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.

'Double target' ultrasound monitoring of biologic therapy in psoriatic arthritis.

OBJECTIVES: We aimed to 1) evaluate by power Doppler (PD) ultrasound (US) the response to therapy of the most inflamed joint and enthesis (target sites) in psoriatic arthritis (PsA) patients starting a biologic disease-modifying anti-rheumatic drug (bDMARD); and 2) to investigate the correlation between the US response and clinical data. METHODS: Consecutive PsA patients with US synovitis and US 'active' enthesitis, starting a bDMARD, were included. The joint with the highest OMERACT-EULAR-US composite score and the enthesis with the highest PD grade (targets) were identified at baseline. The US examination and clinical assessment were performed at 0, 3 and 6 months. The response of OMERACT-EULAR-US synovitis composite score was defined as reaching a grade = 0 at follow-up examination; synovial and entheseal PD responses were defined as a PD=0 and/or a reduction of ≥2 PD grades at follow-up examination. RESULTS: Thirty patients were included. Synovitis composite score, synovial PD and entheseal PD showed significant responses at 3 and 6 months compared to baseline (p<0.01). Synovial PD responses were higher than entheseal PD responses at 3 months (71.4% vs 40.0%, p=0.01) and 6 months (77.8% vs. 46.7%, p=0.02). US synovitis responses were correlated with DAPSA (p<0.01) and MDA responses (p=0.01 for composite score, p=0.02 for PD). CONCLUSIONS: US was found sensitive for monitoring treatment response in PsA patients starting a biologic drug. Entheseal PD was less responsive than synovial PD, suggesting that enthesitis may represent a 'difficult-to-treat' domain in PsA.

Prevalence and clinical associations of ultrasound-confirmed enthesitis in systemic lupus erythematosus.

OBJECTIVES: To assess the prevalence of US-confirmed enthesitis in a cohort of patients with SLE and to analyse the clinical associations to enthesitis during the course of SLE. METHODS: In a retrospective analysis of the SLE cohort of the Lupus Unit of the Careggi University Hospital, US examinations of SLE patients presenting with tender and/or swollen joints were retrieved to assess the presence of enthesitis. Patients with US-proven enthesitis were compared with SLE controls with tender and/or swollen joints who showed no US evidence of enthesitis. Clinical and laboratory features were compared at disease onset and during follow-up. RESULTS: A total of 400 patients fulfilling EULAR/ACR classification criteria for SLE were assessed. Of these, 106 underwent articular US examination. Evidence of enthesitis was found in 31/106 (29.2%) patients. Seventy-one patients without US-enthesitis were included as controls; four were excluded due to lack of follow-up data. Laboratory and clinical features were comparable between cases and controls at disease onset. Throughout a median follow-up of 10.0 (interquartile range [IQR] 8.3-23.3) years for cases and 12.4 (IQR 7.2-13.3) years for controls, patients with enthesitis were less likely to develop renal involvement (22.6% vs 46.5%, P = 0.028) and failed B cell depletion more frequently (75.0% vs 0%). CONCLUSION: In SLE patients with clinically active joints, US-proven enthesitis is a fairly common finding. Enthesitis in SLE could be the hallmark of a distinct disease phenotype with less renal involvement, more arthritis and low response to anti-CD 20 therapy, potentially requiring a tailored treatment.

Efficacy of secukinumab on dactylitis in patients with active psoriatic arthritis from the FUTURE 5 study.

