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Archives of Medical Science - Civilization Diseases
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Clinical research

Prevalence and impact of fibromyalgia on disease activity in a sample of Iraqi patients with rheumatoid arthritis

Faiq Isho Gorial
1
,
Wisam Saloom Ahmad
2
,
Huda Shakir Abbood
2

1.
Rheumatology Unit, College Of medicine, University of Baghdad, Baghdad, Iraq
2.
Rheumatology Unit, Baghdad Teaching Hospital, Baghdad, Iraq
Arch Med Sci Civil Dis 2021; 6: e125–e131
Online publish date: 2021/10/04
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Introduction

Rheumatoid arthritis (RA) is the most common chronic autoimmune inflammatory disease, which leads to massive joint damage and deformity; it is also associated with extra articular and systemic effects that can lead to increased morbidity and premature mortality [1, 2]. The normally used disease activity indices are typically composite scores that can include the physician’s assessment of symptoms, patient-reported measures, and laboratory measurements. The Disease Activity Score (DAS), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI), for example, rely on joint counts, patient self-assessment and (with the exception of CDAI) laboratory tests. Although physician evaluation and patient self-reporting are critical components of patient assessment and management, they are influenced by intra- and inter-assessor variability and can be accompanied by comorbidities or joint damage resulting from long-standing disease [3]. The CDAI, which does include the C-reactive protein (CRP), is more widely used in typical clinical practice where a laboratory measure may not be available in a timely manner to make routine management decisions. The CDAI ranges in value from 0 to 76 and was examined as a continuous variable in our main analysis. We used the standard categories of the CDAI as a secondary definition, where a score of ≤ 2.8 indicates remission, 2.9–10.0 indicates a low level of disease activity, 10.1–22.0 indicates moderate activity, and above that indicates high activity [4]. Fibromyalgia (FM) is a chronic pain syndrome in multiple body regions leading to clinically significant impairment in everyday life. FM is characterized by diffuse and chronic musculoskeletal pain lasting at least 3 months [5]. Additional symptoms such as fatigue, lack of sleep, anxiety, and cognitive problems are also significant features of this syndrome [6].
Pain remains the most serious problem for people with RA. Active inflammation leads to pain, but pain due to non-inflammatory mechanisms can confound the assessment of disease activity. The presence of FM in several rheumatic diseases with a structural pathology is common [7]. The diagnosis of fibromyalgia syndrome (FMS) was made depending on the 1990 ACR criteria when the patients had characteristic symptoms of fibromyalgia as well as multiple tender points [8]. Secondary FM is common among patients with inflammatory arthritis, but little is known about its incidence and the factors leading to its development. A study in Canada done by Lee et al. in 2012 on 1487 patients with inflammatory arthritis showed that the cumulative incidence rate was 6.77 cases (95% CI: 5.19–8.64) per 100 person-years during the first 12 months after inflammatory arthritis diagnosis, and decreased to 3.58 cases (95% CI: 1.86–6.17) per 100 person-years 12–24 months after arthritis diagnosis [9].
Another study to determine the prevalence of FM and to evaluate the possible relationship between the existence of FM and disease activity among rheumatic diseases was done in 2014 by Haliloglu et al. showed that the prevalence of FM in patients with rheumatologic diseases was 6.6% for RA, 13.4% for systemic lupus erythematosus (SLE), and 12.6% for AS. With the exception of SLE and FMF, disease activity scores were significantly higher in patients with FM than in patients without FM, and people with RA and FM show higher pain and higher measures of disease activity. The 28-joint disease activity score (DAS28), which combines 4 components into an overall measure of RA inflammatory disease activity; 28 swollen joint count, 28 tender-joint count, acute-phase response (ESR), and a general health assessment using a visual analogue score, is commonly used in RA as a clinical measure of inflammatory disease activity. It appears that higher pain levels contribute to higher DAS28 scores [10]. Up to our knowledge, there was no previous study on the impact of FM on disease activity in RA patients. This study aimed to find the prevalence of FMS in RA patients attending the Rheumatology Unit in Baghdad Teaching Hospital and to explore the impact of FMS on disease activity of RA patients

Material and methods

Study design

A cross-sectional study was conducted at outpatient clinics in Baghdad Teaching Hospital/Medical City Complex during the period from September 2019 to the end of April 2020.

Participants

A total of 170 Iraqi patients (16 males and 154 females) were included, who were known cases of RA diagnosed by rheumatologists according to the 2010 ACR/EULAR classification criteria for diagnosis of RA [11], with 1 year or more disease duration, and age > 18 years. Patients were excluded if they had overlapping inflammatory arthritis disease or systemic diseases like diabetes, liver/kidney failure, thyroid gland diseases, hyperparathyroidism, osteomalacia, or malignancy.

