Modification of a sonographic enthesitis score to differentiate between psoriatic arthritis and young healthy volunteers

Objectives: We aimed to describe sonographic structural and inflammatory changes in entheses of patients with recently diagnosed psoriatic arthritis (PsA), patients with established PsA, and young healthy volunteers, and to investigate whether the MAdrid Sonographic Enthesitis Index (MASEI) enables us to distinguish these groups in an extreme comparison. Method: New and established PsA patients and healthy volunteers (aged 20–30 years) were recruited. The triceps, quadriceps, patellar, Achilles and elbow extensor tendon insertion, and plantar fascia entheses were investigated sonographically for structural changes, erosions, calcifications, increased thickness, bursitis, and power Doppler (PD) signal according to the MASEI. Results: The study included 25 new and 25 established PsA patients, and 25 healthy volunteers. Increased thickness and PD signal in knee entheses were common for patients and healthy volunteers, while changes at other locations predominantly occurred in patients only. PD was recoded (1, one spot; 1.5, two or three spots; 2, confluent signal; 3, severe confluent signal) and thickness of knee entheses excluded. This resulted in different modified MASEI scores between PsA patients and young healthy controls: median (interquartile range) modified MASEI of 13 (10–22.5) in new PsA, 13.5 (9.5–18) in established PsA, and 3 (1–8.5) in healthy volunteers (p = 0.002). Conclusions: Structural ultrasound changes and PD in entheses are common in both new and established PsA and healthy controls. MASEI score did not differentiate PsA patients from young healthy volu

Ultrasound Imaging in Psoriatic Arthritis: What Have We Learnt in the Last Five Years?

Psoriatic arthritis (PsA) is a complex heterogeneous disease with multiple inter-related pathologies such as synovitis, enthesitis, tendinopathy, and dactylitis. Clinical assessment is limited in its detail to assess pathology, thus in recent years, ultrasound (US) has become more popular, given its high sensitivity to detect inflammatory arthritis and ability to inform clinical decisions. Although a qualitative technique, US findings can be graded semi-quantitatively for grayscale (GS) and power Doppler (PD). Synovitis is frequently present in inflammatory arthritis pathologies, and in PsA, recent evidence shows a propensity for tendon and entheseal lesions. The presence of flexor tenosynovitis and flexor tendon insertional enthesopathy at accessory pulleys is supportive of the “Deep Koebner” concept. Peri-tendinous inflammation—mutual to PsA or rheumatoid arthritis (RA), is associated with soft tissue oedema with PD signal frequently at the flexor tendon compartments in PsA. Research on enthesitis in PsA/PsO has improved understanding in subclinical and clinical PsA, explored associations with progression to PsA, and investigated links to prognosis assessment. Dactylitis is a pathognomonic PsA lesion where US has enhanced knowledge of the disease course and pathology of lesions such as: flexor tenosynovitis; synovitis; and soft tissue oedema. Increased US sensitivity has also brought innovation including promising automated ultrasound scanning techniques. So, what have we learnt in recent years and what are the unmet needs to focus future research initiatives in this disabling disease? This narrative review article assesses the neoteric evidence, bringing into context the knowledge gained and highlighting potential areas of research

Enthesopathy as early manifestation in psoriatic arthritis

Background: Despite the progress made in the study of psoriasis and psoriatic arthritis, their early diagnosis and treatment for practicing physicians continue to be a difficult problem. Material and methods: 100 people were examined, including 70 patients with psoriatic arthritis aged between 18 and 60 years (23 men and 47 women), admitted to the rheumatology and arthrology departments of the Timofei Mosneaga Republican Clinical Hospital 2019-2022 (Favorable opinion of the Committee for Research Ethics, No 21 of 21.12.2019). The control group included 30 people with rheumatoid arthritis. Results: Ultrasound signs of damage to the joint structures were detected, such as synovitis (p=0.26), cartilage changes (p=0.433), enthesopathy (p=0.980) and tenosynovitis, statistically significant differences (p=0.800). Magnetic resonance imaging determined that fluid was the predominant symptom in frequency (n=13, 92.86%), including in the small joints of the hands (n=1, 100%) and feet (n=2, 100%). Conclusions: In large joints, the proliferation of the synovial membrane was detected in 51.67% of the joints and had predominantly high echogenicity. At small joints, synovial proliferation with predominantly low echogenicity occurred only in 6.1% of the joints

