INTRODUCTION
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of complex pathogenesis with a wide range of clinical manifestations (1). It is characterized by multi-system inflammation with the production of autoantibodies and the formation of immune complexes and their deposition into tissues. Affection of the musculoskeletal system is one of the most common and earliest manifestations of the disease, occurring in 95% of patients (1,2). The joint involvement may range from mild arthralgia and arthritis to a rare non-erosive deforming arthropathy (Jaccoud arthropathy) (1), and almost all joints can be affected. In older studies, the most commonly affected joints were the small joints of the hands, the wrist, and the knee, while recent studies point to the frequent involvement of the joints of the feet (3,4). Periarticular structures may also be affected by inflammation. Tendonitis, tenosynovitis, and changes or ruptures of the tendons have also been described in SLE patients, sometimes being the only cause of pain and instability in these patients. Affection of the ankle often occurs in patients with inflammatory rheumatic diseases. Clinical examination of the ankle may underestimate the type and distribution of the pathological changes due to the complexity of the anatomical structures of that area. Conventional radiological examination of the ankle provides bone structure data while providing very little information about the surrounding soft tissue. Magnetic resonance imaging (MRI) is a high-resolution imaging that can show both bone and soft tissue structures. It is very sensitive to changes in joints, but it is expensive and often unavailable in routine clinical practice.
High resolution Power Doppler (PD) and musculoskeletal ultrasound (MSUS) has been proven to be a useful and non-invasive diagnostic technique for assessing and tracking pathological changes in joints, tendons, and entheses (5). There is extensive literature on the benefits of MSUS in various inflammatory rheumatic diseases, mostly in rheumatoid arthritis, psoriatic arthritis, and other spondyloarthropathies (6,7). However, so far few ultrasound studies have been conducted that evaluate the joints in SLE patients (4,8,9).
PATIENTS AND METHODS
The pilot study included 10 consecutive SLE patients diagnosed according to the 1997 revised ACR criteria, who were treated at the Division of Clinical Immunology and Rheumatology at the University Hospital Center Zagreb (10). The study protocol included an ultrasound and physical examination performed the same day as the regular rheumatologist follow-up and laboratory reevaluation. The MSUS examination was performed in all patients, regardless of the presence or absence of pain and swelling in the joints and tendons. The study was conducted according to the guidelines of good clinical practice as well as the Helsinki Declaration. All patients signed an informed consent form.
Clinical and demographical data (date of diagnosis, disease duration, system involvement, current and previous therapy, previous presence of pain and swelling of the ankle) were collected from each study patient. All patients were subjected to a standardized physical examination that evaluated the presence of painful and swollen joints and deformities (44 joints), with the evaluation of tendons and joints of the feet and ankles. To assess the disease activity, the SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index 2000) and ECLAM (European Consensus Lupus Activity Measurement) were used (11,12). For the purposes of the study, data on patients with SLE included in the hospital register were used as well. A single rheumatologist, who was blinded to the clinical and laboratory data, performed the MSUS examination and scored the static images. The images were also scored by another independent rheumatologist expert in MSUS.
A high-resolution US equipped with a multifrequency linear array transducer (4–15 MHz) with PD was used. Multiplanar examination techniques were performed in accordance with the International Guidelines for MSUS in Rheumatology for imaging of the TC and ST joints, ankle tendons, second and third MCP joints, second and third PIP joints, second and third MTP joints, and wrists (13). A total of 18 joints and 20 tendons were examined in each patient and the inflammatory US score and global inflammatory US score were calculated. The joints for global inflammatory US scoring were selected according to the shown frequency of the joint involvement in recent studies. The presence of joint effusion, synovial hypertrophy, bone erosion, tenosynovitis, and enthesitis was defined according to the OMERACT definitions (13). US-detected elementary lesions were evaluated with a dichotomous score (absence/presence). A semi-quantitative scale (0–3) was used for scoring joint effusion, synovial proliferation, and PD.
