Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of autoimmune nature. The development of RA is considered a continuum that begins with a high-risk or susceptibility stage (pre-clinical RA) that can lead to articular inflammation and contribute to joint damage and irreversible disability.1 The European Alliance of Associations of Rheumatology (EULAR) has defined several phases up to the development of RA, including one that is characterized by the presence of symptoms without clinical arthritis (phase D).2 Early referral of patients highly suspected of rheumatoid arthritis (RA) has an impact on prognosis.3 Nevertheless, from all the patients with musculoskeletal symptoms visiting primary care physicians (PCP), only a small proportion had been considerate to have arthritis.

The large majority of the patients presenting with arthralgia of uncertain cause are not considered at risk of RA by their rheumatologist.4 The delay from symptom onset to the first visit with a rheumatologist ranges from several weeks to months.5,6 In Mexico, it has been described a mean time of 112.8 weeks from the onset of symptoms to the evaluation by a rheumatologist in a second-level public hospital.7 The EULAR has developed a definition of arthralgia suspicious for progression to RA that includes seven clinical items.8 Its use by a rheumatologist has been validated. However, its utility by PCP is unknown.9 We hypothesized that the characterization of patients visiting PCP with arthralgias of uncertain cause who later are referred to rheumatologists could be helpful to improve early diagnosis of inflammatory arthritis.

Our study aimed to evaluate the clinical characteristics of the patients with hands arthralgia attending PCP and explore their association with the referral to the rheumatology clinic in a tertiary care academic hospital from Mexico.

We developed a descriptive, observational, prospective cohort study. The study was conducted in the Department of Family Medicine from the University Hospital “Dr. Jose Eleuterio Gonzalez” from the Autonomous University of Nuevo Leon in Monterrey, Mexico between October 2018, and November 2020. The first patient was recruited October 2nd, 2018, and the last, March 3rd, 2020. The follow-up period according to the protocol stablished, was for at least a year.

A total of 109 patients were evaluated. The mean age was 49.9 years (SD±14.8), and 89 (81.6%) patients were female. 106 (97%) patients had right-hand dominance. The criteria for arthralgia suspicious for progression to RA and the complementary questions are shown in Table 1.

A total of 33 (30.3%) patients were referred to the rheumatologist. From the 33 patients referred, 13 (11.9%) patients were referred after their first visit with PCP, 15 (13.8%) patients were referred at their second visit, and 5 (4.6%) patients were referred after their third visit to PCP (Fig. 1). Since the first visit with PCP, the time to referral was a median of 38 days (IQR: 20.5–62.5; Min: 7, Max: 233).

Fig. 1.

Flowchart of patients since their first visit in primary care until their referral to the rheumatologist.

(0.11MB).

There was no difference between referred and non-referred patients in the pressure needed to provoke pain in the right hand (median 3.0 [IQR=2.0–7.4]kg vs. median 2.5 [IQR=1.5–5.2]kg, P=0.277) or the left hand (median 3.0 [2.0–6.7] vs. median 2.5 [1.6–4.4]kg, P=0.267).

There was no difference in the proportion of patients with ≥4 criteria for arthralgia suspicious for progression to RA (15 [45.5%] vs. 26 [34.2.%], P=0.265) between referred and non-referred patients, respectively.

From the clinical characteristics evaluated by the combined questionnaire with the EULAR criteria for arthralgia suspicious for progression to RA and the added complementary questions, the factors associated with referral to the rheumatologist were the “most severe symptoms are present after midnight” (OR=6.29, 95% C.I. 1.72–22.97, P<0.005) and the “difficulty with making a fist” (OR=3.67, 95% C.I. 1.087–12.36, P=0.036). Paradoxically, the presence of a “positive squeeze test of metacarpophalangeal joints” during the first visit to PCP (as documented in medical chart) was associated with a lower probability to be referred with the rheumatologist (OR=0.16, 95% C.I. 0.05–0.51, P=0.002) (Tables 2 and 3).

The diagnosis more frequently assigned during the first PCP visit was “arthralgia in study” in 86 (78.9%) patients, followed by osteoarthritis in 8 (7.3%) patients, and only 4 (3.7%) patients were diagnosed with RA. At the review of medical charts of patients under follow-up, 53 (48.6%) patients continued with the diagnosis of “arthralgia in study”, 23 (21.1%) were diagnosed with osteoarthritis, and 15 (13.8%) patients had the diagnosis of RA, one year after the first visit. From the 33 patients that were referred to the rheumatology clinic, 19 (57.6%) had a type of inflammatory arthritis, being RA the most frequent (39.4%). Only 3 (9.1%) patients continued with the diagnosis of “arthralgia in study” after a visit with the rheumatologist. More details about the diagnoses established are shown in Table 4.