OBJECTIVES: Dactylitis is an important clinical domain of psoriatic arthritis (PsA) associated with significant burden of disease and impaired function. Post-hoc analysis of the FUTURE 5 study was performed to evaluate the efficacy of secukinumab in patients with dactylitis at baseline over 2 years. METHODS: Randomised patients received secukinumab 300mg with loading dose (LD)/150mg LD/150mg without loading dose/placebo. Assessment of dactylitis was based on Leeds Dactylitis Index. Exploratory analyses included resolution of dactylitis based on severity, time to first resolution of dactylitis (Kaplan-Meier estimate) and resolution of dactylitis (heatmap analysis). Clinical efficacy outcomes, composite domains of disease activity, health-related quality of life (HRQoL) and radiographic progression using van der Heijde-modified total Sharp score were assessed in patients with/without dactylitis at baseline. RESULTS: Overall, 389/996 (39%) patients presented with dactylitis at baseline, had more active clinical disease and greater disease activity than those without dactylitis at baseline. Resolution of dactylitis was observed across all treatment groups at Week 104. Improvement in joints, enthesitis, skin psoriasis, nail outcomes, physical function and HRQoL were sustained over 2 years in patients with dactylitis at baseline. With secukinumab treatment, >80% of patients did not show structural radiographic progression. The proportion of non-structural radiographic progressors were comparable across patients with/without dactylitis at baseline with secukinumab treatment over 2 years. CONCLUSIONS: Patients with dactylitis at baseline were associated with higher burden of disease. Secukinumab provided sustained improvements across all clinical outcomes, QoL and inhibition of radiographic progression in PsA patients with dactylitis at baseline over 2 years.

Are the Pathologic Features of Enthesopathy, Tendinopathy, and Labral and Articular Disc Disease Related to Mucoid Degeneration? A Systematic Review.

BACKGROUND: Tendinopathy, enthesopathy, labral degeneration, and pathologic conditions of the articular disc (knee meniscus and ulnocarpal) are sometimes described in terms of inflammation or damage, while the histopathologic findings are often consistent with mucoid degeneration. A systematic review of the histopathology of these structures at diverse locations might reconceptualize these diseases as expected aspects of human aging. The potential benefits of this evolution might include healthier patient and clinician mindsets as well as a reduced likelihood of overdiagnosis and overtreatment resulting from greater awareness of base rates of pathology. QUESTION/PURPOSE: In this systematic review of studies of surgical specimens, we asked: Are there are any differences in the histopathologic findings of structural soft tissue conditions (mucoid degeneration, inflammation, and vascularity) by anatomic site (foot, elbow, or knee) or structure (tendon body, muscle or tendon origin or insertion [enthesis], labrum, or articular disc)? METHODS: Studies between 1980 and 2021 investigating the histopathologic findings of specimens from surgery for trigger digit, de Quervain tendinopathy, plantar fasciitis, lateral and medial elbow enthesopathy, rotator cuff tendinopathy, posterior tibial tendinopathy, patellar tendinopathy, Achilles tendinopathy, or disease of the hip labrum, ulnocarpal articular disc, or knee meniscus were searched for in the PubMed, EMBASE, and CINAHL databases. Inclusion criteria were the prespecified anatomic location or structure being analyzed histologically and any findings described with respect to inflammation, vascularity, or mucoid degeneration. Studies were excluded if they were nonhuman studies or review articles. Search terms included "anatomy," "pathology," and "histopathology." These terms were coupled with anatomic structures or disorders and included "trigger finger," "de Quervain," "fasciitis, plantar," "tennis elbow," "rotator cuff tendinopathy," "elbow tendinopathy," "patellar tendonitis," "posterior tibial tendon," and "triangular fibrocartilage." This resulted in 3196 studies. After applying the inclusion criteria, 559 articles were then assessed for eligibility according to our exclusion criteria, with 52 eventually included. We recorded whether the study identified the following histopathologic findings: inflammatory cells or molecular markers, greater than expected vascularity (categorized as quantitative count, with or without controls; molecular markers; or qualitative judgments), and features of mucoid degeneration (disorganized collagen, increased extracellular matrix, or chondroid metaplasia). In the absence of methods for systematically evaluating the pathophysiology of structural (collagenous) soft tissue structures and rating histopathologic study quality, all studies that interpreted histopathology results were included. The original authors' judgment regarding the presence or absence of inflammation, greater than expected vascularity, and elements of mucoid degeneration was recorded along with the type of data used to reach that conclusion. RESULTS: Regarding differences in the histopathology of surgical specimens of structural soft tissue conditions by anatomic site, there were no differences in inflammation or mucoid degeneration, and the knee meniscus was less often described as having greater than normal vascularity. There were no differences by anatomic structure. Overall, 20% (10 of 51) of the studies that investigated for inflammation reported it (nine inflammatory cells and one inflammatory marker). Eighty-three percent (43 of 52) interpreted increased vascularity: 40% (17 of 43) using quantitative methods (14 with controls and three without) and 60% (26 of 43) using imprecise criteria. Additionally, 100% (all 52 studies) identified at least one element of mucoid degeneration: 69% (36 of 52) reported an increased extracellular matrix, 71% (37 of 52) reported disorganized collagen, and 33% (17 of 52) reported chondroid metaplasia. CONCLUSION: Our systematic review of the histopathology of diseases of soft tissue structures (enthesopathy, tendinopathy, and labral and articular disc) identified consistent mucoid degeneration, minimal inflammation, and imprecise assessment of relative vascularity; these findings were consistent across anatomic sites and structures, supporting a reconceptualization of these diseases as related to aging (senescence or degeneration) rather than injury or activity. CLINICAL RELEVANCE: This reconceptualization supports accommodative mindsets known to be associated with greater comfort and capability. In addition, awareness of the notable base rates of structural soft tissue changes as people age might reduce overdiagnosis and overtreatment of incidental, benign, or inconsequential signal changes and pathophysiology.

