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.

Extraarticular manifestations of juvenile idiopathic arthritis and their impact on health-related quality of life.

OBJECTIVES: The objective of this study is to investigate extraarticular manifestations (EAMs) in patients with juvenile idiopathic arthritis (JIA) and assess their impact on health-related quality of life (HRQoL) among these patients. METHODS: This cross-sectional analytic study was carried out on 117 patients with JIA. EAMs were identified clinically by history and examination. Sicca symptoms, peripheral neuropathy, enthesitis, and skin lesions were picked up during clinical examination. Pulmonary involvement was evaluated by high-resolution CT chest. Patients were assessed by abdominal ultrasonography to assess the size of liver and spleen. Atlantoaxial subluxation was evaluated by cervical spine x-rays. Patients were evaluated by Pediatric Quality of Life Inventory-4 (PedsQL-4) and PedsQL-3 arthritis module. RESULTS: The median age of patients was 14 years with a median disease duration 4 years, 82.9% were females. Of the studied 117 JIA patients, 85 patients (72.6%) had at least one EAM. Persistent fatigue (51.3%) was the most prevalent EAM, followed by recurrent skin rash (16.2%), enthesitis (15.4%), recurrent fever (13.7%), and uveitis (12%). Patients with EAMs scored significantly lower in physical functioning (p = 0.001), emotional functioning (p < 0.001), social functioning (p = 0.005), and school functioning (p = 0.001). Regarding PedsQL arthritis module, patients with EAM had also significantly lower scores than did patients without EAM on the domains of pain and hurt (p < 0.001), daily activities (p = 0.008), and worry (p = 0.001). RESULTS: EAMs are prevalent among JIA patients and have a negative impact on their HRQoL. So, early identification and treatment are highly recommended. Key Points • A large percentage of JIA patients experienced at least one extraarticular manifestation (EAM). • Persistent fatigue and recurrent skin rash are the most prevalent EAMs in JIA patients. • JIA patients with EAMs have worse scores in almost all domains of HRQoL.

Presentation of enthesitis-related arthritis and juvenile-onset spondyloarthritis: a cross-sectional study in a pediatric and adult clinic.

BACKGROUND: Juvenile idiopathic arthritis (JIA) comprises a whole spectrum of chronic arthritis starting before 16 years of age. The study aims to explore the clinical and demographic descriptors, treatment, and disease progression of enthesitis-related arthritis (ERA) in comparison with juvenile-onset spondyloarthritis (SpA). METHODS: Cross-sectional analysis of consecutive patients in two dedicated clinics, with a single visit and retrospective case-notes review. Arthritis, enthesitis and sacroiliitis were evaluated by scoring disease activity and damage. Continuous variables were reported by median, interquartile range; categorical variables were reported by the frequency comparison of the two groups. RESULTS: Thirty-three cases were included, being 23 (69.7%) with ERA. The median age at diagnosis was 12.5 y (SpA) vs. 9 y (ERA) (p < 0.01); the time from symptom onset to diagnosis was 5.5 y (SpA) vs. 1.5 y (ERA) (p < 0.03). In both groups, the predominant presentation was a single joint or < 5 lower limb joints and asymmetric involvement, with a high frequency of enthesitis. There was a higher frequency of mid-tarsal and ankle synovitis in the ERA group and hip involvement in those with SpA. The comparison of the frequency of spine symptoms at presentation, 30% SpA vs. 21.7% ERA (p = 0.7), was not significant, and radiographic progression to spinal involvement occurred in 43.5% of ERA patients. The median time for spinal progression and age at onset was 2.2 and 12 y for ERA, and 4 and 16.5 y for SpA, respectively. Activity and damage scores were not significantly different between the groups. Treatment comparison resulted in 91.3% of ERA and 100% SpA being treated, predominantly with NSAIDs in both groups, followed by DMARDs and biologics, with a higher frequency of biologics in SpA. CONCLUSION: The main differences were the late diagnoses of SpA, and the hip and spine involvement, with higher frequency of biologic treatment in juvenile-onset SpA compared to ERA.

