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Changes in the clinical presentation of patients with rheumatoid arthritis from the early 1990s to the years 2010: earlier identification but more severe patient reported outcomes
  1. Wouter P Nieuwenhuis1,
  2. Maarten PT de Wit2,
  3. Annelies Boonen3,
  4. Annette HM van der Helm-van Mil1
  1. 1 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2 Department of Medical Humanities, VU University, Amsterdam, The Netherlands
  3. 3 Division of Rheumatology, Department of Internal Medicine, Maastricht University Medical Center and CAPHRI, Maastricht University, Maastricht, The Netherlands
  1. Correspondence to Wouter P Nieuwenhuis, Department of Rheumatology C1-R, Leiden University Medical Center, PO Box 9600, Leiden 2300RC, The Netherlands; W.P.Nieuwenhuis{at}

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The relevance of early identification of rheumatoid arthritis (RA) is acknowledged for several decades. Over time the interpretation of early has changed: in the early 1990s a symptom duration <2 years was considered early. Nowadays earlier identification is recommended,1 some suggest that identification within 12 weeks after symptom onset is optimal. In this study, we evaluated the presentation of RA over the past decennia. We assessed whether patients with RA were recognised earlier and if this affected the phenotype of RA at first presentation. We observed that patients with RA are indeed identified after a shorter symptom duration, that this was paralleled with less severe inflammation at presentation, but paradoxically also with increased severity of patient reported outcomes (PROMs).

All patients in the Leiden Early Arthritis Clinic (EAC) cohort that fulfilled the 2010 European League Against Rheumatism/American College of Rheumatology RA criteria were studied (n=1406).2 ,3 In short, the EAC was started in 1993 and inclusion criteria were arthritis at physical examination and symptom duration <2 years. At baseline, hence before treatment initiation, 68-tender and 66-swollen joint counts were performed, blood samples taken and the PROMs fatigue, pain, morning stiffness and disease activity obtained. Initially PROMs were recorded as visual analogue scales (VASs), from 2010 onwards numerical rating scales were used. Both scales correlate strongly.4 Because changes in presentation were expected to occur gradually, patients with RA were compared over five periods. Variables were compared using Kruskal-Wallis H-test.

Symptom duration at presentation decreased over the years from median 138 days in 1993–1996 to 97 days in 2011–2015 (p<0.001, table 1). The frequency of autoantibodies did not differ significantly. Patients with RA presented with less swollen joints (median 11 decreased to six joints, p<0.001) and lower levels of acute phase reactants (median C-reactive protein (CRP)-level 24 decreased to 10 mg/L, p<0.001). The health assessment questionaire (HAQ) (measuring functional disability) remained stable (table 1). PROM values increased: patients reported more pain (p<0.001), more fatigue (p=0.005) and higher disease activity (p<0.001) (figure 1). Furthermore, the disease activity score (DAS)28-CRP (combining joint counts, CRP and patient global health) decreased (p=0.001).

Table 1

Characteristics of patients with RA (according to the 2010-criteria) at first presentation to the rheumatological outpatients clinic

Figure 1

The severity of inflammation and of several patient reported outcomes measures for patients with 2010-criteria positive rheumatoid arthritis that presented in different time periods. Depicted are the medians per period. The IQRs are shown in table 1. CRP, C-reactive protein; VAS, visual analogue scale.

These findings are paradoxical: while patients with RA over time presented with shorter symptom duration and less inflammatory findings, PROMs worsened. The finding that all evaluated PROMs increased makes it unlikely to be a coincidental finding. The VAS fatigue and pain are known to be strongly correlated5 and it is known that patient perceptions are minimally explained by inflammatory findings.6 ,7

Presumably, the present findings are not specific for RA, but reflect a general increase in societal pressure posed upon the individual over the years (ie, society has become more demanding), whereby smaller health problems, which might be less visible, could be experienced as more disabling.8 In parallel, patients may also have higher health expectations themselves. Both phenomena likely contribute to a shift of reference when reporting outcomes.

This is the first study describing temporal changes in presentation of new patients with RA, but discordance between inflammatory measures (SJC and erythrocyte sedimentation rate) and PROMs has been reported. First, differences in inflammatory outcomes between countries were not paralleled by similar differences in VAS fatigue and global health.9 Similarly, comparing patients with RA treated in 1985 with patients treated in 2000 revealed that the latter group had less inflammation, but similar VAS pain.10

The previous observations that PROMs were not responsive to changes in the severity of inflammation combined with the present finding raise the question if it is known what PROMs actually measure. Furthermore, this may have consequences for the monitoring of RA using PROMs or composite scores (eg, DAS or simple disease activity index (SDAI)) for defining remission.

In conclusion, over the last 23 years patients with RA in Leiden (the Netherlands) have presented with shorter symptom duration. Even though patients with RA presented with less inflammation, the disease burden as experienced by patients is higher.


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  • Contributors Study concept and design and drafting of the manuscript: WPN, AHMvdH-vM. Acquisition, analysis or interpretation of data and critical revision of the manuscript for important intellectual content: WPN, MPTdW, AB, AHMvdH-vM. Statistical analysis: WPN.

  • Funding This work was supported by the Dutch Arthritis Foundation and the Netherlands Organization for Health Research and Development (Vidi grant).

  • Competing interests None declared.

  • Ethics approval Medical ethical committee of the Leiden University Medical Center.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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