Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.

OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Assessment of enthesopathy in conventional pelvis radiography: Another tool for spondyloarthritis diagnosis beyond sacroiliitis.

INTRODUCTION/OBJECTIVES: Enthesitis is a cardinal feature of spondylarthritis (SpA), and the pelvis is a common site of enthesitis. This study aimed to establish the association between pelvic enthesis involvement on pelvic X-ray and SpA diagnosis through a radiographic enthesis index (REI) and to assess the reliability and accuracy of this REI. MATERIALS AND METHODS: The participants were SpA patients and a control group composed of patients with chronic lumbar pain without SpA. Three blinded observers assessed each pelvic radiography three times. Three zones were used: Zone I (ZI), the iliopubic ramus; Zone II (ZII), the pubic symphysis, and Zone III (ZIII), the ischiopubic ramus. A grading system was created from 0 to 3 [Grade 0, normal; Grade 1, minimal changes (subcortical bone demineralization and/or periosteal wishkering, seen as radiolucency and trabeculation of the cortical bone upon tendon insertion); Grade 2, destructive changes (Grade 1 findings and erosions at the enthesis site); and Grade 3, findings of Grade 2 plus >2 mm whiskering out of the cortical bone) for the REI. The sum of the results of the three zones was called the total REI. For statistical analysis, we used the weighted kappa statistic adjusted for prevalence and bias using Gwet's agreement coefficient. RESULTS: We enrolled 161 patients, 111 of them with SpA (39.6 % with axial SpA and 47.7 % with peripheral SpA) and 50 without SpA. In the SpA group, 36.7 % and 25.7 % had REI Grades 2 and 3 in ZIII, respectively, while only 6 % of the controls had these grades. For ZI, the frequency of Grades 1 to 3 was 42.3 % in the SpA group (8.1 %, 14.4 %, and 19.8 %, respectively), compared to only 2 % in the controls. ZII was unaffected in most of the patients with SpA (82.9 %) and in the controls (98 %). In the control group, Grade 0 was the most common REI grade in all three zones. The agreement was almost perfect for each zone and between the independent readers. The ROC-curve analysis showed that the highest performance areas were the total REI, ZIII, and ZI. Most (75 %) of the SpA patients without sacroiliitis on X-ray were REI-positive. The sensitivity of the REI for SpA diagnosis was 82 %, while the sensitivity of sacroiliitis on X-ray was 38.7 %. CONCLUSIONS: The assessment of pelvic enthesis using the REI on pelvic radiography may be useful for SpA diagnosis. Total REI, ZIII, and ZI had the highest accuracy and almost perfect reliability. The REI is especially helpful in patients without sacroiliitis on imaging.

Ultrasonography of heel entheses in axial spondyloarthritis patients: frequency and assessment of associated factors.

PURPOSE: Foot entheses involvement is a common manifestation of spondyloarthritis. The superiority of ultrasonography examination in foot entheses damages detection has been reported. We aimed to compare the ultrasonography findings of foot entheses between spondyloarthritis patients. and healthy controls and to identify factors associated with enthesitic heel involvement. METHODS: We conducted a cross-sectional study including 37 patients with axial spondyloarthritis (G1) and 37 healthy subjects matched by age and gender (G0). The following pro-inflammatory cytokines were measured: Interleukin (IL-)1, IL-6, IL-17, and IL-23. A blind ultrasonography of foot entheses was performed to examine calcaneal tendon (CT) and plantar fascia (PF). RESULTS: The mean age was 44.62 ± 12.31 years. Non-steroidal anti-inflammatory drugs were taken in 92% of patients. Clinical heel enthesopathy was noted in 10 patients (27%) of G1. No participant has enthesitic pain in G0. Ultrasonography changes in CT and PF were more frequent in G1 than G0 (p = 0.001 and p = 10-3, respectively). In the PF, tendon thickening was significantly higher in G1 than G0 (p = 0.03). Power Doppler in both enthesitic sites was exclusively observed in G1 (p = 10-3). Regarding associated factors, CT enthesophytes were less frequent in patients taking non-steroidal anti-inflammatory drugs continuously or having regular physical activity. PF structural damages were associated with higher erythrocyte sedimentation rate (p = 0.02), higher IL-23 level (p = 0.01), and higher disease activity (p = 0.04). CONCLUSION: Ultrasonography lesions of heel entheses were frequent in spondyloarthritis. Disease activity and inflammatory markers were higher in patients with heel enthesitis. Non-steroidal anti-inflammatory drugs intake and regular physical activity may prevent enthesophytes' occurrence.