Dactylitis is an indicator of a more severe phenotype independently associated with greater SJC, CRP, ultrasound synovitis and erosive damage in DMARD-naive early psoriatic arthritis.

OBJECTIVE: To characterise the impact of dactylitis in disease-modifying antirheumatic drug (DMARD)-naive early psoriatic arthritis (PsA). METHODS: Patients with early PsA meeting the classification criteria for PsA (CASPAR) were recruited. Clinical outcomes were recorded, and ultrasonography was conducted to assess grey scale (GS) and power Doppler (PD) synovitis, periarticular cortical bone erosions and enthesitis. The cohort was dichotomised by the presence or absence of dactylitis. RESULTS: Of 177 patients with PsA, those with dactylitis (dactylitic PsA (81/177, 46%)) had higher tender joint count (p<0.01), swollen joint count (SJC) (p<0.001) and C reactive protein (CRP) (p<0.01) than non-dactylitic PsA. Dactylitis was more prevalent in toes (146/214 (68.2%)) than fingers (68/214 (31.8%)); 'hot' dactylitis was more prevalent than 'cold' (83.6% vs 16.4%). Ultrasound (US) synovitis and erosions were significantly more prevalent in dactylitic PsA (p<0.001 and p<0.001, respectively). Exclusion of dactylitis in dactylitic PsA confirmed significantly greater SJC (3 vs 1, p=0.002), US synovitis (GS ≥2: 20.6% vs 16.1%, p<0.001, or PD ≥1: 5.1% vs 3.3%, p<0.001) and erosions (1.1% vs 0.5% joints, p=0.008; 26.1% vs 12.8% patients, p=0.035%) than non-dactylitic PsA. Synovitis (GS ≥2 and/or PD ≥1) occurred in 53.7% of dactylitis. No substantial differences were observed for US enthesitis. CONCLUSION: Dactylitis signifies a more severe disease phenotype independently associated with an increased disease burden with greater SJC, CRP, US-detected synovitis and bone erosions in DMARD-naive early PsA and may be a useful discriminator for early risk stratification.

Musculoskeletal pain in psoriasis-relation to inflammation and additional value of ultrasound in psoriatic arthritis classification.

OBJECTIVE: To investigate and compare clinical features and US signs of inflammation in joints and entheses in patients with psoriasis with and without musculoskeletal pain, and the additional value of US in classification of PsA. Furthermore, to explore the association between such findings and patient-reported outcomes (PROs) and the performance of screening-questionnaires for identifying patients with PsA. METHODS: Patients with psoriasis (n = 126) recruited from a nationwide survey were evaluated at one of four rheumatology departments. The evaluation included clinical examination, laboratory tests, radiography, greyscale and colour Doppler US of 48 joints and 12 entheses, PROs, and four screening questionnaires for PsA. Patients were classified with Classification for PsA (CASPAR), US-modified CASPAR, and US-only criteria. RESULTS: When subgroups of self-reported pain (63%), no pain (29%) and diagnosed PsA (9%) were compared, patients with pain had higher tenderness-related clinical scores (tender joints, entheses and FM points) and US greyscale sum-scores, compared with 'no pain' patients. PROs were negligibly moderately correlated with pain-related clinical scores (Spearman's rho = 0.11-0.59, all patients), and negligibly weakly with US sum-scores (rho = 0.01-0.34). More patients could be classified as PsA when US synovitis/enthesitis was included as an entry criterion (US-modified CASPAR, 66% of all patients) compared with conventional CASPAR (35%) or US-only criteria (52%). Sensitivities of screening questionnaires were low for fulfilment of CASPAR (0.23-0.66), US-modified CASPAR (0.17-0.57), and US-only (0.20-0.57) criteria. CONCLUSION: Self-reported pain in psoriasis is related to US inflammation. US-modified CASPAR criteria identified almost twice as many patients as conventional CASPAR criteria. Screening questionnaires showed limited value.

