ decrease, there is a tendency to increase anxiety and depression, the factors of antioxidant protection of the body are depleted, inflammatory activity increases, and personal perception of pain increases. The revealed features significantly limit the mental, physical, and social activity of patients and adversely affect the prognosis of the disease.

The obtained data can be used to assess and predict the effect of the duration of AS, changes in psychosocial status on clinical and laboratory activity, components of the physical and psychological health of patients.