Reappraisal of the Diagnostic and Prognostic Value of Morning Stiffness in Arthralgia and Early Arthritis

Results From the Groningen EARC, Leiden EARC, ESPOIR, Leiden EAC and REACH

Jessica AB van Nies; Celina Alves; Audrey LS Radix-Bloemen; Cécile Gaujoux-Viala; Tom WJ Huizinga; Johanna MW Hazes; Elisabeth Brouwer; Bruno Fautrel; Annette HM van der Helm-van Mil

Disclosures

Arthritis Res Ther. 2015;17(108) 

In This Article

Abstract and Introduction

Abstract

Introduction Morning stiffness is assessed daily in the diagnostic process of arthralgia and arthritis, but large-scale studies on the discriminative ability are absent. This study explored the diagnostic value of morning stiffness in 5,202 arthralgia and arthritis patients and the prognostic value in early rheumatoid arthritis (RA).

Methods In arthralgia patients referred to the Early Arthritis Recognition Clinics (EARC) of Leiden (n = 807) and Groningen (n = 481) or included in the Rotterdam Early Arthritis Cohort (REACH) study (n = 353), the associations (cross-sectional analyses) between morning stiffness and presence of arthritis at physical examination were studied. In early arthritis patients, included in the Leiden Early Arthritis Clinic (EAC) (n = 2,748) and Evaluation et Suivi de POlyarthrites Indifférenciées Récentes (ESPOIR) (n = 813), associations with fulfilling the 2010-RA criteria after one year were assessed. In 2010-RA patients included in the EAC (n = 1,140) and ESPOIR (n = 677), association with the long-term outcomes of disease-modifying antirheumatic drug (DMARD)-free sustained remission and radiological progression were determined. Morning stiffness was defined as a duration ≥60 minutes; sensitivity analyses were performed for other definitions.

Results In arthralgia, morning stiffness (≥60 minutes) associated with the presence of arthritis; Leiden EARC odds ratio (OR) 1.49 (95% CI 1.001 to 2.20), Groningen EARC OR 2.21 (1.33 to 3.69) and REACH OR 1.55 (0.97 to 2.47) but the areas under the receiver operating characteristic curve (AUCs) were low (0.52, 0.57, 0.54). In early arthritis, morning stiffness was associated with 2010-RA independent of other predictors (Leiden EAC OR 1.72 (95% CI 1.31 to 2.25, AUC 0.68), ESPOIR OR 1.68 (1.03 to 2.74, AUC 0.64)). Duration of ≥30 minutes provided optimal discrimination for RA in early arthritis. Morning stiffness was not associated with radiological progression or DMARD-free sustained remission.

Conclusions Morning stiffness in arthralgia and early arthritis is associated with arthritis and RA respectively. This supports the incorporation of morning stiffness in the diagnostic process.

Introduction

Morning stiffness is common in patients with rheumatoid arthritis (RA); it affects the ability to function in the morning,[1] the quality of life and is associated with work loss.[2] Presence of morning stiffness, together with fatigue, are often mentioned as one of the first symptoms of RA. Therefore, morning stiffness is usually assessed in the diagnostic process of patients presenting with arthralgia or arthritis.[3]

The scientific data on the diagnostic value of this symptom are surprisingly scanty. In the literature, it has been mentioned that morning stiffness is a poor discriminator between RA and other rheumatologic disorders.[4,5] However, these conclusions are predominantly based on two studies, with relatively small sample sizes. The first study compared 93 RA patients and 46 patients with non-inflammatory joint diseases.[4] The second study compared 31 RA patients with 23 systemic lupus erythematosus (SLE) patients and 34 osteoarthritis (OA) patients.[5] It has also been suggested that morning stiffness is commonly present in the general population and not specific for RA.[6,7] This notion is also based on only two studies. A large study revealed a prevalence of morning stiffness of 37% when defined as stiffness of ≥15 minutes; this definition is generally not considered as typical for RA.[6] The other study originated from the early 1950s and reported morning stiffness in 19% of persons without RA, but a definition of morning stiffness was not provided.[7] Altogether, there is not much evidence on the diagnostic value of morning stiffness. It is also not part of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA, whereas it had been included in the 1958 American Rheumatism Association (ARA) criteria and the 1987 ACR criteria for RA.[8–10] Because of the paradox of the lack of large-scale studies focusing on morning stiffness, and the use of morning stiffness in daily practice by rheumatologists and general practitioners, we set out to study the diagnostic value of morning stiffness in arthralgia and early arthritis by studying different European datasets and cohorts. The basic aim to this study was to evaluate the diagnostic value of morning stiffness. Because the diagnostic value is dependent on the patient population in which a test is performed, we studied the discriminative ability of morning stiffness in two situations. First, in cross-sectional analyses on patients with arthralgia, the association between morning stiffness and the presence of arthritis at physical examination was studied. This information is relevant for general practitioners (GPs) and other physicians who encounter patients with joint symptoms in their practices and who have limited experience in joint examination. Second, in early arthritis, the ability of morning stiffness to discriminate patients with RA from other early arthritis patients was assessed.

Although it is known that morning stiffness is associated with the disease activity,[11] functional disability[12] and work loss[2] in RA, it is undetermined whether morning stiffness at first presentation is a risk factor for a more severe disease reflected by structural damage or disease persistence. To evaluate this, associations with radiographic progression and achieving DMARD-free sustained remission (the absence of disease persistence) were assessed in two longitudinal cohort studies.

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