Disease activity at the entheses and joints are correlated in psoriatic arthritis when explored with ultrasound.

OBJECTIVES: The aim of this study is to explore the link between the severity of the joint and entheses involvement in psoriatic arthritis (PsA) using musculoskeletal ultrasound (US). METHODS: PsA patients from two centres in the Psoriatic Arthritis International Database (PsArt-ID) (n=126) underwent an ultrasound assessment of 46 joints and 12 large entheses. The correlation between joint and enthesitis scores on the US was analysed, in addition to the clinical indices versus the US. RESULTS: Grey-scale (GS) synovitis score for the joints was moderately correlated with the total enthesitis score (r=0.410, p<0.001). The Global Outcome Measure in Rheumatology in Clinical Trials-European League Against Rheumatism Synovitis Score (GLOESS) score was also found in correlation with the total enthesitis score (r=0.400, p<0.001). The link between the US and clinical examination findings only showed a poor correlation between swollen joint counts (SJC) and joint-US scores (r=0.298, p=0.001 for GLOESS). Assessment of the entheses on US showed a poor-moderate correlation between the entheseal damage scores and tender joint counts (TJC) (r=0.217, p=0.018) and SJC (r=0.326, p<0.001). In terms of the clinical examination and activity parameters, none of the clinical parameters and acute phase reactants were correlated to Leeds Enthesitis Index. CONCLUSIONS: Our study showed a link between the severity of the sonographic findings in the joints and the entheses. Imaging using US to assess enthesitis in clinical trials may improve our understanding on the role of enthesitis in disease pathogenesis.

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.

Endoscopic resection of enthesopathy via a direct midline transtendinous approach with associated reattachment of the Achilles tendon (endo-REDMTART): a cadaveric feasibility study.

PURPOSE: The aim of our study was to determine the feasibility of an all-posterior endoscopic resection of enthesopathy via direct midline transtendinous approach with detachment and reattachment of the Achilles tendon (endo-REDMTART). MATERIALS & METHODS: Endo-REDMTART was performed in 10 ankles by two foot and ankle surgeons. Posterolateral and posteromedial portals were utilized. Three accessory, more distal portals were utilized (one posterolateral, one posteromedial, and one midline transtendinous). We measured the quality of the resection of the calcaneal spur and the length of tendon that was able to be reattached to the calcaneus. RESULTS: The procedure was successful in all 10 cases. The mean minimum thickness of resected calcaneal spur was 7 mm (5-9 mm) thick, and the mean anteroposterior distance was 23 mm (20-25 mm). In all 10 cases, the maximum distance between the distal Achilles tendon and calcaneus was 1 mm (0-1 mm), with good tendon-bone contact. CONCLUSIONS: The data here suggest that endo-REDMTART is feasible. This procedure provides all of the advantages of endoscopic technique without compromising the efficacy of Haglund deformity resection. TRIAL REGISTRATION: No Clinical Trials Registration or IRB is required. LEVEL OF EVIDENCE: Anatomy study; cadaveric dissection.

Resolution of enthesitis by guselkumab and relationships to disease burden: 1-year results of two phase 3 psoriatic arthritis studies.

