Prevalence of chronic widespread pain in a population-based cohort of patients with spondyloarthritis – a cross-sectional study

Pain is a frequent and multidimensional symptom in patients with arthritis [1, 2]. Apart from the common inflammatory nociceptive pain, inflammation and nociceptive stimuli in peripheral and axial joints may also cause a heightened pain perception due to both peripheral sensitization, with nociceptors responding to light pressure and normal movement, and central sensitization with hyperexcitability of the neurons in the spinal cord [1, 3, 4]. This heightened pain perception could lead to a persistence of the pain and development of a chronic pain condition [5]. Chronic pain can be divided into chronic regional pain (CRP) and chronic widespread pain (CWP). CWP is usually defined as pain present in both sides of the body, above and below the waist and in axial body regions [6], and has a prevalence of about 11% in the adult population [7, 8]. In patients with rheumatoid arthritis (RA), CWP has been reported in one-third of the patients [9], but in other chronic rheumatic diseases such as spondyloarthritis (SpA), information regarding prevalence rates for CWP are limited.

SpA is a group of chronic rheumatic diseases with similar clinical features such as back pain, asymmetrical peripheral arthritis, enthesitis, and extra-articular manifestations, and includes―among others―AS and undifferentiated spondyloarthritis (USpA) [10]. In Sweden, all diagnoses in clinical practice are set in accordance with the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). The AS diagnosis confirms with both the 1984 modified New York criteria [11] and the more recent criteria for axial spondyloarthritis (axSpA) [12]. The USpA diagnosis refers to a less well studied and variable group of patients [10, 13], including patients with non-radiographic axial SpA and peripheral SpA, or a combination [12, 14, 15]. It has been argued that USpA, in some cases, can represent an early form of AS [16–19], and in a recent review, a relatively large group of patients with USpA (39.9%) developed into AS after 10 years [20]. Functional impairment, reduced quality of life, fatigue, reduced ability to work, anxiety, and depression, are well-known findings for patients with SpA in general [21–25].

There is an increased attention regarding difficulties of managing chronic pain in SpA in the clinic. But as to date, the few studies exploring chronic pain in SpA have mainly concentrated on patients with AS and pain corresponding to the more complex fibromyalgia (FM) syndrome [6], with prevalence estimates of FM varying between 4% and 15%, and with higher frequencies in women [26–29]. CWP can include pain from different origins, and be seen as a continuum, with FM representing the more severe form. Therefore, studies that aim to identify patients with early and less severe CWP could be important. Not only, for an accurate diagnosis, but most importantly, for optimal and early treatment of both the inflammatory disease, and a possible co-existing sensitization of the nervous system, requiring other treatment strategies.

The aim of the study was to assess differences in prevalence of self-reported CWP in a population-based cohort of patients diagnosed with AS or USpA, including differences between women and men.

Five per cent (53/940) of the patients could not be categorized into any of the pain groups (NCP, CRP, or CWP) due to missing responses on the chronic pain question and the pain mannequin, leaving 536 patients with AS and 351 patients with USpA. The patients not responding to the chronic pain questions had a mean age of 55.5 (SD 12.9) years (AS 57.5 (SD 12.8) vs. USpA 52.0 (SD 12.7), p = 0.137), and were more often men (62.3%). In addition, 64.2% of the non-responders had AS.

In this study, we found a high prevalence of self-reported chronic pain in both AS and USpA. CWP was present in half of the patients with USpA, and just slightly less in patients with AS, and was overall more common in women. About one-fifth of the patients with either AS or USpA reported having CRP, with no differences between women and men. Female sex, a higher BMI, and being an ever-smoker were associated with CWP in contrast to NCP/CRP, while diagnosis (AS or USpA) and disease duration were not. These findings can complicate the evaluation of disease activity and response to treatment in patients with AS and USpA, and emphasise the need of an early and thorough clinical examination, including not only evaluation of inflammation, but also an accurate and careful pain analysis.

The results from the present study are difficult to compare in relation to previous research on SpA, since to our knowledge, there have been no studies on the prevalence of CWP in AS and USpA without limiting it to FM. However, the prevalence of CWP in AS and USpA was clearly higher than in the general population [7, 8], and also, higher than in a previous report on the prevalence of CWP in RA (34%) [9]. We used the same pain mannequin and definition of chronic pain as the two previous Swedish studies [7, 9].