Nail and enthesis assessment in patients with psoriatic disease by high frequency ultrasonography: findings from a single-centre cross-sectional study.

PURPOSE: To characterize nail and enthesis abnormalities using high frequency ultrasound (HFUS) in patients with psoriasis (PSO), psoriatic arthritis (PSA) with PSO, and PSA sine PSO. MATERIAL AND METHODS: Patients with PSO, PSA with PSO, and PSA sine PSO were evaluated and compared in a cross-sectional single centre study. Nail and enthesis abnormalities were evaluated by HFUS using high frequency probes (27 MHz). After a descriptive assessment, Brown University Nail Enthesis Scale (BUNES) and Madrid Sonography Enthesitis Index (MASEI) were used to assess nail and enthesis, respectively. RESULTS: Fifty-nine patients were enrolled (19 PSO, 22 PSA with PSO, 18 PSA sine PSO). In patients with PSO and in those with PSA and PSO, HFUS evaluation identified the following nail alterations characterised by thickened matrix, inhomogeneous echogenicity of the nail bed, and increased blood flow by power Doppler. In 38.9% patients with PSA sine PSO, a subclinical nail involvement was described. No difference was observed comparing BUNES values in three groups. In PSA patients with PSO and in those with PSA sine PSO, HFUS assessment of entheses mainly showed a hypoechoic aspect and thickness of the tendon, focal cortical erosion, and ossification. A subclinical enthesis involvement in 47.4% patients with PSO was observed. No difference was reported comparing MASEI values in three groups. CONCLUSION: Qualitative and quantitative abnormalities of nail and enthesis were demonstrated by HFUS in patients with PSO, PSA with PSO, and PSA sine PSO, suggesting a practical additional tool to be used in clinical settings. Furthermore, HFUS highlighted a subclinical nail involvement in patients with PSA sine PSO and enthesis subclinical alterations in patients with PSO.

Ultrasonographic assessment of entheseal sites of upper and lower extremities in hemodialysis patients using Madrid Sonography Enthesitis Index.

BACKGROUND: There is no much information about the entheseal involvement among hemodialysis (HD) patients. The aim of this study was to assess the frequency and distribution of ultrasonographic (US) entheseal alterations in HD patients and to evaluate the association between US abnormalities and both clinical and laboratory data. METHODS: This study was conducted on 41 HD patients and 23 sex- and age- matched controls. All participants were evaluated clinically for any signs of enthesopathy. Six entheses sites were scanned bilaterally using grey scale (GS) and power Doppler (PD) US and were scored using Madrid Sonography Enthesitis Index (MASEI) scoring system. RESULTS: In HD patients, at least one clinical sign suggestive of enthesopathy was found in 69 (14%) of 492 entheses. HD patients had statistically significant higher scores of structural tendon abnormalities (p < 0.001), enthesis thickening (p < 0.001), bone erosions (p < 0.001) and calcification (p = 0.037) than the healthy controls. Total MASEI score was higher in HD patients than healthy controls (median;18 vs 8, p < 0.001), also, MASEI-inflammatory (median;11 vs 3, p < 0.001) and damage scores (median;6 vs 0, p < 0.001). There was a statistically significant positive association between total MASEI score and both age (p = 0.032) and duration of HD (p = 0.037). Duration of HD was predictive for both MASEI-damage component (p = 0.004) and total MASEI score (p = 0.014). CONCLUSION: There is a high prevalence of subclinical enthesopathy in HD patients. The entheseal US alterations is much higher in HD patients than in healthy subjects. The duration of HD is the significant predictor of enthesopathy in HD patients.

