Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes deterioration of diarthrodial joints, leading to functional impairment, impaired quality of life, decreased life expectancy and social1–3 dependence. This generates a very elevated care cost.4,5 This bleak picture has improved in the last 10 years with the emergence of biological therapies but, above all, with the implementation of treatment strategies aimed at achieving targets based on composite indices for evaluating the activity of the disease.6,7 However, it has been recently proposed that these indices may be biased in the evaluation of patients.8,9 In some cases, personality factors related to the patients may also interfere. In this sense, RA is a clear example of a biopsychosocial model of disease. This model proposes that, in addition to the organic component, the emergence and subsequent evolution of diseases, especially chronic ones, are influenced by the environment in which the person lives, as well as the reality of every individal.10,11 Therefore, the tools used to assess the clinical activity of RA and its functional impact may be influenced by the psychological characteristics of the patients we serve.

As part of the individual psychological characteristics, the structure of affect consists of 2 dimensions or dominant factors commonly labeled as positive affect (PA) and negative affect (NA). This division between positive and negative affective states is manifested from early childhood, and can already be seen, as positive emotions correlate with increased activity of the left hemisphere, while the right is more affected by negative ones.12 Therefore, PA and NA are considered personal provisions of emotionality with little variability over time, influenced by genetics and, in part, by the individuals first experiences.13 Elevated levels of PA are associated with high energy, focus and dedication of the individual, while low levels are characterized by sadness and lethargy; on the other hand, high levels of NA reflect a variety of moods including anger, guilt, fear and nervousness, while low NA is a state of calm and serenity.14 Clark and Watson developed in 1988 the PANAS questionnaire to adequately weigh PA and NA.14 Subsequently, the results obtained with its application to patients and healthy controls were used to establish their tripartite model of anxiety-depression.15 In this model, scores of NA and PA, along with distress in response to environmental stimuli, lead the authors to properly classify cases of anxiety, depression or mixed cases.

With respect to RA patients, previous studies have shown that there is an association between higher pain scores and higher levels of NA.16,17 Therefore, the objective of this study was to investigate the influence of NA and PA in two of the most widely used measurement instruments in clinical practice employed to assess RA: the DAS28 activity index and the HAQ questionnaire to assess functional capacity.

Registration of patients with recent onset arthritis at the Hospital Universitario de La Princesa includes patients referred from primary care who have had one or more swollen joints for at least 4 weeks and a maximum of one year. The only exclusion criterion is that along the course of their follow up, patients are diagnosed microcrystalline arthritis, septic arthritis or viral infections, spondyloarthropathies or connective tissue diseases. The study protocol provides for four follow-up visits in a period of 2 years: baseline, at 6 months, one year and two. At each visit, we collect demographic data (gender, educational level and marital status), clinical data (date of onset of illness, 28 tender joint count [TJC28] and swollen [SJC28], global assessment of disease by the physician [GADP] and by the patient [GADPa] and assessment of pain on a visual analog scale (VAS) from 0 to 100mm) and laboratory data (erythrocyte sedimentation rate [ESR, measured by the Westergren method], C-reactive protein [CRP, nephelometry], rheumatoid factor [FR; nephelometry], levels of anti-CCP antibody [AAPCC; determined by ELISA: Immunoscan CCPlus®, Euro-Diagnostica, Arnhem, Netherlands]) and hematology and blood biochemistry. Functional capacity is estimated by a HAQ questionnaire validated in Spanish population18 and DAS28 with ESR is calculated every visit as described previously: 0.56*√(TJC28)+0.28*√(SJC28)+0.70*ln(ESR)0.014+(GADP).19

For the present study we analyzed the clinical data of 282 visits (86 first visits, 52 visits after 6 months follow-up, 71 visits at one year and 73 visits at two years), performed between September 2001 and November 2009, with 86 patients having RA according to the American College of Rheumatology (ACR) criteria of 1987.20 75.7% of patients were women, with a median age at disease onset of 54.6 years (interquartile range: 44.3–68.6). As shown in Table 1, the characteristics of this group are similar to those of other cohorts in our environment. In these patients the evaluation of PA and NA was performed by applying, on one occasion, the PANAS (Positive and Negative Affect Scale) as adapted to the Spanish population, which scores for both PA and for NA, ranging from 10 to 50 points.21

Both the record of recent onset arthritis and the study described in this paper have been approved by the Ethics Committee of the Clinical Health Research Institute of the Hospital Universitario de La Princesa. Patients signed informed consent at the time of inclusion into the registry and another specifically made for performing the PANAS scale.

Statistical analysis was performed using Stata 10.1® software for Windows (StataCorp LP, College Station, TX, USA). We calculated the median and interquartile range (RI) for continuous variables and non-Gaussian distribution and the median and standard deviation for those with normal distribution. To evaluate differences between groups we used the “U” test of Mann and Whitney for continuous independent variables. For qualitative variables we used the chi-square test. We considered P<.05 as statistically significant.