Patients With Psoriatic Arthritis-Related Enthesitis and Persistence on Tofacitinib Under Real-World Conditions.

OBJECTIVE: Information on the persistence of tofacitinib (TOF) in psoriatic arthritis (PsA) is scarce in real-world conditions. Our objective was to analyze the persistence and safety of TOF under these conditions. METHODS: This was a single-center retrospective longitudinal observational study of all patients with PsA who received at least 1 dose of TOF. The main focus was on adverse events (AEs) and drug survival. Drug survival was analyzed by Kaplan-Meier curves and persistence explanatory factors by multivariate Cox regression models. The hazard ratio (HR) was used to measure association. RESULTS: Seventy-two patients were included, 54 women and 18 men, mean age 51.9 (SD 11.1) years, mean disease duration of 10.4 (SD 6.99) years. TOF was ≥ third line of therapy in > 70% of cases. The median survival was 13.0 (IQR 5.3-29.0) months. One-year retention rate was 52.7% (95% CI 42.4-65.6). TOF survival was not influenced by sex, disease duration, comorbidities, or line of treatment. Younger patients (HR 0.96, P = 0.01) and those with enthesitis (HR 0.37, P = 0.03) showed lower odds of drug discontinuation. The overall rate of AEs was 52.9 (95% CI 38.5-70.6)/100 person-years. Most AEs occurred during the first 6 months of exposure. CONCLUSION: In this real-world study, TOF showed a reasonably good retention rate in a PsA population that was mostly refractory to biologic and oral targeted synthetic disease-modifying antirheumatic drugs. There were no new causes for concern regarding safety. Patients with refractory PsA and enthesitis might be a specific target population for this drug.

Hematological indices in psoriatic enthesopathy: relation to clinical and ultrasound evaluation.

BACKGROUND: Enthesopathy is considered a crucial aspect of assessment and outcome in psoriatic arthritis (PsA). Musculoskeletal ultrasound (MSUS) is a critical tool for accurately detecting enthesitis. Recent research focuses on identifying simple biomarkers for detecting and monitoring psoriatic enthesopathy. Red cell distribution width (RDW), mean platelet volume (MPV), and neutrophil/lymphocyte ratio (NLR) are components of a complete blood count (CBC) and are reliable bio-inflammatory markers in various rheumatic diseases. AIM OF WORK: To measure MPV, RDW, and NLR in psoriatic enthesopathy and determine their relationship to disease activity and MSUS findings. PATIENTS AND METHODS: This study focused on 30 people with psoriatic arthritis (PsA) as per CASPAR criteria, along with 20 control subjects. Enthesopathy was evaluated clinically using the Leeds Enthesitis Index (LEI). The modified Disease Activity Index of Psoriatic Arthritis (DAPSA28) was calculated, and RDW, MPV, NLR, CRP, and ESR were measured. Each enthesis in LEI was radiologically assessed using plain radiography and MSUS according to OMERACT definitions. RESULTS: There was a significant relationship between clinical tenderness, the presence of enthesophytes on plain radiography, and MSUS findings at entheses sites (p < 0.001 for each). Psoriatic patients had higher levels of RDW and MPV (p < 0.001 and 0.01, respectively) than controls, with no significant differences in NLR (p = 0.189) between the two groups. RDW and MPV levels were positively correlated with the DAPSA28 score. CONCLUSION: Monitoring PsA disease activity can be improved by considering RDW and MPV as reliable indicators and using them to screen for psoriatic enthesopathy with MSUS indices. Key points • Clinically identifying enthesitis in patients with PsA can be challenging. Imaging MSUS indices hold promise for objective analysis, but there is no consensus on which indices to use in clinical trials and daily practice. • Patients with psoriatic enthesopathy have higher RDW and MPV levels, which are positively correlated with DAPSA28 score. • RDW and MPV can be considered in the turn of improved screening of psoriatic enthesopathy with MSUS scores.

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.

Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis.