The impact of psoriasis on the clinical characteristics, disease burden and treatment patterns of peripheral spondyloarthritis.

OBJECTIVES: To evaluate the clinical characteristics, disease burden, and treatment patterns of peripheral spondyloarthritis (pSpA) patients with and without psoriasis using data from the ASAS-perSpA study. METHODS: We included 433 patients who had a diagnosis of pSpA according to the rheumatologist's diagnosis from the ASAS-PerSpA study. The presence of a personal history of psoriasis was defined as the presence of signs of psoriasis at physical examination or the presence of psoriatic nail dystrophy, including onycholysis, pitting and hyperkeratosis, or a history of psoriasis diagnosed by a physician. Clinical characteristics, patient-reported outcomes and treatment pattern were compared between subgroups with and without psoriasis. RESULTS: A total of 83 patients (19.2%) had a personal history of psoriasis. Patients with psoriasis were older (48.4 vs 43.2 years) and had a longer diagnostic delay (7.4 vs 3.5 years), a higher frequency of dactylitis (36.1 vs 20.0%) and enthesitis (65.1 vs 55.4%) than patients without psoriasis. A longer diagnostic delay (odds ratio [OR] = 1.06 [95% CI 1.01, 1.11]), lower odds for HLA-B27 positivity (OR = 0.31 [95% CI 0.15, 0.65]) and higher odds for enthesitis (OR = 2.39 [95% CI 1.16, 4.93]) were associated with the presence of psoriasis in a multivariable regression analysis. While patient-reported outcomes were comparable between groups, a higher use of biologic DMARDs was observed in patients with vs without psoriasis. CONCLUSION: The presence of psoriasis has an impact on clinical characteristics of pSpA. pSpA patients without psoriasis were less frequently treated with biologic DMARDs despite similar disease burden as compared with patients with psoriasis.

Reliability assessment of the definition of ultrasound enthesitis in SpA: results of a large, multicentre, international, web-based study.

OBJECTIVES: To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA. METHODS: In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light's kappa, Cohen's kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs. RESULTS: Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light's kappa: 0.77 (0.76-0.78), 0.72 (0.71-0.73), respectively; PABAK: 0.86 (0.86-0.87), 0.73 (0.73-0.74), respectively], followed by enthesophytes/calcifications [Light's kappa: 0.65 (0.64-0.65), PABAK: 0.67 (0.67-0.68)]. This was moderate for entheseal thickening [Light's kappa: 0.41 (0.41-0.42), PABAK: 0.41 (0.40-0.42)], and fair for hypoechoic areas [Light's kappa: 0.37 (0.36-0.38); PABAK: 0.37 (0.37-0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation. CONCLUSIONS: The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis.

Integrating imaging and biomarker assessment to better define psoriatic arthritis and predict response to biologic therapy.

The treatment options for PsA have substantially expanded over the last decade. Approximately 40% of patients will not respond to first-line anti-TNF-α therapies. There is limited data to help clinicians select the most appropriate biologic therapy for PsA patients, including guidance for decisions on biologic therapy switching. In this review we will examine the current understanding of predictors of response to treatment. Imaging technology has evolved to allow us to better study psoriatic disease and define disease activity, including synovitis and enthesitis. Enthesitis is implicated in the pathogenesis, diagnosis and prognosis of PsA. It appears to be a common thread among all of the various PsA clinical presentations. Enthesitis mainly manifests as tenderness, which is difficult to distinguish from FM, chronic pain and mechanically associated enthesopathy, and it might be relevant for understanding the apparent 40% failure of existing therapy. Excess adipose tissue makes if more difficult to detect joint swelling clinically, as many PsA patients have very high BMIs. Integrating imaging and clinical assessment with biomarker analysis could help to deliver stratified medicine in PsA and allow better treatment decision making. This could include which patients require ongoing biologic therapy, which class of biologic therapy that should be, and who alternatively requires management of non-inflammatory disease.