Data collection and measurements

The data were collected using a sheet containing a questionnaire for the patients. The questionnaire included general socio-demographic data: age, gender, body mass index (BMI), marital status, educational level, occupation, and smoking history (smoker, non-smoker). BMI was calculated according to the following equation (weight in kilograms divided by the square of height in metres), divided into 5 categories: underweight if BMI < 18 kg/m2, normal if 18.5–24.9 kg/m2, overweight if 25–29.9 kg/m2, and obesity if ≥ 30 kg/m2, in accordance with the international classification system of the WHO [12].
The disease activity of the patients was measured by using the CDAI and DAS28 scores [13]. Diagnosis and assessment of fibromyalgia were done by using the fibromyalgia criteria 2016 revision [14]. Disease characteristics of RA were collected through the standardized questionnaire including time since diagnosis and type of drug treatment for RA (classified as use of non-steroidal anti-inflammatory drugs (NSAIDs), oral steroids, disease-modifying anti-rheumatic drugs (DMARDs), and biological treatment or combinations). Presence of comorbidities was excluded by a full history, appropriate examination and doing a basic investigations including complete blood count, erythrocyte sedimentation rate, renal function test, liver function test, fasting blood sugar and thyroid function test (if needed).

Ethical approval

The study protocol was approved by the Department of medicine, College of medicine, University of Baghdad with the number 1319 and date 13.10.2019. Informed consent was obtained from patients who participated in the study. Data and information on the participants were kept confidential, and any personal or private information that identified the participants was kept secret.

Statistical analysis

The collected data were entered on a Microsoft excel 2016 spreadsheet and loaded into SPSS V26 statistical software. Descriptive statistics were presented using tables and graphs. The 2 test was used to find out the association between related categorical variables, 2 independent samples t-test was used to find out the significance of differences between the means of the numerical variables, Pearson’s correlation was used to find the significance of correlation between related numerical variables, multiple regression was used to test the effect of FMS severity on RA disease activity, and p-values > 0.05 were considered statistically significant.

Results

The results of this cross-sectional study show that 170 (16 males, 154 females) RA patients were included in this study. The mean age of FMS patients was 51.263 ±11.531 years, and for non-FMS it was 48.469 ±13.932 years. There was no statistically significant difference between the mean age of FMS and non-FMS patients (p = 0.167). The prevalence of FMS among female patients (36.4%) was significantly higher than that among male patients (6.3%) (p = 0.015). There was no statistically significant difference between the mean BMI of FMS and non-FMS patients (p = 0.324), and no statistically significant association was found between marital status, education level, occupation, smoking status, and FMS proportion in RA patients (p = 0.074, p = 0.311, p = 0.096, and p = 0.173, respectively). There was no statistically significant association noticed between duration of disease in both FMS and non-FMS patients (p = 0.232). The disease activity according to CDAI was significantly higher among FMS patients, with mean 22.2 ±7.300, than among non-FMS patients, with mean 15.1 ±5.668 (p = 0.001). Disease activity according to DAS 28 score was also significantly higher in FMS patients than non-FMS patients. FMS prevalence was increased among higher functional class RA patients (p = 0.001). Regarding disease activity class, there was no significant correlation seen between active RA and inactive RA patients both with and without FMS (p = 0.552). Regarding drug use, it shows that patients with no FMS used NSAIDs more frequently than patients with FMS RA, while no statistical significant deference was noticed between use of steroids, DMARDs, and biological treatment in association with FMS and non-FMS RA patients (p = 0.455, p = 0.297, p = 0.973, respectively). There was no statistically significant difference between the mean level of ESR in FMS 40.965 ±26.415 and non-FMS RA patients 37.478 ±23.912 (p = 0.388). There was significant association found between positive CRP and FMS RA patients (p = 0.002), while there was no statistically significant association between positive RF or positive ACPA and the presence of FMS in RA patients (p = 0.230 and p = 0.072, respectively), as shown in Table I.
Table II shows the impact of fibromyalgia severity on disease activity measured by DAS28 score after multiple linear regression, which revealed that female gender, functional class, and fibromyalgia severity positively increase the disease activity (= 0.142, p = 0.032;  = 0.396, p > 0.001;  = 0.241, p = 0.001, respectively). Table III shows the impact of fibromyalgia severity on disease activity measured by CDAI, using multiple linear regression, which revealed that only functional class and fibromyalgia severity increase the disease activity ( = 0.373, p > 0.001;  = 0.359, p > 0.001, respectively). Figure 1 shows the prevalence of FMS in both active and inactive RA patients, in whom it is present in 33.5% of active RA patients and in 0% of inactive RA patients