OBJECTIVES: To evaluate the association between enthesitis resolution (ER) and dactylitis resolution (DR) and meaningful improvements in patient-reported outcomes (PROs) among biologic-naïve patients with PsA receiving guselkumab in the DISCOVER-2 study. METHODS: Enthesitis and dactylitis, characteristic lesions of PsA, were evaluated by independent assessors using the Leeds Enthesitis Index (range, 0-6) and Dactylitis Severity Score (range, 0-60). Proportions of patients with ER or DR (score = 0) among those with score > 0 at baseline were determined at weeks 24, 52, and 100. PROs included: fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]), pain (0-100 visual analog scale), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and health-related quality of life (36-item Short-Form Health Survey physical/mental component summary [SF-36 PCS/MCS]). Meaningful responses were defined as: improvements of ≥ 4 for FACIT-Fatigue, ≥ 0.35 for HAQ-DI, and ≥ 5 for SF-36 PCS/MCS and absolute scores of ≤ 15 for minimal pain and ≤ 0.5 for normalized HAQ-DI. Associations between ER/DR status and PRO response status were tested using a Chi-square test. RESULTS: Guselkumab-treated patients with ER were more likely than those without ER to achieve minimal pain (p < 0.001), normalized HAQ-DI (p < 0.001), and PCS response (p < 0.05) at weeks 24, 52, and 100. Patients with DR were more likely than those without DR to achieve FACIT-Fatigue response at week 24 and week 52 (both p ≤ 0.01) and minimal pain at week 24 and normalized HAQ-DI at week 52 (both p ≤ 0.03). CONCLUSION: In biologic-naïve patients with active PsA treated with guselkumab, achieving ER or DR was associated with durable improvements in selected PROs, including those of high importance to patients. TRIAL REGISTRATION: ClinicalTrials.gov ( https://clinicaltrials.gov ) NCT03158285; Registered: May 16, 2017. Key Points • At week 100, 65% and 76% of guselkumab-treated patients achieved enthesitis and dactylitis resolution (ER/DR). • Achieving ER was associated with achieving DR and vice versa through the end of study. • Achieving ER or DR was associated with durable and meaningful improvements in selected patient-reported outcomes.

Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study.

OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.

Guselkumab provides durable improvement across psoriatic arthritis disease domains: post hoc analysis of a phase 3, randomised, double-blind, placebo-controlled study.

OBJECTIVE: Evaluate long-term guselkumab effectiveness across Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-recognised domains/related conditions of psoriatic arthritis (PsA). METHODS: Post hoc analyses used data from DISCOVER-2 (NCT03158285) biologic/Janus-kinase inhibitor-naïve participants with active PsA (≥5 swollen/≥5 tender joints, C-reactive protein ≥0.6 mg/dL), randomised (1:1:1) to guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo with crossover to guselkumab. Outcomes aligned with key GRAPPA-recognised domains of overall disease activity, peripheral arthritis, axial disease, enthesitis/dactylitis and skin psoriasis (nail psoriasis was not evaluated). PsA-related conditions (inflammatory bowel disease (IBD)/uveitis) were assessed via adverse events through W112. Least squares mean changes from baseline through W100 in continuous outcomes employed repeated measures mixed-effects models adjusting for baseline scores. Binary measure response rates were determined with non-responder imputation for missing data. RESULTS: 442/493 (90%) of guselkumab-randomised patients completed treatment through W100. Following early reductions in disease activity with guselkumab, durable improvements were observed across key PsA domains (swollen/tender joints, psoriasis, spinal pain, enthesitis/dactylitis) through W100. Response rates of therapeutically relevant targets generally increased through W100 with guselkumab Q4W/Q8W: Disease Activity Index for PsA low disease activity (LDA) 62%/59%, enthesitis resolution 61%/70%, dactylitis resolution 72%/83%, 100% improvement in Psoriasis Area and Severity Index 59%/53%, Psoriatic Arthritis Disease Activity Score LDA 51%/49% and minimal disease activity 38%/40%. Through W112, no cases of IBD developed among guselkumab-randomised patients and one case of uveitis was reported. CONCLUSION: In biologic-naïve patients with active PsA, guselkumab provided early and durable improvements in key GRAPPA-recognised domains through 2 years, with substantial proportions achieving important treatment targets.