Hidden in plain sight: Is there a crucial role for enthesitis assessment in the treatment and monitoring of axial spondyloarthritis?

OBJECTIVE: To review the evidence surrounding the pathophysiology of enthesitis in axial spondyloarthritis (axSpA), its prevalence and contribution to the overall disease burden, and response to treatment at axial and peripheral sites. METHODS: Literature searches of the Cochrane Library, PubMed, and Embase / Medline using the terms "enthesitis", "enthesopathy", "spondyloarthritis", "axial spondyloarthritis", and "ankylosing spondylitis" were conducted. Publications mentioning enthesitis or enthesopathy in the context of pathophysiology, diagnosis, or treatment were included. RESULTS: Enthesitis is a common symptom of axSpA, occurring with high prevalence at axial and several peripheral sites. Inflammation at the site of enthesis is an early key manifestation of axSpA. Clinically evaluable enthesitis contributes significantly to the burden of disease, correlating with worse symptomatology and downstream structural damage. Despite its importance in driving axSpA disease processes, enthesitis is somewhat neglected in current approaches to disease assessment and management. Enthesitis is excluded from some commonly used disease activity measures, is not routinely assessed in clinical practice, and many methods of clinical assessment omit key accessible axial sites, such as the spinous processes. CONCLUSION: Enthesitis plays a central role in driving the pathophysiology of axSpA. There is a need for a renewed focus on the early detection, measurement and treatment of enthesitis.

Role of ultrasound for assessment of psoriatic arthritis patients with fibromyalgia.

OBJECTIVE: To investigate whether ultrasonography (US), as an objective imaging modality, can optimise the evaluation of disease activity in psoriatic arthritis (PsA) patients with concomitant fibromyalgia syndrome (FMS). METHODS: The study population included 156 consecutive PsA patients who were recruited prospectively and fulfilled the ClASsification criteria for Psoriatic ARthritis criteria. The patients underwent complete clinical evaluation including assessment of fulfilment of the 2016 fibromyalgia classification criteria. All of the patients underwent US evaluation including 52 joints, 40 tendons and 14 entheses. The US score was based on the summation of a semiquantitative score (including synovitis, tenosynovitis and enthesitis). Scoring was performed by a sonographer blinded to the clinical data. Spearman's correlation coefficient and multivariate linear regression models were used to examine the association of FMS with clinical and the US scores. RESULTS: Forty-two patients (26.9%) with coexisting PsA and FMS were compared with 114 (73.1%) PsA patients without FMS. Patients with PsA and FMS had significantly increased scores for clinical composite indices, including non-Minimal Disease Activity, Composite Psoriatic Disease Activity Index (CPDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS) (p<0.001). In contrast, the total US score and its subcategories were similar for those with and without FMS. The total US score significantly correlated with CPDAI, DAPSA and PASDAS (p<0.001) in the PsA without FMS but not in the PsA with FMS group. FMS was significantly associated with higher clinical scores (p<0.001) but not with the US score (multivariable linear regression models). CONCLUSIONS: US has significantly greater value than composite clinical scores in the assessment of disease activity in PsA patients with FMS.

Assessment of enthesopathy in patients with acne vulgaris: A case-controlled trial.

