Introduction
Autoimmune rheumatic diseases are a series of chronic diseases that involve multiple systems, mainly including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjogren's syndrome (SS), etc. Patients with these diseases are often hospitalized due to severe arthritis, nephritis, or interstitial pneumonia, and pay less attention to ocular changes, especially in RA and SLE [
1‐
3]. Studies have shown that ocular involvement is a sign of immune reactivation in many rheumatic diseases. In fact, ocular involvement is very common. A total of 90% of SS patients, 27% of RA patients and 31% of SLE patients had ocular involvement. Among them, ocular surface disorders are frequently reported, especially dry eye disease (DED), which is the most common ocular disorder [
4]. Early eye examination and intervention are of great significance for the prognosis and outcome of these diseases [
5,
6]. Additionally, in patients with SS, ocular examination assists in the diagnosis [
7].
Ocular surface disorders may lead to blurred vision and decreased vision, further affecting work efficiency, severely reducing the quality of life and increasing the financial burden [
8,
9]. In autoimmune rheumatic patients, the disease status and severity inevitably affect the degrees of stress, anxiety, and sleep quality[
10,
11]. However, emotional disorders, poor sleep and some immunomodulatory medicine had been confirmed to deteriorate the ocular surface situations [
12], especially intensified dry eye [
13], which may impact the diagnosis and assessments of autoimmune rheumatic disease [
11,
14]. It becomes a vicious cycle. Nowadays, few studies focus on the mutual and direct effects between physical and mental states with ocular surface states in autoimmune rheumatic patients [
15].
Here, we selected five questionnaires to provide a comprehensive assessment of the physical and mental states of RA, SLE and SS patients. The Ocular Surface Disease Index (OSDI) is the most widely used questionnaire to assess subjective ocular surface conditions in DED patients, including the frequency of ocular symptoms [
16,
17]. The Short Form 36-Health Survey (SF-36) is a general quality of life questionnaire developed by the American Medical Research Group [
18,
19] and is wildly used, including the Physical Component Summary (PCS) and Mental Component Summary (MCS) subscales. The Health Assessment Questionnaire-Disability Index (HAQ-DI) measures difficulties in activities of daily living [
20]. It’s originally developed to assess physical function in autoimmune rheumatic patients [
21]. The Hospital Anxiety and Depression Scale (HADS) is one of the most commonly used tools for screening anxiety and depression in chronic physical diseases [
22‐
24]. The Pittsburgh Sleep Quality Index (PSQI) is a 19-item self-report questionnaire measuring subjective sleep quality in patients with organic or nonorganic sleep disorders over the past 1 month [
25,
26].
Therefore, in addition to collect ocular surface signs and symptoms, we also used several scales to evaluate the physical and emotional states (sleep, mood, quality of life, mental state, etc.) of patients during hospitalization to explore whether the various conditions are directly related to the ocular surface disorders, aiming at better understanding and treatment of ocular surface disorders in patients with autoimmune rheumatic diseases.
Discussion
Autoimmune rheumatic diseases are chronic conditions characterized by an overactive and uncontrolled immune response, involving multiple organs of the body (including eyes) [
1,
3,
44,
45]. At present, the multifactorial pathogenesis is still partially understood [
46]. As the disease has a long course and is difficult to cure, patients often suffer from both physical pain and mental stress. Additionally, patients with autoimmune rheumatic diseases also have an increased burden of life [
1,
3,
45,
47].
Our study demonstrated that autoimmune rheumatic patients had poor health-related quality of life compared to controls. Both physical and mental health quality were reduced. Among these, role physical (role limitations due to physical health problems) was the most affected indicator. Our finding is in accord with previous reports [
48,
49], and perhaps suggests the potential benefit of the patient's physical and mental health care as part of a comprehensive management of autoimmune rheumatic diseases [
48,
50]. Moreover, autoimmune rheumatic diseases exacerbate the difficulty of daily living. This is consistent with Lorand's study [
51]. Autoimmune rheumatic patients are often unable to take care of themselves due to the involvement of vital organs such as joints, lungs and kidneys [
1,
2]. Studies have shown that autoimmune rheumatic diseases can increase levels of depression and anxiety and decrease sleep quality [
52‐
55]. Our study also revealed that autoimmune rheumatic patients were more anxious than controls. However, depression and sleep quality had no differences between the two groups. At present, in addition to conventional disease-modifying antirheumatic drugs (DMARDs) and glucocorticoid-sparing regimens, psychological interventions (for example, relaxation, stress management and cognitive coping skills) are recommended to help these patients adjust to living with their condition and have the potential to increase their quality of life and life expectancy. National Institute for Health and Care Excellence (NICE) guidelines (
https://www.nice.org.uk/guidance/ng100/chapter/Recommendations) stipulate that these patients should be periodically assessed for the impact of their disease on their lives, including health-related quality of life and mood.