Discussion

This study aimed to show the prevalence of FMS in RA patients attending the Rheumatology Unit in Baghdad Teaching Hospital, by using the new 2016 criteria for diagnosis of FMS, as well as to explore the impact of FMS on disease activity of RA patients and finally to find out the association between sociodemographic variables and FMS in RA patients. The prevalence of fibromyalgia in this study was 33.5% in RA patients (170 participants were studied), in contrast to other studies in which the prevalence of fibromyalgia was 12% and 15.4% in patients with RA [15–17]. The possible explanation for this difference could be the high number of bad socioeconomic factors that people living in Iraq suffer from, and due to starting use of the new 2016 criteria for FMS diagnosis. Fibromyalgia prevalence is greater in rheumatic diseases and chronic illnesses compared to primary fibromyalgia, and the probable reason is that pain remains the most serious problem for people with RA, making their everyday life and work difficult, so any additional syndrome like FMS will make it worse by reducing the threshold to pain perception [8].
Disease activity according to CDAI and DAS28 in the present study was significantly higher among the fibromyalgia RA group than the non-FMS group. This is in agreement with a study performed in 2019, which revealed that fibromyalgia appears to affect and increase the disease severity in RA patients, particularly in terms of patient-reported outcome measures, and it confirms the results of previous studies showing an association between concomitant FM and a higher degree of disease activity [15–18]. The study also shows that fibromyalgia severity, functional class, and female gender significantly increase the disease activity measured by DAS28 while only fibromyalgia severity and functional class increase the disease activity when measured by CDAI, due to the lack of ESR measurement in the latter index. The mechanism that explains FMS impact on RA patients was attributed to the subjective measures of the score: the tender joint count and patient assessment of general health (VAS-GH), which were significantly higher in the fibromyalgia group [19–21]. Up to our knowledge, this is the first study to assess the impact of fibromyalgia on diseases activity for RA patients in Iraq.
Another previous study that agrees with this one also showed the impact and severity of FMS on disease activity of RA patients using the DAS28 score index [22]. RA treatment requires accurate evaluation of disease activity in order to adapt the (DMARDs) regimen as closely as possible. Tools such as the Disease Activity Score (DAS) were used for this aim. This index is based in part on the patient’s self-reported assessment, which is valuable in estimating the personal burden of the disease. However, if there is an associated illness, these subjective variables may be partially flawed by the patient’s psychological condition, leading the physician to overestimate the patient’s status [23]. Concerning the effect of gender, this study shows obvious differences between males and females regarding the prevalence of FMS, which was found to be significantly higher among females 36.4% than in males 6.3% (p = 0.015).
This finding is in agreement with 9 previous studies and with a one in 2017 for patients suffering from the same problem, in which the prevalence of FMS among women was 8–9-fold greater than that among men, and pain and disability were as high as in RA, which affects the personal activity and recreation, leading to occupational problems [24]. Also, it confirms another study on 124 participants done in the USA in 2015, in which the prevalence of fibromyalgia was 2.38% in women compared with 1.06% in men [21]. The study also did not reveal any significant difference in medications used by RA patients, except for NSAIDs, which were used more frequently in non-FMS patients than in patients with FMS. Positive CRP showed a significant association with fibromyalgia in RA patients (p = 0.002), while there was no statistical significant association between ESR, positive RF, or positive ACPA and the presence of FMS in RA patients (p = 0.388, p = 0.230, p = 0.072, respectively), which is in agreement with a previous study in which ESR, RF, ACPA, and ANA, in addition to other markers, were not used to diagnose FMS but were obtained to evaluate other possible causes of symptoms or signs (diagnose other diseases), which means that these markers are not associated significantly with FMS [25].
The strength of this study comes from the fact that it is the first study in Iraq to assess the effect of FMS on disease activity and its outcomes in patients with RA, which is important, knowing that additional syndromes like (FMS) can lead to greater pain, impaired function, and worse general health, which can make it difficult to assess the response to medications that are used by RA patients. Some limitations of the study included being a cross-sectional study, and we cannot assess the causality. Also, there was some difficulty in performing some laboratory investigations because they were not available in the hospital and were costly. In addition, our diagnosis of FMS was dependent on a questionnaire, which is variable from one patient to another. Finally, there was no follow-up for these patients.
In conclusion, the occurrence of FM in RA patients was common. There was significant positive relation between FMS severity and disease activity in CDAI and DAS28. Female gender and functional class were significantly associated with FMS. This may suggest that early screening for FMS in patients with RA to obtain an early diagnosis and appropriate treatment will subsequently decrease the disease activity and subsequently improve the patient’s quality of life. However, a multicentre study with larger sample size is important to obtain more representative and accurate results.

Conflict of interest

The authors declare no conflict of interest.

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