AIM: This case-controlled study aimed at evaluating whether enthesitis is possibly associated with acne vulgaris. METHODS: This study was carried out on 90 patients with acne vulgaris and 30 normal individuals who were subjected to full history talking, acne scoring system, general, dermatological, musculoskeletal examination, and musculoskeletal ultrasonography with Doppler flow. RESULTS: A significant relation (P < 0.05) was discovered between left femoral condyle tenderness, which increased left femoral condyle hypoechogenicity on ultrasound. Moreover, a highly significant relation (P < 0.001) was established between tenderness on clinical examination and hypoechogenicity on ultrasound at three sites (right humerus epicondyle, right femoral condyle, and left humerus epicondyle). An association between tenderness and ultrasound increased thickness was significantly reported in the left femoral condyle (P < 0.05). Hypoechogenicity on ultrasound examination was more statistically evident with increased acne severity at the left Achilles tendon (LA), while enthesis calcifications (enthesophytes) were significantly associated with increased acne severity in the left humerus epicondyle (LA) and the right Achilles tendon (RA) (P < 0.05). CONCLUSION: There is a solid possibility acne is a systemic disease triggering other co-morbidities beyond skin which needs to be fully elucidated by further research evidence.

Prevalence and real-world management of vedolizumab-associated enthesitis in successfully treated IBD patients.

BACKGROUND: Some studies have reported the development of moderate and severe de novo SpA-associated disease under vedolizumab (VDZ) treatment for IBD. Herein, we report a case series who developed severe enthesitis under VDZ therapy from a cohort of 90 treated cases. METHODS: In a single Italian IBD Unit in which 90 cases were on VDZ therapy, we identified 11 cases who developed severe enthesitis. The onset of disease in relationship to VDZ initiation, clinical and sonographic imaging features, and outcomes (including therapy switches) was described. RESULTS: A total of 11 cases, including 8 prior anti-TNF failures, with new-onset entheseal pathology were identified: multifocal (n = 4), unifocal (n = 6), and enthesitis/synovitis/dactylitis (n = 1). The mean duration of symptoms was 46 weeks (range 6-119), the mean CRP was 5.1 mg/dl, and the majority were HLA-B27 negative and showed good clinical response for gut disease. Clinical features and US showed severe enthesitis, including power Doppler change in 7 patients. All patients were initially treated with NSAIDs, and 5 patients underwent local steroid injections. At 12 months, 5/7 cases continued VDZ and 2 were switched to ustekinumab. At 12 months follow-up of 7 cases, 5 patients were in clinical remission and 2 patients had mild enthesitis with minimal increase of power Doppler signal. In addition, 4/7 severe patients developed marked post-inflammatory entheseal calcifications. CONCLUSIONS: A predominant isolated severe enthesitis pattern of SpA may develop under VDZ therapy with severe disease in 8% of cases. Most cases continued VDZ therapy.

Nail Psoriasis: Diagnosis, Assessment, Treatment Options, and Unmet Clinical Needs.

OBJECTIVE: An estimated 40-50% of patients with psoriasis (PsO) have psoriatic nail disease, which is associated with and directly contributes to a greater clinical burden and worse quality of life in these patients. In this review, we examine how recent advances in the use of new diagnostic techniques have led to improved understanding of the link between nail and musculoskeletal manifestations of psoriatic disease (PsD; e.g., enthesitis, arthritis) and we review targeted therapies for nail PsO (NP). METHODS: We performed a literature search to identify which systemic therapies approved for the treatment of PsO and/or psoriatic arthritis (PsA) have been evaluated for the treatment of NP, either as a primary or secondary outcome. A total of 1546 articles were identified on February18, 2019, and evaluated for relevance. RESULTS: We included findings from 66 articles on systemic therapies for the treatment of NP in PsD. With several scoring systems available for the evaluation of psoriatic nail disease, including varied subtypes and application of the Nail Psoriasis Area Severity Index, there was a high level of methodological heterogeneity across studies. CONCLUSION: NP is an important predictor of enthesitis, which is associated with the early stages of PsA; therefore, it is important for rheumatologists and dermatologists to accurately diagnose and treat NP to prevent nail damage and potentially delay the onset and progression of joint disease. Further research is needed to address the lack of both standardized NP scoring systems and well-defined treatment guidelines to improve management of PsD.