Detection of subclinical enthesitis by ultrasonography in patients with psoriasis and controls.

INTRODUCTION: Psoriasis is a widespread chronic inflammatory skin disease; enthesitis is inflammation of the tendon, ligament, and joint capsule insertion, prevalent in patients with psoriatic arthritis. OBJECTIVES: The aim of study to evaluate the utility of the Madrid Sonography Enthesitis Index scoring system for accurate detection of subclinical enthesitis in patients with Psoriasis compared with healthy controls. Another objective was to assess increase in enthesis area and Psoriatic arthritis incidence, in a prospective 1-year follow-up. METHOD: Patients aged ≥18 years who were diagnosed with Psoriasis, without musculoskeletal complaints, and who did not have any clinical sign and/or symptom of enthesitis and synovitis were included in the study. The patients and healthy controls were evaluated with ultrasonography. Ultrasonography evaluation consisted of the detection of gray-scale enthesitis and power Doppler signal in the enthesis areas. The Madrid Sonography Enthesitis Index scoring system was used to quantify the extent of the sonographic enthesis abnormalities. RESULTS: The mean MASEI score, structure, thickness, erosion, and calcification were significantly higher in the Psoriasis group than in the control group. The mean MASEI score, structure, erosion, and calcification measurements were significantly higher at the last examination when compared to the first examination. The triceps was the most commonly affected tendon in both groups. CONCLUSION: Ultrasonography is an important tool for diagnosis and follow-up of subclinical enthesitis in patients with psoriasis. Regardless of disease duration and severity, patients should be screened using ultrasonography at yearly intervals.

Ultrasonographic Evaluation of Nail Involvement in Patients With Axial Spondyloarthritis.

OBJECTIVES: This study aimed to evaluate the nail units of patients with axial spondyloarthritis (ax-SpA) using ultrasound and to identify any subclinical changes. We also aimed to examine the relationship between clinical enthesitis scores and nail involvement in patients with ax-SpA. METHODS: The study included 40 patients with ax-Spa, 40 patients with psoriatic arthritis (PsA), and 40 healthy controls. The thickness of the nail plates, morphological changes, the thickness of the proximal nail units, the thickness of the nail beds, and power Doppler signal intensities were evaluated and compared. Maastricht Ankylosing Spondylitis Enthesitis Score and Spondyloarthritis Research Consortium of Canada Enthesitis Index were also evaluated in patients with ax-SpA. RESULTS: There was no significant difference between the thickness of the nail plates of the three groups (P > .05). The first nail bed thickness of ax-SpA cases was significantly higher than the control group (P = .046), and the fourth and fifth nail proximal unit thicknesses of the control group were significantly lower than the ax-SpA and PsA groups (P = .023, P = .017). We also found that the Wortsman scores of the cases with PsA were significantly higher than the ax-SpA and control groups (P = .0001). CONCLUSION: The thickness of the proximal nail unit adjacent to the insertion of the digital extensor tendon, which is considered as the enthesis area, is similar to the patients with PsA in patients with ax-SpA, especially in the fourth and fifth fingers compared to the control group. On the other hand, almost no structural changes in nail plates were observed in patients with ax-SpA group.

DKK-1 in psoriatic arthritis: Correlation with disease activity and enthesopathy / DKK-1 en artritis psoriásica: correlación con la actividad de la enfermedad y la entesopatía