Measuring Disease Activity and Outcomes in Early Psoriatic Arthritis

Psoriatic Arthritis (PsA) is a heterogeneous disease, characterized by manifestations of peripheral arthritis, dactylitis, enthesitis, spondylitis, and psoriasis. Patients with PsA experience the impact of disease as loss of functional ability, decreased health-related quality of life (HRQOL) and loss of productivity. Treatment is aimed at preventing these consequences. It is recommended that treatment is given as early as possible, with all manifestations taken into account, and in a treat-to-target strategy. In a treat-to-target strategy, treatment is intensified if a certain target – a composite disease activity measure – has not been achieved. Good measures of disease activity are needed to improve outcomes for patients with PsA. For this purpose, more information is needed on disease activity and outcomes early in the disease course. These are studied in the Dutch southwest Early Psoriatic Arthritis cohoRt (DEPAR) and related sub-studies. This thesis aims to investigate the following four aspects of disease activity and outcomes in early PsA: ultrasound abnormalities of the entheses, burden of disease at time of diagnosis and its relation with disease manifestations, the relation between time to minimal disease activity and outcomes, and the performance of disease activity measures

More Than Skin Deep: Detection of subclinical enthesopathy and early psoriatic arthritis in patients with psoriasis in primary and secondary care and assessment of the response to anti-IL-12/IL-23p40 monoclonal antibody skin-directed therapy using ultrasound and whole-body MRI

Objectives: Primary care cohort: To determine the rates of undiagnosed psoriatic arthritis (PsA) amongst patients with psoriasis using clinical examination and screening questionnaires, and test the performance a new PsA screening questionnaire alongside the current standard (Psoriasis Epidemiology Screening Tool, PEST). Secondary care cohort: To develop novel ultrasound and whole body magnetic resonance imaging (WBMRI) protocols to facilitate the comprehensive assessment of subclinical abnormalities within the peripheral and axial skeleton of immunomodulatory therapy-naïve patients with psoriasis referred to secondary care, and to use these protocols to assess the imaging response of abnormalities over 52 weeks of skin- directed treatment with a licensed IL-12/23p40 inhibitor (ustekinumab). Methods: Primary care cohort: 932 patients, across five diverse primary care practices, who were coded as having a diagnosis of psoriasis, were invited by their General Practitioner to attend an evening appointment at their surgery for a consultation with a dermatologist and a rheumatologist. Half of patients were sent an educational leaflet regarding PsA with their invitation letter. Attendees were examined and asked to complete a PEST questionnaire and a new PsA screening questionnaire (CONTEST). Secondary care cohort: 73 immunomodulatory therapy-naive patients, without musculoskeletal disease or symptoms, who were referred to dermatology for treatment of moderate to severe psoriasis were screened using an extensive ultrasound protocol to assess for the presence of subclinical enthesitis. Patients who had at least one inflammatory abnormality, and in whom biologic therapy was not contraindicated, were invited to receive standard-dose skin directed therapy with ustekinumab for 52 weeks. Ultrasound examination of 13 entheses and structures within the adjacent synovio- entheseal complex were performed at weeks 0, 12, 24 and 52. WBMRI was performed at week 0, 24 and 52, to assess the axial skeleton and sites in the peripheral skeleton inaccessible by ultrasound. 23 healthy volunteers had one ultrasound scan and WBMRI using the same protocols, for comparison. Results: Primary care cohort: 20.5% of patients invited for screening attended. The provision of an educational leaflet did not have an impact on attendance for screening, except in the most deprived areas. 191 patients were examined, of which 169 had current or previous psoriasis (11.5% misdiagnosis rate). 17 patients were newly diagnosed with PsA (10.1%). The best sensitivity and specificity of the CONTEST questionnaires were 76.5% and 56.5% respectively, without the joint mannequin (cut off 33), and 70.6% and 63.3% respectively, with the joint mannequin (cut off 34). The sensitivity and specificity of the PEST questionnaire in this cohort, using the validated cut off 33, was 52.9% and 66.0%. Lowering the cut off 32, the sensitivity improved to 82.4% with a specificity of 44.9%. Secondary care cohort: 36 patients (49.3%) had at least inflammatory subclinical abnormality on screening ultrasound. 28 of these 36 were eligible for a biologic therapy and agreed to undergo a more detailed ultrasound scan and WBMRI. 5 patients subsequently chose conventional therapy, and 23 patients consented to treatment with ustekinumab and long-term review. 23 patients reached the primary end point of week 24, and 20 reached week 52. Inflammatory and chronic damage abnormalities were seen with greater frequency in the peripheral rather than axial skeleton, mostly involving the larger entheses of the knee, foot, ankle and elbows. Healthy volunteers exhibited a similar pattern of abnormalities but at a significantly lower frequency (inflammatory lesions 4.5% vs. 31.1%, chronic damage lesions 6.0% vs. 27.0%, both p<0.00001). Synovitis was seen in 82.1% of patients, while bursitis and tenosynovitis were uncommon. Following treatment with ustekinumab, ultrasound inflammation scores reduced by 42.2% at the primary end point (week 24, p<0.001), and by 51.5% after 52 weeks (p=0.01). Chronic damage scores remain unchanged (p=0.082 week 24, p=0.512 week 52). In the axial skeleton, more patients than volunteers had vertebral unit bone marrow oedema (64.3% vs. 30.4%, p<0.00001). Sacroiliac joint inflammation was minimal in both groups. Axial structural changes occurred in 14.3% in patients and were absent in volunteers. No significant change in spine or SIJ osteitis (p=0.656 week 24, p=0.627 week 52), or structural abnormalities were observed after ustekinumab therapy. Conclusions: A proportion of patients with psoriasis have undiagnosed PsA in primary care, even with signs and symptoms of inflammatory arthritis. Screening questionnaires are useful to detect some, but not all patients and further measures are required to capture all cases of PsA. Early identification and treatment is essential to prevent future pain, functional limitation and disability. Treating patients for psoriasis with a therapeutic agent that is effective at reducing the development of PsA is one means of addressing the failings of clinical examination and screening questionnaires, although the evolution from subclinical enthesitis (a common finding in patients with psoriasis) to PsA is not understood. This thesis provides preliminary data to suggest that anti-IL-12/23p40 therapy may reduce the burden of subclinical inflammation at the primary site of lesion development in PsA (the enthesis), and further longitudinal studies are now encouraged to confirm these observations with ustekinumab and other immunomodulatory therapies