Ultrasound assessment, unlike clinical assessment, reflects enthesitis in patients with psoriatic arthritis.

OBJECTIVES: Enthesitis is a major musculoskeletal manifestation of psoriatic arthritis (PsA). It is conventionally assessed clinically, by the presence of tenderness, despite its low reliability. However, ultrasound (US) provides a sensitive and feasible method for evaluating enthesitis. We investigated enthesitis as assessed clinically and by US in patients with PsA. METHODS: Forty-seven patients with PsA underwent US examination of the bilateral humeral medial epicondyles and insertions of the triceps, distal quadriceps, proximal/distal patellae, Achilles tendons, and plantar fascia. These 14 entheses were also clinically evaluated by tenderness. The correspondence between US and clinical enthesitis was evaluated, as well as their associations with inflammatory markers (C-reactive protein [CRP], matrix metalloproteinase-3 [MMP-3]), disease activity indices (Disease Activity in Psoriatic Arthritis [DAPSA], Disease Activity Score 28 joints [DAS28-CRP], Psoriatic Arthritis Screening and Evaluation [PASE], Psoriasis Area Severity Index [PASI]), radiographic damage (modified Total Sharp Score [mTSS]), and functional status (health assessment questionnaire [HAQ]), and axial involvement. RESULTS: Among 47 patients with PsA, 37 and 23 had US and clinical enthesitis, respectively. US and clinical enthesitis had very low concordance (kappa coefficient 0.04), with no correlation between enthesitis counts (r=0.15, p=0.30). The US enthesitis count correlated only with the MMP-3 level (r=0.41, p=0.007), whereas the clinical enthesitis count correlated with the DAPSA, DAS28-CRP, HAQ, and PASE (r=0.50, p<0.001; r=0.44, p=0.002; r=0.41, p=0.008; r=0.54, p<0.001, respectively). CONCLUSIONS: US and clinical enthesitis are completely different entities. US enthesitis, but not clinical enthesitis, reflects inflammatory conditions.

Prologue: 2019 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

The 2019 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) was held in Paris, France, and was attended by rheumatologists, dermatologists, representatives of biopharmaceutical companies, and patients. As in previous years, GRAPPA members held a symposium for trainees to discuss their research in psoriatic disease with experts in the field. Other subjects featured during the annual meeting included a composites workshop to review continuous composite measures; the GRAPPA-Collaborative Research Network's third annual meeting; the need for a precision medicine approach to the treatment of psoriatic disease; updates from working groups in International Dermatology Outcome Measures and Outcome Measures in Rheumatology; a debate on the effectiveness of methotrexate in the treatment of psoriatic arthritis (PsA); updating recommendations for optimal treatment approaches for patients with PsA; an update on GRAPPA's research and educational projects; and the GRAPPA ultrasound (US) working group's goal to optimize the evaluation of enthesitis in patients with PsA using US through the development of a diagnostic US enthesitis tool. In this Prologue, we introduce the papers that summarize that meeting.

Assessment of the many faces of PsA: single and composite measures in PsA clinical trials.

PsA is a complex, heterogeneous disease that can place a large burden on patients' psychological and physical well-being. The multifaceted nature of PsA poses a significant assessment challenge, both in randomized control trials and in clinical practice. In recent years, there has been much progress in the development of unidimensional and composite measures of disease activity, as well as of questionnaires that capture the patient's perspective of the condition. Despite these advances, there remains uncertainty around which tools to implement within a research setting. This review aims to summarize the currently available clinical and patient-derived assessment tools, providing a practical and informative resource for the assessment of PsA. This review will also explore recent advancements in digital approaches to the assessment of rheumatological conditions. This will highlight the potential for digitalization in the assessment and monitoring of PsA, outlining innovative means of capturing disease activity and treatment response.

