Ultrasound of the forefeet besides the hands in patients at risk for rheumatoid arthritis: is it worth the effort? A longitudinal cohort study

Abstract

Objective: US can detect subclinical joint-inflammation in patients with clinically suspect arthralgia (CSA), which is valuable as predictor for RA development. In most research protocols both hands and forefeet are scanned, but it is unclear if US of the forefeet has additional value for predicting RA, especially since synovial hypertrophy in MTP-joints of healthy individuals is also common. To explore the possibility to omit scanning of the forefeet we determined if US of the forefeet is of additional predictive value for RA-development in CSA patients.

Methods: CSA patients of two independent cohorts underwent US of the hands and forefeet. We analysed the association between RA-development and US-positivity for the full US-protocol, the full US-protocol with correction for gray scale (GS)-findings in the forefeet of healthy and the protocol without forefeet.

Results: In total, 298 CSA patients were studied. In patients with a positive US, subclinical joint-inflammation was mostly present in the hands (90-86%). Only 10-14% of patients had subclinical joint-inflammation solely in the forefeet. US-positivity was associated with inflammatory arthritis development in both cohorts, with HRs 2.6 (95% CI 0.9-7.5) and 3.1 (95% CI 1.5-6.4) for the full protocol, 3.1 (95% CI 1.3-7.7) and 2.7 (95% CI 1.3-5.4) for the full US-protocol with correction, and 3.1 (95% CI 1.4-6.9) and 2.8 (95% CI 1.4-5.6) without the forefeet. AUROCs were equal across both cohorts.

Conclusion: The forefeet can be omitted when US is used for the prediction of RA-development in CSA patients. This is due to the finding that subclinical joint-inflammation in the forefeet without concomitant inflammation in the hands is infrequent.

Keywords: diagnostic imaging; foot; observational studies; rheumatoid arthritis; ultrasonography.

Figure 1.

Positive US per MTP-joint according to the full protocol (A) and the full protocol with correction (B), for cohort 1. Represented are the US-findings based on GS and/or PD per joint depicted, for cohort 1. Frequencies for cohort 2 are depicted in Supplementary Fig. S1, available at Rheumatology online.The circles represent an MTP-joint (MTP1–5 from left to right), the percentage depicted is the percentage of patients who had a positive ultrasound within that specific joint (right and/or left sided), according to the full protocol (based on a GS score ≥2 and/or PD signal of ≥1) (A) or with additional correction for MTP2 and 3 (B). The US full protocol with correction applies a stricter correction for positivity for MTP2 and MTP3 (gray scale 3 only). Only MTP2–5 are included in the US-protocols. CSA: clinically suspect arthralgia; GS: gray scale; N/A: not applicable; PD: power Doppler

Figure 2.

Donut graph representing all patients with US-positivity in the full protocol with correction, illustrating that patients with US-positivity based on the MTP-joints only is less common. In total, 60% (n = 85) of the patients in cohort 1 had a positive US defined in the full protocol with correction. In cohort 2, this was 33% (n = 51). Presented are the percentages of patients with a positive US in the full protocol with correction (100%). Of these patients, 14% (cohort 1) and 10% (cohort 2) of the patients had positivity of the US based on MTP-joints only

Figure 3.

Kaplan–Meier curves for IA development in patients with a positive US for the three different US-protocols in cohort 1. Presented are the Kaplan–Meier curves towards arthritis development for the patients who had a positive ultrasound in the different US-protocols. In the US full protocol MCP2–5, flexor digitorum MCP2–5, wrist, wrist extensor/flexor and MTP2–5 are included. US-positivity was defined as GS ≥ 2 and/or PD ≥ 1. The US full protocol with correction applies a stricter correction for positivity for MTP2 and MTP3 (gray scale 3 only). The US-protocol without forefeet did not include MTP2–5. GS: gray scale; HR: hazard ratio; IA: inflammatory arthritis; PD: power Doppler

Figure 4.

Hazard ratios for arthritis development for the three different US-protocols in both cohorts GS and/or PD (A) and PD only (B). Presented are the hazard ratios with the corresponding 95% confidence intervals towards arthritis development for the patients who had a positive ultrasound in the different protocols. In the US full protocol MCP2–5, flexor digitorum MCP2–5, wrist, wrist extensor/flexor and MTP2–5 are included (GS ≥ 2 and/or PD ≥ 1). The US full protocol with correction applies a stricter correction for positivity for MTP2 and MTP3 (gray scale 3 only). The US without forefeet did not include MTP2–5. As the correction for GS-findings is not applicable in the B-part of the figure, only the US full protocol and the US without forefeet are presented. GS: gray scale; HR: hazard ratio; PD: power Doppler

Figure 5.

Positive predictive values (PPVs) and negative predictive values (NPVs) of the different US-protocols to predict inflammatory arthritis. Presented are the PPV and NPV for the different US-protocols. In the US full protocol MCP2–5, flexor digitorum MCP2–5, wrist, wrist extensor/flexor and MTP2–5 are included (US-positivity GS ≥ 2 and/or PD ≥ 1). The US full protocol with correction applies a stricter correction for positivity for MTP2 and MTP3 (gray scale 3 only). The US without forefeet did not include MTP2–5. For determination of the test characteristics patients of cohort 1 were selected ≥1 year of follow-up time to allow time towards arthritis development (n = 108). NPV: negative predictive value; PPV: positive predictive value