Patients with autoimmune rheumatic diseases often have ocular manifestations, especially ocular surface disorders such as conjunctivitis, keratitis and dry eye disease [
56]. An observational study has shown that 46% meibomian gland dysfunction, 49% superficial punctate keratopathy and 44% shortened TBUT are observed in patients with primary and secondary Sjögren syndrome [
57]. Our study indicated that among autoimmune rheumatic patients, 48.89% ocular symptoms, 63.89% reduced tear secretion, 88.33% shortened TBUT, 25.56% corneal fluorescein staining, 41.11% abnormal meibomian gland secretion, 25% LIPCOF, no symblepharon and 1.11% corneal opacity are showed. In addition, 52.22% of eyes of patients are diagnosed with DED with 20.56% aqueous deficiency type, 16.11% evaporative type and 15.56% mixed type. Autoimmune rheumatic diseases are associated with an overactive and uncontrolled immune response, the tear glands of autoimmune rheumatic patients attacked by autoantibodies often fail to secrete tears [
58]. In our study, patients produced fewer tears than the control group. This observation is in accordance with Guannan’s and Kim’s [
59] study. We futher found that the difference in tear film stability was not statistically significant between patients with autoimmune rheumatic diseases and controls. This result is also consistent with the study of Usuba [
60] and Marsovszky [
61]. The mechanism of DED in most autoimmune rheumatic diseases is focal lymphocytic infiltration and chronic inflammation of the exocrine glands rather than meibomian gland dysfunction [
58,
62‐
64]. This is the reason why most types of DED associated with autoimmune rheumatic diseases are the aqueous-deficient type [
38,
65,
66]. Corneal fluorescein staining is an important index to evaluate the severity of dry eye [
37]. Autoimmune rheumatic patients had more severe corneal staining than controls. Liang’s research also confirms this trend [
67]. From what has been discussed above, ocular involvement in autoimmune rheumatic patients is more severe than that in people without autoimmune rheumatic diseases.
Currently, there is a growing belief that ocular surface disorders especially DED are associated with psychological, psychosocial and social factors, especially anxiety and depression [
68,
69]. Studies have shown that in a healthy population, reduced sleep duration, higher psychological stress, and poorer self-perceived health status were independently associated with DED [
70]. Therefore, we should not only focus on the pathological damage of autoimmune rheumatic disease on ocular surface but also pay attention to the indirect impact of the psychological problems caused by the disease. Due to the higher incidence of ocular surface disorders in Sjogren's syndrome (SS), relevant research has focused on SS at present. Studies have demonstrated that autoimmune rheumatic patients have a reduced quality of life, poorer sleep quality and an increased risk of anxiety and depression [
49,
71‐
73]. For patients with SS, psychological factors significantly impact the quality of life, wellbeing, cognitive functions and disease activity of the patients [
74,
75]. Additionally, ocular symptoms including pain, dryness, and itching, pose serious physical limitations and cause psychological distress [
76]. Researchers suggest that the biopsychosocial perspective is crucial for treatment [
77]. However, there is a lack of research on the correlation between the physical and mental state and ocular surface disorders in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
Our study demonstrate that unlike controls, lower health-related quality of life, more anxiety and depression, poorer sleep quality were moderately associated with DED symptoms among autoimmune rheumatic patients. DED is a disease in which symptoms and signs are separated according to DEWS II[
16]. No signficant association was observed between other ocular surface signs and systemic factors. It indicates that DED affects health-related quality of life, anxiety, depression and sleep quality of rheumatic immune patients more than people without autoimmune rheumatic diseases. These systemic conditions can aggravate DED [
70]. Management of systemic problems is essential when treating autoimmune rheumatic patients. Improving the patient's physical and mental condition is also beneficial to DED. As a series of systematic chronic diseases, autoimmune rheumatic diseases are expected to pay more attention to the patients' physical and mental state while focusing on ocular involvement [
78]. Holistic thinking is necessary when treating a patient with autoimmune rheumatic disease-related ocular involvement. It is important to address comorbid conditions such as depression and poor sleep quality. These conditions are thought to exacerbate one another and contribute to the overall burden of disease [
10,
79]. In addition, patients with dry eye disease sometimes show the different disease state of the two eyes. Perhaps the same patient in a state of anxiety is diagnosed with dry eye in one eye while the other eye is normal. In order to avoid potential bias, we used of averaged ocular surface indexes of both eyes of the same patient to conduct the correlation analysis with the systemic indicators [
80].
In addition, the influence of gender and age on DED cannot be ignored, although in our study age and sex are matched. The risk of DED increases with age in both sexes, while its incidence is higher among females. In addition, the condition of menopause in aging women may also contribute to dry eye onset or worsening as a consequence of an overall hormonal imbalance [
81‐
83]. Autoimmune rheumatic diseases are also more common in women. For different age stages of autoimmune rheumatic patients, the ocular surface conditions are different. We need to pay more attention to the changes in hormone levels to observe whether it is hormone that causes the severity of dry eye, rather than the primary disease. This also needs more research in the future.
There are some limitations in this study. First, the disease group we studied only included hospitalized patients and ignored non-hospitalized patients. Hospitalized patients with autoimmune rheumatism are more severe and have more comorbidities than those who are not hospitalized. This will cause bias to some extent. Second is the small sample size. Finally, due to the non-representative nature of participants, the volunteer bias can’t be ignored.
In general, autoimmune rheumatic patients have poorer health-related quality of life, more difficulties in daily living and suffer from ocular surface disorders. Factors including lower quality of life, more anxiety and depression, and poorer sleep quality are associated with DED symptoms in autoimmune rheumatic patients. Management of systemic conditions and psychotherapy should also be considered as part of the treatment and have benefits for DED among autoimmune rheumatic patients.
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