Enthesitis in psoriatic arthritis (Part 3): clinical assessment and management.

Enthesitis is a common clinical feature of PsA, which is characterized by inflammation at the site of insertion of tendons, ligaments and joint capsule fibres into bone. Enthesitis is relatively unique to the spondyloarthritides, setting this group of diseases apart from other rheumatological conditions. The pathophysiological underpinnings of this clinical domain, and the imaging assessment of it, are described in accompanying articles in this supplement. The focus of this article is on the assessment of enthesitis by physical examination, the impact of enthesitis on function and quality of life, the impact of concomitant FM on clinical assessment, and the evidence for therapy of enthesitis garnered in trials of biologic and targeted synthetic DMARDs. Several physical examination measures of enthesitis have been developed and have proved reliable in assessment of enthesitis. Enthesitis has a significant deleterious impact on function and quality of life. The presence of concomitant FM in ≤20% of patients may result in artefactual worsening of assessment of disease severity and hinder achievement of the goal of low disease activity or remission. Several targeted therapies, which, for example, target the TNF, IL-17, IL-23, phosphodiesterase 4 or Janus kinase pathways, have shown significant efficacy in the treatment of enthesitis, resulting in improvement of function and quality of life for patients with PsA.

Entheses ultrasound assessment in primary Sjogren's syndrome.

OBJECTIVE: Musculoskeletal pain is a common complaint among patients with primary Sjogren's syndrome (pSS). Joints clinical examination is oftenly normal. A periarticular origin of this pain may be possible. Since clinical examination lacks sensitivity and precision, the use of musculoskeletal ultrasound (US) is more interesting in the evaluation of the entheses involvement, as it is shown to be a more sensitive tool. Our objective was to assess, by an ultrasonographic study, the entheses involvement in the widespread pain of patients with pSS. METHODS: This is a prospective study including 25 women with pSS and 25 age and sex matched healthy controls. An ultrasound examination, using grey scale and Doppler US, of five enthesitic sites (distal quadricipital, proximal patellar, distal patellar, distal Achillian and distal brachial tricipital) sought bilaterally the following lesions: hypoechogenicity, thickening, loss of fibrillar structure, erosions, enthesophytes, calcifications or Doppler hypervascularisation. A final score was calculated by summing the abnormalities scores of all entheses. RESULTS: The mean age was 53.2±11.3 years in the pSS group and 50.6±9.7 years in the control group. The mean number of pathological entheses on ultrasound was 3.92±1.93 in the pSS group versus 4.52±2.27 in the control group (P>0.05). The total score for enthesitis abnormalities was 4.96±2.59 versus 5.72±2.92 (P>0.05), respectively. There was a positive correlation between total score of ultrasound enthesitic abnormalities and age in both groups. CONCLUSION: In patients with pSS, clinically painful sites were more frequently found than in US. Musculoskeletal pain was not due to enthesitis.

Assessment of enthesis in patients with psoriatic arthritis and fibromyalgia using clinical examination and ultrasound.