OBJECTIVE: To further characterize the effect of guselkumab, a selective IL-23p19-subunit inhibitor approved for PsA, on enthesitis and assess relationships between enthesitis resolution and patient status/outcomes. METHODS: Adults with active PsA despite standard therapies in the phase 3 DISCOVER-1 and DISCOVER-2 studies were randomized 1:1:1 to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, Q8W; or placebo through week 20 followed by guselkumab 100 mg Q4W. Independent assessors evaluated enthesitis using the Leeds Enthesitis Index (LEI; total score 0-6). Enthesitis findings through week 24 were pre-specified to be pooled across studies; post hoc and week 52 analyses also employed pooled data. RESULTS: Among 1118 randomized, treated patients in DISCOVER-1 and 2 who had ≥1 LEI site evaluated, 65% had enthesitis at baseline. These patients exhibited numerically more swollen and tender joints, systemic inflammation and impaired physical function than patients without enthesitis. Guselkumab Q4W and Q8W were superior to placebo in resolving pre-existing enthesitis at week 24 (45 and 50% vs 29%; both adjusted P = 0.0301). Enthesitis resolution rates continued to rise; 58% of guselkumab-randomized patients achieved resolution at week 52, including patients with mild (LEI = 1; 70-75%), moderate (LEI = 2; 69-73%) or severe (LEI = 3-6; 42-44%) enthesitis at baseline. Among guselkumab-randomized patients with resolved enthesitis at week 24, 42% achieved minimal disease activity at week 52, vs 17% of patients with unresolved enthesitis. CONCLUSION: Guselkumab resulted in higher proportions of PsA patients with resolved enthesitis by week 24, with maintenance of resolution rates through 1 year. As enthesitis confers greater disease burden, sustained resolution could portend better patient outcomes. CLINICAL TRIAL REGISTRATION: DISCOVER 1 (NCT03162796) and DISCOVER 2 (NCT03158285).

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.

Challenges in the clinical diagnosis of psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic heterogeneous inflammatory musculoskeletal disease. The non-specific and often subtle manifestations make early diagnosis and subsequent treatment challenging. In the absence of diagnostic criteria and biomarkers, the diagnosis is often delayed leading to poor long-term outcomes. In addition, the differential diagnosis of a patient presenting with arthritis in the setting of skin psoriasis is wide due to symptom overlap with many other diseases. Peripheral arthritis, dactylitis, enthesitis and axial arthritis are the 4 domains of musculoskeletal involvement in PsA and careful examination of each domain by a rheumatologist is the first step for a correct diagnosis. Other extra-musculoskeletal features such as the presence of uveitis, inflammatory bowel disease, nail psoriasis and elevated acute phase reactants aid in the diagnosis of PsA. Screening patients with skin psoriasis using validated questionnaires might help in early diagnosis especially when coupled with imaging.

The management of enthesitis in clinical practice.

PURPOSE OF REVIEW: Enthesitis is a hallmark feature of the spondyloarthropathies (SpA). This review provides an overview of recent insights on diagnosis and management of enthesitis. RECENT FINDINGS: Recent studies support the use of imaging for diagnosis because of its higher sensitivity and specificity compared with clinical examination. Several new MRI and ultrasound scoring systems have been developed for enthesitis, which may facilitate the use of imaging in research. Enthesitis has been evaluated as a primary study outcome mainly in psoriatic arthritis (PsA); however, the use of different indices and definitions of improvement limits comparison across studies. There is very limited information about the efficacy of synthetic disease modifying antirheumatic drugs (DMARDs) for the treatment of enthesitis. In contrast, targeted and biologic DMARDs have all shown efficacy in treating enthesitis compared with placebo. There have been only a few head-to-head trials that compared two different cytokine inhibitors for the treatment of enthesitis. Preliminary data suggest that targeting IL-17 or IL12/23 may be more efficacious for controlling enthesitis than TNF inhibition. SUMMARY: Emerging data suggest interleukin-17 and 12/23 inhibitors may be the first choice in PsA patients with enthesitis. Further head-to-head studies are needed before making definitive recommendations.

Intestinal and enthesis innate immunity in early axial spondyloarthropathy.