Background: Psoriatic arthritis (PsA) is a complex inflammatory disease with varied clinical characteristics. A pathognomonic characteristic of PsA is enthesitis. Entheseal inflammation ultimately leads to the production of new bone (enthesophytes). Dickkopf-related protein-1 (DKK-1) is a wingless (Wnt) inhibitor that inhibits osteoblast function. Objectives: Assessment of the serum level of DKK-1 and its association with disease activity and enthesopathy in PsA patients. Methods: This observational case–control study included 50 PsA patients and 50 healthy volunteers matched for age and gender. All participants were subjected to full medical history, clinical assessment, PSA activity using Disease Activity Index for Psoriatic Arthritis (DAPSA) score, the severity and extent of psoriasis were determined by the Psoriasis Area and Severity Index (PASI). Ultrasonographic assessment of the entheses was done in accordance with the Madrid Sonographic Enthesitis Index (MASEI). Serum level of DKK-1 and correlation with disease activity and enthesopathy in PsA patients were assessed. Results: There was no significant difference between patients and controls regarding age and sex. The mean value of SPARCC index, DAPSA score and PASI score were 6.74±4.58, 33.24±15.26, and 8.35±10.93, respectively. There was significant difference between patients and controls regarding the serum levels of DKK-1 and MASEI score (p<0.0001). There was a significant positive correlation between serum DKK-1 and MASEI (r: 0.43527, p: 0.00158), MASEI inflammatory (r: 0.37958, p: 0.00655), and MASEI damage (r: 0.38384, p: 0.00593). Conclusions: Serum DKK-1 levels were elevated in PsA patients and were found to be correlated with MASEI score for enthesopathy.(AU)

Antecedentes: La artritis psoriásica (APs) es una enfermedad inflamatoria compleja con características clínicas variadas. Una característica patognomónica de la artritis psoriásica es la entesitis. La inflamación entesófila finalmente conduce a la producción de hueso nuevo (entesófitos). La proteína 1 relacionada con dickkopf (DKK-1) es un inhibidor sin alas (Wnt) que inhibe la función de los osteoblastos. Objetivos: Evaluación del nivel sérico de DKK-1 y su asociación con la actividad de la enfermedad y la entesopatía en pacientes con APs. Métodos: Este estudio observacional de casos y controles; incluyó a 50 pacientes con artritis psoriásica y 50 voluntarios sanos emparejados por edad y sexo. Todos los participantes fueron sometidos a historia clínica completa, evaluación clínica, actividad de APs utilizando la puntuación del Índice de Actividad de la Enfermedad para la Artritis Psoriásica (DAPSA), la gravedad y la extensión de la psoriasis fueron determinadas por el área de psoriasis y el índice de gravedad (PASI). La evaluación ultrasonográfica de las entesis se realizó de acuerdo con el índice de entesitis sonográfica de Madrid (MASEI). Se evaluó el nivel sérico de DKK-1 y la correlación con la actividad de la enfermedad y la entesopatía en pacientes con artritis psoriásica. Resultados: No hubo diferencias significativas entre los pacientes y los controles con respecto a la edad y el sexo. El valor medio del índice SPARCC, la puntuación DAPSA y la puntuación PASI fueron 6,74±4,58, 33,24±15,26 y 8,35±10,93 respectivamente. Hubo diferencia significativa entre pacientes y controles con respecto a los niveles séricos de DKK-1 y la puntuación MASEI (p <0,0001). Hubo correlación positiva significativa entre DKK-1 sérico y MASEI (r: 0,43527, p = 0,00158), y daño MASEI (r: 0.38384, p = 0,00593). Conclusiones: Los niveles séricos de DKK-1 se elevaron en pacientes con APs y se encontró que estaban correlacionados con la puntuación MASEI para la entesopatía.(AU)

DKK-1 in psoriatic arthritis: Correlation with disease activity and enthesopathy.