OBJECTIVES: The primary aim of this study was to compare the prevalence of clinical and particularly ultrasonographic signs of enthesitis in patients with psoriatic arthritis (PsA), fibromyalgia (FM), or both. The secondary aim was to assess the impact of FM on disease activity and clinimetric scores. METHODS: This single-centre, observational cross-sectional study involved 101 consenting patients: 39 with PsA (CASPAR criteria), 23 with FM (2016 criteria), and 39 with both. Standard PsA and FM clinical, laboratory and clinimetric data were recorded, and entheses were assessed using the Leeds Enthesitis Index (LEI) and the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES). All of the patients underwent B mode (grey scale) and Power Doppler (PD) ultrasonography bilaterally at the insertions of the quadriceps tendons, the proximal and distal patellar tendons, the Achilles tendons, and the plantar fascia insertions of the calcaneus, to evaluate the thickness of entheses, the hypoechogenicity, the presence of bony erosions, the enthesophytes, and the bursitis. The US findings were scored using the Glasgow Ultrasound Enthesitis Scoring System (GUESS). The data were statistically analysed using univariate and multivariate analyses, and receiver-operating characteristic (ROC) curves, concentrating on the shared clinical features of the two condition. RESULTS: The mean age of the patients as a whole was 53.6±9.47 years. Females accounted for 64.1% of the PsA patients (disease duration 9.13 years), 95.6% of the FM patients (disease duration 5.09 years), and 92.3% of the patients with PsA-FM (disease duration 7.9 years). There were no between-group differences in the patients' body mass index (BMI). In accordance with the study inclusion criteria, none of the FM subjects had PsA or reported any personal or family history of psoriasis. The mean Psoriasis Area and Severity Index was 2.3±3.1 in the PsA group, and 1.2±2.45 in the PsA-FM group. Clinical evidence of enthesopathy was found in 43% of the patients with PsA, 51.3% of those with PsA-FM, and 50.8% of those with FM, while US entheseal abnormalities were detected in respectively 77%, 74% and 35%. The median Bath Ankylosing Spondylitis Disease Activity Index was significantly higher in the patients with PsA-FM than in those with PsA (7.7 [IQR 2.1] vs. 5.0 [IQR 3.8]; p<0.001), as was the median ESR-assessed Ankylosing Spondylitis Disease Activity Score (3.69 [IQR 1.00] vs. 2.82 [IQR 1.55; p=0.004), or CRP- assessed (median 3.27 [IQR 1.07] vs. 2.66 [IQR 1.26]; p=0.006). There was a correlation between GUESS scores and disease duration in the patients with PsA (rho=0.37; p=0.019, 95% CI 0.10-0.61) or PsA-FM (rho=0.38; p=0.016, 95% CI 0.10-0.61), but not in the FM group, and GUESS scores correlated with BMI (rho=0.2; p=0.05, 95% CI 0.00-0.37) and dyslipidemia (rho=0.34; p=0.006, 95% CI 0.11-0.58) in all three groups. CONCLUSIONS: The use of a clinical examination and clinimetric scores alone may overestimate active enthesitis in FM patients. As US was more frequently positive in patients with PsA and PsA-FM than in those with FM, it may be useful in differentiating pain due to enthesitis from entheseal pain due to FM.

Clinical applications of nuclear medicine in the diagnosis and assessment of musculoskeletal sports injuries. / Aplicaciones clínicas de la medicina nuclear en el diagnóstico y evaluación de las lesiones deportivas musculoesqueléticas.

Increased participation in sports and physical exercise are widely promoted as an approach to a physically active lifestyle which has a positive effect on healthy aging, in patients and athletes of all ages, beginners and experts, including amateur athletes and professional athletes. Unfortunately, this has caused a higher incidence of sports-related injuries. In the sports context, the early and accurate diagnosis of injuries is of the utmost importance in order to enable early treatment to achieve a full recovery. Imaging techniques are increasingly important for the successful diagnosis and management of the patient. The nuclear medicine techniques with bone tracers provide physiological and metabolic information in the early phases of musculoskeletal injuries, which often precede anatomical changes and they reflect changes in bone turnover. This allows early diagnosis, along with evaluation of the activity and phase of the injury. In this article, the applications of nuclear medicine techniques, focusing on bone scintigraphy, alongside the important contribution of hybrid studies (SPECT/CT), in the diagnosis of bone and soft tissue sports injuries, will be described. In addition, we explain their usefulness in the expression of the pathophysiology of these lesions and their scintigraphic patterns. The article will also describe biomechanical and physiopathological aspects, injury mechanisms and clinical presentations of bone and joint sports injuries, knowledge of this is essential for the correct diagnostic assessment of imaging studies.