Axial SpA (axSpA), encompassing AS, is a multifactorial disease that localizes to sites of high spinal biomechanical stress. Much has been written on T cells and adaptive immunity in axSpA, which is understandable given the very strong HLA-B27 disease association. Extra-axial disease characteristically involves the anterior uveal tract, aortic root, lung apex and terminal ileum. Under recent classification, axSpA is classified as an intermediate between autoimmunity and autoinflammatory disease, with the latter term being synonymous with innate immune dysregulation. The purpose of this review is to evaluate the 'danger signals' from both the exogenous intestinal microbiotal adjuvants or pathogen-associated molecular patterns that access the circulation and endogenously derived damaged self-tissue or damage-associated molecular patterns derived from entheses and other sites of high biomechanical stress or damage that may serve as key drivers of axSpA onset, evolution, disease flares and eventual outcomes.

Prevalence of extra-articular manifestations in psoriatic arthritis: a systematic review and meta-analysis.

OBJECTIVE: To describe the prevalence of extra-articular manifestations-enthesitis, dactylitis, nail disease, uveitis and IBD-in PsA, and their impact on longitudinal disease outcomes. METHODS: We searched Medline, PubMed, Scopus and Web of Science using a predefined protocol in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies using imaging to define extra-articular manifestations (EAMs) were excluded. Where possible, we performed meta-analyses of prevalence estimates, reported as percentages (95% CI). Heterogeneity (I2 statistic) was examined according to study characteristics. RESULTS: We identified 65 studies amounting to a total of 163 299 PsA patients. Enthesitis was assessed in 29 studies with an average prevalence of 30% (95% CI: 24%, 38%). Dactylitis was reported in 35 studies with an average prevalence of 25% (95% CI: 20%, 31%). Nail disease was present in 60% (95% CI: 52%, 68%) across 26 studies, but definitions were often unclear. Uveitis (3.2%; 95% CI: 1.9%, 5.3%) and IBD (3.3%; 95% CI: 1.5%, 7.1%) were less common. Heterogeneity was high (>95%) in all meta-analyses, but could not be explained by study characteristics. No studies examined the impact of EAMs on longitudinal disease outcomes, except that dactylitis increases radiographic progression. CONCLUSION: Enthesitis, dactylitis and nail disease are highly prevalent in PsA, but not uveitis and IBD. EAM patterns differ from axial SpA despite their shared disease mechanisms, which may help further understand differences between spondyloarthritides. More studies are needed on the impact of EAMs on disease outcomes such as response to treatment.

Hip and Shoulder Involvement and Their Management in Axial Spondyloarthritis: a Current Review.

PURPOSE OF REVIEW: Hip and shoulder disease can occur in patients with spondyloarthritis (SpA). While hip involvement has been widely assessed in axial SpA patients, studies in the overall SpA population as well as studies focused on shoulder involvement are scarce. Here, we review the most recent studies on the epidemiology, evaluation, and treatment of root joint involvement in SpA patients. RECENT FINDINGS: Radiological hip involvement can affect up to 25% of patients with SpA, reflecting more severe disease and associated with functional impairment. Shoulder involvement in SpA patients is characterized by cuff tendinitis and enthesitis, while primary glenohumeral joint involvement is rare. Anti-tumor necrosis factor (anti-TNF) treatment in SpA patients seems to have an effect on hip arthritis, showing a change in trend in the frequency of hip replacement in this population. The majority of studies evaluating hip involvement have focused on axial SpA patients, but further studies evaluating root joint involvement in the overall SpA population are needed. Anti-TNF therapy should be considered in patients with hip involvement, and root joint involvement should be assessed routinely in clinical practice.

CT-Based Evaluation of Diffuse Idiopathic Skeletal Hyperostosis in Adult Population; Prevalence, Associations and Interobserver Agreement.

Diffuse idiopathic skeletal hyperostosis (DISH), being an asymptomatic condition, is generally discovered incidentally on imaging and it has not received much attention for research on clinical grounds. We assessed the prevalence of DISH, its associated factors, and interobserver agreement for computed tomography (CT)-based diagnosis of DISH. CT scans of chest, abdomen, and pelvis performed for various clinical indications were retrospectively reviewed. Resnick criteria were used for the diagnosis of DISH. Moreover, enthesopathy along with comorbidities was assessed. CT scans were observed by 3 observers having different experience levels. Out of total 416 patients, the prevalence of DISH was 30.8%. Strong positive agreement was observed between observer 1 and 2 (k = 0.89), observer 1 and 3 (k = 0.91), and observer 2 and 3 (k = 0.94). Reporting rate of DISH was 59.3%. Regression analyses showed that enthesopathy was 2.45 times (adjusted odds ratio [AOR]: 2.45, 95% confidence intervals [CI]: 1.48-4.05), diabetic patients were 4.74 times (AOR: 4.74, 95% CI: 2.89-7.78) while hypertensive patients were 2.17 times (AOR: 2.17, 95% CI: 1.30-3.62) more likely to have DISH in comparison to those who do not have DISH. A high prevalence of DISH was observed in our cohort. Enthesopathy and comorbidities like diabetes and hypertension were significant factors associated with DISH. Moreover, excellent agreement was observed in defining DISH on CT according to Resnick criteria.