Previous research has found that it is important to consider that the evaluation and diagnosis of SpA, particularly in women, can be delayed [35] and complicated by the presence of CWP. Symptoms such as chronic back pain, stiffness, and fatigue are common in patients with both SpA and FM, and can be interpreted, as indicating an increase in disease activity [26, 27, 36, 37]. Also difficulties in distinguishing fibromyalgia tender points and enthesitis sites in SpA have been reported [38], with an overlap of about 30% between the inflammatory back pain (IBP) criteria and the FM criteria. Even though we could not examine for tender points or enthesitis and the study population was different, it is important to acknowledge that CWP can include pain from different causes. CWP is a prerequisite for FM, and patients with CWP could already have FM, or be at risk of developing FM at a later date [39]. Interestingly, the opposite scenario has also been found, where almost half of the patients, particularly women, were incorrectly diagnosed with FM instead of an inflammatory rheumatic condition [40]. With the above in mind, it is important to stress the fact that a thorough evaluation, including a pain assessment to identify signs of a widespread nature, is important in all patients who report prolonged and increased pain, and other symptoms such as fatigue and poor quality of life. In addition, the origin of pain is important when it comes to treatment, but the presence of enthesitis does not exclude a co-existing sensitivity in the pain system―which is why individualized pain management, including both non-pharmacological and pharmacological treatment, is emphasized.

The women in our study had a higher prevalence of CWP, and CWP was associated with female sex in the logistic regression analysis. These findings are in accordance with the results of previous studies that have investigated FM in SpA [26–29, 36], and with a recent review [41], reporting evidence of a higher risk of developing chronic pain in women than in men. In the same review, some evidence―although inconclusive―was found that women experience more severe clinical pain than men, and this was contributed to multiple bio-psychosocial mechanisms including hormones, neurochemistry, social roles, and coping mechanisms [41]. In the present study, no sex-related difference in the prevalence rates of CRP were found, and although the prevalence of CWP was lower in men than in women, men with AS and USpA reported a high prevalence of CWP, compared to men in the general population [7]. Interestingly, we also found that pain intensity was not significantly different in women and men, when studied separately in those with CRP or CWP, and that an overall higher pain intensity in women was due to the higher prevalence of CWP in women. These findings are new, and highlight the fact that it is important to be aware of and recognize a concomitant CWP also in men with SpA.

In agreement with earlier studies in the general population [42, 43], CWP was also associated with being an ever-smoker and having a higher BMI. People with obesity can have a low-grade systemic inflammation, due to the production of pro-inflammatory cytokines and adipokines in the white adipose tissue [44]. The association between obesity and chronic pain has accordingly, been reported to partly be mediated by pro-inflammatory cytokines, but biomechanical and structural changes, mood, poor sleep, lifestyle factors and personal factors have also been found to be important mediators [45].

We found no association between SpA disease duration and chronic pain in this study. One reason for this may be that personal or other factors are more important than disease duration when it comes to developing chronic pain, and especially CWP.

Strengths of the present study were that patients from both primary and specialist health care were included, and the relatively large sample size. Another strength was that the instruments represent different dimensions of pain (duration, distribution, and intensity), and are commonly used and validated [7, 46, 47]. There were also some important limitations of the study. One was the low response rate, even though this was comparable to that in other population-based surveys [7, 42, 43]. Another limitation was that the patients were identified by their clinical ICD-10 diagnosis so we cannot be certain how many patients with USpA that would be categorized as having axial or peripheral SpA. However, in this study patients with psoriatic arthritis, IBD-related arthritis, or reactive arthritis were excluded, and 65% of the patients with USpA (M46.0-1 and M46.8-9) reported current chronic axial involvement, possibly representing an early form of AS. Moreover, the questionnaire lacked information on other comorbid diseases that could have impact on chronic pain. Also, information regarding socio-demographic variables would have been interesting with regard to CWP. The self-reported data regarding medication should due to the large proportion of missing data, be interpreted with care. Finally, the cross-sectional design makes us unable to draw conclusions as to the causality of the associations detected. In future research, longitudinal studies will be important to help us gain a better understanding of predictive factors for development of CWP in patients with SpA.

We found a high prevalence of concomitant CWP in patients with AS or USpA, with an even higher prevalence in women, but with no difference in the intensity of pain in women and men who experienced CWP. The results highlight the importance of a thorough pain analysis included in the clinical examination, to identify patients with high and/or increasing pain levels and multiple pain regions. It may also guide appropriate and individualized treatment decisions, including non-pharmacological and pharmacological treatment options.