To estimate the effect of PA and NA on DAS28, HAQ and pain, we performed a multivariable linear regression for each, where to get the best fit, and the model initially included all sociodemographic and clinical variables available, and later we phased out the variables with worse P values one by one repeating it in every step of the model, until all remaining variables in the model had a P<.15. This was considered for each dependent variable (pain, HAQ and DAS28) the best possible model and we were forced to include PA and NA variables to estimate the effect on these dependent variables.

The current model proposes a close relationship between the presence of chronic illness with biological, psychological and social aspects throughout the process. However, the personal disposition of the emotion scale assessed by the PANAS does not seem to be intensely affected by the occurrence or persistence of the disease. Thus, our data show that the development of the clinical phase of the disease is not incident on the basic psychological factors detected by the PANAS scale, since the average score of our populations’ positive or negative emotions is similar to that obtained in other studies with healthy Spanish population.22,24 Rated in reverse, our data indicate that the structure of affect does not affect the risk of developing RA. However, the main finding of this study is that the structure of affect has an important influence on the assessment of the disease by the patient using three of the most frequently found tools in daily clinical practice to assess RA.

With respect to the assessment of pain by the patient, as expected, our data show that the activity of the disease is the variable that most affects the score on the visual analog pain scale. Moreover, sociodemographic factors such as the gender25,26 or level of schooling27,28 are also related to the level of sensitivity to pain. Although in our study there was a tendency to confirm these associations with sociodemographic variables, the second variable most associated with increased pain perception was the NA score. The negative affect represents a state of subjective distress that includes unpleasant aversive states such as nervousness, fear or disgust,22 so logically, it leads these patients to a more intense perception of the pain experience. In this sense, our data are similar to that previously reported both in general health and in patients with RA.16,17

Moreover, even when adjusting for the level of disease activity and perceived pain in our patients with early arthritis, high NA scores were also associated with higher scores of the HAQ. However, this effect was less important in patients in remission and detected more clearly than in patients with moderate and high activity. Because patients with higher scores tend to have higher NA somatic14 complaints, it seems logical to have a greater sense of disability when their disease is not well controlled. Previous studies indicate that psychosocial factors can explain up to 9% of disability when assessed with the HAQ, almost radiological progression could explain as much as 11%, with the disease activity which is involved in up to 51% of the HAQ.29 In our study, the NA score, as a psychological endpoint, achieved very manifest significance. It is possible that in a larger sociodemographic population sample, factors such as gender, educational level and marital status would have attained greater significance, but our data seem to derive its clinical relevance less than that of psychological parameters.

Finally, with respect to the assessment of disease activity in DAS28, we describe here for the first time that patients with higher PA scores showed a better evolution of disease activity. This effect was more pronounced in the follow-up visits at baseline where practically no effect was observed on the PA score. A possible explanation for our finding is that patients with high scores on PA are more optimistic when assessing clinical response to treatment and that two of the parameters included in the DAS28 depend on the patient's subjectivity. Thus, neuroimaging studies have shown that positive affect is associated with high levels of left prefrontal activation, effective modulation of activation in the amygdala and rapid recovery in response to negative and stressful events.30 Another possibility is that patients with high PA scores on treatment performed better than those with low scores on this subscale of the PANAS. Although the impression is that adherence to treatment can significantly influence psychological characteristics, there are no studies to confirm this suspicion and the greater is the influence of other factors such as comfort of medication or educacional31 level that have been well demonstrated.

Possible limitations of the study include the small number of patients in which the study was conducted and no healthy population control. In the latter case, this gap was filled with a comparison with previously published data by Sandin et al. in a Spanish22 population, although the age in that group was lower than that in our patients. Regarding the limited number of cases studied, we think it could prevent some variables from reaching statistical significance in the multivariate models, but the effect of PA and NA on the pain, disability and disease activity variables is solid, as has been detected even in this sample. Clearly, further studies would be needed to validate these findings in other populations and confirm the influence that the affect structure seems to have on the tools we use routinely to evaluate patients with RA.

In conclusion, our data indicate that the affective structure of our patients may have an impact on the results obtained after the application of the tools to evaluate our patients with RA. It is very likely that rheumatologists unconsciously evaluate these conditions. This aspect is relevant because today we make important decisions, such as starting biological therapy, according to the DAS28 score, so it is probably better to objectify parameters in our patients, such as the PA and NA scales, taking into account that they are easy to fill out in a questionnaire and have a high reproducibility over time.

Protection of human and animal subjects. The authors declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration.

Confidentiality of Data. The authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.

Right to privacy and informed consent. The authors have obtained the informed consent of the patients and /or subjects mentioned in the article. The author for correspondence is in possession of this document.

This work was funded by Health Research Fund PI080754 and the RETICS Program (RD08/0075-RIER), both of the Carlos III Health Institute (ISCIII).

The authors have no conflict of interest to declare.