Our study found that 30.3% of the patients with hands arthralgia who attend a PCP were referred to the rheumatologist. From these, only 11.9% were referred after their first visits with PCP. The median time elapsed from their first visit with PCP until their first visit with the rheumatologist was 38 days. Patients with most severe symptoms after midnight and difficulty making a fist were six and more than three times as likely to be referred to the rheumatology clinic. Our findings suggest that identifying certain clinical characteristics may be useful to identify patients who might benefit from a prompt referral to the rheumatologist.

It has been proposed that all patients with suspected inflammatory arthritis should be referred urgently to the rheumatologist even before obtaining results of tests,11 but only half of all patients with RA are first seen by a rheumatologist within three months.12 In a survey of English PCP, the patient history and physical examination had the most significant impact on the decision to refer compared to acute phase markers and serology; despite this, only 26% of PCP referred suspected RA immediately without investigations.13 In our study, we found that only one out of ten patients with hands arthralgia were referred immediately after the first visit; this could be explained by the broader inclusion of patients who might have a lower suspicion of RA.

We did not find any significant difference in the pressure needed to provoke pain in the metacarpophalangeal joints using an automatic squeeze test machine or using the physician's strength between referred and non-referred patients. This meaning that the tests are equally helpful. The simplicity to perform this maneuver has made it highly recommended; nevertheless, only 17% of Dutch PCPs recorded this test in the electronic medical record of patients with inflammatory arthritis.14

In patients with arthralgia of recent onset referred to a rheumatology outpatient clinic, a positive squeeze test was associated with local joint inflammation detected with MRI, yet, it has a low sensitivity.15 Furthermore, in a more recent study in the same center, a positive squeeze test was not associated with inflammatory arthritis development. However, when it is positive in clinically suspect arthralgia, it doubled the probability of subclinical synovitis.16 We consider these findings relevant because they highlight the utility of this maneuver only when symptoms are present. Also, a negative squeeze test does not rule out the disease.

We evaluated the utility of the EULAR definition of arthralgia suspicious for progression to RA in primary care practice, assessing if these clinical items could be helpful to identify patients who would be referred to rheumatologists early in their disease. The single independent clinical item strongly associated with the referral was the “difficulty with making a fist”; this has been described as a sign of underlying flexor tenosynovitis.17 From the complementary questions evaluated, we found an item associated with an increased probability to be referred, the “most severe symptoms are present after midnight.” Prior studies suggested that a positive rheumatoid factor,18 disease severity,19 exposure to rheumatology during residency,20 and belief in the rheumatologist's efficacy19 were factors associated with referral to a rheumatologist by the PCP, but also additional factors have been described besides clinical characteristics of the patients that influenced the decision to refer or not refer in primary care, such as patient preferences, access issues, administrative leadership, physician confidence and expectations, and interpersonal relationship.21 We did not find any difference in the proportion of patients with ≥4 criteria for arthralgia suspicious for progression to RA, a cut-off previously described with a specificity of 93.4% in the rheumatologist practice.8

This is the first study that evaluates the utility of the EULAR definition of arthralgia suspicious for progression to RA in primary care to the best of our knowledge.

Some limitations of our study were the sample size, but this was also the natural pattern of presentation of hands arthralgia in primary care. The patients included were from a single center, a family medicine outpatient clinic from a University Hospital; PCPs were not included in patient inclusion for this study. Notice that our population could be different from those who are attended by other PCPs or Internal Medicine clinics. Furthermore, the complementary questions evaluated have not been validated.

The prospective and observational design are among the strengths that allow us to describe the original characteristics at the onset of presentation in primary care practice without the influence of researchers or a controlled environment. To the best of our knowledge, this was the first evaluation of the utility of the EULAR definition of arthralgia suspicious for progression to RA in primary care to identify patients who will be referred to a rheumatologist. We also added complementary clinical items not included in the EULAR definition that could improve the identification of these patients. We used the manual and the automatic standardized method to evaluate the squeeze test in primary care. The manual method previously has shown to have low sensitivity and moderate-high specificity practiced by a rheumatologist, who is accepted as the expert performing this maneuver; including the automatic method improved the supposed lack of experience of the PCP, being this another strength.

We concluded that among patients who attended PCP for hands arthralgia, those with the most severe symptoms after midnight and difficulty making a fist were more likely to be referred to the rheumatology clinic. Our findings suggest that identifying specific clinical characteristics may be useful to identify patients who might benefit from a prompt referral to the rheumatologist. Isolated positive squeeze tests are not a parameter for referral, it should only be performed if arthralgia is clinically suspected.

The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.

All authors declare there is no conflict of interest.