RESULTS
Ten consecutive patients, all females, were enrolled in the study. The mean age was 45.3 years and the mean disease duration 164 months. Half of the enrolled subjects did not have musculoskeletal symptoms at the time of examination. The demographic, clinical, and serologic data are reported inTable 1. For the majority of patients, treatment was based on corticosteroids alone or combined with various different disease-modifying anti-rheumatic drugs.
Ultrasonographic findings
A total of 180 joints and 200 tendons were examined. Preliminary results in 10 patients showed US-detected inflammatory joint abnormalities in 7/10 (70%) patients and tendon involvement in 1/10 (10%). Both the MTP and TC joints were affected in 60% of the patients, MCP joints in 50%, ST in 40%, wrists in 30%, and PIP joints in 10% of the patients. According to these findings, the TC and MTP were the most frequently involved joints. The most severely affected joints were the TC and MCP, with clinical and ultrasound synovitis at the time of evaluation. The most prevalent pathological US findings in all examined joints were joint effusion and synovial hypertrophy (present in 80% of the patients), while a positive PD signal was rarely detected (30%). Only one patient had bone erosion verified. Furthermore, the most prevalent pathological US finding in the ankles was also joint effusion (60%), less frequently synovial hypertrophy (40%), while a positive PD signal was present in 10% of the patients. As many as 62.5% of the patients without inflammatory joint symptoms had pathological US findings in the ankle joints. The mean value of the global US inflammatory score was 5.6, while the mean value of the ankle US inflammatory score amounted to 2.9.
DISCUSSION
Existing studies indicate a high prevalence of joint and tendon inflammatory changes in SLE patients and it is apparent that ultrasound changes of the hand and wrist joints are common in those patients, depending on the type of arthropathy (4,8,9,14,15). Furthermore, most studies have shown that there is significant subclinical joint involvement in SLE patients (4,14,15). This leads to the conclusion that reliance on the physical examination of the joints can underestimate the presence of active joint inflammation. In the systematic review by Lins and Santiago from 2015, which included a literature overview from 1950 to 2015, the high frequency of subclinical joint and tendon US pathology was also shown (14). Most articles in this review demonstrated hand and wrist joint changes (14). In the research by Iagnocco et al. in 2014, ultrasonographic changes of the joints were described in a large proportion of patients (87%), while only 40% of them presented with clinical involvement of the joints. That study unexpectedly showed that the MTP joints were more commonly affected (72% of the patients) compared with the wrist (53%), MCP (46%), and PIP joints (19%) (4). In addition, the MTP joints were affected by more severe inflammatory changes compared with other examined joint levels. There are very few other studies that have evaluated the MTP joint region (4,15). The high prevalence of MTP joint ultrasound pathology was also demonstrated in a pilot study by Mukherjee in 2016 (15). This study also showed a high frequency of US-detected forefoot bursal prevalence and bursal PD (100% of patients). Significant associations between bursal prevalence and MTP joint PD were noted (15).
Studies conducted in other rheumatic diseases have found US with PD a useful tool for the assessment of pathologies in ankle joint and tendons, as well as the differentiation of inflammatory and degenerative changes (16). To the best of our knowledge, this is the first US study aimed at an analysis of inflammatory changes in the ankle joints and tendons in SLE patients. In our study we found that the most commonly affected joints were the TC and MTP joints (60% of the patients). That correlates with the research of Iagnocco et al., although it has to be noted that ankle joints were not analyzed in that study. Gabba et al., in a study that was conducted in 108 SLE patients with musculoskeletal symptoms, found that patients with active musculoskeletal disease had more US pathology in the joints, while asymptomatic subjects had more pathological findings in the tendons (9). Our findings showed that the most common changes in joints were joint effusion followed by synovial hypertrophy, while a positive PD signal was rarely observed, which correlates with other studies (4,5). It is important to emphasize that joint effusion was also present in 40% of asymptomatic patients in our study.
Data on the correlation between ultrasound findings and the inflammatory activity index SLEDAI-2k are contradictory. In our study both the SLEDAI-2k and ECLAM indexes were higher in the group of patients with pathological ultrasound findings in the ankle joints than in the group of patients without US changes. SLEDAI was 4.66/2 and ECLAM 2.5/1.375.