Methotrexate achieves major cDAPSA response, and improvement in dactylitis and functional status in psoriatic arthritis.

OBJECTIVE: Despite the widespread clinical use of MTX in PsA, data from published randomized controlled studies suggest limited efficacy. The objective of the present study was to document the efficacy of MTX. METHODS: This was an open-label, prospective study of patients satisfying the ClASsification criteria for Psoriatic ARthritis study (CASPAR) criteria for PsA who received MTX in doses of ⩾15 mg/week throughout the follow-up period of 9 months. Disease activity was assessed across various domains by tender and swollen joint count, physician and patient global assessment, DAS-28 ESR, Clinical Disease Activity Index for PsA (cDAPSA), Leeds Dactylitis Instrument basic, Leeds Enthesitis Index (LEI), Psoriasis Area and Severity Index (PASI), Minimal Disease Activity and HAQ (CRD Pune version) at baseline and at 3, 6 and 9 months of follow-up. Response to therapy was assessed by EULAR DAS28 ESR, Disease Activity Index for PsA (cDAPSA) response, HAQ response and PASI75. MTX dose escalation and the use of combination DMARDS were dictated by disease activity. RESULTS: A total of 73 patients were included, with mean (s.d.) age 44 (9.7) years. The mean (s.d.) dose of MTX used was 17.5 (3.8) mg/week. Seven patients received additional DMARDS (LEF/SSZ). At the end of 9 months, significant improvement (P < 0.05) was noted in the tender joint count, swollen joint count, global activity, DAS-28ESR, cDAPSA, Leeds Dactylitis Index basic, LEI, PASI and HAQ. Major cDAPSA response was achieved in 58.9% of patients. EULAR DAS28 moderate and good response was achieved in 74% and 6.8% of patients, respectively. Minimal Disease Activity was achieved in 63% of patients. A PASI75 response and HAQ response was achieved in 67.9% and 65.8% of patients, respectively. CONCLUSION: MTX initiated at ⩾15 mg/week with targeted escalation resulted in significant improvement in the skin, joint, dactylitis, enthesitis and functional domains of PsA.

Greater magnitude of entheseal microdamage and repair in psoriatic arthritis compared with ankylosing spondylitis on ultrasound.

Objectives: AS and PsA share clinical and immunological features centred on enthesitis. However, a strong association between PsA and preceding injury has been recognized. The aim of this study was to test the hypothesis that the entheseal damage seen by US is commoner in PsA patients than in AS patients. Methods: Seventy-nine AS and 85 PsA patients had US scans of 1640 entheses to calculate entheseal inflammation (hypoechogenicity, thickening and Doppler) and damage scores (calcifications, enthesophytes and erosions). Regression modelling was done to evaluate the effect of diagnoses on outcomes, controlling for age, gender, BMI, clinical enthesitis, HLA-B27, and anti-TNF use. Results: Both inflammation and damage scores on US were correlated with BMI (r = 0.392; r = 0.320) and age (r = 0.308; r = 0.538) (P < 0.001), and men had higher inflammation scores than women [12.3 (7.5) vs 8.9 (7.3), P = 0.001]. In multivariate analysis, despite similar (anti-TNF-treated patients) or slightly less inflammation (anti-TNF-naïve patients) in the PsA group, they had 4.22 times more US damage than their counterparts with AS. The difference was even higher in the anti-TNF-naïve patients (5.6 times). Conclusion: On US assessment, PsA patients have greater entheseal insertion damage scores compared with AS, suggesting potential differences in tissue repair, immunobiology or response to injury at insertions.