BACKGROUND: Psoriatic arthritis (PsA) is a complex inflammatory disease with varied clinical characteristics. A pathognomonic characteristic of PsA is enthesitis. Entheseal inflammation ultimately leads to the production of new bone (enthesophytes). Dickkopf-related protein-1 (DKK-1) is a wingless (Wnt) inhibitor that inhibits osteoblast function. OBJECTIVES: Assessment of the serum level of DKK-1 and its association with disease activity and enthesopathy in PsA patients. METHODS: This observational case-control study included 50 PsA patients and 50 healthy volunteers matched for age and gender. All participants were subjected to full medical history, clinical assessment, PSA activity using Disease Activity Index for Psoriatic Arthritis (DAPSA) score, the severity and extent of psoriasis were determined by the Psoriasis Area and Severity Index (PASI). Ultrasonographic assessment of the entheses was done in accordance with the Madrid Sonographic Enthesitis Index (MASEI). Serum level of DKK-1 and correlation with disease activity and enthesopathy in PsA patients were assessed. RESULTS: There was no significant difference between patients and controls regarding age and sex. The mean value of SPARCC index, DAPSA score and PASI score were 6.74±4.58, 33.24±15.26, and 8.35±10.93, respectively. There was significant difference between patients and controls regarding the serum levels of DKK-1 and MASEI score (p<0.0001). There was a significant positive correlation between serum DKK-1 and MASEI (r: 0.43527, p: 0.00158), MASEI inflammatory (r: 0.37958, p: 0.00655), and MASEI damage (r: 0.38384, p: 0.00593). CONCLUSIONS: Serum DKK-1 levels were elevated in PsA patients and were found to be correlated with MASEI score for enthesopathy.

'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.

Subclinical enthesitis in enthesitis-related arthritis and sacroiliitis associated with familial Mediterranean fever.

OBJECTIVES: In our study, we investigated the presence of subclinical enthesitis by ultrasonography (US) in asymptomatic patients with enthesitis-related arthritis (ERA) and sacroiliitis associated with familial Mediterranean fever (FMF). METHODS: A total of 50 patients, including 35 patients with ERA and 15 with sacroiliitis associated with FMF, were included in the study. All patients were evaluated with US by a paediatric radiologist. Enthesis of seven tendons (common extensor and flexor tendons, quadriceps tendon, proximal and distal patellar tendon, Achilles tendon, and plantar fascia) was examined on both sides. RESULTS: Subclinical enthesitis was detected in 10 ERA (28.5%) and three FMF (20%) patients. Enthesitis was radiologically diagnosed in 16 (2.3%) out of 700 evaluated entheseal sites. The most frequent sites of enthesitis were Achilles (37.5%) and quadriceps (31.3%) tendons. All patients were in clinical remission and had no active complaints, and acute phase reactants were within normal limits. Therefore, the patients were followed up without treatment change. However, disease flare-up was observed in three of these patients (23.1%) during the follow-up, and their treatments were intensified. CONCLUSIONS: Our results showed that the US can be particularly helpful in detecting subclinical enthesitis and predicting disease flare-ups.

The association between sonographic enthesitis with sonographic synovitis and tenosynovitis in psoriatic arthritis patients.

OBJECTIVES: To examine the association between sonographic enthesitis with sonographic synovitis and tenosynovitis in PsA patients, and the association between sonographic enthesitis and clinical characteristics. METHODS: Consecutive PsA patients that fulfilled the ClASsification criteria for Psoriatic ARthritis (CASPAR) were prospectively recruited. Each patient was evaluated by comprehensive clinical and sonographic assessment (greyscale and Doppler), the latter including 52 joints, 40 tendons and 14 entheses [according to MAdrid Sonography Enthesitis Index (MASEI) plus lateral epicondyles] performed by an experienced sonographer blinded to the clinical data. The US enthesitis score was further categorized to inflammatory (hypoechogenicity, thickening, bursitis and Doppler) and structural (enthesophytes/calcifications and erosions) subcategories. Multivariate linear regression models assessed the association between enthesitis and the selected variables. RESULTS: A total of 158 PsA patients [mean (s.d.) age 52.3 (13) years, 88 (55.7%) females] were analysed. Multivariate linear regression analyses showed a significant association between sonographic enthesitis and sonographic synovitis (ß = 0.18, P = 0.008) and between sonographic enthesitis and sonographic tenosynovitis (ß = 0.06, P = 0.02). These associations were derived from the enthesitis inflammatory subcategory of the MASEI (P < 0.05). Associations between enthesitis and synovitis were also demonstrated on the level of the elbow, knee and ankle joints (P < 0.05). In addition, sonographic enthesitis was significantly associated with older age, male sex, swollen joint count, CRP level and physical occupation. CONCLUSIONS: Sonographic enthesitis is associated with sonographic synovitis and tenosynovitis. The severity of sonographic enthesitis may represent a marker for inflammatory activity in other musculoskeletal domains.

