Improvement in symptoms and signs in the forefoot of patients with rheumatoid arthritis treated with anti‐TNF therapy

Abstract

BackgroundInhibition of tumour necrosis factor (TNF) is an effective way of reducing synovitis and preventing joint damage in rheumatoid arthritis (RA), yet very little is known about its specific effect on foot pain and disability. The aim of this study was to evaluate whether anti-TNF therapy alters the presence of forefoot pathology and/or reduces foot pain and disability.MethodsConsecutive RA patients starting anti-TNF therapy (infliximab, etanercept, adalimumab) were assessed for presence of synovial hypertrophy and synovitis in the 2nd and 5th metatarso-phalangeal (MTP) joints and plantar forefoot bursal hypertrophy before and 12 weeks after therapy. Tender MTP joints and swollen bursae were established clinically by an experienced podiatrist and ultrasound (US) images were acquired and interpreted by a radiologist. Assessment of patient reported disease impact on the foot was performed using the Manchester Foot Pain and Disability Index (MFPDI).Results31 patients (24 female, 7 male) with RA (12 seronegative, 19 seropositive) completed the study: mean age 59.6 (SD 10.1) years, disease duration 11.1 (SD 10.5) years, and previous number of Disease Modifying Anti Rheumatic Drugs 3.0 (1.6). Significant differences after therapy were found for Erythrocyte Sedimentation Rate (t = 4.014, p < 0.001), C-reactive protein (t = 3.889, p = 0.001), 28 joint Disease Activity Score (t = 3.712, p = 0.0001), Visual Analog Scale (t = 2.735, p = 0.011) and Manchester Foot Pain and Disability Index (t = 3.712, p = 0.001).Presence of MTP joint synovial hypertrophy on US was noted in 67.5% of joints at baseline and 54.8% of joints at twelve weeks. Presence of plantar forefoot bursal hypertrophy on US was noted in 83.3% of feet at baseline and 75% at twelve weeks. Although there was a trend for reduction in observed presence of person specific forefoot pathology, when the frequencies were analysed (McNemar) this was not significant.ConclusionsSignificant improvements were seen in patient reported foot pain and disability 12 weeks after commencing TNF inhibition in RA, but this may not be enough time to detect changes in forefoot pathology.

Comparative Distribution of Ultrasound‐Detectable Forefoot Bursae in Patients With Osteoarthritis and Rheumatoid Arthritis

“…We hypothesized that, in patients who have RA, the increased prevalence of FFB may be related to increased inflammation. This concurs with other investigators who have suggested that the synovium, which lines the otherwise inconspicuous intermetatarsal (IM) anatomical bursae, becomes hypertrophied as a consequence of excessive disease activity (). Conversely, other investigators have hypothesized that adverse mechanical pressure and shearing forces may result in the accumulation of interstitial fluid within the subcutaneous tissues, often termed adventitial bursae ().…”

“…All US scans were performed after completion of a clinical assessment, as per the standardized protocol for the study. The primary study outcome, the presence of FFB, was determined for all participants using a predetermined US scanning protocol for the forefoot region (). Both forefeet were imaged in all participants from plantar and dorsal approaches, in longitudinal and transverse scanning planes, using 8–16‐MHz and 5–10‐MHz linear array transducers, and imaging was completed prior to the assessment of mechanical foot characteristics.…”

The relevance of ultrasound examination of the foot and ankle in patients with rheumatoid arthritis – a review of the literature

“…The intermetatarsal bursae are visible at US evaluation when pathologically inflamed as the accumulation of fluid (anechoic area that is compressible) surrounded by thickened, hypoechoic walls (due to the hypertrophy of the synovial layer), that bulges more than 1 mm under the metatarsal head level. The US examination of submetatarsal bursae shows a hypoechoic/anechoic or heterogenous fluid accumulations located at the level of submetatarsal fat tissue [6,[31][32][33][34][35]. The intermetatarsal bursae are located just above the deep transverse metatarsal ligament, never extending below this structure.…”

“…Subclinical involvement of the feet and ankles joints (with the aspect of synovitis in US examination), frequently overlooked by clinicians, also impairs feet functionality and patients' quality of life [5]. Foot and ankle disability and pain in RA patients significantly improve after initiation of biological therapy [6] but this is valuable if the treatment is initiated before the advance/irreversible lesions appeared.…”

Visualizing arthritic inflammation and therapeutic response by fluorine-19 magnetic resonance imaging (19F MRI)

“…Inflammation of the synovial membrane is a hallmark of the disease, with the disease eventually progressing to cartilage and osseous degradation. There is no known cure, however therapeutic treatments are available and recent advances in the imaging of the disease and associated inflammation have allowed earlier diagnosis and intervention [3,4], with the possibility for increased mobility and quality of life for patients through disease management [5-7]. …”