Modification of a sonographic enthesitis score to differentiate between psoriatic arthritis and young healthy volunteers

<p><b>Objectives</b>: We aimed to describe sonographic structural and inflammatory changes in entheses of patients with recently diagnosed psoriatic arthritis (PsA), patients with established PsA, and young healthy volunteers, and to investigate whether the MAdrid Sonographic Enthesitis Index (MASEI) enables us to distinguish these groups in an extreme comparison.</p> <p><b>Method</b>: New and established PsA patients and healthy volunteers (aged 20–30 years) were recruited. The triceps, quadriceps, patellar, Achilles and elbow extensor tendon insertion, and plantar fascia entheses were investigated sonographically for structural changes, erosions, calcifications, increased thickness, bursitis, and power Doppler (PD) signal according to the MASEI.</p> <p><b>Results</b>: The study included 25 new and 25 established PsA patients, and 25 healthy volunteers. Increased thickness and PD signal in knee entheses were common for patients and healthy volunteers, while changes at other locations predominantly occurred in patients only. PD was recoded (1, one spot; 1.5, two or three spots; 2, confluent signal; 3, severe confluent signal) and thickness of knee entheses excluded. This resulted in different modified MASEI scores between PsA patients and young healthy controls: median (interquartile range) modified MASEI of 13 (10–22.5) in new PsA, 13.5 (9.5–18) in established PsA, and 3 (1–8.5) in healthy volunteers (p = 0.002).</p> <p><b>Conclusions</b>: Structural ultrasound changes and PD in entheses are common in both new and established PsA and healthy controls. MASEI score did not differentiate PsA patients from young healthy volunteers. After recoding of PD severity and excluding thickness of knee entheses, marked differences between PsA patients and healthy controls were observed.</p