Enthesitis in patients with psoriatic arthritis treated with secukinumab or adalimumab: a post hoc analysis of the EXCEED study.

OBJECTIVES: To evaluate enthesitis treatment response, including time to resolution and data from multiple enthesitis instruments, in patients with PsA treated with secukinumab or adalimumab for 52 weeks. METHODS: In this post hoc analysis of the EXCEED study, patients receiving secukinumab 300 mg or adalimumab 40 mg per the label were grouped by presence or absence of baseline enthesitis based on the Leeds Enthesitis Index (LEI) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Efficacy was assessed according to several enthesitis-related instruments using non-responder imputation for the achievement of enthesitis resolution (LEI/SPARCC = 0), Kaplan-Meier analysis for time to resolution, and as-observed data for other outcomes. RESULTS: Enthesitis was present at baseline in 498 of 851 patients (58.5%) as assessed by LEI and in 632 of 853 patients (74.1%) as assessed by SPARCC. Patients with baseline enthesitis generally presented with greater disease activity. Similar proportions of patients receiving secukinumab or adalimumab achieved resolution of LEI and SPARCC at weeks 24 (secukinumab: LEI/SPARCC, 49.6%/45.8%; adalimumab: LEI/SPARCC, 43.6%/43.5%) and 52 (secukinumab: LEI/SPARCC, 60.7%/53.2%; adalimumab: LEI/SPARCC, 55.3%/51.4%), with comparable mean time to enthesitis resolution. Improvements were similar for both drugs at individual enthesitis sites. Resolution of enthesitis with secukinumab or adalimumab was associated with improvements in quality of life at week 52. CONCLUSION: Secukinumab and adalimumab showed similar efficacy, including time to resolution, with respect to resolution of enthesitis. Inhibition of IL-17 with secukinumab reduced clinical enthesitis similarly to TNF-α inhibition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02745080.

The posterolateral ligament of the elbow: anatomy and clinical relevance.

BACKGROUND: The posterolateral capsule was recognized in the past as an important structure for elbow stability but was later disregarded. Two recent biomechanical studies demonstrated its role in preventing posterolateral instability, and thus it should be identified as a distinct ligament: the posterolateral ligament (PLL). This study includes 2 parts: an anatomic study of the PLL's footprint and a collection of 5 cases of pathologic lesions of the PLL. METHODS: Six cadaveric upper limbs were assessed. The attachments of the PLL were dissected, the footprints were marked and photographed, and the 2-dimensional area and length were measured. RESULTS: The mean proximal attachment dimensions were a length of 13 mm and an area of 101 mm2, and the mean distal attachment dimensions were 19 mm and 111 mm2, respectively. There were 2 cases of posterolateral elbow pain in professional cricket bowlers, diagnosed radiographically as enthesopathy of the PLL's proximal attachment on the posterior capitellum, probably due to repeated forced hyperextension of the elbow. Both patients were treated by débridement of the posterior capitellum and reattachment of the PLL, with complete resolution of symptoms. In addition, there were 3 cases of clinical posterolateral rotatory instability in young patients. Two athletes had an isolated acute tear of the PLL, and on physical examination, both had positive posterior draw test results but negative pivot-shift test results. Both underwent elbow arthroscopy and repair of the PLL with resolution of symptoms. The third patient had long-standing recurrent elbow instability, following a failed lateral ulnar collateral ligament reconstruction, in the presence of an Osborne-Cotterill lesion. He underwent revision lateral ulnar collateral ligament reconstruction, bone grafting of the bony lesion, and reattachment of the PLL, with complete resolution of symptomatic posterolateral rotatory instability. CONCLUSIONS: The PLL of the elbow has a significant role in the elbow's posterolateral stability. Its footprints were described, and its clinical significance was demonstrated in cases of elbow instability caused by acute ligament tears and elbow pain due to ligament enthesopathy. Surgeons should be aware of this structure and potential pathology related to its injury.